Bone Marrow Transplant - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

BONE MARROW TRANSPLANT A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES...

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BONE MARROW TRANSPLANT A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1 Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Bone Marrow Transplant: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84358-9 1. Bone Marrow Transplant-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on bone marrow transplant. 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 BONE MARROW TRANSPLANT ................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bone Marrow Transplant ............................................................. 7 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 73 CHAPTER 2. NUTRITION AND BONE MARROW TRANSPLANT ..................................................... 121 Overview.................................................................................................................................... 121 Finding Nutrition Studies on Bone Marrow Transplant .......................................................... 121 Federal Resources on Nutrition ................................................................................................. 127 Additional Web Resources ......................................................................................................... 128 CHAPTER 3. ALTERNATIVE MEDICINE AND BONE MARROW TRANSPLANT ............................... 129 Overview.................................................................................................................................... 129 National Center for Complementary and Alternative Medicine................................................ 129 Additional Web Resources ......................................................................................................... 156 General References ..................................................................................................................... 158 CHAPTER 4. DISSERTATIONS ON BONE MARROW TRANSPLANT ................................................. 159 Overview.................................................................................................................................... 159 Dissertations on Bone Marrow Transplant ............................................................................... 159 Keeping Current ........................................................................................................................ 160 CHAPTER 5. CLINICAL TRIALS AND BONE MARROW TRANSPLANT............................................ 161 Overview.................................................................................................................................... 161 Recent Trials on Bone Marrow Transplant ............................................................................... 161 Keeping Current on Clinical Trials ........................................................................................... 183 CHAPTER 6. PATENTS ON BONE MARROW TRANSPLANT ............................................................ 185 Overview.................................................................................................................................... 185 Patents on Bone Marrow Transplant ........................................................................................ 185 Patent Applications on Bone Marrow Transplant..................................................................... 190 Keeping Current ........................................................................................................................ 196 CHAPTER 7. BOOKS ON BONE MARROW TRANSPLANT ............................................................... 199 Overview.................................................................................................................................... 199 Book Summaries: Federal Agencies............................................................................................ 199 Book Summaries: Online Booksellers......................................................................................... 200 Chapters on Bone Marrow Transplant ...................................................................................... 201 CHAPTER 8. MULTIMEDIA ON BONE MARROW TRANSPLANT..................................................... 205 Overview.................................................................................................................................... 205 Audio Recordings....................................................................................................................... 205 CHAPTER 9. PERIODICALS AND NEWS ON BONE MARROW TRANSPLANT.................................. 207 Overview.................................................................................................................................... 207 News Services and Press Releases.............................................................................................. 207 Newsletter Articles .................................................................................................................... 210 Academic Periodicals covering Bone Marrow Transplant......................................................... 210 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 211 Overview.................................................................................................................................... 211 U.S. Pharmacopeia..................................................................................................................... 211 Commercial Databases ............................................................................................................... 212 Researching Orphan Drugs ....................................................................................................... 213 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 217 Overview.................................................................................................................................... 217 NIH Guidelines.......................................................................................................................... 217

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NIH Databases........................................................................................................................... 219 Other Commercial Databases..................................................................................................... 221 APPENDIX B. PATIENT RESOURCES ............................................................................................... 223 Overview.................................................................................................................................... 223 Patient Guideline Sources.......................................................................................................... 223 Associations and Bone Marrow Transplant .............................................................................. 229 Finding Associations.................................................................................................................. 230 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 233 Overview.................................................................................................................................... 233 Preparation................................................................................................................................. 233 Finding a Local Medical Library................................................................................................ 233 Medical Libraries in the U.S. and Canada ................................................................................. 233 ONLINE GLOSSARIES................................................................................................................ 239 Online Dictionary Directories ................................................................................................... 240 BONE MARROW TRANSPLANT DICTIONARY ................................................................. 241 INDEX .............................................................................................................................................. 319

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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 bone marrow transplant is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about bone marrow transplant, 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 bone marrow transplant, 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 bone marrow transplant. 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 bone marrow transplant, 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 bone marrow transplant. 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 BONE MARROW TRANSPLANT Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bone marrow transplant.

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

Long-Term Oral and Craniofacial Complications Following Pediatric Bone Marrow Transplantation Source: Pediatric Dentistry. 22(1): 57-62. January-February 2000. Contact: Available from American Academy of Pediatric Dentistry. Publications Department, 211 East Chicago Avenue, Suite 700, Chicago, IL 60611-2616. Summary: Bone marrow transplantation (BMT) has become a common form of treatment for childhood diseases and disorders that directly or indirectly affect the production of stem cells which give origin to blood and immune system elements. The pre transplant treatment regimens can include, but are not limited to, chemotherapy or radiation therapy, both of which can cause considerable acute and long term undesired

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effects in the oral cavity and the craniofacial complex. This article discusses the complications that a pediatric dentist may encounter when treating a child or adolescent who has undergone BMT. Systemic effects of BMT can include immunologic dysfunction, pulmonary dysfunction, endocrine dysfunction (leading to growth and development problems), and central nervous system abnormalities (neuropsychological deficits, lower IQ scores, problems with visual motor, fine motor, abstract thinking, and spatial processing tasks). The authors focus on the role of dental care, chronic oral graft versus host disease (GVHD), xerostomia (dry mouth) and taste dysfunction, infections, non gingival (gum) soft tissue growths, dental hypersensitivity, and dental and craniofacial developmental abnormalities. The authors stress the importance of the dentist's role in discussing these possible sequelae with the patient and his or her caregivers, as many physicians are not aware of these potential problems and may not inform the family. With this information, the patient and caregivers become aware of the importance of good oral and dental care in decreasing the chances of oral complications. 6 figures. 44 references. •

Oral Cavity Complications of Bone Marrow Transplantation Source: Seminars in Cutaneous Medicine and Surgery. 16(4): 265-272. December 1997. Summary: Bone marrow transplantation, once regarded as experimental, has evolved into a standard treatment for a variety of malignancies. Considerable advances have been made in histocompatibility typing, pretransplantation chemotherapy, and posttransplantation immunosuppressive therapy, as well as prophylaxis and treatment of infections. This article reviews the oral cavity complications that may result from bone marrow transplantation. The authors note that oral complications develop in almost all patients, and their early recognition may result in the institution of prompt treatment and prolonged survival. Mucositis, often severe and extremely painful, develops in more than three quarters of bone marrow transplant recipients, and its prevention, unfortunately, remains unsatisfactory. Herpes simplex virus and Candida albicans account for most oral infections, although their incidence has been dramatically reduced by the institution of prophylactic agents. Graft versus host disease (GVHD) continues to be a significant complication of marrow transplantation, and the detection of commonly occurring oral changes may support its diagnosis. The authors conclude with a discussion of the prevention options available for these patients. 4 figures. 47 references. (AA-M).

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Changes in the Periodontal Status of Patients Undergoing Bone Marrow Transplantation Source: Journal of Periodontology. 71(3): 394-402. March 2000. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Patients receiving an HLA matched bone marrow transplant (BMT) from a relative or unrelated donor undergo a permanent alteration of their immune system, followed by a prolonged period of immunodeficiency. This article reports on a study that examined alterations in the periodontal status of patients for the 6 months post bone marrow transplantation. Patients scheduled for BMT (n = 37) participated in the study. One examiner carried out periodontal examinations (clinical and radiographic) immediately prior to 3 and 6 months after transplantation. All patients followed an intense oral care program. Subgingival (under the gum) plaque samples were analyzed by ELISA for the presence of pathogens, including Porphyromonas gingivalis,

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Actinobacillus actinomycetemcomitans, and Prevotella intermedia. Gains in clinical attachment level (CAL) at 4 or more sites from baseline to 6 months post BMT were noted in 9 of 16 patients (56 percent), while 6 of 16 patients (38 percent) experienced a loss of CAL at 4 or more sites in the same period. A significant improvement in the gingival index occurred between all sequential time periods when assessed at a site level. At a patient level, 11 of 18 patients (61 percent) showed a significant change in gingival index between baseline and 3 months, and 10 of 16 patients (63 percent) between baseline and 6 months. There was no significant relationship between clinical changes and the prevalence of the periodontal pathogens at the various time periods. The authors conclude that an improvement in periodontal health was recorded between baseline and 6 months post transplantation. Most of the improvement in periodontal status was noted in the first 3 months after BMT, with a slight decline in periodontal health between 3 and 6 months posttransplant. This improvement was noted despite the profound changes occurring in the immune system. No significant alteration was noted in the prevalence of periodontal pathogens during the study period. The results of this study highlight the benefits of a stringent oral health care protocol as evidenced by the improvement of periodontal health in the BMT patients despite profound immunosuppression. 5 figures. 3 tables. 48 references. •

Bone Marrow Transplants: Current Applications and Implications for Oral Health Source: New York State Dental Journal. 65(4): 28-31. April 1999. Contact: Available from Dental Society of the State of New York. 7 Elk Street, Albany, NY 12207. (518) 465-0044. Summary: The application of bone marrow transplantation (BMT) to address a variety of pathologies has increased dramatically in the last decade. Side effects of BMT include a variety of documented untoward effects on oral health, many of which are age dependent. With the increasing number of people, particularly children, receiving BMT, it is entirely possible that these recipients may appear as 'routine, healthy' patients in a general practice or other oral health care setting. This article reviews the treatment modality of BMT, its current applications, and the short and long term effects that the oral health care practitioner must identify, understand, and address. Diseases treated with BMT include bone marrow disorders, malignancies, metabolic diseases, inherited disorders, and severe combined immunodeficiencies. Oral complications in pediatric MBT patients can include mucositis and ulcerations, salivary flow decrease and compositional change, xerostomia (dry mouth), caries (cavities) rate increase, and oral infections. The authors stress that preventing oral problems in patients who have undergone BMT is critical. 2 tables. 6 references. (AA-M).

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Guidelines for the Management of Pediatric Dental Patients Receiving Chemotherapy, Bone Marrow Transplantation, and/or Radiation Source: Pediatric Dentistry. 20(6): 53-54. November 1998. Contact: Available from American Academy of Pediatric Dentistry. Publications Department, 211 East Chicago Avenue, Suite 700, Chicago, IL 60611-2616. Summary: The pediatric patient who is beginning, currently receiving, or has received chemotherapy, a bone marrow transplant (BMT), or radiation requires special consideration and altered oral and dental treatment schemes due to the systemic impact of any of these cancer treatments. This Guideline, published by the American Academy of Pediatric Dentistry (revised in 1993), summarizes the guidelines for the management of these patients. Since there are a myriad of protocols for chemotherapy, BMT, and

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radiation, oral and dental care must be provided in consultation with the oncologist and tailored to the individual needs of the patient. The Guideline offers five management objectives: decrease the morbidity and mortality due to infection; decrease the morbidity due to hemorrhage; facilitate the patient's nutritional status; improve the patient's comfort; and increase the education of the patient, family, and physician relative to the importance of maintaining oral health and the methods to achieve it. The Guideline then divides management of the pediatric cancer patient into three phases of care. For each phase (pretreatment, during treatment and immediate posttreatment, and long term followup), the Guideline reviews assessment, diagnosis, and treatment. The long term followup phase also addresses hematologic guidelines and antibiotic prophylaxis guidelines. •

Gastrointestinal and Nutritional Sequelae of Bone Marrow Transplantation Source: Archives of Disease in Childhood. 75(3): 208-213. September 1996. Contact: Available from Archives of Disease in Childhood. Subscription Manager, BMA House, Tavistock Square, London WC1H 9JR, England. Summary: This article outlines the gastrointestinal (GI) and nutritional sequelae of bone marrow transplantation. The authors note that the nature of the GI injury following bone marrow transplantation and its clinical and nutritional sequelae are poorly defined. The authors report on a study in which prospective assessments of GI function, nutritional status, and well-being were carried out in 47 patients (28 males, 19 females; mean age 8.4 years) undergoing bone marrow transplant. Thirty-one episodes of diarrhea occurred in 27 patients at a median of 10 days after transplantation. Ninety-one percent of episodes were associated with protein losing enteropathy. Protein losing enteropathy was more severe in graft-versus-host disease (GVHD) compared with other causes. Transient pancreatic insufficiency developed in 18 patients, and pancreatitis in one. Intestinal permeability was normal in 12 patients who had no diarrhea during the conditioning treatments. Patients with diarrhea had a significantly greater decrease in nutritional status and well-being than patients without diarrhea. The authors conclude that GI injury following bone marrow transplantation is complex and has profound effects on nutritional status and well being of the patients. 5 figures. 1 table. 39 references. (AA-M).

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Bone Marrow Transplant Nephropathy: A Case Report and Review of the Literature Source: JASN. Journal of the American Society of Nephrology. 8(1): 166-173. January 1997. Summary: This article presents a case of bone marrow transplant nephropathy, including a review of the clinical and pathologic features. Bone marrow transplantation can be complicated by renal failure resulting from a variety of causes. Early renal injury most often results from infection and its subsequent treatment with nephrotoxic medications. Late renal injury after bone marrow transplantation is characterized by a syndrome similar to the hemolytic uremic syndrome. This renal syndrome, called 'bone marrow transplant nephropathy,' is thought to evolve from the late effects of radiation therapy and cytotoxic chemotherapy on the kidney. The histopathology is characterized by mesangiolysis with focal aneurysmal dilatation, fibrin thrombi in capillary loops, and marked widening of the subendothelial space resulting from deposition of amorphous material, similar to the appearance of radiation nephritis. No definitive treatment is currently available for bone marrow transplant nephropathy, except for supportive

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therapy. One table summarizes adult and pediatric cases of bone marrow transplant nephropathy. 2 figures. 5 tables. 26 references. (AA-M). •

Dental Evaluation in Bone Marrow Transplantation Source: General Dentistry. 43(4): 369-371. July-August 1995. Summary: This article presents a case report that demonstrates the importance of thorough presurgical dental radiographic and clinical examinations in bone marrow transplantation. The authors stress that general dentists should become familiar with the procedure of bone marrow transplantation (BMT) and their potential role in the success of this technically simple but immunologically complex treatment. Dentists have three roles: pretransplant oral evaluation and treatment of existing and potential dental infections; inpatient treatment of oral complications during immunosuppression and graftings; and long-term prevention and management of posttransplant dental complications. The case report describes the case of a 38-year-old woman who needed dental restorative work performed before her BMT procedure could be approved. The authors reiterate the importance of dentists understanding the implications of BMT and the need to eliminate all potential dental infection before the procedure. In the case presented, thorough radiographic and clinical examinations would have precluded misinforming the patient and prevented a six-week delay of the bone marrow transplant. 1 figure. 8 references. (AA-M).

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Long-Term Effects of Bone Marrow Transplantation on Dental Status in Children with Leukaemia Source: Bone Marrow Transplantation. 20(10): 865-869. November 15, 1997. Summary: This article reports on a study of the dental status of 27 children (19 males and 8 females) with leukemia, with the aim of studying the oral and dental health in long term survivors after bone marrow transplantation (BMT). The children were followed up with a routine oral examination, panoramic tomogram and, when necessary, an endoral radiograph at a median range of 2 years after BMT. Community periodontal index treatment necessity (CPITN), dental caries, missing or filled permanent teeth (DMFT), and dento-facial alterations according to World Health Organization criteria were registered and evaluated. Median age of the patients at BMT was 9 years (range 1.1 to 17.9 years). The mean DMFT score ranged from 1.6 to 12.4 according to age at examination and was slightly higher than the rate reported in children who received chemotherapy alone. CPITN showed the presence of soft deposits in 77.7 percent, serious gingivitis in 59.2 percent, and parodontal involvement in 3.7 percent of cases. Dento-facial abnormalities were found in 55.5 percent of patients, while 62.9 percent of the patients had tooth abnormalities or agenesis. Nine out of 27 patients (33 percent) had root hypoplasia. A negative impact on DMFT index due to multiple post-BMT factors was found. The authors conclude that age is the crucial factor in determining a developmental defect of enamel and root. The follow up of long term survivors after BMT should include regular dental examination. 1 figure. 3 tables. 26 references. (AA-M).

Federally Funded Research on Bone Marrow Transplant The U.S. Government supports a variety of research studies relating to bone marrow transplant. These studies are tracked by the Office of Extramural Research at the National

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Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to bone marrow transplant. 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 bone marrow transplant. The following is typical of the type of information found when searching the CRISP database for bone marrow transplant: •

Project Title: A NOVEL APPROACH TO PREVENT GRAFT-VERSUS HOST DISEASE Principal Investigator & Institution: Mcclure, G D.; Apoimmune, Inc. 1044 E Chestnut St Louisville, Ky 40204 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-OCT-2002 Summary: (provided by the applicant): Bone marrow transfusion (BMT) holds the potential to cure many blood diseases. However, BMT recipients often develop graftversus-host disease (GvHD), a life-threatening condition in which immune cells from the infused transplant attack the recipient's tissues. Current treatments using nonspecific immunosuppressants have limited effectiveness. Moreover, there is no clinically proven method of preventing GvHD. We have developed a therapy that can prevent GvHD. In this therapy we place a recombinant protein, mFasL, on the surface of immune cells in the graft to target these cells for destruction. It is superior to current treatments since it can prevent GvHD. Another variant of our therapy can cure existing GvHD without using nonspecific immunosuppressants. During this project we will produce more mFasL and show that it can prevent or cure GvHD in vivo. In the longer term, once in vivo efficacy is shown, we will develop and market a therapeutic biologic based on mFasL. Use of the biologic will lower mortality and morbidity associated with GvHD and allow BMT to be used much more routinely in the clinic. The long-term success of this project will expand therapeutic use of BMT to cure blood diseases and to prevent allograft and xenograft rejection. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: A SEARCH FOR GENES THAT REGULATE STEM CELLS Principal Investigator & Institution: Weissman, Irving L.; Professor; Pathology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2007 Summary: Hematopoietic stem cells (HSC) are the cells responsible for perpetual production of blood cells in the body, and the only cells in a bone marrow transplant that provide sustained hematopoiesis. The unique property of self renewal enables HSC,

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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in the steady state, to maintain a constant number of HSC and, in states of stress, allows them to expand their numbers by symmetric self-renewing divisions. In the first phase of this grant, we set into place a diverse set of searchers for the genes that are responsible for stem cell self-renewal. These studies revealed a strong candidate pathway involving Wnt, beta-catenin and axin; a second pathway involving Bmi-2; several other candidate genes selectively expressed in self-renewing HSC, and the unpaired/domeless-JACK-STAT pathway that specifies self-renewal in the drosophila male germ line. Here the 4 collaborating labs continue the search for the complete set of expressed genes that govern HSC behaviors including self-renewal, avoidance of apoptosis, differentiation to downstream myeloid or lymphoid lineages, and the decision to leave the bone marrow to circulate. We also introduce the use of a massive parallel sequencing (MPSS) effort to get the complete transcriptomes of LT-HSC, STHSC/MPP, CLP and CMP to allow electronic analyses and subtractions. We also concentrate efforts not only to continue a deep examination of the Wnt/beta?catenin signal transduction pathway (a pathway activated in oncogenesis) by quantitative methods of proteomics and system perturbation, but also the genes translocated in leukemias that have acquired the capacity to self-renew. Candidate genes identified from the library and microarray studies will be screened rapidly for function by transduction of native resting HSC with regulatable lentiviral vectors and tested in vivo and in vitro for effects on HSC numbers and functions. We continue the Drosophila genetic approach for identification of more extrinsic (hub cell) and intrinsic genes regulating spermatogenic stem cells, as well as using epistasic assays to clarify interacting gene expression networks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ABI-ABI SIGNALING IN NEOPLASTIC HEMATOPOIESIS Principal Investigator & Institution: Dai, Zonghan; Medical Oncology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The overall objective of this proposal is to delineate the mechanisms associated with Bcr-Abl-induced leukemogenesis. Previous studies have identified two Abl interactor (Abi) proteins, Abi-1 and Abi-2, that bind to cellular Abl (c-Abl) and are substrates of Abl tyrosine kinase. Abi-1 is tyrosine-phosphorylated in hematopoietic cells transformed by Bcr-Abl. Recent studies indicate that Abi-1 is a key regulator of Rac signaling, a pathway important for regulation of hematopoietic cell migration and homing. Abi-2, on the other hand, is degraded in Bcr-Abl-expressing hematopoietic cells. The expression of Abi-2 is lost in cell lines and bone marrow cells isolated from patients with aggressive Bcr-Abl-positive leukemia. This proposal is based on the hypothesis that the signal transduction from Bcr-Abl to Abi-1 and Abi-2 may play an important role in Bcr-Abl-induced leukernogenesis. We postulate that the tyrosine phosphorylation of Abi-1 and subsequent activation of Rac pathway may represent an important mechanism by which Bcr-Abl induces abnormalities of cytoskeletal function and metastatic phenotype in leukemic cells. We believe that loss of Abi-2 may be a component in the progression of Bcr-Abl-positive leukemia. The goals of this proposal, therefore, are to examine the leukemogenic potential of a mutant Bcr-Abl that is defective in signaling to Abi-1 and Abi-2; to determine the role of Abi-1 and Abi-2 in Bcr-Abl-induced leukemogenesis; and to define the mechanisms by which Bcr-Abl regulates Abi signal transduction. To achieve these goals, biochemical and genetic approaches are designed to disrupt or inactivate signal transduction of Abi-1 and Abi-2 in hematopoietic system. Bone marrow transplant mouse models will be employed to

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evaluate the effect of disruption of Abi signaling on Bcr-Abl-induced leukemogenesis. Sequences in Abi-1 and Abi-2 that are critical for regulation of signal transduction will be defined and mutations wilt be made for functional analysis. Collectively, these studies may provide insight into the regulatory mechanisms of cell migration, homing, and metastasis. Understanding the role of Abi signaling in neoplastic hematopoiesis should shed light on development of more effective therapies for the treatment of human leukemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALLOSPECIFIC IMMUNOREGULATORY T CELLS IN BMT RECIPIENTS Principal Investigator & Institution: Truitt, Robert L.; Professor; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2002; Project Start 20-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Distinct and identifiable populations of regulatory T cells control the physiological outgrowth and function of autoreactive cells in peripheral tissues. In animal models, loss or dysfunction of regulatory T cells can lead to autoimmune disease. We have identified a unique population of thymus-derived T cell receptor (TCR)+, CD4+ regulatory T cells in murine models of allogeneic bone marrow transplantation (BMT) and donor leukocyte infusion (DLI) therapy that specifically suppress the GVH reactivity of donor T cells. These cells may help establish and maintain peripheral tolerance to host and donor antigens. Regulatory TCR+ CD4+ T cells from DLI-treated mice suppress alloreactivity in an alloantigen-specific manner in vitro and GVH disease after adoptive transfer in vivo. We hypothesize that similar regulatory T cells emerge from the human thymus post-transplant, but that diminished capacity to generate regulatory T cells (due to age, prior chemotherapy, radiation, etc.) contributes to a higher risk of GVH disease after DLI therapy and, possibly, to the onset of chronic GVH disease. Quantitative measurements of TRECs in combination with unique phenotypic markers now allow for a definitive assessment of the kinetics and extent of the thymic contribution to post-transplant immune reconstitution in humans. Using these techniques, we propose to identify and isolate human regulatory T cells in the high TREC-expressing recent thymic emigrant (RTE) population and correlate their presence (or absence) with clinical outcome after allogeneic BMT (with or without DLI therapy). The purpose of this R21 exploratory grant is to generate data in humans that supports our hypothesis and validates the extension of observations made in preclinical models to human BMT. Thymic regulatory T cells may be critical to the success of DLI therapy without GVH disease as well as to the successful induction of tolerance by costimulatory blockade. We propose to determine: (a) whether regulatory T cells can be detected within the population of RTE cells in the peripheral blood of human recipients of HLA-disparate BMT; (b) whether regulatory T cells can be induced and expanded ex vivo from the peripheral blood of BMT patients for possible use in adoptive transfer protocols to prevent GVH disease, and (c) whether induction of anergic T cells by costimulatory blockade ex vivo induces allospecific regulatory cells in either the BMT patient or the donor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANIMAL MODEL TO STUDY THE ROLE OF CYTOTOXICITY IN GVHD Principal Investigator & Institution: Levy, Robert B.; Professor of Immunology; Microbiology and Immunology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract): The overall focus of the proposed studies in this application is to determine how cytotoxic function following allogeneic bone marrow transplantation influences the outcome of the transplant. Experiments will address related questions utilizing cytotoxically defective donor strains of mice. Single (i.e., perforin or CD95L = csd) and double cytotoxic deficient (cdd) strains will be employed to assess the role of donor cytotoxic function in GVH responses contributing to progenitor cell engraftment and GVH disease using experimental BMT models involving MHC mismatched and minor histocompatibility antigen mismatch donor/recipient combinations. Studies are designed to generate mouse strains deficient in tumor necrosis factor receptor-1 and/or 2 expression to be used to establish an allogeneic BMT model lacking three major effector pathways mediating cytotoxicity. These models will be used to analyze GVHD induced weight loss, clinical signs, tissue damage and immune deficiency. The use of CD4+ and CD8+ T cell subsets in this model will be of interest to determine if the "subtraction" of these effector pathways differentially affects their capacity to induce GVH responses. The "triple deficient" model can subsequently be used for the design of experiments to address the potential contribution of additional cytotoxic pathways involving TWEAK and TRAIL dependent signaling. These approaches will permit further testing of the hypothesis that differing effector molecules play more and less important roles in differing GVHD target compartments. Finally, experiments are proposed to examine the potential application of infused recipient (i.e., syngeneic) populations to kill donor cells following BMT to inhibit or reverse ongoing GVHD. Cell populations to be examined will include cytotoxic T cells and antigen presenting cells transduced with death receptor ligands. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AZOLE-RESISTANT CANDIDA IN MARROW TRANSPLANT PATIENTS Principal Investigator & Institution: Marr, Kieren A.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BEHAVIORAL EFFECTS OF CANCER AND ITS TREATMENT Principal Investigator & Institution: Redd, William H.; Professor and Associate Director; Ruttenberg Cancer Center; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Description (adapted from investigator's abstract): The proposed research investigates longitudinal determinants of distress among mothers of children undergoing bone marrow transplant (BMT) in the treatment of pediatric cancer. Data would be collected from up to 509 mothers during 5 structured interviews to occur at 2-

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weeks before BMT, immediately before BMT, and 6, 12, and 18 months post BMT. The proposed work would be guided by a conceptual integration of research in the areas of parental responses to BMT, cognitive/social processing of negative life events, and the impact of dispositional characteristics and prior stressful life events on adjustment to a severe negative life event. Stated aims are to 1) examine the longitudinal course of distress in the mothers of children undergoing BMT; 2) determine the role of cognitive and social processing in the development and maintenance of mothers' distress during and after BMT; and 3) assess how dispositional optimism, monitoring coping style, and prior negative life events influence mothers' cognitive and social processing of their distress after BMT. The proposed data analysis consists of latent growth curve and structural equation modeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLOOD AND MARROW TRANSPLANT CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Appelbaum, Frederick R.; Director; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 05-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The objective of this grant application is to become one of the core clinical centers in the proposed Blood and Marrow Transplant Clinical Research Network. There are a number of features of the Fred Hutchinson Cancer Research Center (FECRC) Marrow Transplant Program that make it an attractive candidate for inclusion in the Network. First, we have maintained a large, stable transplant program for several decades transplanting between 450 and 550 patients per year with excellent clinical outcomes. Thus, we have access to a relatively large number of patients. Second, our group includes a large number of investigators focused on the general topic of transplantation. This group is supported by seven P0ls and 23 R0ls, and last year published 142 papers on the topic. Thus, our inclusion will help assure a source of possible studies for future testing in the Transplant Network. Third, our program is deeply committed to cooperative clinical research. For example, last year 231 of 451 patients transplanted in Seattle (51%) were entered onto multi-institutional trials. Finally, the FHCRC provides an outstanding environment in which to conduct the sorts of studies described, with state-of-the-art clinical and laboratory facilities. The proposed Blood and Marrow Transplant Clinical Research Network has the potential to facilitate studies leading to substantial improvements in the outcome of transplantation. Inclusion of the Fred Hutchinson Cancer Research Center in this network should help it achieve this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BLOOD VS. BONE MARROW STEM TRANSPLANT Principal Investigator & Institution: Djulbegovic, Benjamin M.; Associate Professor of Medicine; Internal Medicine; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Peripheral blood stem cells (PBSC) are used increasingly as an alternative to bone marrow (BM) as a source of stem cells for allogeneic (allo) transplantation in the management of hematologic malignancies. This shift in practice was based on the results of several small randomized controlled trials (RCTs), which indicated possible survival and disease-free survival advantages of PBSC

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over BM transplant (T). However, some trials showed that the use of PBSC is linked to higher levels of graft versus host disease, which in turn can compromise the survival of patients who received PBSC. Since these small trials could not individually achieve conclusive results about the relative effects of PBSC vs. BM transplant, substantial controversy about a possible advantage of PBSCT over BMT on mortality and disease free survival exists. This is a classic situation when the techniques of the systematic review (SR), aimed at assembling the totality of the evidence on the relative benefit and risks of the use of allogeneic PBSCT or BMT, should be used to solve this controversy and existing disagreement. Indeed, we recently performed such a systematic review with a meta-analytic (MA) quantitative summary to show that in comparison with alloBMT, allo-PBSCT leads to better overall survival, less transplant related deaths, fewer relapses and prolonged disease free survival. We like to note here that by combining existing data sets, using a technique of SR/MA, we were able to demonstrate what none of the individual study was able to do: PBSCT is superior to BMT for the most of clinical outcomes. However, our study was based on the data extracted from the published studies. This is known to be an inferior type of SR/MA and may not provide definitive evidence. The gold-standard method to combine the totality of existing evidence is to perform individual patient data meta-analysis (IPD MA). Thus, by collecting individual patient data (from the existing data sets), we will be able to focus on the following objectives: 1. Is allo-PBSCT superior to allo-BMT in the management of hematological malignancies for a number of clinical end-points, including overall mortality, transplantrelated mortality, relapse rates, disease-free survival, incidence of acute and chronic graft-versus-host disease (GVHD), incidence of chronic. Since some retrospective studies suggest that PBSCT may be more effective in hematological malignancies with a poor risk, while BMT may be more beneficial for the patients with good risk malignancies, we will test the following hypothesis: 2. Is there a subgroup of patients for whom BMT is superior to PBSCT? The technique of IPD MA is an ideal method to perform a subgroup analysis. Finally, since the main expected differences in outcomes might be the result of a different composition of allo-graft, we will test an additional hypothesis: 3. Is there a relationship between the composition of the graft (e.g. number of CD3 cells, number of CD34 cells) and the probability of development of acute and chronic GVHD? 4. Is there an effect of the GVHD prophylaxis regimen on the development of acute or chronic GVHD? Using IPD from studies that utilized different prophylaxis regimens it may be possible to test the interaction of GVHD prophylaxis among these studies. We will test all these hypotheses by collecting individual-patient data on each outcomes of interest from the existing data sets (i.e. from published and unpublished randomized studies) using the techniques of SR/MA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE MARROW TRANSPLANT (BMT) SURVIVORS STUDY Principal Investigator & Institution: Bhatia, Smita; City of Hope National Medical Center Duarte, Ca 91010 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2003 Summary: (Adapted from the Applicant's Abstract): Through collaboration between the City of Hope National Medical Center and the University of Minnesota, we propose to define a cohort of patients who have undergone bone marrow transplantation (BMT) at these two centers and have survived at least two years, regardless of their current lifestatus. The objective of this Bone Marrow Transplant Survivors' Study (BMT-SS) is to establish and characterize a cohort of 1,894 pediatric and adult long-term survivors of BMT, to address the following aims: i) Identify detailed information on the incidence

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and risk factors for cardiopulmonary disease, endocrine abnormalities, fertility, and subsequent cancers; ii) Describe the impact of the above complications on the quality of life in this cohort of BMT survivors; iii) Characterize the health-related behaviors and patterns of medical care in survivors. The methodology involves a mailed survey of two questionnaires: (i) the BMT-SS Questionnaire, a validated, self-administered (subjects > 18 years) or parent-administered (subjects 18 years) or the Child's Health Questionnaire (subjects < 18 years). A frequency-matched sample of 500 siblings will be enrolled into the study. The sibling controls will provide: i) the ability to make direct comparisons with the survivors, ii) data on outcomes in a noncancer population, not available from other sources (vital statistics, NHIS, etc.). For selected reported outcomes (second cancers, etc.) we will conduct additional analyses using a nested case-control approach. This will allow us to collect additional, more extensive data on survivors experiencing the outcomes (cases), and those not experiencing the outcome (controls). The cohort will be of sufficient size and heterogeneity with respect to primary malignancy, type of transplant age at transplant, and ethnic background to allow for the study of endpoints of interest in this population. The results will provide important information that may be used in the design of future therapeutic strategies and/or interventions to decrease the occurrence of deleterious effects related to treatment exposures and host factors. Having such a cohort in place will give us the opportunity in the future to continue to collect information on major study end-points (e.g., second cancers, births, cardiac complications, etc.) that may have occurred since the completion of the initial questionnaire. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BONE MARROW TRANSPLANT CLINICAL NETWORK Principal Investigator & Institution: Stadtmauer, Edward A.; Associate Professor of Medicine; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: This project is part of a Blood and Marrow Transplant Clinical Research Network which is conducting multicenter clinical trials in hematopoietic stem cell transplantation. The purpose of the network is to promote the efficient comparison of novel treatment methods and management strategies of potential benefit for children and adults undergoing blood or marrow transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation after marrow ablation, the development of non-myeloablative transplant regimens, and the best ways to avoid infections in transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CANCER AND LEUKEMIA GROUP B Principal Investigator & Institution: Crawford, Jeffrey; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 31-MAR-2003 Summary: (adapted from the applicant's abstract): Duke Medical Center is currently completing its second five year grant cycle as a member of Cancer and Leukemia Group B (CALGB). Throughout Duke's involvement with CALGB, this institution has consistently been one of the top institutions in overall patient accrual and specifically has been one of the leading institutions in patient accrual from a main member

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institution. Over the period of the last grant cycle, Duke has developed an affiliate program through the Duke Oncology Consortia (DOC) which involves cancer centers and hospitals throughout the Southeast United States. This affiliate membership is still growing in number of sites and level of participation in clinical trials. In addition, the Duke Oncology OutReach Services (DOORS) network provides onsite cancer care at small hospitals and clinics in neighboring counties. Both intramural and extramural clinical trial participation are coordinated through centralized clinical trials offices at Duke. This includes personnel support for core administrative functions, clinical trial coordination provided by disease and modality specific clinical research nurses, and data management and follow-up by dedicated CALGB data managers. This organizational structure is further strengthened by close interaction with the CALGB biostatistics and data management center under the direction of Dr. Stephen George who is also director of biostatistics for the Duke Cancer Center, Scientifically, Duke has active cadre members in all the disease and modality related CALGB committees. Duke investigators serve as study chairs on Phase III trials in AML, stage IV breast cancer, the national high priority trial of bone marrow transplant in the adjuvant treatment of breast cancer patients (9082), as well as numerous Phase II studies. Duke is also a center for Phase I studies for pharmacology/experimental therapeutics. This has been further strengthened by the recruitment of Dr. Michael Colvin to become Director of the Cancer Center. Furthermore, Dr. Harvey J. Cohen, Director of the Aging Center has become an active member of CALGB and was instrumental in the formation and leadership of a working group evaluating cancer and aging. The recruitment of Dr. David Harpole in Thoracic Surgery, led to Duke becoming a major site for participation in CALGB surgical trials. Multimodality support has also been provided by active participation from other members of surgical oncology as well as radiation oncology, pathology, and correlative sciences. Areas of expansion by Duke investigators within CALGB over the next grant cycle will be particularly targeted to multimodality trials, Phase I studies, bone marrow transplant trials, and the continued participation in ongoing phase II and III trials. In addition, our participation in community trials addressing minority issues, gero-oncology, and cancer control will expand with the participation of Dr. Barbara Rimer and Dr. Colleen McBride. As a leading institution in CALGB activities over the last decade, Duke is looking forward to funding support appropriate to our current and anticipated level of patient accrual and scientific involvement in CALGB trials during the next grant cycle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CANCER CENTER CALGB PARTICIPATION Principal Investigator & Institution: Muss, Hyman B.; Professor of Medicine; Vermont Regional Cancer Center; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 20-APR-1998; Project End 31-MAR-2003 Summary: (adapted from the applicant's abstract): The Vermont Cancer Center (VCC), an NCI designated Comprehensive Cancer Center, joined the CALGB in 1995. In that short time the VCC has made significant headway in becoming a major participant in CALGB activities. Eight VCC members have made major commitments to supporting CALGB efforts. Dr. Hyman Muss continues to be extremely active in CALGB and serves as the Co-Chair of the Working Group for the Elderly and the Vice Chair of the Breast Cancer Committee, in addition to chairing two CALGB protocols (8869 and 9670). Dr. Steven Grunberg, a member of the Clinical Economics Committee, is currently developing a clinical protocol that will compare cost with symptom control for

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antiemetics. Dr. David Krag is an active member of the Breast Core Committee and is helping CALBG develop a protocol for sentinel node staging for women with early stage breast cancer. Dr. Seth Harlow will assume Dr. Krag's role as member of the Surgery Committee. Dr. Donald Weaver participates extensively in pathology group activities and has a major interest in breast cancer. Drs. Michael Cooper, Barbara Grant, and Richard Branda have major interest in urologic cancer, leukemia and lymphoma, and nutrition and cancer, respectively, and have developed concepts for CALGB clinical investigations. The development of multidisciplinary, disease-site oriented, affinity groups within our Center has established major liaisons between laboratory and clinical scientists. This will strengthen our institutional commitment to the group and allow VCC members to develop innovative companion trials for the CALGB. Recently, Drs. Grant and Branda presented two concepts-one related to assessing the importance of folate status on chemotherapy toxicity in women with early breast cancer, and a second that utilizes a novel reporter gene (hprt) to monitor and possibly define women with early stage breast cancer who might be at high risk for developing secondary acute nonlymphocytic leukemia. Drs. Weaver and other VCC scientists are drafting a concept that will explore the role of erbB-2 associated signaling proteins as mediators of apoptosis for women with early stage breast cancer treated with anthracyclines (CALGB 8541). We anticipate a major increase in accrual in the next year. The Green Mountain Oncology Group (CCOP) selected the VCC as its research base beginning in April, 1997. In one month they have entered 10 patients on CALGB protocols. Two new faculty will join the VCC this summer who have major interests in genetics and high-dose therapy; it is anticipated they will be active in CALGB activities. Also, we are developing a major outreach program and expect to add several affiliates with interest in clinical trials. In addition, we have developed a high-dose chemotherapy autologous stem cell support program and expect to become a CALGB Transplant Center by the start of the next funding period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION AND TREATMENT OF MURINE MPS VII Principal Investigator & Institution: Soper, Brian W.; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2002; Project Start 01-AUG-1989; Project End 31-DEC-2006 Summary: provided by applicant): Mucopolysaccharidosis Type VII (MPS VII) is one of ten human heritable lysosomal storage diseases (LSD's). MPS VII mice and human patients suffer cognitive dysfunction, reduced hearing and sight, skeletal defects, poor joint mobility, hepatosplenomega1y, and early death. The lysosomal enzyme, betaglucuronidase (GUSB), involved in degradation of glycosaminoglycans (GAG's) is absent in MPS VII. Enzyme replacement therapy (ERT) in the mouse model demonstrates early intervention is essential to attenuate skeletal deformities and progressive learning defects. Continuous infusions can result in anaphylactic shock. Myeloablative bone marrow transplantation (BMT) alleviates disease in visceral organs, but poorly corrects the brain. Mild myeloablation is disruptive to normal brain and skeletal development and increases morbidity in neonatal recipients. Murine MPS VII provides a model to test treatment efficacy pathology), dissemination of GUSB+ donor cells (histochemistry), levels of donor enzyme (biochemistry), and functional correction (bone density, Morris water maze, retinograms, sterility, etc.). We have shown that, in the absence of myeloablation, high-dose syngeneic BMT in neonatal MRS VII mice is therapeutic in visceral and osteoid tissues. Human patients often require allogeneic BMT due to the unavailability of a matched donor. Subsequent complications are GvHD

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and HvGD. The specific aims of this study test the hypotheses that in non-ablated MRS VII neonates: (1) immature tissues such as umbilical cord blood (UCB) or fetal liver (FL) have an engrafiment advantage compared to adult bone marrow (ABM) due to reduced immunogenicity.This will be examined by competitive repopulation of allogeneic FL and ABM after prior syngeneic titration to remove stem cell (SC) content and proliferation affects that give FL competitive advantage; (2) blockage of the T cell costimulatory pathway can lead to increased frequency and/or levels of allogeneic engraftment in non-myeloablated recipients and donor lymphocyte infusion (DLI) can amplify allografts. MPS VII recipients will receive anti-CD 154 antibody and/or CTLA4Ig fusion protein and GUSB allogeneic cells. Engrafted mice will be treated with donormatched lymphocytes to competitively expand the donor graft; (3) GUSB+ SC from the brain, ABM, or FL can expand post brain ventricle implantation, reduce lysosomal storage, and improve cognitive function. Plasticity will be examined by coculture of SC from ABM and FL with neurospheres and brain SC with marrow stroma. Differentiation capacity will be compared to directly brain implanted SC. Behavioral studies will determine long-term neurological function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHIMERISM IN CORD BLOOD TRANSPLANTATION IN MICE Principal Investigator & Institution: Weinberg, Rona S.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 05-SEP-2000; Project End 31-AUG-2005 Summary: (Investigator's abstract) Sickle cell disease (SCD) can be cured by bone marrow transplantation (BMT); however because of the morbidity and mortality associated with the procedure, BMT has been used only as a last resort for the most severely affected patients. In order for BMT and/or gene therapy to become a realistic curative therapeutic option for most sickle cell patients, it is imperative to develop less toxic preparative regimens, increase the number of available donors, develop gene therapy/transplantation protocols in which genetically manipulated autologous cells can be used, and determine the proportion of mixed chimerism required to prevent the sequelae of SCD. Umbilical cord blood (CB) has been used as an alternative source of stem cells for BMT and may provide a unique source of stem cells for gene therapy because of its easy and safe availability from individuals prenatally diagnosed with genetic disorders such as SCD. The goal is to provide effective, safe, and minimally toxic BMT and/or gene therapy for SCD patients. The hypothesis to be tested is: CB transplantation can provide stable mixed chimerism in non-ablated or minimally ablated recipients. The specific aims are to utilize a near-term fetal/newborn mouse blood (FNPB) model of CB transplantation which we and others have developed to: 1) determine the minimum number of FNPB cells which can provide long-term full engraftment or mixed chimerism in non-ablated and minimally ablated recipients; 2) transplant transgenic mice that are models of human SCD with normal FNPB stem/progenitor cells (S/PC) and to determine the proportion of donor:recipient chimerism required to ameliorate or "cure" sickle cell sequelae in these recipients; 3) use retroviral vectors containing human gamma- and beta-globin genes to transduce FNPB S/PC capable of long term engraftment and to transplant these transduced cells into non-ablated and/or minimally ablated normal and sickle cell mice. These studies are designed to define the characteristics of FNPB S/PC with regard to frequency, stem cell cycle kinetics, "stemness," and gene transducibility. BMT, including competitive repopulation assay, short-term and long-term liquid cultures, and methylcellulose cultures will be employed. These "pre-translational" studies form the basis for

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developing effective human CB transplantation and autologous CB gene therapy protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL APPLICATIONS OF A NOVEL FANCONI ANEMIA ASSAY Principal Investigator & Institution: Shimamura, Akiko; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-JUL-2002; Project End 31-MAY-2007 Summary: Congenital bone marrow failure syndromes are characterized by abnormal hematopoietic cell growth, differentiation, and survival. Bone marrow transplant is the only available curative treatment, but is associated with significant side effects and limited by donor availability. The development of new therapeutic modalities calls for investigators with: 1. Expertise in bone marrow failure syndromes, 2. An understanding of the clinical implications of new molecular discoveries, 3. Experience in the design and implementation of clinical trials. Dr. Shimamura is a pediatric hematologist/oncologist with a molecular background in signal transduction and apoptosis. The proposed training program is designed to allow her to develop expertise in bone marrow failure syndromes and to gain experience in the design and implementation of patient-oriented research. Her long-term goal is to become an independent investigatory applying our understanding of molecular mechanisms of bone marrow failure to solve clinical problems. Dr. Shimamura will pursue her career development under the co- mentorship of Dr. Alan D'Andrea and Dr. David Nathan. Dr. D'Andrea's studies have uncovered a novel Fanconi anemia (FA) biochemical pathway. She proposes to study the clinical applications of these findings as follows: 1. Investigate the FANCD activation assay as a new functional screen for the FA pathway, 2. Screen for pharmacological agents that augment FANCD activation, and 3. Assess the effect of FA gene replacement therapy on the restoration of FANCD activity as part of the on-going Dana-Farber/Children's Hospital FA gene therapy project directed by Dr. Nathan. Dr. Shimamura has assembled a committee of expert advisors and collaborators to assist her in this project. Her project will be supported by several local core facilities and programs including the Fanconi Anemia Center, the Harvard Vector Laboratory, the Cell Manipulation and Gene Transfer Laboratories, the Clinical Gene Therapy Program, and the General Clinical Research Center at Children's Hospital. To complete her training, she will attend a bone marrow failure clinic at Children's Hospital, build a bone marrow failure repository for future independent studies, and complete course work on clinical research design, implementation and analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL RESEARCH IN STEM CELL TRANSPLANTATION Principal Investigator & Institution: Bearman, Scott I.; Cancer Center; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 14-SEP-2000; Project End 31-AUG-2005 Summary: The ongoing work and the proposed studies described in this application have, as a common theme, the use of immunotherapy as an adjunct to high-dose chemotherapy for patients with advanced or high-risk primary breast cancer. Three feasibility studies are described which form the basis for the proposed clinical trials, two of which are phase II and one of which is a randomized study. A retrospective analysis performed by Dr. Bearman's fellow, Dr. Yago Nieto, has resulted in the development of

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a model to predict patients with high-risk primary breast cancer who are at high-risk of relapse after autologous transplant. That model will identify candidates for two of the proposed clinical trials. This application also describes how Dr. Bearman will trainee young investigators in patient-oriented research. The UCHSC Bone Marrow Transplant Program has sufficient patients to conduct these studies, actively conducts both laboratory and clinical research, and is funded by both peer-reviewed and pharmaceutical support. Dr. Bearman will devote 50 percent effort to this 5 year program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE CLINICAL CENTER APPLICATION FOR DUKE UNIVERSITY ME* Principal Investigator & Institution: Kurtzberg, Joanne K.; Professor; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: This project is part of a Blood and Marrow Transplant Clinical Research Network which is conducting multicenter clinical trials in hematopoietic stem cell transplantation. The purpose of the network is to promote the efficient comparison of novel treatment methods and management strategies of potential benefit for children and adults undergoing blood or marrow transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation after marrow ablation, the development of non-myeloablative transplant regimens, and the best ways to avoid infections in transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--FLOW CYTOMETRY Principal Investigator & Institution: Griffin, James D.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Goal: The goal of this unique core will be to provide cost-effective high speed flow cytometry and related services to the Program Project members. Two major uses are anticipated: 1) rapid purification of high numbers of cells transfected with a fluorescent protein, typically for experiments involving multiple samples. The purified cells need to be >95% pure and will be used for biochemical, immunological, or short term cell culture assays. 2) rapid purification of murine hematopoietic stem cells and progenitor cells for subsequent infection with retroviruses containing an oncogene or signaling molecule. These cells are typically present in low numbers, and final purity needs to be 95-99%. They will be used either for in vitro cell culture assays (such as colony assays) or for re-injection in mice as part of a bone marrow transplant experiment. Sterile sorting is essential for both types of experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORRECTING DYSREGULATED PERIPHERAL TOLERANCE IN NOD MICE Principal Investigator & Institution: Gill, Ronald G.; Professor; None; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005

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Bone Marrow Transplant

Summary: (provided by applicant): Beyond the expression of autoimmune diabetes, NOD mice appear to harbor inherent defects in peripheral tolerance that renders these animals refractory to the induction of allograft tolerance. Combined, these issues make successful islet allotransplantation extraordinarily difficult in this model. Importantly, much of the autoimmune propensity in NOD mice maps to the bone marrow compartment. Depending on the donor, bone marrow transplantation can transfer either disease susceptibility or protection. In most previous studies involving tissue/organ transplantation, bone marrow has been used as a tolerogen for a specific donor and has been successfully applied in the NOD mouse. However, while conceptually very important, the toxic induction therapies involved and subsequent risk of graft-versus-host disease associated with MHC-mismatched bone marrow engraftment may preclude this approach for clinical application in the near future. In this proposal, rather than using bone marrow as a donor islet transplant-specific tolerogen, MHC-matched (H-2g7), disease-resistant bone marrow allografts will be used as a means of 're-programming' the NOD peripheral immune system to make the host amenable for tolerance induction. Thus, this proposal will test the general working hypothesis: MHC-matched, disease-resistant hematopoietic cells will dominantly regulate disease-prone cells and restore normal peripheral tolerance propensity. This hypothesis will be tested by the following specific aims: (1) Determine the extent of disease protection afforded by introducing MHC-matched, disease-resistant bone marrow in NOD mice, (2) Determine whether mixed chimerism with disease-resistant marrow will correct the inherent allograft tolerance defect in NOD mice, and (2) Determine the components within protective marrow that confer restoration of peripheral tolerance propensity in NOD mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COSTIMULATION, CHIMERISM, AND TOLERANCE Principal Investigator & Institution: Larsen, Christian P.; Professor of Surgery Transplant Center; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-MAY-2007 Description (provided by applicant): Transplantation has emerged as the preferred method of treatment for many forms of end-stage organ failure. While the short-term results have improved long-term outcomes remain inadequate. To maintain their allografts, patients must rigidly adhere to life-long treatment regimens using costly immunosuppressive agents that dramatically increase the risks of cardiovascular disease, infections and malignancies. The development of strategies to promote the acceptance of allogeneic tissues without the need for chromic immunosupression could not only reduce the risk of these lifethreatening complications, but also greatly expand the application of organ, tissue and cellular transplantation for diseases such as the hemoglobinopathies and genetic immunodeficiencies, Type I diabetes, and possibly other autoimmune diseases. We have developed novel nonmyelosuppressive protocols using axiti-CD40L and CTLA4-Ig to permit the induction of titratable levels hematopoietic chimerism and robust deletional donor-specific tolerance in rodents. The goal of this project is to develop and optimize protocols to induce stable macrochimerism and transplantation tolerance to renal allografts in non-human primates. Specifically, in this proposal we will test the effects recipient conditioning with non or minimally myelosuppressive doses of busulfan or total body irradiation on the level and durability of hematopoietic chimerism when used in conjunction with a regimen consisting of anti-CD40L, CTLA-Ig, sirolimus and donor bone marrow, 2) determine whether escalating doses of G-CSF mobilized CD34+ cells will a) increase the

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level of hematopoietic chimerism, b) decrease the requirement for recipient conditioning, and c) induce transplantation tolerance to renal allografts in MHCdisparate Rhesus macaques and 3) determine the effects of an optimized tolerance induction protocol on the survival of concurrently placed renal allografts, anti-donor immune responses and protective memory T cell responses in MHC-disparate Rhesus macaques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CTLA-4 BLOCKADE TO STIMULATE ALLOGENEIC GRAFT VS TUMOR Principal Investigator & Institution: Ball, Edward D.; Professor and Chief; Cancer Center; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: This project is part of a Blood and Marrow Transplant Clinical Research Network which is conducting multicenter clinical trials in hematopoietic stem cell transplantation. The purpose of the network is to promote the efficient comparison of novel treatment methods and management strategies of potential benefit for children and adults undergoing blood or marrow transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation after marrow ablation, the development of non-myeloablative transplant regimens, and the best ways to avoid infections in transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOKINE GENE THERAPY OF RESIDUAL LEUKEMIA Principal Investigator & Institution: Gautam, Subhash C.; Senior Staff Investigator; Internal Medicine; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (Applicant's Abstract) Our long-term goal is to develop novel biotherapies that will specifically target and destroy residual leukemia. The proposed studies will test the general hypothesis that site-directed gene therapy with hematopoietic progenitor cells, genetically modified to secrete human tumor necrosis factor-alpha (hTNF-a), will significantly increase the destruction of leukemia cells remaining after high-dose chemotherapy/bone marrow (BM) transplantation. Our preliminary data show that administration of hTNF-a secreting progenitor cells following chemotherapy with cyclophosphamide (CY) and BM transplantation dramatically enhances survival (80 percent) of mice inoculated with a lethal dose of 32Dp210 murine myeloid leukemia cells without toxic side effects. We will test the hypothesis that combined therapy with CY, BM-transplant, and TNF-a secreting progenitor cells generates a greater antileukemic effect than is produced by any modality alone. We will accomplish this by the following specific aims: 1) determine the extent to which immunomodulatory effects of CY on T-helper (Th) cells and cytotoxic effector cells (CTLs and NK cells) contribute toward the antileukemic activity of CY/TNF-a gene therapy, 2) identify the cell population(s) within BM-transplant (e.g., T cells, mesenchymal cells or progenitor cells) that enhances the efficacy of combined therapy, and 3) determine whether the mechanism(s) of the antileukemic effect of CY/TNF-a treatment involves: a) augmentation of leukemia antigen presentation by dendritic cells, b) generation of

22

Bone Marrow Transplant

leukemia specific (CTLs) and non-specific (NK cells/macrophages) cytotoxic effector cells, c) production of secondary cytokines with antileukemic activity, and d) the induction of programmed cell death (apoptosis) in leukemia cells. The results of these studies will demonstrate the value of combining this novel approach of site-directed TNFa gene therapy with other commonly used anticancer treatment strategies to achieve maximum destruction of residual leukemia. This would make possible the rapid implementation of this novel treatment strategy to eradicate residual leukemia in humans, without the toxic side effects of systemic TNF-a therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEFINING HEMATOPOIETIC PROGENITORS IN MOUSE BONE MARROW Principal Investigator & Institution: Spangrude, Gerald J.; Associate Professor; Oncological Sciences; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: The early progenitors of the lymphoid lineages in the mouse are not yet clearly defined. New studies regarding the nature of lymphoid progenitors have suggested that an intermediate progenitor with potential to differentiate only into T and B lineages (common lymphoid progenitor, CLP) can be isolated from adult mouse bone marrow. Other studies have demonstrated progenitors with restricted lympho-myeloid potential in fetal development, but have failed to confirm the existence of CLP. A newly developed selection protocol that completely separates hematopoietic stem cells from early progenitor cells will be utilized to investigate the characteristics of early progenitors for the lymphoid lineages in adult mouse bone marrow. In Specific Aim 1, the early stages of B cell development will be investigated to determine the identity, growth requirements, developmental potential, and genes expressed by cells defined as B cell progenitors by the new selection protocol. In Specific Aim 2, an in vivo assay for T cell development will be utilized to isolate and characterize bone marrow progenitors able to localize to and proliferate within the thymus. In Specific Aim 3, we will test the hypothesis that fate determination of CLP can be regulated by extrinsic cytokine stimulation. We propose that cells normally destined to differentiate as B lymphocytes can be redirected to T cell differentiation in short-term in vitro cultures, and that this redirection of T cell progenitor activity can account for previous discrepancies in defining lymphoid progenitors. The studies outlined in this proposal will define the early stages in the process of lymphoid lineage commitment in mouse hematopoiesis, providing a framework within which future studies aimed at mechanistic analysis of this process can be initiated. In addition, the feasibility of utilizing progenitor populations as a means to replenish the lymphoid lineages through transplantation will be evaluated. Collectively, the proposed experiments will contribute to both basic and clinical research efforts aimed at understanding the nature of early lymphoid lineage commitment in hematopoiesis and the potential of hematopoietic progenitor cells to be utilized in clinical transplant settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EBV GENOME EXPRESSION--LOCALIZATION OF SPECIFIC FUNCTION Principal Investigator & Institution: Hayward, S D.; Professor; Pharmacology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-1981; Project End 31-MAR-2005

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Summary: Epstein-Barr virus (EBV) immortalizes B cells and is associated with human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's disease and lymphoproliferative disease in immunosuppressed patients such as AIDS patients and organ and bone marrow transplant patients. Primary infection by EBV may cause infectious mononucleosis in young adults. Primary infection leads to a proliferative expansion of the infected B cells. This is followed by the establishment of life-long persistence in which the EBV genome resides in resting B cells. Lytic viral replication occurs in the oropharynx and results in virus shedding into the saliva. Different patterns of EBV latency gene expression are seen in latently infected resting B cells and in EBV associated tumors. This application addresses factors that may regulate these expression patterns and contribute to the different aspects of EBV pathogenesis. EBV replication is necessary for virus spread and Zta is a key regulator of the EBV lytic cycle. Zta not only regulates EBV lytic DNA replication but may also influence the maintainance of latent infection. The Specific Aims are: (Aim 1). To characterize the role of Zta in replication of the EBV origin of lytic replication, orilyt. Transfection assays will be used to analyse the role of Zta in the formation of replication compartments, to analyze the relative contributions of Zta's transcriptional and replication activities to orilyt activation and to relate Zta mediated regulation of the cell cycle to Zta replication function. (Aim 2). To evaluate the contribution of the JAK-STAT signaling pathway to the regulation of EBV latency gene expression in in vivo latency and tumorigenesis. STAT regulation of individual EBV latency promoters will be examined in transient assays. The role of activated STATs and Zta expression in the maintainance of EBV positive epithelial tumor cell lines in culture will be pursued and negative regulation of the EBV lytic cycle by STATs will be examined. (Aim 3). A role for EBNA-1 in the regulation of EBV latency gene expression will be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENTERAL TRANSPLANT

NUTRITION

&

SAFETY

IN

BONE

MARROW

Principal Investigator & Institution: Malone, Frances R.; Physiological Nursing; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Bone marrow transplant has now been expanded to include other sources of stem cells, thus the emergence of the use of the term hematopoietic stem cell transplant, as it includes stem cells from sources other than the bone marrow. Cytotoxic myeloablative therapy (chemotherapy and radiation intended to destroy bone marrow and to make room for new cells through a transplant) destroys the mucosa of the intestinal tract, impairing functions of the epithelium that are essential to health. Enteral nutrition (taking nutrients from food via the intestinal tract) is essential for the mucosa to adequately absorb nutrients from food. Enteral nutrition promotes the structural integrity of the gut. The provision of enteral nutrition during chemotherapy has protective effects on the gut, and the provision of early enteral feedings has a beneficial effect on complication and sepsis rates after surgery. Since hematopoietic cell transplant recipients experience many of the factors that facilitate movement of bacteria into the bloodstream, invasion by enteric microorganisms might commonly occur in this population. Therefore, early enteral feeding to restore the mucosa can be expected to decrease bacterial translocation and its consequences. The specific aims of the study are to investigate the safety and feasibility of early enteral feeding in pediatric cell transplant patients. Secondary and long term goals of this study are to (1) describe the clinical impact of early luminal feedings on oral intake, (2)

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Bone Marrow Transplant

describe the physiologic impact of early luminal feedings on cytokine production, and (3) describe the physiologic impact of early luminal feedings on bacterial translocation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVOLUTION OF HIV-1 IN GENETICALLY HUMANIZED MOUSE MODELS Principal Investigator & Institution: Su, Lishan; Associate Professor; Microbiology and Immunology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): This project extends our long-standing interests in establishing a murine model to study HEV replication, pathogenesis and therapy. HIV-1 is unable to infect murine cells. Attempts to "genetically humanize" the mouse with HIV-1 receptors have yielded only limited success. HIV-1 can establish initial infection in vitro or in vivo in cells or transgenic mice expressing human CD4, CCR5 (or CXCR4), and the Tat cofactor cyclin TI, but with no sustained replication and spread. Therefore, additional human factors, and possible murine factors that inhibit HIV-1 replication, will make further humanization of the mouse for H N replication difficult. However, a highly mutable virus like HIV-1 will be able to adapt to replicate in such Genetically Humanized Mouse (GHM) cells. I propose to make HN-1 "do the work" to evolve in GHM cells both in vitro and in vivo. The putative HIV-1 variants will depend on human CD4lCCRS and Tat/cyclin TI to infect the GHM cell. The specific aims are: 1. To adapt HIV-1 to replicate in GHM cells with GHM/human cell co-cultures in vitro and in vivo. The GHM mouse has overcome three blocks for HIV-1 infection. The failure of HIV-1 to replicate efficiently in the GHM cell, either due to a lack of additional human factors or presence of negative murine factors, provides a genetic selection system for HIV-I to "evolve" in these cells. As successfully demonstrated with murine hepatitis virus (MHV), it is possible to direct host (species)-range shift by using escalating ratios of restrictive/permissive target cells. I will start a similar evolution process with CXCR4tropic, CCR5-tropic and CXCR4/CCRS dual-tropic HIV-1 isolates in vitro in GHM and human cells. In addition, I will use GHM bone marrow (BM) cells to reconstitute SCIDhu ThyLiv mice which have been infected/depleted with HIV- 1. This allows HIV-1 adaptation from human cells to GHM cells in vivo at an increasing GHM/human cell ratio. Murine T cells developed in the HIV-1 infected ThyLiv organs will be activated in vitro to expand and recover the HIV- 1 variants. 2. To derive HIV-1 variants evolved to replicate in the GHM mouse in vivo. I will use two different approaches. First, I will inoculate HIV-1 (evolved from aim 1 or infected human cells) in the thymus of newborn GHM mice, whose immune system is actively developing (but immature) and should be permissive to viral infection. Second, I will infect the GHM BM cells (containing T, macrophage and progenitor cells) with. the evolved WN-1 (or infected human cells) and reconstitute lethally irradiated GHM mice with the HIV-infected BM cells. The HIV infection and bone marrow transplant procedure will be repeated to expand the NIV- 1 variants. A murine model for studying HIV-1 pathogenesis and host immune responses will be obviously invaluable for studying HIV-1 replication, pathogenesis and therapy. The adapted HIV-1 will infect the GHM model via human CD4 and coreceptors, and human cyclin T1. It is likely that the adapted HIV in the GHM model will lead to AIDSlike diseases because 1) human CD4 is essential for CD4 T development and function in the GI-IM mouse; 2) both CD4 T and macrophage cells are HIV targets; and 3) expression of nef in transgenic mouse models can lead to AIDS like diseases. Even if no AIDS-like pathology were developed, the GHwf model infected with the HIV-1 variants

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will be still useful for testing therapeutics that target HIV- 1 entry, tat- mediated gene expression and neutralizing antibody response in this model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXTRACELLULAR MATRIX IN RENAL FIBROSIS Principal Investigator & Institution: Fogo, Agnes B.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-MAR-2007 Summary: Description (provided by applicant) Transforming growth factor-beta 1 (TGFbeta) has been implicated as a key molecule in fibrosis, and its expression is increased in numerous fibrotic conditions. The relationship of TGFbeta to other profibrotic mechanisms, such as angiotensin and plasminogen activator inhibitor-1 (PAI-1), and the differential role of infiltrating versus parenchymal cells are complex. TGFbeta can be locally activated by alphavbeta6, which is an integrin heterodimer that is expressed in epithelia in lung, skin and kidney and mediates cleavage of TGFbeta from latency associated peptide. Mice deficient in avB6 lack the ability to activate local TGFbeta through this alphavbeta6 integrin dependent mechanism and had marked protection against fibrosis in the unilateral ureteral obstruction model, with decreased PAI-1 expression, despite robust infiltration of macrophages. A full fibrotic response was restored by infusion of angiotensin or aldosterone, together with restoration of local increase of PAI-1. These projects will examine the TGFbeta1 dependent and independent mechanisms of fibrosis. We hypothesize that PAI-1 induction occurs even in the absence of local TGFbeta, and that PAI-1 by itself can effect fibrosis. We further hypothesize that both parenchymal and infiltrating cell mechanisms are necessary for full fibrotic response. We postulate that injury promotes epithelial-mesenchymal transdifferentiation, and that inadequate macrophage clearance of apoptotic cells both contribute to fibrosis. We will use the alphavbeta6 knockout mouse and bone marrow transplant, to experimentally manipulate parenchymal versus infiltrating cells combined with pharmacological manipulations, to determine mechanisms of interstitial fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTION OF CD34 STEM/PROGENITOR CELLS Principal Investigator & Institution: Sharkis, Saul J.; Professor; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: Hematopoietic stem cells are a rare population of cells which have a unique biological profile. This population can be used for cellular therapy of hematological malignancy, bone marrow failure disorders, as well as gene therapy. for more than a decade the CD34 antigen has been used to help isolate this rare population in humans. Transplantation of CD34 positive cells in patients has resulted in prompt engraftment of donor cells. Recently, through the development of antibodies to the CD34 antigen on mouse tissues, it has become possible to study the stem cell biology (i.e., proliferation, differentiation, survival, and self- renewal) using a transplant strategy to determine the importance of CD34 in identifying stem cells. Most stem cell biologists will agree that the stem cell pool is heterogenous with the earliest (highest quality) stem cell having potentials for proliferation, differentiation, survival, and self-renewal but as the stem cell matures these potentials are lost. It becomes critically important in diseases with stem cell intrinsic defects to use the highest quality stem cell for cellular therapy.

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Bone Marrow Transplant

Recently, conflicting reports have appeared which have made it more difficult to assess functional significance of the CD34 antigen. Our first specific aim will examine the role of CD34 for self-renewal, proliferation, and differentiation. This will involve transplantation of CD34 null stem cells into normal mice and normal cells into null mice to test the competence of these cells in a transplantation protocol. We will also examine the recovery of endogenous stem cells to either radiation or 5-fluorouracil exposure to assess the endogenous competence of CD34 null stem cells. Specific aim 2 will study the compensatory mechanisms that may be at play in allowing CD34 null mice to survive to adulthood with mildly affected hematopoietic phenotypes. Finally, we will study the homing potential of stem cells from CD34 null mice to engraft normal recipients using a recently developed homing assay in which we will tag stem cells in vivo. We expect that the results of our studies will be directly applicable to treatment of hematological disorders, genetic diseases, and malignancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECEPTORS

FUNCTIONAL

HIERARCHY

OF

REMNANT

LIPOPROTEIN

Principal Investigator & Institution: Fazio, Sergio; Associate Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from applicant's abstract): The focus of this grant is the elucidation of the mechanism by which remnant lipoprotein particles are cleared by hepatic receptors. The Principal Investigator and his colleague, Dr. M. Linton, have pioneered the use of bone marrow transplant to study apo E delivery into genetically altered mice via transplanted macrophages. The critical observation in the preliminary data, which serves as the basis for the grant proposal, is that BMT into apo E deficient mice is capable of fully restoring normal lipid levels, but the same transplantation does not normalize lipids in animals that are deficient in both apo E and the LDL receptor. Apo E deficient animals who are homozygous for the LDL-R have a good response to BMT, but lipid values are higher than in animals with two intact genes encoding the LDL-R. Importantly, the apo E levels in the double ko animals are even higher than those found in normal mice, and data presented in the grant indicates that this apo E is present in the space of Disse in the liver, where lipoprotein capture by hepatic lipoprotein receptors should occur. These findings indicate that the apo E provided by macrophages does not substitute fully for endogenous hepatic apo E in generating a pathway that can metabolize remnant particles. The PI lists three major specific aims, each of which is divided into three subaims. The first aim is designed to assess the roles of the LDL receptor and the LRP receptor in the clearance of remnant lipoproteins using bone marrow transplantation of apo E expressing macrophages to partially re-constitute apo E expression in mice genetically deficient in apo E and the LDL-R. Turnover studies of apo B-48 and apo B-100 remnants will be analyzed before and after transplantation and the fate of lipoprotein associated apo E after internalization by either the LRP or LDL-R will be studied. In Specific Aim 2, the investigators will test their hypothesis that secretion-capture of lipoproteins in the space of Disse is critical to remnant uptake and that this process requires local apo E production by the hepatocyte. This will be accomplished using an adenovirus to express E locally in E deficient animals, before and after BMT. The effect of apo E expression on LRP activity will be assessed by radiolabeled antibodies directed against LRP in vivo, complemented by in vitro studies of apo E enriched B-VLDL binding to fibroblasts deficient in either the LDL-R or the LRP. The third specific aim will focus on the role of apo E and LRP in macrophage foam

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27

cell formation and atherosclerosis. BMT into LDL-R /apo E double ko's will permit the assessment of macrophage-specific E expression on atherosclerosis development in animals with persistently elevated lipids. Fetal hepatocyte transplantation is proposed as a method for generating LRP deficient macrophages to determine what activities of wild type macrophages are attributable to LRP. Finally, in vitro studies will be conducted to assess the role of LRP in the binding and degradation of B-VLDL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC MANIPULATION OF T CELLS--PRECLINICAL MODELS Principal Investigator & Institution: Dipersio, John F.; Cheif, Division of Oncology; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Description Verbatim): Allogeneic bone marrow transplantation is a curative therapy for hematologic malignancies, marrow failure states, and selected inherited metabolic diseases. Unfortunately, BMT is associated with significant morbidity and mortality related to graft vs. host disease (GvHD). Attempts to mitigate GvHD using T-cell depletion resulted in increased rates of graft failure, post-transplant lymphoproliferative diseases, leukemia relapse and opportunistic infections. We propose to genetically modify T-cells using novel cell surface chimeric suicide genes. We will test the expression and purification of novel fusion suicide genes in vitro and in vivo using instructive transgenic and "knock-in" murine pre-clinical models. The optimal method and potential role of genetically manipulated T-cells to mitigate GvHD while maintaining engraftment and graft vs. leukemia can only be defined by developing new reagents and novel pre-clinical murine transplant models. We propose to generate important new reagents to study T-cell transduction by suicide genes and to use a number of well-defined pre-clinical models to develop a rational approach and a clear foundation for future clinical trials. In Aim I, we will design methods to optimize transduction, selection, and expansion of transduced T-cells, using OKT3 and 11-3 and CD3/CD28 magnetic beads. In addition, we will generate novel second-generation suicide genes designed to optimize detection and killing in response to prodrug. We will also test the survival and function of transduced murine and human T cells using in vivo using allogeneic transplant models and several murine SCID models. Aims II and III, we will use the chimeric suicide genes developed in Aim I to generate informative transgenic and knock-in pre-clinical murine models in which these suicide genes will be expressed in all (Aim II) or in subsets (Aim III) of peripheral T-cells. Allogeneic bone marrow transplantation will be performed using the transgenic and knock-in mice developed in Aims II and III to further develop the optimal method of suicide in vivo, its effect on GvHD and engraftment, and its possible role in clinical trials. In Aim 1V, we will utilize three novel murine leukemia models in which the effects of genetically modified T-cells and their in vivo suicide on GvHD, engraftment and graft vs. leukemia can be compared to animals receiving unmanipulated T-cells and T-cell depleted BM. These studies will provide new insights into the pathophysiology of GvHD and its effective treatment. Issues regarding the use of genetically manipulated T-cells to control GvHD can best be investigated through the use of informative animal models and the comprehensive studies described in this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEMATOPOIETIC CELL TRANSPLANTATION FOR MALIGNANCY Principal Investigator & Institution: Forman, Stephen J.; Director; City of Hope National Medical Center Duarte, Ca 91010

28

Bone Marrow Transplant

Timing: Fiscal Year 2002; Project Start 01-JUL-1981; Project End 31-MAR-2003 Summary: This Program Project Grant application seeks support for clinical and experimental studies concerning the major obstacles to successful allogeneic and autologous stem cell transplantation for the treatment of hematologic malignancies. These problems include recurrence of the underlying disease, graft-versus-host disease and infectious with cytomegalovirus. The program consists of two clinical and four experimental projects that are supported by six cores. The two clinical projects propose studies designed to eradicate leukemia and lymphoma utilization innovations in the preparatory regimen as well as in the treatment of minimal residual disease following either allogeneic and lymphoma antigens in the preparatory regimen of patients undergoing allogeneic for leukemia and myelodysplasia or autologous transplantation for lymphoma. It is also the goal of our studies to use antigen-specific cytolytic T cells in the treatment of minimal residual disease in patients undergoing autologous transplantation for B cell lymphoma and allogeneic transport for Ph+ ALL. Two transplant studies involve genetic manipulation of hematopoietic cells to convey resistance to HIV in patients with HIV-related lymphoma utilizing adeno-associated virus and lentiviruses. Studies will also continue on the prevention of graft-versus- host disease and will develop novel immunologic strategies to prevent cytomegalovirus disease after allogeneic transplantation. The two clinical projects in allogeneic and autologous transplantation serve as a resource for the experimental projects in the program. The four experimental projects address biologically important questions related to transplantation including acquisition of immunity to CMV, the development of antigen-specific cytolytic T cells, treatment of minimal residual disease after autologous and allogeneic transplantation, and genetic modification of stem cells to induce HIV resistant immune reconstitution. These projects attempt to bring laboratory based innovative concepts to clinical use in the treatment of Administration for the coordination of research, Biostatistics, Cellular and Molecular Correlative studies, radioimmunotherapy, Long-Term Follow-Up and a new Biomedicine Production Facility for the production of antibodies, antigen specific cells and viral vectors to be used in the experimental studies proposed in this grant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMATOPOIETIC PROGENITOR CELLS Principal Investigator & Institution: Shpall, Elizabeth J.; Associate Director; Blood & Marrow Transplantation; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 17-SEP-1993; Project End 31-MAR-2008 Summary: (provided by applicant): Umbilical cord blood (CB) is used to restore hematopoiesis in bone marrow transplant patients lacking sibling or unrelated donors. A major disadvantage of CB is the low cell dose with resultant delays in neutrophil engraftment and a high rate of engraftment failure. The major hypothesis of this grant is that CB progenitors expanded ex vivo prior to transplantation will provide more rapid neutrophil engraftment and less engraftment failure than unmanipulated CB. There are two populations that have been proposed to be responsible for rapid myeloid recovery: 1) mature progenitor cells, and 2) primitive hematopoietic stem cells. In this grant we will conduct three sequential phase II clinical trials to evaluate CB grafts expanded ex vivo to generate mature progenitors or primitive stem cells. The first trial, a continuation of the previous R01, will evaluate CB grafts in which committed CD34+ precursors have been selectively expanded. The second trial will evaluate CB grafts in which more primitive CB cells are expanded, using earlier-acting growth factors and novel

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technology described in the grant. Based upon the findings of these studies, the third trial will randomize patients to receive CB progenitors which are unmanipulated vs. expanded, using the expansion methodology in the first two trials that results in the fastest engraftment. We anticipate that infectious complications will be a major cause of morbidity and mortality in these trials. Although expanded CB may hasten neutrophil engraftment and reduce infections early posttransplant, it may not affect infections associated with delayed immune recovery. Delays in immune reconstitution in CB recipients are frequently reported. It is possible that the CB purification and expansion methods proposed in this grant, which result in selective loss of lymphoid cells, could further compromise immune reconstitution. Thus, we plan to comprehensively evaluate the immune reconstitution of CB recipients enrolled on the proposed trials. General immune function and CMV-specific immune reconstitution will be studied, because of the multiple, complimentary assays available and the expertise of the co-investigators who will be performing them. By randomizing patients in the third trial, we will be able to make an estimate of the relative efficacy of CB expansion technology as well as immune reconstitution in recipients of unmanipulated vs. expanded CB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMATOPOIETIC TRANSFORMATION BY TYROSINE KINASE FUSIONS Principal Investigator & Institution: Gilliland, D Gary.; Associate Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The overall hypothesis of this proposal is that a detailed characterization of the signal transduction properties of constitutive activated tyrosine kinases associated with human leukemias will identify the critical targets that are required for transformation of hematopoietic cells. These targets can then be exploited for the development of novel therapeutic approaches to leukemia. During the previous funding period, we accomplished each of the goals that were set forward. In particular, we cloned and characterized the transforming properties of a spectrum of tyrosine kinase fusions associated with recurring chromosomal translocations in human leukemias, using both cell culture systems and murine models of leukemia. These include, in addition to the TEL/PDGFbetaR and TEL/ABL fusions, the HIP1/PDGFbetaR, H4/PDGFbetaR, TEL/JAK2 and TEL/TRKC fusion proteins. The availability of a spectrum of constitutively activated tyrosine kinases provides a unique opportunity to identify critically important pathways of transformation through comparative analysis of the signal transduction pathways and target genes activated by these fusion proteins, with validation in animal models. In Specific Aim 1, we will address the hypothesis that characterization of the signal transduction pathways and target genes activated by TEL/PDGFbetaR, TEL/JAK2, TEL/TRKC, and TEL/ABL, and BCR/ABL, will identify critical pathways and targets that are required for transformation. We will utilize standard approaches to analysis of signal transduction, as well as expression arrays. In Specific Aim 2, we will test the hypothesis that the putative critical effectors of transformation identified in Specific Aim 1 can be evaluated and validated in our model systems. We will utilize a combination of approaches that focus on inhibition of transformation in cell culture systems, as well as murine bone marrow transplant models of leukemia using hematopoietic progenitors from donor mice are that are genetically deficient in one or more of the putative targets. In Specific Aim 3, we will test the hypothesis that acute leukemia phenotypes are a collaboration between constitutively activated tyrosine kinases and transcription factor fusion genes

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Bone Marrow Transplant

such as AML1/ETO, AML1/EVI1 and NUP98/HOXA9. We hypothesize that coexpression of tyrosine kinase fusions and transcription factor fusions will cause an acute leukemia phenotype in murine models, and that these leukemias will retain sensitivity to specific tyrosine kinase inhibitors. This proposal will provide insights into signal transduction and target genes critical for transformation of hematopoietic cells, as well as novel therapies for leukemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMOSTASIS CLINICAL RESEARCH NETWORK PROTOCOLS Principal Investigator & Institution: Leissinger, Cindy A.; Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Patients with disorders of hemostasis are subject to long term problems and risks, difficult treatment decisions and risks associated with treatment itself. Many of these risks and complications can be lessened or prevented by appropriate intervention strategies. Advances in the management of patients with bleeding disorders of relatively low incidence require: 1) that clinical studies utilize a multi-institutional cooperative network in order to accrue sufficient numbers of patients to achieve meaningful answers; and 2) that patients be educated on the vital importance of participation in such studies. The purpose of this project is to develop a Hemostasis Core Clinical Research Unit at Tulane University as part of the NIH Transfusion Medicine/Hemostasis Clinical Research Network. This Unit will be developed using some of the basic infrastructure and services of the Tulane Center for Bleeding Disorders, which is dedicated to the care and advancement of patients with disorders of hemostasis. Once established, this Core Research Unit will provide access to clinical trials for hemostasis patients from the Center for Bleeding Disorders, the Bone Marrow Transplant Unit and from throughout the network of Tulane affiliated hospitals and clinics. In addition, two clinical trial protocols have been developed as part of this proposal. The first, A prospective randomized crossover study of activated prothrombin complex concentrates (aPCCs) as prophylactic therapy in hemophilia A patients with inhibitors, is a long-term protocol designed to evaluate the efficacy of aPCCs in the prevention of bleeds in this very complicated group of patients. The second, short-term protocol, A prospective study of ribavirin for the treatment of HIVassociated immunopathic thrombocytopenic purpura (ITP), was developed to test a novel pharmacologic agent in the management of HIV-ITP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIGH PERFORMANCE MAGNETIC CELL SORTING Principal Investigator & Institution: Chalmers, Jeffrey J.; Professor; Chemical Engineering; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 21-JUL-2003; Project End 31-MAR-2007 Summary: (provided by the applicant): An area of increasing interest, and potentially significant clinical use, is performing mismatched stem cell transplants for high-risk and refractory hematological malignancies using related donors. Such patients currently undergo transplants using HLA matched sibling or unrelated donor stem cells. Using haplotype-mismatched donors from siblings, parents or children would permit the availability of suitable donors for more than 90-95% of candidate patients. However, the main limitation is graft-versus-host disease (GVHD). GVHD can be almost eliminated by extensive T-cell depletion (>5 logs). While T cell depletion increases the risk of graft

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rejection, this can be overcome by the use of very large doses of stem cells. Therefore, it is desirable to have a system where very large numbers of stem cells can be efficiently processed to deplete T-cells, and with minimal loss of these stem cells. A second area of increasing interest, and potentially significant clinical use, is the isolation of Natural Killer (NK) Cells for Immunotherapy. NK cells are important cells of the innate immune system that are not involved in specific antigen recognition. These cells are important in the defense against infections, but also have potent anti-tumor effects. Currently, there is growing interest in the use of both autologous and allogeneic activated NK cells for cancer immunotherapy. In particular, the use of allogeneic NK cells mismatched for HLA-C alleles of the recipient can exert very potent anti-leukemic effect in vitro. Infusion of NK cells may also assist engraftment of stem cells in the bone marrow transplant setting. This project will focus on the development/application of a high throughput, flow through immunomagnetic cell separation system currently under development for clinical scale T-cell depletion and NK isolation. While several systems have been developed, none are currently approved for these indications, and their performance is generally suboptimal. With respect to the recovery of stem cells during T-cell depletion, a significant increase in stem cell recovery is needed, from reported mean values of 41 to over 80%, to facilitate 'mega-dose' CD34 cell therapy in mismatched transplants. Less research has been carried out for clinical scale NK cell separation technology, with current methods performing sub-optimally due to loss of over 50% of the NK cells. Specifically, therefore, our objectives are: 1.To demonstrate significantly superior performance for T-cell depletion with the aim of achieving 5 log10 depletion of T cells, with >90% recovery of CD34+ cells in greater than or equal too 80% of clinical apheresis samples obtained from normal donors. 2. To demonstrate significantly superior performance of NK cell isolation with the aim of isolating CD56+ CD3- NK cells with > 90% recovery and with <1 x 10/5 CD3+ cell contamination in greater than or equal to 90% of peripheral blood apheresis products processed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYDROXYCHLOROQUINE THERAPY AND BIOLOGY OF GVHD Principal Investigator & Institution: Gilman, Andrew; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Abstract) Allogeneic bone marrow transplantation offers curative therapy for patients with leukemia and other diseases. However, transplantrelated complications, like chronic graft-versus-host disease (GVHD) result in significant morbidity and mortality. Chronic GVHD results from donor lymphocytes reacting to tissues of the bone marrow recipient (alloreactivity). Standard treatment of chronic GVHD includes prednisone alone or in combination with cyclosporine. Complete resolution of extensive chronic GVHD occurs in only 30-40 percent of patients treated with standard therapy. The proposed study will examine the benefit of adding hydroxychloroquine (HCQ) to standard therapy for the treatment of newly diagnosed extensive chronic GVHD. The study will be conducted as a randomized, placebocontrolled, double-blinded Phase III trial under the auspices of The Children's Cancer Group. This study will be the first large cooperative group trial of therapy for chronic GVHD. The trial will include laboratory studies to improve our understanding of the biology of GVHD. A better understanding of the factors involved in GVHD will allow the development of targeted therapies for GVHD in the future. HCQ inhibits alloreactivity in vitro. Mechanisms of action of HCQ include interference with antigen processing and presentation, reduction of cytokine production, inhibition of

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cytotoxicity, and interference with T cell signal transduction. HCQ can prevent acute and chronic GVHD in murine models. A recently completed Phase II trial of HCQ for the treatment of patients with steroid-resistant or steroid-dependent chronic GFHD, or who were experiencing toxicity from other immunosuppressive drugs needed to control their GVHD, showed that HCQ had activity for chronic GVHD. Thirty-eight patients were enrolled. 55 percent of 29 evaluable patients with chronic GVHD had a response. No significant toxicity was seen. HCQ is a well-tolerated drug with activity in chronic GVHD, and with non-overlapping toxicities with other immunosuppressive drugs. The proposed study will evaluate the efficacy of a treatment regimen of hydroxychloroquine, cyclosporine, and alternate-day prednisone compared to the standard regimen of cyclosporine and alternate-day prednisone for newly diagnosed extensive chronic GVHD. Patients will be randomized to one of the two regimens and will receive nine months of therapy. Patients will be followed to determine their response to therapy, degree of disability, and survival. Blood from patients will be examined at study entry and then every three months to examine the biology of chronic GVHD, and to see if the different treatment regimens affect the immune system differently. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOGENETICS OF MARROW ALLOGRAFTING Principal Investigator & Institution: Hansen, John A.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-MAR-2007 Summary: (provided by applicant): Hematopoietic stem cell transplantation (HSCT) has become life saving therapy for patients with various congenital, acquired and malignant diseases of the immune and hematopoietic systems. Graft rejection, graft-versus-host disease (GVHD) and prolonged immune deficiency remain significant causes of morbidity and mortality. The overall theme of this Program Project grant is to understand alloimmunity and how T cells and natural killer cells interact with alloantigen. Studies in this Program Project are focused on the genomics and function of the human major histocompatability complex (MHC), on genetic matching for transplantation and the definition of optimal criteria for donor selection, on the identification of minor histocompatability (mHA) that function as peptide ligands for alloreactive T cells, and on the development of new strategies for inducing immunological tolerance to alloantigen. Availability of a suitably matched donor has been a significant factor limiting access to clinical HCT. The development of large files of HLA typed volunteer donors, now numbering more than five million worldwide, has greatly improved the therapeutic options of many patients, but more detailed criteria for optimal matching and improved methods for modulating alloimmunity in patients with mismatched grafts are urgently needed. Due to the extreme nature of HLA polymorphism and the significant allograft reactions caused by disparities for mHA, improved genetic matching and larger donor registries alone will not solve the problem for all patients. Successful management of these problems will depend on improving our understanding of alloimmune responses and development of new strategies for achieving tolerance. There are four scientific projects in this Program Project and two administrative and shared resource core components. Project 1 is aimed at a comprehensive analysis of the human MHC and discovery of single nucleotide polymorphism (SNPs). An HLA SNP data set has broad implications for genetic analysis, the study of HLA and disease associations and donor recipient matching. Project 2 is aimed at developing adoptive immune-therapy employing lymphoid

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dendritic cells (DC) to induce tolerance. Project 3 is aimed at analyzing T cell alloreactivity in HCT recipients and identification of the genetic determinants most relevant to favorable transplant outcome. Core A provides administrative support and shared resources, including biostatistic consultation and a cell bank containing reference materials and donorrecipient cells for analysis of genetic matching and transplant outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOTHERAPY WITH PEPTIDE MHC TETRAMER ISOLATED T CELLS Principal Investigator & Institution: Lyerly, Herbert K.; Director; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Recent advances in T cell phenotyping and high speed sorting have coalesced to allow the direct testing of an important basic tenet in immunotherapy-specifically that adoptive immunotherapy with antigen specific T cells will eradicate antigen expressing cells in vivo. Although immunotherapy with T cells activated and expanded in vitro have shown promise, an alternative broadly applicable strategy may allow therapy with antigen specific T cells prior to significant activation. Specifically, peptide major histocompatibility complex (MHC)-tetramers allow the identification of T cells that specifically bind to unique nanopeptides in the context of a specific human leukocyte antigen (HLA) allele. This technology allows for the sorting and isolation of highly purified populations of antigens specific T cells from peripheral blood mononuclear cells (PBMC). We have hypothesized that the adoptive immunotherapy with purified populations of antigen specific T cells will have clinical benefits in patients immunosuppressed following bone marrow/peripheral blood stem cell transplant. A relevant model system to test this hypothesis exists in immunocompromised patients with cytomegalovirus (CMV) infection or Epstein Barr virus (EBV) associated LPD (LPD). Clinical benefit has been achieved with administration CMV specific clones expanded in vitro and as few as 10(7) cells/M2PBMC activated in vitro with autologous EBV transformed B cells. While these strategies are clinically effective, they cannot be widely applied because they are complex and time-consuming, taking as long as to 3 to 4 months to generate the appropriate cells for administration. An exciting alternative to this laborious process would be to directly isolate CMV or EBV specific T cells from peripheral blood samples by high speed sorting with CMV or EBV peptide MHC tetramers. This strategy would allow for the rapid isolation of up to 10-40 x 10(6) antigen specific T cells. These cells could then be directly administered, or administered after a brief period of ex vivo activation and expansion. This application proposes pre-clinical studies and pilot clinical trials of adoptive immunotherapy with peptide MHC tetramer sorted T cells. It is anticipated that these studies would provide an important proof of principle for this general concept which would have wide application for antigen specific adoptive immunotherapy of vial disorders and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LENTIVIRAL VECTORS FOR GENE THERAPY FOR BETATHALASSEMIA Principal Investigator & Institution: Malik, Punam; Assistant Professor of Pediatrics and Pa; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2002; Project Start 08-MAY-2002; Project End 31-MAR-2007

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Summary: (provided by applicant): The B-thalassemias are the most common single gene defect in humans and result from absent or decreased B-globin synthesis, leading to severe anemia. Patients with B-thalassemia major are treated with life-long transfusions. Bone marrow transplantation can be curative, but is limited to a few with matched donors, and has potentially serious complications. Replacement of a normal Bglobin gene into hematopoietic stem cells (HSCs) can potentially correct the disorder permanently, avoiding the complications associated with a transplant. With the advent of better vectors, improved gene transfer techniques and a better understanding of stem cell and vector biology, gene therapy is going from the bench to the bedside, in diseases like SCID and hemophilia B. 'Globin' gene therapy has suffered from problems of vector instability, low titers and variable expression. The recently developed lentiviral vectors transduce the non-dividing HSCs and stably export large genomic fragments by unique RNA export mechanisms, imparting stability to globin vectors. Self-inactivating (SIN) lentiviral vectors are even more advantageous: the viral LTR is deleted upon integration into cells, completely inactivating viral transcription. This feature is ideal for the expression of a highly lineage-restricted gene such as globin, and additionally improves their bio-safety. We have recently shown remarkably lineage-specific and long-term expression of GFP and gamma-globin from SIN lentiviral vectors in mouse erythroleukemia (MEL) cells, primary murine and human cells. We propose to capitalize on these findings by examining the capabilities of SIN lentiviral vectors to carry the human B-globin gene and erythroid regulatory elements for gene transfer into HSCs that results in stable, lineage-specific and sustained expression of B-globin in RBCs. The aims of the study are to: 1) Develop SIN-lentiviral vectors carrying the human B-globin gene under control of erythroid regulatory elements, and screen them in MEL cells for stable transmission and high level expression. 2) Determine the efficacy, lineage specificity and long term expression of B-globin SIN lentiviral vectors in vivo, in thalassemic mice. 3) Determine the gene transfer capacity and efficacy of B-globin SIN lentiviral vectors in the RBC progeny of human thalassemia progenitor cells, using a unique model of human RBC production developed in our laboratory from hematopoietic progenitor cells. Together, these aims comprise a focussed research program to produce therapeutic and sustained levels of B-globin in human thalassemia RBCs, and form the basis for future preclinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LLME TREATED T LYMPHOCYTE THERAPY AFTER ALLOGENEIC BMT Principal Investigator & Institution: Flomenberg, Neal; Professor; Kimmel Cancer Center; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 26-SEP-2001; Project End 31-AUG-2004 Summary: (Provided by applicant): Allogeneic bone marrow transplantation has emerged as the preferred therapy for a variety of disorders. Unfortunately, outcome is limited by development of graft-versus-host disease (GVHD) and by the opportunistic infections which often ensue as a consequence of efforts to prevent or treat GVHD. Following the resolution of neutropenia early after BMT, infectious risk correlates with the patients' CD4 counts, much as is the case in HIV infected patients. CD4 counts remain low for 4-6 months after either T-cell depleted or T-cell replete marrow transplants. In contrast CD8 counts have the ability to rapidly recover with either form of BMT. GVHD appears to be mediated by T cells bearing cytotoxic effector granules. These cells can be selectively destroyed through the action of Leucyl Leucine Methyl

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Ester (LLME), which undergoes polymerization by dipeptidyl peptidase-I, one of the components of cytotoxic granules. LLME treatment destroys approximately 90 percent of the CD8 T cells, but only 10 percent of the CD4 cells. After LLME treatment, large numbers of mismatched T cells can be adoptively transferred in animals without GVHD. Prior clinical trials of LLME were successful in preventing GVHD, but limited by stem cell toxicity and graft failure when the marrow was treated. Since that time, T cell depletion techniques have been improved, such that the majority of patients can be successfully engrafted with little or no GVHD, even when thetransplants are performed across major histocompatibility barriers. The limitation of these approaches is the prolonged CD4 deficiency and opportunistic infections which ensue. We therefore hypothesize that transplant outcome can be substantially improved by treating recipients of T cell- depleted transplants with donor lymphocyte infusions (DLI) which have been treated with LLME. This will potentially provide safe transfer of large numbers of CD4 T cells and small numbers of CD8 T cells without appreciable GVHD risk. The prior problems of stem cell toxicity will be avoided, as the patients will previously have been engrafted. CD8 recovery would occur through the stem cell graft and CD4 recovery through the DLI. The proposed grant will support a trial to administer increasing numbers of LLME-treated DLI to patients and monitor patients for CD4 recovery and other parameters of immune reconstitution as well as for development of GVHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF AGE RELATED FIBROSIS Principal Investigator & Institution: Agnes, Fogo; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (Taken directly from the application) Aging is a complex physiological condition in which the function of many organ systems becomes altered. The changes in kidney function along with progressive renal fibrosis are among the most dramatic. We have recently shown that high dose angiotensin (Ang) type 1 receptor antagonist (AT1RA) in the aged rat not only prevents ongoing age-related changes but reverses existing glomerulosclerosis, an effect linked to normalization of dysregulated extracellular matrix (ECM) metabolism and decreased plasminogen activator inhibitor-1 (PAI-1). This regression was also linked to altered cortical cell turnover, with abolishment of apoptosis. AT1 and AT2 receptors are postulated to be key in modulation of the balance of proliferation and apoptosis. In addition, cyclooxygenase-2 (COX-2) has been implicated in cell turnover in addition to arachidonic acid metabolism. COX-2 abrogates RAS responsiveness, implicating COX-2 in RAS actions. We further hypothesize that the immune system could also contribute to age-related changes. With aging, there is a decrease in antigen-stimulated immunity, and an increase in innate, i.e., macrophage-driven immunity. We hypothesize that aging changes of parenchymal cells, involving altered cell cycle proteins, lead to apoptosis, and that aging macrophages are defective in clearing these apoptotic cells. We will explore the following mechanisms of age-related renal fibrosis in studies of knockout mice with selective manipulation of macrophage vs. parenchymal cell genotype by bone marrow transplant: dysregulated ECM metabolism in aging, and the potential and mechanisms of regression of this injury; cell cycle events in aging related to the renin angiotensin system and COX-2, and their impact on injury; and the potential role of macrophages and defective clearance of apoptosis in age-related organ fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF LUNG INJURY FOLLOWING AUTOLOGOUS BMT Principal Investigator & Institution: Folz, Rodney J.; Associate Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Lung toxicity following high dose chemotherapy (HDC) and bone marrow transplantation (BMT) or hematopoietic stem cell support develops in up to 70% of patients, with the most severe form of toxicity, termed idiopathic pneumonia syndrome (IPS), accounting for up to 40% of non-graft versus host disease related deaths. We have described a lung toxicity syndrome that occurs following HDC and autologous bone marrow transplant (autoBMT) that we termed delayed pulmonary toxicity syndrome (DPTS). DPTS may be an early form of IPS, is a risk factor for increased mortality, and manifests as an interstitial pneumonitis no sooner than 4 to 6 weeks following autoBMT (mean onset 11 weeks). To begin to better understand its pathogenesis, we developed a novel HDCIautoBMT mouse model of lung toxicity that shows remarkable similarity to the human condition. Based on clinical and bronchoalveolar lavage studies of patients undergoing HDC/autoBMT and our mouse model, we hypothesize three specific mechanisms the development of DPTS. First, HDC induces an intense oxidative stress resulting in both lung tissue injury and increases in monocyte chemo attractant protein-1 (MCP-1). Second, in response primarily to MCP-1 (and MIP-1a), pulmonary inflammatory cells are recruited into the lung, which possess antigen presenting cells (APC) features and may further stimulate a T cell lymphocyte response. Finally, fibroblast growth factors, like FGF-2, initiate a lung repair and fibrotic response. We plan to test these hypotheses by utilizing mouse strains that 1) overexpress and under express (knockout) antioxidant enzymes, 2) overexpress MCP-1, and 3) are deficient in CCR2. Additional studies designed to characterize the pulmonary inflammatory cells, determine their activation status, and their ability to stimulate T cells will be performed. Finally, we plan to identify BALF growth factors responsible for the development of restrictive lung. This proposal should provide new insights into the pathophysiology of lung injury following autologous bone marrow transplant and provide the basis for future clinical studies to prevent or treat this serious pulmonary complication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENTORED DEVELOPMENT AW

PATIENT-ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Rizzieri, David A.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract): Myeloablative allogeneic bone marrow or stem cell transplantation has been successfully used to cure patients with various types of malignant and nonmalignant diseases. Unfortunately, the risks of this therapy include pulmonary hemorrhage, hepatic failure, severe infections and graft versus host disease. For these reasons, patients who may benefit most from the allogeneic procedure are commonly ineligible for the allogeneic transplant, including those over age 55 years, those with significant prior organ damage, or those with severe infections. Therefore, the investigators and others have developed a less toxic preparative regimen that will successfully allow engraftment of the donor hematopoietic cells while minimizing the risk to the patient of dying of the procedure, thereby making

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this approach available to a broader array of potential beneficiaries. Importantly, standard post-transplantation care to minimize graft versus host disease still requires aggressive medications with potential severe toxicities. Therefore, they have developed a T-cell depletion protocol using an antibody to CD52 which has been previously shown to be effective for graft versus host disease prophylaxis while maintaining a high engraftment rate and anti-tumor effect of allogeneic therapy. The primary purpose of the translational study in this proposal is to assess the toxicity, engraftment, immune reconstitution and anti-tumor effects of a nonablative conditioning regimen of in vivo Campath-1H, fludarabine, and cyclophosphamide for patients with high risk malignancies. This will be followed by matched-sibling allogeneic peripheral blood stem cell and marrow transplantation (allo, PBSCT) utilizing hematopoietic progenitor cells which are being purged in-vitro with Campath-1H. T-cell depletion with CAMPATH1H will obviate the need for post-transplant exposure to the toxicities of cyclosporine and methotrexate. These results will lead to future improvements in maximizing the anti-tumor effects of allogeneic therapy, hastening immunologic recovery, and minimizing the toxicity of this procedure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MIXED CHIMERISM IN THE HEMOGLOBINOPATHIES Principal Investigator & Institution: Blau, C Anthony.; Associate Professor; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The investigators of this proposal have developed two tools that may be of value in establishing stable mixed chimerism of patients with sickle cell anemia and beta thalassemia. The first tool is directed toward developing a minimally toxic method for producing stem cell depletion using the combination of flt-3 ligand (FL) and 5fluorouracil (5-FU). This approach may be a useful component of transplant conditioning regimens that are directed at achieving mixed chimerism. The second tool uses chemical inducers of dimerization (CIDs) to specifically deliver a mitogenic signal to genetically modified cells. Transfer of a gene that encodes a CID-responsive protein may render normal donor stem cell responsive to CID-mediated proliferation. This approach may allow the proliferative status of normal donor stem cells in mixed chimeras to come under direct pharmacological control. Specific Aim 1 tests whether CIDs can expand genetically modified stem and progenitor cells in vivo. Specific Aim 2 develops a mouse model of mixed chimerism in beta thalassemia, and seeks to determine the level of normal donor stem cell engraftment needed to reverse the thalassemic phenotype. Specific Aim 3 tests whether CID-mediated in vivo expansion of normal donor stem cells can correct the thalassemic phenotype of mice with mixed chimerism. Specific Aim 4 evaluates whether FL can sensitize stem ells to 5-FU. In Specific Aim 5, the FL/5-FU combination is added to an immunosuppressive condition regimen for studies in allogeneic models of mixed chimerism. In Specific Aim 6, findings from the previous specific aims are combined to test CID-mediated in vivo expansion of normal donor stem cells in an allogeneic model of mixed chimerism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR AND CELLULAR ANAYLSIS OF T CELLS DURING DLI Principal Investigator & Institution: Margolis, David A.; Associate Professor; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801

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Timing: Fiscal Year 2002; Project Start 25-SEP-1998; Project End 31-AUG-2004 Summary: The potential of the graft versus leukemia (GVL) effect to cure leukemia is illustrated by the success of adoptive immunotherapy with donor leukocyte infusions (DLI) to treat patients who have relapsed with CML after an allogeneic bone marrow transplant. Understanding the immunologic mechanisms underlying this could lead to a significant advancement in the treatment of leukemia in both children and adults through adoptive immunotherapy. The following hypothesis will be tested in the proposed research project: The therapeutic effect of DLI is mediated by a distinguishable population of donor-derived, MHC- restricted T cells responding to both allogeneic and leukemia-specific stimuli. Three Specific Aims are proposed: 1) To characterize at cellular and molecular levels the T cell response to a leukemia-specific peptide (bcr-abl) in the absence (autologous) and presence (allogeneic) of various degrees of major and minor histoincompatibility; (2) To characterize at cellular and molecular levels the T cell response to intact CML cells, compare this response to that generated by the bcr-abl peptide, and evaluate how alloreactivity alters these responses; and (3) To assess the repertoire of T cells in the peripheral blood of patients given DLI for CML and compare the in vivo T cell repertoire to that identified in vitro in Specific Aims 1 and 2 to distinguish alloreactive and leukemia-reactive T-cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BIOLOGY OF HUMAN ERYTHROCYTE ALPHASPECTRIN Principal Investigator & Institution: Gallagher, Patrick G.; Associate Professor & Assist Director; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2004 Summary: (Investigator's abstract) The long-term goals of this proposal are to elucidate the molecular mechanisms involved in normal and abnormal expression of the erythrocyte membrane protein a-spectrin. Erythrocyte a-spectrin is an important component of the erythrocyte membrane skeleton. The first aim of this proposal is to identify a-spectrin mutations in patients with recessively inherited hereditary spherocytosis and hereditary pyropoikilocytosis, severe hemolytic anemias, and to analyze the structural and/or functional significance of these abnormalities. The second aim of this proposal is to identify and characterize the promoter and other key regulatory factors that control expression of the erythrocyte a spectrin gene. These results will be applied to the study of the role of a-spectrin gene transcription in erythropoiesis and membrane biogenesis and to the genetic study of patients with hemolytic anemia who have been found to have mutations in the putative a-spectrin gene promoter. The third aim of this proposal is to correct the defect in an a spectrin deficient murine erythroleukemia cell line and in the erythroid cells of sph/sph mice, an a-spectrin deficieny model of inherited hemolytic anemia, via retroviral transduction of the a-spectrin cDNA. The general methodology tc be utilized in this research includes: study of genomic DNA from patients with a-spectrin linked rHS and HPP using PCRbased single stranded conformational polymorphism (SSCP) analysis, followed by nucleotide sequence analysis cloning and structural analysis of the cDNA and genomic fragments of the a-spectrin gene relevant to its expression and regulation by the use of recombinant DNA technology; study of cis-acting sequences by gene manipulation followed b, gene transfer/expression studies in tissue culture cells; studies of transacting factors by electrophoretic mobility shift assays, DNAse-I footprinting, methylation interference techniques and site-directed mutagenesis followed by in vitrc

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and in vivo analyses, and guanine-adenine ligation-mediated PCR (GA-LMPCR) dimethyl sulfate in vivo footprinting developmental and tissue-specific studies of the regulatory sequences of the a-spectrin gene promoter in transgenic mice; In vitro transduction of a-spectrin deficient MEL cells with a retrovirus containing the a-spectrin cDNA transduction of hematopoietic stem cells (HSCs) from a-spectrin deficient sph/sph mice with an ecotropic retrovirus containing the a-spectrin cDNA, followed by HSC-retroviral gene transplant into the sph/sph mice. These studies will provide important insights into our studies of the role of a-spectrin in normal and disease states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR DETECTION OF OCCULT NEUROBLASTOMA Principal Investigator & Institution: Cheung, Irene Y.; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 08-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Measurements of occult tumor cells in bone marrow and peripheral blood, besides providing prognostic impact, are potential sensitive indicators of tumor response in leukemia and metastatic solid tumors. The advent of RTPCR and novel tumor markers has greatly improved detection sensitivity and enabled retrospective analysis of archived tissue samples. In small cohorts of patients with neuroblastoma and melanoma who were in apparent clinical remission, the presence of GD2 synthase mRNA and cancer/testis antigen GAGE in blood and marrow was found to be strongly prognostic of patient survival. They can potentially be molecular markers of minimal residual disease (MRD), one of the final hurdles to cancer cure. In this grant, we propose to test two hypotheses: (1) immunotherapy is as effective as marrow/stem cell transplant in the adjuvant setting when patients are in apparent clinical remission, and (2) MRD at the end of induction, and at 2 years from diagnosis have the strongest prognostic impact on patient survival. In aim 1, MRD response will be tested in a large consecutive patient cohort diagnosed with high-risk neuroblastoma undergoing marrow/stem cell transplant (patient N=139), or anti-GD2 monoclonal antibody 3F8 immunotherapy (N=269). MRD response will be correlated with the level of pretreatment tumor content, as well as clinical/biologic markers known to impact on patient outcome. Host factors that mediate tumor killing by 3F8 will also be tested for correlation with MRD response. In aim 2, we will test if MRD has an independent prognostic impact on patient survival as adverse tumor biology continues to be neutralized by effective treatment strategy. For this analysis, MRD will be assayed among newly diagnosed stage 4 patients treated by consecutive neuroblastoma protocols (age 1-17 years, N=130) with their marrows obtained at diagnosis, end of induction (right before transplant or 3F8 adjuvant treatment), 12, 18, and 24 months from diagnosis. The relative importance of MRD at these time points will be tested against known prognostic factors. If these two molecular markers of MRD can independently predict patient outcome, they will in the future provide an objective endpoint for stopping further treatment, and serve as sensitive surrogates for evaluating adjuvant therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUSCLE-DERIVED HEMATOPOIETIC STEM CELLS Principal Investigator & Institution: Goodell, Margaret; Assistant Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2005

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Summary: (Investigator's abstract) Primitive stem cells are found in many adult tissues and, throughout life, replenish mature cells lost through attrition or injury. Although thought to be committed to differentiate into cells of their native tissues, some stem cells now appear capable of generating several different cell types, an indication that they have retained considerable plasticity in their genetic programs. The biologic and therapeutic implications of "transdifferentiation" potential are far reaching but will remain speculative until the concept is better substantiated and the mechanisms that might drive this process are known. Evidence from the applicant's laboratory indicates that adult murine skeletal muscle contains stem cells capable of complete hematopoietic regeneration. Thus, the central hypothesis to be tested is that these stem cells are a subset of myogenic stem cells known to participate in muscle regeneration, they share certain characteristics of bone marrow stem cells, have myogenic activity, are transducible with retroviral vectors, and can be found in human muscle. The major objectives of this proposal are to characterize the biologic properties and markers of muscle-derived hematopoietic stem cells by cell sorting and bone marrow transplantation experiments (Aim 1) so that the cells can be readily identified and purified, and their salient features an be compared with those of marrow-derived stem cells. It will also be important to assess the in vitro and in vivo myogenic potential of purified and clonal populations of muscle-derived hematopoietic stem cells (Aim 2). The results will establish whether or not the stem cells are bipotential precursors of both muscle and blood and therefore an extremely primitive stem cell with a flexible program of differentiation. If the muscle stem cells can be readily transduced with retroviral vectors and the modified cells shown to engraft and stably express a marker gene in transplant recipients (Aim 3), they may afford a novel means of delivering therapeutic genes of interest. Finally, results obtained in mice will need to be verified, both in vivo and in vitro, with stem cells derived from human muscle (Aim 4). Answers from these studies will be crucial in determining if human muscle could provide a source of hematopoietic stem cells for therapeutic exploitation. Successful completion of these aims will not only provide an estimate of the hematopoietic potential of adult musclederived stem cells, but also a foundation for future studies into the mechanisms of stem cell transdifferentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NK RECEPTORS AND BONE MARROW TRANSPLANT OUTCOME Principal Investigator & Institution: Hsu, Katharine C.; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2004; Project Start 27-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Dr. Katherine C. Hsu is a junior faculty member at Memorial SIoan-Kettering Cancer Center, whose research interest is in the impact of killer immunoglobulin-like receptors (KIR) on allogeneic hematopoietic stem cell transplantation. AIIogeneic hematopoietic stem cell transplantation (AHSCT) is a valuable therapy for acute leukemias and chronic myelogenous leukemia. Natural killer (NK) cells may influence early and late post-transplant complications, such as graftversus-host disease (GVHD), disease relapse, and viral infection. The overall objective of this study is to gain insight into the influence of NK killer Ig-like receptors (KIR) on AHSCT outcome. Typing for the 14 known genes encoding activating and inhibitory KIR will be performed for transplant donors and recipients from HLA-A, -B, and -DRmatched allogeneic transplants. Dr. Hsu hypothesizes that KIR genotypes can predict NK-mediated influence on AHSCT outcome: lack of donor activating KIR genes will predispose to post-transplant viral infection and to disease relapse for certain leukemias

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but not others; donor-recipient inhibitory KIR gene disparity will influence disease relapse/survival in patients receiving transplants from HLA-C disparate donors (KIR epitope mismatched); and donor-recipient KIR gene disparity may influence engraftment and GVHD in nonmyeloablative transplants. Dr. Hsu aims to address these hypotheses through: 1) determining the influence of donor KIR on overall survival and post-transplant complications in patients receiving T-cell depleted HLA-identical sibling AHSCT for CML and AML; 2) determining in a multi-center analysis, the influence of donor KIR genotype and donor-recipient KIR disparity in patients undergoing unrelated AHSCT; and 3) evaluating prospectively the influence of NK receptors, including both donor and host KIR, on engraftment, GVHD and overall survival in patients undergoing transplants with non-myeloablative conditioning. Dr. Hsu has two mentors, Dr. Bo Dupont and Dr. Richard O'Reilly who have previously served as mentors for both clinical research and basic research scientists. Dr. Glenn Heller is the biostatistician for the proposed studies. As her immediate goals, Dr. Hsu hopes to demonstrate conclusively the influence of the activating KIR on transplant outcome and to identify in which clinical setting the inhibitory KIR may play a role in affecting transplant outcome. In addition, she seeks to understand the interplay between donor and recipient NK cells in non-myeloablative transplants and to determine if KIR may direct their interaction and influence on transplant outcome. Eventually, she hopes to utilize this information to develop adoptive cell therapy using NK cells. Dr. Hsu intends to develop a career as an independent investigator in the field of NK cell immunogenetics and allogeneic hematopoietic stem cell transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATIENTS, CLINICS, AND SYSTEMS: SCREENING FOR ALCOHOL Principal Investigator & Institution: Chang, Grace; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 24-SEP-1999; Project End 31-AUG-2004 Summary: The majority of patients with alcohol problems present to general medical and other clinical settings, rather than directly to alcohol treatment. The consequences of untreated alcohol problems are well known, and include a whole range of medical and social complications. The identification and treatment of alcohol problems, when patients present for prenatal care, emergency services, or a medical appointment, has been a longstanding clinical research interest. A Midcareer Investigator Award in Clinical Research would allow the applicant to focus on patient-oriented research interests during a critical professional period. The purpose of the current project, "Alcohol Abuse in Bone Marrow Transplant," is to test the hypothesis that alcohol abuse or dependence has an adverse impact on survival after bone marrow transplant, the second most frequent major organ transplant in the United States and the transplant with the least limited donor organ supply. A prospective cohort study of 124 patients with Chronic Myeloid Leukemia undergoing allogeneic bone marrow transplant is underway. The purpose of the proposed project, "Alcohol Screening in Medicaid Managed Care," is to test the hypothesis that routine alcohol and substance abuse screening of Medicaid members at health plan (HMO) enrollment is less effective than alcohol and substance abuse screening at the HMO primary care site. A sample of 2,000 Medicaid enrollees screened at enrollment will compared with a sample of 715 patients who will be screened for alcohol and substance abuse as they initiate care at primary care HMO sites. Their utilization of alcohol and substance abuse treatment, psychiatric and medical treatment for 12 months subsequent to screening will be compared. A sample of 150 patients with positive primary care screens will be studied more

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intensively. Both of these studies will focus on patients, but will have important practice and policy implications, as transplant medicine and managed care are increasingly prevalent and underscore the need for alcohol and drug screening of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC BLOOD AND MARROW TRANSPLANT CONSORTIUM Principal Investigator & Institution: Gamis, Alan S.; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: This project is part of a Blood and Marrow Transplant Clinical Research Network which is conducting multicenter clinical trials in hematopoietic stem cell transplantation. The purpose of the network is to promote the efficient comparison of novel treatment methods and management strategies of potential benefit for children and adults undergoing blood or marrow transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation after marrow ablation, the development of non-myeloablative transplant regimens, and the best ways to avoid infections in transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC BRAIN TUMOR RESEARCH CENTER Principal Investigator & Institution: Blaney, Susan; Assistant Professor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The Texas Children s Cancer Center(TCCC) Brain Tumor Program (BTP) is a multidisciplinary, highly integrated program of clinical and laboratory research dedicated to improving survival rates of children with central nervous system(CNS) tumors. The Program is one of the largest of its kind in the United States, each year evaluating more than 50 children. The BTP is composed of clinical and laboratory investigators whose research encompasses the entire spectrum of pediatric neurooncology. They are exceptionally qualified to design, conduct, and monitor clinical trials for children with brain tumors. In national cooperative group clinical research and in numerous studies sponsored by the National Cancer Institute and private industry, the BTP has led new approaches to the treatment of infants with brain tumors, introduced new agents against brain tumors through Phase I and Phase II clinical trials, and pioneered the use of highly conformal radiation therapy (RT) to decrease toxicity to normal structures surrounding brain tumors. The BTP works closely with the Gene Therapy Program, Molecular Neuro-Oncology Program, and Clinical Pharmacology Group, all within TCCC, to translate advances in laboratory and pre-clinical science to treatment of children with brain tumors. Examples of ongoing clinical trials include those seeking to determine the impact of intrathecal chemotherapy and highly conformal radiation therapy on the survival of infants with brain tumors, the activity of various new agents against leptomeningeal disease, the activity of various agents against malignant glioma, the use of bone marrow transplant for recurrent medulloblastoma, and the efficacy of gene therapy for children with refractory brain tumors. The BTP utilizes the most modern diagnostic neuroimaging modalities and innovative technologies such as functional MR, MR spectroscopy, and 18F imaging. Its neurosurgeons utilize state- of-the-art operating microscopes and guidance systems. RT is delivered through the most technically advanced conformal system. The BTP

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neuropathologists have complete diagnostic capabilities to classify tumors according to WHO criteria. The BTP maintains a storage bank of tumor specimens for institutional and cooperative group correlative studies. The BTP has an innovative molecular neurooncology program that uses high-throughput technologies to study differential gene expression in pediatric brain tumors. BTP investigators are committed to utilizing their resources for the Pediatric Brain Tumor Clinical Trial Consortium (PBTCTC) studies. The TCCC BTP serves a culturally and ethnically diverse population. It receives considerable research support from Texas Children s Hospital, the largest children s hospital in the United States and from Baylor College of Medicine, one of the top ten medical schools in the country. The unique expertise of the TCCC BTP make it ideally suited to be a Participating Member of the PBTCTC. It offers leadership in the development of new agents, in new uses of sophisticated radiotherapy, and in the application of new approaches to brain tumor therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Cohn, Susan L.; Associate Professor of Pediatrics; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2002; Project Start 01-DEC-1978; Project End 31-DEC-2002 Summary: The objectives of this project are to enroll children with cancer in clinical trials, to develop clinical trials and study the biologic behaviors of childhood cancer, and to improve and evaluate the disease- free survival of patients enrolled in these clinical trials. In order to achieve these goals, the member institutions of the Pediatric Oncology Group (POG) meet biannually to discuss, develop, and implement clinical trials for the most common childhood malignancies and to supply the reference research laboratories of the proper material or tissue necessary for the research. Since 1989, CMH has been one of the member institutions of POG who is actually involved in the accrual of children with cancer to clinical trials. CMH's faculty is also involved in the coordination of studies either as the Principal Investigator or co-Investigator. These protocols are POG 9443, POG 9240/41/42, POG 9135/6, POG 9410, NTWS #5. Participation in administrative activities within POG include the POG Chairperson, the POG Executive Officer, the Head of the Neuroblastoma Biology Committee, the Head of the Neuroblastoma Bone Marrow Transplant Working Group, along with members of the following committees: Non- Hodgkin's Lymphoma, Neuroblastoma, Bone Marrow Transplantation, Hodgkin's Disease, New ALL, Wilms' Tumor, Nursing, and Surgery, Radiotherapy, and Pathology Disciplines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PEDIATRIC ONCOLOGY GROUP Principal Investigator & Institution: Grier, Holcombe E.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-1986; Project End 31-DEC-2002 Summary: The principal activity of this grant is to improve the care and treatment of children with cancer by participating in the Pediatric Oncology Group (POG). The three specific goals of the participation of the Dana-Farber Cancer Institute/Children's Hospital (DFCI/CH) and Maine Children's Cancer Program (MCCP) are to 1) enter and follow children with malignancies on appropriate Pediatric Oncology Group (POG) protocols 2) provide leadership in planning and executing POG protocols and 3) provide pilot clinical studies and scientific leadership to POG. 1) Patient entry: the

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referral patterns at the two institutions has not changed and the commitment to POG protocols remains high. Therefore, patients accrual will continue at the high level previously noted over the last grant period. 2) Leadership within POG: Drs. Weinstein and Grier respectively are the disease chairs for the Myeloid and Sarcoma Committees. The disease committee chairs have primary responsibility for all scientific and clinical activities within POG. Investigators from these institutions are currently or were in the last cycle chairs for 7 separate POG protocols and co chairs of 35 more. They also have 18 positions on disease or discipline committees within POG. Enthusiasm remains strong, and involvement at the current level will continue. 3) Pilot POG protocols and scientific leadership: Scientific leadership is detailed in part above. Dr. Arceci provided scientific leadership for and analyzed the samples of the MEC protocol (#9222) that piloted the use of multidrug resistance reversal agents (cyclosporine) in relapsed AML. This protocol provided the background for the about to open group wide AML up-front protocol (#9394) that will randomize whether or not patients will receive cyclosporine during maintenance therapy. DFCI ALL protocols have provided the background for one of the arms of the proposed new T- cell protocol (#9404). In addition, the background for the current stereotactic protocol (#9373) was in part developed at the Joint Center for Radiation Therapy and the DFCI. Finally, POG has embarked on a major effort to study the autologous transplant protocols for ALL (#9421) developed at the DFCl. Finally Dr. Lipshultz ran at DFCI/CH the pilot studies of late cardiac toxicity from anthracyclines that provides the background data for the randomized trial of enalapril for patients with elevated after load. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHASE III TRIAL OF UCB +/- MSCS IN HEMATOLOGIC CANCERS Principal Investigator & Institution: Lazarus, Hillard M.; Professor/Director, Bone Marrow Transpla; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: This project is part of a Blood and Marrow Transplant Clinical Research Network which is conducting multicenter clinical trials in hematopoietic stem cell transplantation. The purpose of the network is to promote the efficient comparison of novel treatment methods and management strategies of potential benefit for children and adults undergoing blood or marrow transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation after marrow ablation, the development of non-myeloablative transplant regimens, and the best ways to avoid infections in transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHENOTYPE SCREENS FOR BONE MARROW FAILURE Principal Investigator & Institution: Barry, Michael A.; Associate Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from the applicant's abstract) The major objective of this proposal is the development and characterization of efficient hematologic, genetic and physiologic assays of hematopoietic failure in the mouse. Although mutagenesis strategies have yielded a number of mouse models of human bone marrow failure syndromes, less attention has been paid to "acquired" disorders that may result from

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polygenic traits or gene-environment interactions. This is due in part to the lack of appropriate analytical models and strategies for the detection of these conditions, particularly in their presymptomatic phases. As an outgrowth of the genome project, rapid advances have been made in the development of comprehensive screens for differential gene expression. In parallel, advances in chemical biology have resulted in the development of sensitive methods for the identification of metabolites that may be altered in disease states. The fusion of these two approaches is likely to yield powerful screening tools and facilitate the detection and analysis of complex disorders. Accordingly, they propose to incorporate these assays in a panel that also includes complete blood counts, hematopoietic colony growth assays, and fluorescence-based techniques for the detection of presymptomatic bone marrow failure in mice, Specifically, they will utilize whole-genome microarrays to characterize genes that may have dysregulated expression patterns in bone marrow failure; tandem mass spectrometry to identify metabolites implicated in known syndromes of bone marrow failure; and fluorescence spectrometry for the detection of oxidative stress. These assays will be validated in inbred mouse strains and in mouse models of bone marrow failure at steady-state and after challenge with agents (mitomycin C and chloramphenicol) that can induce bone marrow failure. The data will be correlated with measurements of blood counts and hematopoietic colony growth, and the resulting pre- and postchallenge databases will provide the elements of a diagnostic algorithm for the highthroughput screening of bone marrow failure in mice. Finally, the algorithm will be applied for the detection of early bone marrow failure in a test trial of chemicallymutagenized mice. These studies should result in the development of well-defined assays for pathways that regulate the organismal response to exogenous and endogenous toxins and yield new insights into the pathogenesis of bone marrow failure. (End of Abstract.) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYMORPHISM & TRANSPLANTATION BIOLOGY OF NOVEL MHC LOCI Principal Investigator & Institution: Geraghty, Daniel E.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-MAY-2005 Summary: The long term goal of this proposal is to define a broad set of genetic polymorphisms spanning the human major histocompatibility complex (MHC) that will be useful for identifying MHC disease associations, including those diseases associated with unrelated donor marrow transplants. The MHC, which is comprised of the HLA class I, II, and III regions, is, from a genetic standpoint, one of the most thoroughly perused areas of the human genome. Since its discovery over 30 years ago, dozens of disease associations have been linked genetically to this region through their associations to the highly polymorphic class I and II antigen- presenting genes. More recently, complete sequence analysis of the class I, II and III regions has defined over 220 genes, and more detailed analyses have given preliminary information on an additional 40 new genes within class I. We will utilize the extensive background of genomic data gathered in the prior years of this grant to develop tools and datasets that will allow us to test the hypothesis that genetic factors within the MHC, but outside of the class I and II loci, can effect and better predict the outcome of an unrelated donor transplant. Thus our original theme of studying the polymorphism and transplantation biology of novel HLA genes can be continued in a logical and effective manner towards testing this hypothesis, by accomplishing the following specific aims: 1) To identify and characterize

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new genes in the HLA class I region. This will be achieved by utilizing existing computational and expressed sequence tagged (EST)-based gene predictions as a starting point for full-length cDNA isolations and characterization. 2) To develop and define a definitive set of SNPs useful as mapping tools in the association with MHClinked diseases. To complete this we will define and relate SNP frequencies, linkage disequilibrium, recombination frequency, and location relative to existing and new genes from a spectrum of ethnic groups, and 3) To carry out SNP-based analysis of the MHC and the relationship of SNPs to HLA haplotypes found in marrow transplant recipients, thus opening the way to study the potential involvement of SNPs in unrelated marrow transplant outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSITRON EMISSION TOMOGRAPHY OF BREAST CARCINOMA Principal Investigator & Institution: Wahl, Richard L.; Professor/Director of Nuclear Medicine; Radiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2000; Project Start 23-JUN-1992; Project End 31-MAR-2004 Summary: The overall goal of this revised competing renewal application remains to carefully define the utility of PET in the management of patients with breast cancer. In the initial funding period we made progress toward this goal, demonstrating that PET appears promising in chemotherapy monitoring, staging for regional metastases, and in detecting primary tumors in radiographically-dense breasts. We also recently described a consistent molecular alteration in breast cancers versus normal breasts, overexpression of the GLUT-1 glucose transporter by the cancers, and showed (in rodent breast cancer) that FDG uptake in the tumors is significantly- correlated with the expression of this marker on viable cancer cells. In this revised renewal application we will build upon our experience addressing the following clinically important questions: 1) Can PET reliably predict the outcome of chemotherapy? Specifically a) can FDG-PET scans after 1 or two cycles of chemotherapy reliably identify women who are destined to subsequently fail non-marrow ablative chemotherapy, thus identifying women whose treatment should be changed to a non-cross reactive salvage regimen? and b) Can FDG-PET identify during the early induction period of treatment (before bone marrow transplant), the women who will benefit most (and least) from bone marrow transplantation? 2) Are PET scan findings at the time of diagnosis predictive of long-term outcome? Patients studied in the axillary node staging and chemotherapy protocols in the initial funding period will be followed for recurrence/death to help ascertain the predictive value of PET. 3) What are the histological correlates of the signal observed by PET scanning before and after cancer treatment? Correlative studies with biopsy samples from patients and in a rat model of breast cancer will be performed. Autoradiographic studies from the animal model of breast cancer will allow us to determine whether FDG is a reliable marker of viable GLUT- 1 positive tumor cell number after chemo or radiotherapy, or if significant tracer uptake is into reactive non-tumor elements. 4) Does 3D FDG-PET offer advantages over the standard 2D methods used to date in detecting axillary lymph node metastases or primary breast cancers? Pilot studies will be performed evaluating primary lesions and axillary nodal imaging to determine if more comprehensive studies should be pursued with the 3D method. The studies we propose will allow us to better define the role of FDG PET in patients with breast cancer and answer basic questions regarding the FDG signal. The results in the breast cancer model should be applicable to FDG PET of other cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFECTIONS/TRANSPLANTATION

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PREVENTION/DIAGNOSIS/FUNGAL

Principal Investigator & Institution: Alexander, Barbara D.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant): The incidence of invasive fungal infections (IFIs) has increased dramatically over the past twenty years. Patients undergoing bone marrow transplantation (BMT) as well as those receiving transplanted solid organs are at particularly high risk for these often lethal infections. IFIs are associated with high mortality owing to currently limited and often toxic antifungal drugs as well as the lack of sensitive, rapid tests to aid in the earlier diagnosis of invasive fungal infections. If an antifungal regimen could be given safely to patients at high risk for developing fungal infections and fungal infections prevented without inducing the development of resistance, the field of transplantation would benefit greatly. Similarly, if an assay could be developed that would reliably diagnose invasive mycoses early in the course of infection, targeted antifungal regimens could be started at a stage of infection more amenable to therapy. The specific aims of this proposal are 1) to assess new prophylactic regimens for the prevention of invasive fungal infections in high risk transplant populations and 2) to assess new laboratory assays for the rapid diagnosis of invasive fungal infections in high risk populations. These aims will be met through a series of clinical trials. The safety and tolerability of inhaled Amphotericin B Lipid Complex (ABLC) will be determined in the allogeneic BMT population through a nonrandomized open-label trial. Large, multicenter randomized, trials designed to assess efficacy will follow. The inhaled route of administration of ABLC for prophylaxis may result in a decreased incidence of toxicity as compared with the systemic administration of the drug. The performance characteristics and the diagnostic value of serial monitoring with different rapid antigen assays and PCR assays will be assessed in prospective studies involving lung transplant recipients. Trials designed to investigate the contribution of these rapid assays to better clinical outcomes will follow. Finally, a multicenter transplant data registry and specimen bank will be established for the purpose of evaluating rapid diagnostic assays currently in development. This approach will shorten the time from development to clinical implementation in therapeutic trials and guidelines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PURGING PROGENITOR CELL BY PULSED ELECTRIC FIELDS Principal Investigator & Institution: Craiu, Abie; Professor; Science Research Laboratory, Inc. 15 Ward St Somerville, Ma 02143 Timing: Fiscal Year 2002; Project Start 06-SEP-2001; Project End 31-DEC-2003 Summary: (Provided by Applicant): High dose chemotherapy is now a commonly used approach for treatment of hematologic and other cancers, but causes severe myelosuppression requiring progenitor cell infusions. Purging cancer cells from infusions, while maintaining progenitor cells, is an important goal in optimizing the curative potential of this technology. Current purging techniques have limited efficiency and demand intensive time, technology and cost. We have demonstrated a new technology that selectively kills larger cells (including tumor cells) while preserving or enriching hematopoietic progenitor cells, and does so rapidly, profoundly and inexpensively. In phase II, we will apply this technology to a relevant hematologic cancer model (multiple myeloma). Process parameters will be refined to achieve

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complete tumor purging and progenitor cell preservation/enrichment from tumorseeded blood or cord blood cells. Sensitive and accurate cell enumeration will be achieved through flow cytometry, tumor regrowth assays, real-time PCR, progenitor cell quieseence/pluripotency assays, and in vivo hematopoietic reconstitution and malignancy assessment in NOD/SCIDt,B2m about mice. We will then apply refined parameters and assessment techniques to clinical volumes of bone marrow cells from myeloma patients, utilizing an optimized, clinical-scale flowing process apparatus. We anticipate the Phase III effort will involve Phase II clinical trials supported by a major biomedical partner. PROPOSED COMMERCIAL APPLICATION: We expect PEF cellsize specific inactivation technology to be an effective transplant tissue purging strategy for post-intensive-therapy patient support. With the propose refinements and assessments, it should provide an approach for rapid, cost-effective, high purity isolation of stem cells from progenitor cell preparations, which will open research, clinical, gene therapy and stem cell banking markets. Our market analysis indicates that the total revenues for this technology may eventually reach $100 million per year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RANDOMIZED TRIAL OF CD8 T-CELL DEPLETION IN PBSC TRANSP* Principal Investigator & Institution: Antin, Joseph H.; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: This project is part of a Blood and Marrow Transplant Clinical Research Network which is conducting multicenter clinical trials in hematopoietic stem cell transplantation. The purpose of the network is to promote the efficient comparison of novel treatment methods and management strategies of potential benefit for children and adults undergoing blood or marrow transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation after marrow ablation, the development of non-myeloablative transplant regimens, and the best ways to avoid infections in transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REDUCED INTENSITY VS MYELOABLATIVE CONDITIONING FOR OLD* Principal Investigator & Institution: Giralt, Sergio A.; Associate Professor; Blood & Marrow Transplantation; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 05-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Hematologic malignancies are important causes of morbidity and mortality in adults. These diseases affect primarily patients over the age of 50, and results of conventional therapy are unsatisfactory. Allogeneic stem cell transplantation has been effective in obtaining long-term disease control in many patients with these disorders including those in whom initial therapy has failed. Allografting has traditionally been limited to younger patients in good medical condition because of the high rates of graft versus host disease (GVHD) and non-relapse mortality associated with increasing age and decreasing performance status. Strategies to decrease morbidity and mortality related to allografting in older patients have included reductions in the intensity of the preparative regimens. In this grant

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application we propose to determine whether unrelated donor transplantation using a reduced intensity conditioning will result in lower rates of acute GVHD and non relapse mortality and better outcomes in older patients (45 to 65 years of age) with myeloid leukemias when compared to a conventional myeloablative protocol, and whether this reduction in non relapse mortality is secondary to lower levels of inflammatory cytokines (IL-1,IL-2,IFN-gamma, TNF-alpha, IL-6, IL-10, and IL12) in patients receiving a reduced intensity conditioning than in patients receiving conventional myeloablative transplants. Within this application we will also determine the relevance of lineage specific chimerism using existing cell sorting and chimerism determination techniques, and correlate degree of chimerism of specific myeloid, lymphoid, and stem cell subsets with engraftment, relapse, and GVHD. The ultimate goal of this study is to optimize transplant strategies for each patient population by defining the best preparative regimen associated with the lowest toxicities and best long term outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REDUCING CONDITIONING THROUGH HOST ANTI-DONOR ALLOREACTI Principal Investigator & Institution: Reisner, Yair; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Bone marrow transplantation following supralethal radiochemotherapy is associated with dangerous infections due to the slow immune reconstitution during the first year post transplant. Thus, the use of reduced intensity conditioning, associated with less severe immune ablation, could have a remarkable potential in the treatment of a variety of non-malignant diseases, or for the induction of 'mixed chimerism' as a prelude for cell therapy in cancer or in organ transplantation. However, the marked level of host hematopoioetic and immune cells surviving mild preparatory regimens represents a difficult barrier for the engraftment of donor cells. In particular, the use of purified allogeneic stem cells, which do not pose any risk for GvHD and which can continuously present donor type antigens in the host thymus, thereby inducing durable tolerance to donor cells or tissues, represents one of the most desirable goals in transplantation biology. The proposed project will address this challenge by investigating the potential of veto CTLs and/or regulatory CD4+CD25+ cells, to allow engraftment of mega dose purified stem cells following reduced intensity conditioning. Initially, the optimal veto CTL numbers which can overcome CD4 and/or CD8 mediated graft rejection will be defined in a mouse model specifically developed for this purpose (aim la). Subsequently, the potential synergism of veto CTLs with rapamycin (aim 1b) and with CD4CD25 cells (aim2a, 2b) will be tested in the same model. In parallel, the minimal myeloablation required to allow durable engraftment of H-2 identical Sca-1+Lin stem cells in a congenic host, will be established (aim 1c). This minimal myeloablative conditioning will serve as a platform on which attempts to achieve engraftment of allogeneic stem cells by minimal immune suppression, will be built. The minimal rapamycin dose and the minimal number of veto CTLs and CD4CD25 cells which lead, together, to durable engraftment of allogeneic stem cells will be defined in this model (aim 1d,2c). The protocols of choice developed in 1d and subsequently in 2c will be evaluated for their contribution to the immune competence of the resulting chimera, compared to full donor type chimera achieved by stem cell transplantation in fully ablated hosts (aim 3). In particular, the immune response of chimeric mice to a challenge of murine CMV infection, at different times post transplant, will serve as an important endpoint prior to clinical application.

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Bone Marrow Transplant

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

Project Title: REDUCING THE TOXICITY OF BMT IN SICKLE CELL ANEMIA Principal Investigator & Institution: Iannone, Robert; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The main objective of the research proposal is to reduce the toxicity of bone marrow transplantation (BMT) for sickle cell disease (SCD) in order to extend this potentially curative therapy to more patients. Despite current therapies, SCD is associated with substantial morbidity and mortality. Myeloablative BMT can cure SCD but its application is limited by a 5-10% mortality risk, a 10% failure rate, graft-versus-host disease (GVHD) and the risk of gonadal and endocrine dysfunction. Nonmyeloablative BMT (NST) can result in mixed hematopoietic chimerism, stable co-existence of host and donor marrow, and may be less toxic than myeloablative BMT. Because normal red blood cells (RBCs) survive much longer than sickle RBCs, a low-level of normal donor chimerism may substantially reduce the fraction of sickle cells in the circulation and prevent their pathologic effects. There is limited experience, however, with NST in patients with SCD. We have studied animal models of mixed chimerism to treat SCD, tested novel NST regimens for inducing donor-specific tolerance and reducing GVHD, and piloted a clinical trial of NST in patients with SCD. Six of seven patients treated had initial donor engraftment and toxicities were mild and reversible, however, all patients experienced late graft failure. We now hypothesize that HLA-identical sibling bone marrow will engraft in >80% of patients with SCD who receive pre-transplantation fludarabine and low-dose total body irradiation, with or without cyclophosphamide (Cy), followed by post-transplantation Cy, tacrolimus and mycophenolate mofetil. We will study in-vitro anti-donor reactivity as a predictor of rejection, track other factors associated with engraftment and GVHD, assess immune reconstitution after NST, and evaluate the effect of this treatment on multiple clinical parameters. I was recently recruited to the Children's Hospital of Philadelphia to establish a clinical research program in BMT for non-malignant diseases, emphasizing SCD. My objective is to become an independent clinical scientist by obtaining formal instruction and conducting mentored patient-oriented research on reducing the toxicity of BMT for SCD. I have a strong mentoring committee composed of scientists with expertise in clinical trial development, SCD, BMT, biostatistics, bioethics and transplant biology. As part of my training, I will obtain a Master's Degree in Clinical Research through the Center for Clinical Epidemiology and Biostatistics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXPRESSION

REGULATION

OF

HUMAN

CYTOMEGALOVIRUS

GENE

Principal Investigator & Institution: Stinski, Mark F.; Professor; Microbiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-1976; Project End 31-MAY-2006 Summary: (provided by applicant): Human cytomegalovirus (HCMV) can cause congenital neurological damage and disseminated infections resulting in pneumonitis, retinitis, hepatitis, and gastroenteritis. HCMV infections have been associated with accelerated atherosclerosis and with coronary restenosis following angioplasty. HCMV infections in solid organ and bone marrow transplant recipients are a significant cause of morbidity. Both hematopoietic cells of the bone marrow and monocytes of the blood

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can be latently infected with HCMV. Productive infection occurs in a variety of terminally differentiated cells including fibroblast, cytotrophoblast, smooth muscle, endothelial, epithelial, and mircoglial cells and in macrophages. Abortive infection occurs in polymorphonuclear cells. Our laboratory is interested in viral DNA regulatory elements and in viral and cellular proteins that regulate latency, persistent infection, and productive infection. In Specific Aim I, we propose to determine the role of specific regulatory elements in the proximal 3'-end of the major immediate early (MIE) enhancer on viral gene expression in undifferentiated cells relevant to HCMV latency. Regulatory elements that function to repress transcription from the MIE promoter upon binding a regulator protein in undifferentiated cells of the myeloid lineage will be mutated in the context of the viral genome, and recombinant viruses will be analyzed. In Specific Aim II, we propose to characterize a repressor-boundary region 5' to the MIE enhancer that prevents the MIE enhancer from affecting transcription from the flanking UL1 27 promoter. We have identified a repressor-boundary region between the UL127 promoter and the MIE enhancer that is unique to HCMV and to date, not found in other herpesviruses or DNA viruses. Due to its location, the repressor-boundary region has a role in the temporal expression of the immediate early (IE) and early HCMV genes that flank the MIE enhancer. Downstream of the MIE promoter are the MIE genes, IE1 and 1E2, which encode for proteins of 72 (1E72) and 86 kDa (lE86), respectively. These viral proteins are key regulatory proteins for efficient productive infection. In Specific Aim Ill, we propose to determine early gene regulation in recombinant viruses with both the IEl and IE2 genes deleted and to determine the effects of HCMV tEl and 1E2 gene products on viral and host cell gene expression relevant to the viral life cycle. We will investigate the functions of this replication defective HCMV in activation of viral or cellular gene expression and compare these functions to those of the 1E72 and 1E86 proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESPIRATORY IMMUNIZATION

SYNCYTIAL

VIRUS

ESCAPE

FROM

Principal Investigator & Institution: Sullender, Wayne M.; Associate Professor; Pediatrics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Adapted from Applicant's Abstract) Respiratory syncytial virus (RSV) is the most common viral agent of lower respiratory tract infections of infants and causes repeat infections throughout life. RSV antigenic variability may contribute to the ability of RSV to cause repeated infections. RSV is also a cause of significant morbidity and mortality in bone marrow transplant (BTM) patients. Neutralizing antibodies to RSV may be pre-existing in and/or may be passively administered to BMT patients. It is hypothesized that due to selective pressure by antibody RSV will accumulate changes in the F and G proteins during prolonged replication in immunocompromised patients. Sequential RSV isolates from BMT patients will be monitored for the development of F and/or G protein genetic changes that are associated with resistance to antibody may result in impaired fitness for replication. Therefore the antibody resistant viruses will be characterized as to their fitness for replication in cell culture and in animals (Aim 2). The ability of the mutant viruses to evade passive immunity in animals will also be determined (Aim 3). In a clinical trial BMT patients with RSV pneumonia will receive therapy with a humanized F monoclonal antibody (palivizumab). This will result in the replication of RSV in the presence of an antibody that is known to select for escape mutants. Thus, palivizumab escape mutants will be selected in cell culture (Aim 4) and characterized as to fitness and capacity to evade passive immunity in the manner

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Bone Marrow Transplant

described for the human derived viruses. These experiments will define the extent to which RSV becomes resistant to antibodies during prolonged replication in immunocompromised host. In addition, the likelihood that resistant viruses derived in cell culture will maintain normal fitness for replication and escape passive immunity in animals will be determined. These studies will provide evidence from humans and from animals as to the clinical challenges that antibody resistant viruses may pose to the current passive immunization approaches against RSV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF VASCULAR HETEROGENEITY IN THROMBOSIS Principal Investigator & Institution: Furie, Barbara C.; Director; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Thrombotic disease in both the arterial and venous circulation is a major cause of morbidity and mortality in the United States. In vivo studies in mouse models of thrombosis are beginning to challenge paradigms of initiation and extension of thrombi largely based on in vitro and ex vivo studies. Interaction of blood proteins and cells with the vessel wall is influenced by shear forces within the vessel and by other vascular bed specific factors including heterogeneity of endothelial cells. This heterogeneity of vascular beds leads to differences in the process of thrombus formation at various vascular sites. We have developed a unique brightfield and confocal intravital microscopy system to study thrombus formation in vivo. Using this instrument we have determined the kinetics of thrombus formation after laser induced endothelial cell injury in the arterioles of the mouse cremaster muscle, have begun to explore the incorporation of components of the thrombus and have shown a role for P-selectin and PSGL-1 in thrombus formation. Here we propose to explore differences in thrombus formation in additional vascular beds including venules of the cremaster muscle and the arterioles and venules of the pia mater with its unique endothelial cell population. We will study the incorporation of thrombus components and kinetics or thrombus formation in the arterioles and venules of the cremaster muscle and the pia materin three mouse models of thrombosis. We will determine incorporation of platelets, fibrin, tissue, factor, white cells, red cells and microparticles into the growing thrombus; the kinetics of thrombus formation; the stability of the thrombus and the exposure of sub-endothelial proteins in the different thrombosis models. We will extend our studies of the role of P-selectin in thrombus formation by determining the importance of endothelial cell and platelet P-selectin in three models of thrombus formation in different vascular beds. To distinguish the roles of P-selectin from platelets and endothelial cells we will use bone marrow transplant to generate mice that have P-selectin in only one cell type and repeat the studies of thrombus formation in these mice in the different vascular beds. In order to explore the importance of thrombin activation of platelets in thrombus formation we will repeat the studies of thrombus formation in the various vascular beds and in the different models of thrombosis in PAR 4 and PAR 3 null mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELECTIVE DISRUPTIVE OF TNFALPHA SIGNALING IN MURINE CIA Principal Investigator & Institution: Scheinman, Robert I.; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508

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Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-JUL-2003 Summary: (provided by applicant): The inflammatory cytokine, TNF alpha, has been shown to play an important role in rheumatoid arthritis (RA) through the study of murine collagen induced arthritis (CIA). These results have propelled several TNF alpha blocking drugs into clinical use. These drugs are not universally effective and can have serious side effects. Importantly, the role of TNF alpha in RA is not fully understood. Blockade of TNF alpha signaling, both in CIA and in RA, does not stop the disease but rather slows disease progression. In the CIA model, signaling through the p55 TNF receptor (TNFRI) has been shown to mediate some TNF alpha effects however signal transduction through TNFRII has not yet been investigated. In addition, TNFRI signaling is complex. Through interactions with the adapter protein TRADD, TNFRI can activate both FADD and caspase mediated apoptosis as well as TRAF2 and RIP, leading to activation of JNK and proliferation as well as NF-KB mediated antiapoptotic and proinflammatory responses. Through interactions with the adapter protein FAN, TNFRI can activate neutral sphingomyelinase and the production of ceramide, which in turn activates a variety of signaling events. The relative importance of these signal transduction cascades for arthritis is currently unknown. TNFRI and TNFRII are present on multiple cell types. Thus it is likely that different cell types may favor different signaling pathways when activated by TNF alpha. We propose to identify specific subsets of tissues in which TNF alpha signaling contributes to the development of arthritis in the CIA system. Our strategy is to use bone marrow (BM) transplant technology to place TNFRI-'- BM into irradiated TNFR+/+ recipients or conversely, TNFRI+/+ BM into TNFRI -/- recipients. Similar experiments will be performed with TNFRII mice. By this means we can distinguish between the contribution of hematopoietic TNF alpha signaling versus non-hematopoietic TNF alpha signaling to CIA as well as the relative importance of TNFRI and TNFRII signaling in this process. We will then begin to dissect the signal transduction cascades mediated by TNF alpha activation of TNFRI by introducing dominant negative adapter proteins using either retroviral mediated gene transfer into hematopoietic BM stem cells or by creating transgenic mice delivering the dominant negative proteins to the synovium. In summary, these experiments will increase our understanding of how TNF alpha signaling in different cell types contributes to CIA. By extension, these data will help us understand more fully the mechanisms of action of TNF alpha blocking drugs and potentially will identify new targets for future arthritis therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOUTHWEST ONCOLOGY GROUP Principal Investigator & Institution: Budd, George T.; Staff Physician; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-JAN-1978; Project End 31-DEC-2003 Summary: The Cleveland Clinic is the largest cancer treatment center in the Mideast: 42 percent of the cancer patients are local, 28 percent have come from other areas of northeast Ohio, 13 percent from the remainder of Ohio, and 16 percent out of state. In 1995, there were 4057 new cancer patients seen at the Cleveland Clinic, 2768 new cases in which the diagnosis was first made or received initial treatment at the Cleveland Clinic. In 1995, there were 9,548 hospital admissions attributed to cancer related diagnoses. The in-patient facilities include 58 dedicated medical oncology beds, 16 laminar flow treatment rooms for bone marrow transplant patients and of importance, 23 beds dedicated to a palliative care service. Overall, cancer patients represent 27 percent of all of the Cleveland Clinic in-patients as compared to 16 percent in 1985. In

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Bone Marrow Transplant

1995, the Cleveland Clinic provided 74,058 out-patient visits for cancer patients or an average of 284 cancer out-patient visits per day. The out-patient visits have increased since 1985 from 8 percent to 11 percent of all patients seen at the Cleveland Clinic. The major divisions of oncology at the Cleveland Clinic include Medical Oncology, Radiation Oncology and Surgical Oncology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOUTHWEST ONCOLOGY GROUP Principal Investigator & Institution: Rivkin, Saul E.; Swedish Medical Center, First Hill 747 Broadway Seattle, Wa 98122 Timing: Fiscal Year 2002; Project Start 01-JAN-1978; Project End 31-DEC-2003 Summary: The Puget Sound Oncology Consortium (PSOC) has been a funded member of the Southwest Oncology Group (SWOG) since 1976. A multi-modality approach is utilized which includes: Pathology, Surgery, Chemotherapy, Radiation Therapy, Biological Response Modifier Therapy and Quality of Life evaluations for the aim of improving cancer care. Overall objectives are prolongation of life, increased quality of life, decreased toxicities, prolonged disease free survival, improvement in techniques of screening, early detection and prevention of cancer and the rapid transfer of innovative therapies from the laboratory to the clinic. PSOC is one of the largest SWOG member groups and altogether comprises a network of 27 hospitals and medical centers throughout the Pacific Northwest (Alaska, California, Montana, Oregon, and Washington). The scientific agenda of PSOC is determined by disease-specific committees who have contributed eight pilot studies to SWOG in the past grant period. PSOC has 22 investigators who coordinate or co-coordinate 26 studies and has 12 members who hold primary or contributing authorship in 42 published reports of SWOG studies. PSOC supports a urological cancer outreach program (UCOP) as well as five prostate cancer prevention trial (PCPT) sites. PSOC ranks number one in follow- up with a total caseload of 1,245 patients and averages an annual accrual of approximately 170 patients. The Prostate Cancer Prevention Trial has accrued 800 patients and the UCOP program has accrued 53 patients in this past grant period. PSOC maintains autologous and allogeneic bone marrow transplant programs as well as an active stem cell transplant program. Cytogenetics laboratories of SHMC and the UWMC are certified as submitting and reference laboratories. The Clinical Practices Committee formed by Saul E. Rivkin, MD, is evaluating resource utilization and cost effectiveness issues for patients receiving treatment on research protocols. Membership has steadily increased in the past grant period with the addition of three new CGOP affiliates and a total of 54 new members over the last five years. PSOC members are active in scientific and administrative activities and are dedicated to support the goals of the Southwest Oncology Group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STEM CELL EFFICIENCY REGULATED BY CDK INHIBITORS Principal Investigator & Institution: Cheng, Tao; Radiation Oncology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Quiescence in cell cycle, a characteristic distinguishing a hematopoietic stem cell from a progenitor cell, has been shown to be a necessary protective feature for maintaining the stemness in vivo but a barrier for therapeutic manipulation in vitro. Current efforts intended to breaking the stem cell

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55

quiescence have been focused on cytokine-driven ex vivo expansion, but have had limited success because of the loss of multi-potentiality and the inefficient gene transduction after ex vivo manipulation. Less attention has been paid on the efficiency of stem cell repopulation in vivo. We have found that the proliferation of stem cells or progenitor cell s regulated by different cyclin-dependent kinase inhibitors (CDKIs) and stem cell characteristic can be well maintained in the absence of a progenitor cell specific CDKI, p27. We hypothesize that an enhanced hematopoietic repopulation can be achieved without necessarily increasing stem cells number by targeting the progenitor specific CDKIs. Therefore, this project is intended to focus on: 1) Determine if stem cell down-stream progeny is specifically expanded in the absence of a new member of CDKI, pl8 or both p18 and p27 using the knockout mice as models by the in vitro and in vivo stem/progenitor assays. 2) Determine if the long-term repopulation efficiency is increased without apparent leukemia in the absence of p18 or/and p 27 in a competitively repopulating transplant model. 3) Determine if human long-term hematopoietic repopulation or gene transduction can enhanced by targeting p27 or pl8 as assessed by an immuno-deficient mouse model. The central hypothesis to be tested is that targeting progenitor-specific CDKIs at stem cell level is able to enhance stem cell efficiency without necessarily affecting stem cell cycling or number. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEM CELL GENE THERAPY FOR LUNG DISORDERS Principal Investigator & Institution: Lutzko, Carolyn M.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2002; Project Start 11-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Gene therapy for respiratory disorders requires stable gene transfer to epithelial progenitor cells, efficient engraftment of these genetically modified progenitors in the respiratory epithelium and regulated transgene expression in differentiated progeny of these cells. Recently, cells have been identified in marrow that can contribute to tissue repair and regeneration in hematopoietic and nonhematopoietic tissues. In preliminary studies by our group, transgene expressing donor epithelial cells were detected in the lung following transplantation of retrovirally transduced bone marrow into murine recipients. At 2-5 months post-transplant, approximately 1% of cytokeratin positive epithelial cells were EGFP transgene positive donor cells. Based on these data our overall hypothesis is that cells derived from the bone marrow engraft in the respiratory epithelium and contribute to alveolar epithelial layer maintenance and regeneration. The hypotheses to be evaluated in this proposal are: 1) Progenitor cells in normal mouse marrow that engraft and contribute to the alveolar epithelium can be characterized and isolated based on physical properties and cell surface markers. 2) Recombinant lentiviral gone transfer vectors can be designed to efficiently transduce bone marrow derived lung epithelial progenitor cells and specifically express transgenes in respiratory epithelial cells. 3) Marrow derived multipotent stem cells can be transduced with lentiviral vectors and contribute to both respiratory epithelial and hematopoietic tissues. In the experiments proposed here we will test these hypotheses in a murine bone marrow transplant model in the following specific aims: 1) Characterize the progenitor population (s) that engraft in the lung epithelia. 2) Develop gene transfer vectors that have stable and epithelial specific transgene expression. 3) Identify and characterize the lineage potential, or plasticity, of individual, gene marked progenitor cells, that contribute to respiratory epithelia. The overall goal of these studies is to advance the development of clinical gene therapy for

56

Bone Marrow Transplant

lung disorders by evaluating the potential of genetically modified epithelial progenitors to engraft in the lung epithelium and deliver therapeutic gene products in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEM CELL TRANSPLANT CENTER FACTORS & CLINICAL OUTCOMES Principal Investigator & Institution: Loberiza, Fausto R.; Health Policy Institute; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (based on application?s abstract): In health services research, it is assumed that there are optimal health care delivery factors that result in superior clinical outcomes. "Center effects" are differences in outcome among centers that cannot be explained by identifiable differences in patients? diseases, or treatments applied, and are presumed to result from differences in the way health care is delivered. Procedure volume is the central focus of many studies on center effects because it is readily available, while cataloguing details of health care delivery across centers in the United States is labor-intensive. It is not known whether procedure volume performed in a center directly affects outcomes or is a surrogate measure for other factors that are associated with improved outcomes and larger volumes. This study will comprehensively evaluate the association of treatment center characteristics and clinical outcomes in the setting of hematopoietic stem cell transplantation (HSCT) for malignant hematologic disorders using a retrospective cohort study design. The following treatment center characteristics will be collected: a) physician and health care provider characteristics; b) transplant unit resources; and, c) medical center organization. Association of these characteristics with treatment-related mortality and overall survival will be evaluated after adjusting for clinical prognostic factors. Models evaluating the impact of modifying treatment center features with clinical outcomes will be constructed. The study will be conducted at the Statistical Center of the International Bone Marrow Transplant Registry / Autologous Blood and Marrow Transplant Registry (IBMTR/ABMTR) in Milwaukee, utilizing available clinical data reported by 175 HSCT centers in the United States, representing 4,675 patients. Results of this study will provide information important for decision making by individual centers regarding program growth and development, and will inform policy makers, accreditation bodies, and third party payers in their attempts to regulate and improve quality of care for transplant recipients. This study should direct attention to health care parameters important for development of standards of medical care for autologous and allogeneic transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRATEGIES MICROENVIRONMENT

TO

IMPROVE

THYMIC

OUTPUT

VIA

Principal Investigator & Institution: Blazar, Bruce R.; Director; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Post-BMT immune deficiency causes significant morbidity and mortality in BMT recipients. Most recipients of T-cell replete matched sibling or unrelated donor HSC grafts experience late post-BMT infections. Strategies are urgently needed to speed thymopoietic recovery. A major cause of post-BMT immune deficiency is the loss of thymopoietic capacity. Normal thymopoiesis depends on the interaction of the thymic

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stroma-derived receptors and ligands. Damage to thymic epithelial cells (TEC) by preBMT conditioning impairs the ability of the thymus to generate mature T lymphocytes after BMT. Our overall hypothesis is that thymic microenvironmental injury is the major limiting factor responsible for slow T cell immune reconstitution and function, as indicated by the predisposition of the recipient to experience late infections post-BMT. Specific cytokines have been shown to regulate the development and proliferation of epithelial cells, key components in the thymic microenvironment which are needed for effective thymopoiesis. Keratinocyte growth factor (KGF) is one such cytokine. Based on the model that TEC are targets for BMT-associated thymic damage, we hypothesized that KGF pre-treatment would prevent TEC damage after BMT. Our preliminary data indicate this to be the case. In this proposal, we will explore the mechanism(s) responsible for the effects of KGF on facilitating thymopoiesis in BMT recipients. Inhibition of p53 has been shown to protect mice from the lethal genotoxic stress induced by conditioning regimen injury. Our preliminary data indicate a p53 inhibitor speeds thymopoietic recovery in lethally irradiated recipients of allogeneic TCD BM. We will determine whether KGF and p53 inhibitors operate on non-overlapping pathways and thus may be additive or syngergistic in protecting TEC against injury. Thymopoiesis is well-known to decline with age, beginning after puberty. The thymic microenvironment is severely disrupted in aging and that blocking sex steroid production normalizes thymopoiesis. We propose to determine whether pre-BMT chemical blockade of sex steroid production using LHRH analogues (agonist or antagonist) will speed thymopoietic recovery in young or aged BMT recipients subjected to intensive conditioning injury. Our specifc aims are: 1. To determine the thymopoietic and peripheral T cell immune functional effects of TEC sparing agents that target epithelial cell proliferation, inhibit apoptetic cell death, or block the negative regulatory effects of endogenous hormones that disrupt thymopoiesis; 2. To determine whether intracellular pathways required for thymic microenvironmental development or radiation resistance are essential for protecting the thymus from the effects of conditioning regimen injury; 3. To perform clinical trials of thymic protective agents in allogeneic transplant recipients. These data will lead to clinical trials designed to protect the thymic microenvironment against chemoradiotherapy injury and augment thymopoiesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRATEGY TO CURE TYPE 1 DIABETES Principal Investigator & Institution: Guo, Zhiguang; Assistant Professor of Surgery; Surgery; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Recent developments in hematopoietic stem cell transplantation provide a new therapeutic opportunity for treating type 1 diabetes. The principal investigator and co-principal investigator, as bench-to-bedside partners, will develop a strategy to cure type 1 diabetes by combining hematopoietic stem cell transplantation with islet transplantation. Our specific approach is to induce mixed chimerism, using a relatively nontoxic protocol that is nonmyeloablative and irradiation-free, to abrogate the autoimmune processes leading to the onset of type 1 diabetes; and then to transplant a small number of donor-specific islets to achieve normoglycemia and insulin independence, thereby curing diabetes. At the clinical onset of type 1 diabetes, it is estimated that patients have about 20% of their beta cell mass remaining. We hypothesize that establishing mixed chimerism using our relatively

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Bone Marrow Transplant

nontoxic approach will abrogate further progression of type 1diabetes and preserve the remaining beta cell mass. Even if the remaining beta cell mass in the recipient's native pancreas is not sufficient to reverse diabetes, only a small number of transplanted islets should be enough to reverse diabetes in chimeric patients. Using MHC-matched, partially MHC-mismatched, and fully MHC-mismatched mice as hematopoietic stem cell and islet donors, we will determine whether the autoimmune processes leading to the development of type 1 diabetes can be reversed and whether remission can be induced in overtly diabetic NOD mice that mixed chimerism will be established through unmodified allogeneic bone marrow transplantation with our relatively nontoxic protocol. We will also determine whether T cell-depleted and purified hematopoietic cell transplantation can be as effective as unmodified bone marrow transplantation. Finally, we will determine whether normoglycemia can be achieved and be maintained by transplanting a small number of donor-specific islet mass into chimeric diabetic NOD mice, if their remaining islet mass is not sufficient to reverse diabetes. Our transplant team, led by Dr. Sutherland, co-principal investigator of this proposal, has successfully performed the largest number of living related segmental pancreas transplantation and islet autotransplantation worldwide. We have the capability to transplant donor-specific islets from living donors. Success in our proposed experiments, combined with our profound clinical experience, will provide a solid foundation for further development of a safe, effective, and clinically applicable approach for curing type 1 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYMPTOMS OF TRANSPLANT PATIENTS NEAR THE END OF LIFE Principal Investigator & Institution: Anderson, Karen O.; Anesthesiology/Crit Care; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-FEB-2000; Project End 31-JAN-2004 Summary: (Adapted from the Applicant's Abstract): Increasing numbers of patients face the end-of-life following technologically advanced medical interventions. Cancer patients receiving autologous blood or marrow transplantations are a good example of this category of patients who face mortality after advanced clinical care. We know little of what happens to these patients at the end of their lives, such as their symptom patterns, emotional status, and when or whether a decision is made to transition to palliative care. The specific objectives of the proposed research are: (1) to assess the symptoms of metastatic breast cancer, high risk non-Hodgkin's lymphoma, and multiple myeloma patients who will die during the year following transplantation in order to identify changes in symptoms and symptom patterns that predict the end-of-life; (2) to determine the relationships among symptoms, functional status, quality of life, and length of survival post-transplant; and (3) to evaluate the efficacy of an IVR system in improving symptom assessment, symptom management, and quality of life for metastatic breast cancer, high risk non-Hodgkin's lymphoma, and multiple myeloma patients after transplantation, and a randomized clinical trial to evaluate the efficacy of an IVR system to monitor and triage the symptoms of patients during the posttransplantation period. The phase I descriptive study will enroll 110 patients with metastatic breast cancer, high risk non-Hodgkin's lymphoma, or multiple myeloma who are scheduled for autologous transplantations. The patients will complete pre-transplant measures of symptoms, quality of life, and functional status. Physical, affective, and cognitive symptoms will be monitored during the patients' hospitalization. Following discharge, the patients' symptoms will be assessed using the IVR system until death or the end of the first post-transplant year. In the phase II study, 154 patients with metastatic breast cancer, high risk non-Hodgkin's lymphoma, or multiple myeloma who

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are scheduled for transplants will be randomly assigned to the experimental (IVR assessment plus triage) or control (IVR assessment only) condition. The symptom data of patients in the experimental condition will be provided to their M.D. Anderson physicians and nurses during the first 30 days after discharge from the hospital. After patients return to their home communities, the IVR system will continue to assess the symptoms of patients in the experimental group and will provide the symptom information directly to the patients' local physicians. Outcome variables will include the patients' symptom intensities and frequencies, functional status, and quality of the end of life. It is predicted that patients in the experimental condition who die during the year will demonstrate better symptom management and quality of the end of life than patients in the control condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T CELL DIVERSITY IN THE INDUCTION OF AUTOIMMUNITY Principal Investigator & Institution: Laufer, Terri M.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): The graft-versus-host-disease (GVHD) which complicates allogeneic bone marrow transplantation is characterized by organ damage including dermatitis, enteritis, and hepatitis. A majority of post-transplant patients also develop antibodies to self-antigens, including anti-dsDNA, which mimic those in systemic lupus erythematosus. The development of both manifestations requires CD4+ T cells; however, the specificity of the inciting T cells is largely unknown. We propose to utilize transgenic models to examine the CD4 cell-antigen presenting cell (APC) interactions which initiate murine GVHD. K14 mice are a model of abnormal thymic development in which CD4+ T cells are autoreactive due to a failure of negative selection. H2-DM-deficient thymi select autoreactive CD4+ cells on restricted class IIassociated peptides. K14 CD4 cells induce anti-dsDNA antibodies in syngeneic hosts; H2-DM-deficient CD4+ do not. 2-2-3 mice carry transgenes for the TCR genes from a B6reactive K14 T cell hybridoma, 2-2-3. Double transgenic 2-2-3/K14 mice spontaneously develop skin disease which histologically resembles cutaneous GVHI); however, 2-231K14 CD4+ cells cannot induce autoantibodies in syngeneic mice. Thus, cutaneous GVHD is induced by monoclonal T cells which interact with keratinocytes; whereas, the production of autoantibodies during GVHD requires the activation of a diverse repertoire of T cells. In Specific Aim I, we will ask why K14, H2-DM, and 2-2-3/K14 CD4 cells induce different spectrums of autoantibodies after transfer to syngeneic hosts. We will examine the localization, division, and cytokine production of transferred CD4+ cells and B cell activation and germinal center production. Specific Aim II will extend these studies to investigate anti-DNA Ab production during GVHD in a mouse transgenic for the heavy chain of an anti-DNA antibody. In Specific Aim III, the keratinocyte/CD4+ cell interactions required for cutaneous GVHD in 2-2-3/K14 mice will be dissected. Temporal requirement for hematopoietic APC, inflammatory cytokines, and MHC class II expression in skin will be determined. Finally, in Specific Aim IV, we will identify the peptide specificity of the autoreactive 2-2-3 CD4 cell response to APC and keratinocytes in GVHD. Understanding the requirements for T cell diversity and the interactions between "graft" T cells and host antigen presenting cells offers improved immunologic targets for preventing GVHD following bone marrow transplant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Bone Marrow Transplant

Project Title: TEMPORALLY CONTROLLED DEPLETION OF ALLOREACTIVE T CELLS Principal Investigator & Institution: Martin, Paul J.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 05-MAR-1999; Project End 31-JAN-2004 Summary: (Applicant's Abstract) Despite improvement in posttransplant immunosuppressive regimens, GHVD persists as a major complication after hematopoietic cell transplantations, especially when the donor is not an HLA-identical family member. Attempts to prevent GVHD by removing all T cells from the graft have been complicated by increased risks of graft rejection and by impaired immune reconstitution. GVHD is known to be initiated by the relatively small subset of donor T cells that recognize recipient alloantigens. This subset of T cells cannot easily by distinguished from the majority of T cells that do not recognize recipient alloantigens. Transgenic T cells that express the herpes simplex virus enzyme thymidine kinase (TK) are killed when they proliferate during exposure to ganciclovir, while nonproliferating cells remain unaffected. Marrow transplant experiments have shown that TK-transgenic donor T cells have a strikingly reduced ability to cause GVHD in mice treated with ganciclovir. Although ganciclovir clearly depleted donor T cells that proliferated after recognizing recipient alloantigens, these studies did not determine whether ganciclovir also depleted the TK-transgenic donor T cells that did not recognize recipient alloantigens. Experiments in this project will measure the proliferation of T cells that cause GVHD as compared to the proliferation of T cells that do not cause GVHD. T cells that recognize recipient alloantigens are expected to proliferate more rapidly than those that do not recognize recipient alloantigens. Information from these experiments will be used to develop regimens of ganciclovir administration, which achieve optimal depletion of TK- transgenic T cells that recognize recipient alloantigens with optimal sparing of cells that do not recognize recipient alloantigens. The long term goals of this project are to test the hypothesis that the TK- transgenic T cells surviving an optimized regimen of ganciclovir 1) will be sufficient to prevent allogeneic marrow graft rejection in sublethally irradiated recipients and 2) will be sufficient to reconstitute immune function in histoincompatible thymus-deficient recipients. Results of these preclinical studies will help to assess the potential risks and benefits of using similar approaches to prevent GVHD in human marrow transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF CREB IN LEUKEMOGENESIS Principal Investigator & Institution: Sakamoto, Kathleen M.; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 20-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Leukemia is the most common form of childhood cancer. Children with acute myeloid leukemia (AML) have less than 50% overall survival despite aggressive chemotherapy and bone marrow transplantation. Therefore, it is critical to understand the molecular pathogenesis of AML. We demonstrated that CREB is overexpressed in bone marrow cells from patients with AML but not in normal bone marrow or bone marrow from patients without active leukemia. Furthermore, CREB overexpression was associated with an increased risk of relapse and decreased event-free survival in patients with AML. Our preliminary results suggest that AML is a heterogeneous disease that is not well understood. We hypothesize that there is an uncoupling of differentiation and CREB expression in myeloid leukemia cells. We

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propose to study the role of CREB in normal and malignant myeloid cells to identify novel mechanisms of leukemogenesis and improve our understanding of the molecular pathways regulating myeloid cell proliferation and differentiation. In Specific Aim 1, we will characterize CREB expression and activation in primary normal myeloid cells and myeloid leukemia cells. Experiments are proposed to determine the expression of CREB in normal mouse embryos at different stages of hematopoietic development. We will also examine CREB expression in normal myeloid progenitor cells at different stages of myeloid differentiation. Finally, we will examine whether CREB is activated in primary leukemia cells. In Specific Aim 2, we will further characterize the biological phenotype of CREB overexpression and down regulation in myeloid leukemia cell lines and primary normal myeloid cells. Our preliminary results demonstrated that CREB overexpression leads to increased proliferation and survival of myeloid leukemia cells. CREB down regulation using RNA interference (RNAi) suppresses the growth and survival of leukemia cells. To study signaling pathways upstream of CREB, we will overexpress activated kinases and use RNAi technology to inhibit expression of kinases. In Specific Aim 3, we will characterize the phenotype of transgenic mice in which CREB overexpression is targeted to myeloid cells. Defects in hematopoiesis and development of leukemia will be determined in both CREB transgenic mice and a mouse bone marrow transplant model. These studies will define the role of CREB in both normal and malignant myelopoiesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF CYCLOXGENISE 2 IN PROGRESSIVE NEPHRON DESTRU Principal Investigator & Institution: Harris, Raymond C.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 31-JUL-2007 Summary: (Taken directly from the application) Cyclooxygenase-2 (COX-2) expression increases in the kidney cortex in both inflammatory and "non-inflammatory" progressive renal injury. We and others have identified three sites in kidney cortex that exhibit increased COX-2 expression in progressive injury: infiltrating leukocytes in glomerulus, the macula densa and surrounding cTALH and tubulointerstitium and glomerular podocytes. The three Specific Aims of this proposal are designed to address mechanisms of regulation of COX-2 expression and the pathophysiologic consequences of increased expression in these cell types. We will utilize three mouse models of progressive renal injury: a model of progressive glomerulosclerosis and tubulointerstitial injury secondary to loss of functioning renal mass, a model of diabetic nephropathy and a model of crescenteric glomerulonephritis In Specific Aim #1, we will examine COX-2 expression in these models of progressive renal injury and will determine the effect of specific COX-I and COX-2 inhibitors on disease progression. Leukocyte infiltration of glomerulus and tubulointerstitium is a hallmark of both inflammatory and non-inflammatory progressive renal injury. In this aim, we will also define the potential role of leukocyte-generated prostanoids derived from COX-2 by subjecting mice to lethal irradiation and bone marrow transplant with cells derived from COX-2-/-mice in order block COX-2 expression in infiltrating cells. In Specific Aim #2, we will examine the effect of increased COX-2 in the macula densa and surrounding cTALH on renal hemodynamics in hyperfiltering states and determine pathophysiologic mechanisms underlying this increased expression. In Specific Aim #3, we propose to examine the role of COX-2 expression on glomerular podocyte function under basal conditions and in response to glomerular injury. For these studies, we will either

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selectively overexpress COX-2 in podocytes by developing transgenic mice in which increased COX-2 expression is directed by the nephrin promoter or selectively delete podocyte COX-2 by developing and crossing loxP targeted COX-2 mice with nephrinCre mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOLERANCE-AN XENOTRANSPLANTS

APPROACH

TO

CARDIAC

ALLO

&

Principal Investigator & Institution: Cosimi, a Benedict.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-MAR-1999; Project End 31-AUG-2008 Summary: (provided by applicant): Significant improvements in early post-transplant survival rates have been achieved with the introduction of newer pharmacologic immunosuppressive agents over the last decade. Nevertheless, the need for further refinement of available therapeutic protocols is emphasized by the morbidity and the annual attrition rate of 3-4% observed in currently treated allograft recipients primarily as a result of chronic allograft vasculopathy. The objective of this Program Project is to improve the outcome following heart transplantation by defining the essential conditions for and clarifying the mechanisms involved in donor-specific tolerance induction. The rationale linking the objectives of the 3 interrelated Projects and 2 Core Units is that since long-term donor-specific nonreactivity following withdrawal of immunosuppressive agents can be induced in many experimental models, including non-human primates, it should be possible to identify and reproducibly provide the immunologic perturbations which lead to this state in man. We have now established "proof of principle" of one approach, employing mixed chimerism, in five patients who received simultaneous kidney and bone marrow transplants from living donors. Our hypothesis is that definition of the mechanisms involved with such tolerance induction will lead to rational modifications of this initial conditioning regimen, making such approaches applicable to broader categories of patients, including recipients of cadaver donor organs. This would be of particular significance for heart allograft recipients in whom tolerance induction could prevent the accelerated atherosclerotic process that develops in at least half of otherwise successful transplants treated with conventional immunosuppression. The specific aims are to characterize in a continuum of models, including mice selected for specific incompatibilities or genetically engineered defects, partially inbred swine, and non-human primates, the mechanisms of action of conditioning regimens, with or without donor bone marrow transplantation, that induce tolerance. The methodology of the studies includes genetic manipulation, renal and cardiac allografts in murine and large animal models, flow cytometry, ELISPOT and functional analyses of direct and indirect pathways of reactivity. The relevance of such detailed studies to the treatment of allograft recipients has been demonstrated by previous successful translation of our observations to such clinical protocols, as monoclonal antibody treatment of rejection and an initial approach to tolerance induction. We anticipate ongoing progress will continue to contribute to a reduction in the morbidity and mortality associated with transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSLATIONAL TRANSPLANTATION

RESEARCH

IN

BLOOD

&

MARROW

Principal Investigator & Institution: Jones, Richard J.; Professor of Oncology; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218

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Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: This project is part of a Blood and Marrow Transplant Clinical Research Network which is conducting multicenter clinical trials in hematopoietic stem cell transplantation. The purpose of the network is to promote the efficient comparison of novel treatment methods and management strategies of potential benefit for children and adults undergoing blood or marrow transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation. Studies under development include a comparison of blood versus marrow stem cell transplantation after marrow ablation, the development of non-myeloablative transplant regimens, and the best ways to avoid infections in transplant patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF BCR/ABL CAUSED LEUKEMIAS WITH FTIS Principal Investigator & Institution: Heisterkamp, Nora C.; Professor; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: The Bcr/Abl oncoprotein causes the development of Ph-chromosomepositive leukemias. Bcr/Abl P210 and P190 share a domain of Abi which encodes a deregulated tyrosine kinase. This activity perturbs a number of downstream signal transduction pathways including that of the small GTPase Ras. Inhibitors of the enzyme farnesyltransferase (FTIs) have been tested as possible therapeutic agents against Rasassociated solid tumors in man. We have generated a transgenic mouse model which clinically mimics Ph-positive acute lymphoblastic leukemia and tested the potential therapeutic properties of an FTI in this model. Our data show that FTIs are surprisingly potent in preventing the emergence of overt leukemia in our mice. We therefore hypothesize that Ffls are effective in the treatment of Bcr/AbI caused leukemias by interfering with specific small CTPases necessary for disease progression. We will explore this by determining which cellular characteristics known to be altered by Bcr/AbI expression including apoptosis, cytokine independence, mitogenesis and adhesion are affected by the FTIs in BaF3 lymphoid cells with regulatable Bcr/Abl expression. It will also be investigated which small GTPases including Ras are activated by Bcr/Abl in cell line and animal models, and which are targeted by treatment with the FTIs. In addition, we will evaluate whether the FTls are effective against terminal-stage disease in the Bcr/AbI P190 transgenic mouse model, whether they can cure P190caused leukemia/lymphoma in a bone marrow transplant model and whether Bcr/Ablexpressing cells develop resistance to FTIs. By utilizing a compound which apparently acts on downstream targets of Bcr/Abl in vivo, these experiments will provide unique insights into the mechanisms by which Bcr/AbI causes leukemia. These studies will also help pinpoint which pathway(s) are critical in transducing the oncogenic signals of Bcr/Abl, which could provide additional targets for therapeutic intervention. Finally, data will emerge which will be invaluable in the assessment nf Using FTIs in the treatment nf Ph-positive leukemia in man Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TUMOR TRANSPLANTATION

VACCINES

IN

AUTOLOGOUS

BONE

MARROW

Principal Investigator & Institution: Borrello, Ivan M.; Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006

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Summary: Bone marrow transplantation (BMT) has shown considerable clinical benefit in a variety of hematologic diseases. Nevertheless, a significant percentage of patients will relapse following this procedure. While associated with significant immunosuppression, the BMT setting offers many advantages for the integration of vaccine strategies. Our data show highly efficient transfer of anti-tumor immunity through adoptive transfer, effective anti-tumor responses in the post-BMT prior to full immune reconstitution, and suggest a role of BMT in mediating a delay in tolerance induction. Our first protocol will integrate autologous tumor cells with a GM-CSFproducing bystander cell in the peripheral stem cell transplant setting for multiple myeloma. The trial endpoints will monitor tumor-specific responses to vaccination at various time-points either pre- or post-BMT and determine the correlation of tumorspecific responses with immune reconstitution. Critical to effective responses of GMCSF vaccines is T cell responsiveness and T cell - antigen presenting cell (APC) interactions. We have shown that T cell tolerance is an early event in tumor progression. Overcoming this barrier offers an attractive opportunity in enhancing vaccine efficacy. The second component of this proposal focuses on the development of future strategies aimed at enhancing the T-cell and antigen presenting cell responsiveness. Integration of these findings into a clinical BMT setting could be easily accomplished and will establish the pre-clinical basis for the next generation of clinical protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: USE OF GENE THERAPY TO INDUCE TRANSPLANTATION TOLERANCE Principal Investigator & Institution: Kearns-Jonker, Mary K.; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 90027 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: The critical shortage of human organs available for transplantation to patients with end-stage diseases has led to an increasing amount of attention directed at developing methods to allow for the use of pigs as an alternative source of donor organs. Humans that have never been exposed to pig cells, however, have antibodies that are capable of rapidly rejecting these organs. These antibodies react predominantly with a specific sugar called the galactose tx1,3 galactose carbohydrate epitope (gal epitope) expressed on pig cells. This sugar is identified as foreign by humans or Old World primates because a mutation has occurred during evolution that prevents this carbohydrate from being expressed in humans and specific types of monkeys. Consequently, humans produce antibodies to gal when exposed to organs derived from other species (xenografts). A special strain of mice has recently been developed that serves as a good small animal model of xenograft rejection because they produce antigal antibodies similar to the antibodies that reject pig xenografts in humans. In this model, production of antibodies that reject pig cells can be prevented by introducing a single gene by bone marrow transplantation before the mouse is exposed to the pig cells. The ability to reproduce this experiment in a preclinical primate model will provide a means by which human patients may be treated prior to xenotransplantation to prevent rejection of pig organs, and will have a significant impact on the field of transplantation. This experiment has not yet been reproduced in primates because introduction of the new gene in primate stem cells of the bone marrow is more difficult compared with the mouse model using conventional methods. We have recently established a new method to introduce genes more efficiently into primate and human stem cells of the bone marrow using a new type of gene delivery vehicle (lentiviral vector). In this application, we propose to introduce the gene responsible for gal carbohydrate expression in primate

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stem cells and determine whether this procedure prevents anti-gal antibody production in primates. Our hypothesis is that this new vector will allow us to introduce the gene responsible for encoding the gal carbohydrate into primate stem cells at levels that are sufficient to prevent the immune response to pig cells in transplanted rhesus monkeys. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRAL COMPROMISE OF TRANSPLANTATION TOLERANCE Principal Investigator & Institution: Welsh, Raymond M.; Professor; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Studies supported by this Program Project have shown that viral infections pose a threat to tolerized recipients of allogeneic transplants by breaking tolerance and inducing the rejection of the allografts. We also have previously demonstrated that viral infections generate virus-specific T cells that cross-react with allogeneic MHC antigens. Here we examine the discrete specificity behind virus-induced allospecific T cells and examine their significance in virus-induced allograft rejection. Specifically, we propose to examine the relationship between viral peptide specificity and allospecificity and how tolerization to alloantigens alters the virus-induced CTL response. We next will determine how viral infections impact the frequency of allospecific T cells in the memory pool and whether these memory allospecific T cells render a host more difficult to tolerize by peripheral and central (bone marrow chimeric) models of anti-CD154induced tolerization. Finally, we will determine whether the observed abrogation of tolerance and induction of allograft rejection by acute viral infections is a direct consequence of cross-reactivity in T cell responses between viral and allo-antigens. This work will be heavily interactive with studies proposed in Projects one and two and will utilize services from the Virology and Morphology Cores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: X-RAYS INDUCE EXOCYTOSIS OF ENDOTHELIAL P-SELECTIN Principal Investigator & Institution: Hallahan, Dennis E.; Professor and Chairman; Radiation Oncology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JAN-1993; Project End 31-DEC-2002 Summary: Preexisting proteins are activated by x-irradiation and contribute to tissue repair and/or tissue injury. These proteins are sequestered in storage reservoirs, and where they are available for rapid dispensing to accomplish hemostasis and leukocyte activation. Weibel Palade bodies (WPB) within the cytoplasm of endothelial cells translocate to the vascular lumen following irradiation of blood vessels. We utilized immunohistochemistry to study the histologic pattern of WPB components and observed that several of these proteins translocate to the vascular lumen in response to ionizing radiation. These proteins included CD62P (P-selectin), CD63, Interleukin-8, and von Willebrand factor (vWF). We have initiated our studies of the biological consequences of WPB exocytosis by use of the P-selectin knockout mouse. We observed two phenotypes in the P-selectin knockout mouse. We observed our studies of the biological consequences of WPB exocytosis by use of the P-selectin knockout mouse. We observed two phenotypes in the P-selectin -/-, which include edema and hemorrhage into the irradiated intestine and lung. Secondly, the absence of absence of platelet aggregation in P-selectin knockouts, whereas aggregation occurred immediately following x- irradiation in wild type mice. We will study physiological mechanisms of these phenotypes in Aims 3 and 4 of this proposal. We will determine whether P-

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selectin within platelets within platelets is sufficient to selectin -/- mice will revert these phenotypes. We will determine whether bone marrow transplantation from P-selectin within platelets is sufficient to restore the wild type phenotype in these knockouts. We will also transplant bone marrow from P-selectin -/- mice into wild type mice to determine whether platelet P-selectin is required to prevent edema and hemorrhage in irradiated tissues. The mechanisms by which ionizing radiation induces exocytosis of storage reservoirs is through membrane transport. Using immunofluorescence confocal microscopy, we observed that P-selectin, CD63, and vWF are translocated to the cell membrane following irradiation of endothelial cells. P-selected remains tethered to the cell membrane, whereas vWF is secreted into medium or vascular lumen. Membrane transport requires motor proteins that move organelles over the cytoskeleton. We observe that microtubule depolymerizing agents inhibit exocytosis, whereas the antagonist of actin (cytochalazin-B) did not prevent x-ray induced exocytosis of WPB. Calcium-dependent signal transduction has been proposed to initiate exocytosis of storage reservoirs. We utilize the intracellular chelator BAPTA to inhibited x-rayinduced translocation of WPB. Calmodulin is a protein that is activated by increased intracellular calcium and participates in the activation of membrane transport. The calmodulin inhibitor W13 abrogated the translocation of WPB to the cell membrane following irradiation. We will study the roles of calcium and calmodulin in the activation of motor proteins that are required for microtubule- dependent translocation of WPB to the cell membrane. 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 “bone marrow transplant” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for bone marrow transplant in the PubMed Central database: •

A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis. by Kern WV, Hay B, Kern P, Marre R, Arnold R.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284481

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Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice. by Ohshima T, Schiffmann R, Murray GJ, Kopp J, Quirk JM, Stahl S, Chan CC, Zerfas P, Tao-Cheng JH, Ward JM, Brady RO, Kulkarni AB.; 1999 May 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26897

3 4

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

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

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•

Aspergillus Galactomannan Antigen in the Cerebrospinal Fluid of Bone Marrow Transplant Recipients with Probable Cerebral Aspergillosis. by Viscoli C, Machetti M, Gazzola P, De Maria A, Paola D, Van Lint MT, Gualandi F, Truini M, Bacigalupo A.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140329

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Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. by Wingard JR, Merz WG, Rinaldi MG, Miller CB, Karp JE, Saral R.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188080

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Bone Marrow Transplantation Corrects the Enzyme Defect in Neurons of the Central Nervous System in a Lysosomal Storage Disease. by Walkley SU, Thrall MA, Dobrenis K, Huang M, March PA, Siegel DA, Wurzelmann S.; 1994 Apr 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43496

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Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation. by ChavollaCalderon M, Bayer MK, Fontan JJ.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152591

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Bordetella bronchiseptica pneumonia and bacteremia following bone marrow transplantation. by Bauwens JE, Spach DH, Schacker TW, Mustafa MM, Bowden RA.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265527

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Catheter-Related Candidemia Caused by Candida lipolytica in a Patient Receiving Allogeneic Bone Marrow Transplantation. by D'Antonio D, Romano F, Pontieri E, Fioritoni G, Caracciolo C, Bianchini S, Olioso P, Staniscia T, Sferra R, Boccia S, Vetuschi A, Federico G, Gaudio E, Carruba G.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140330

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Catheter-related Rahnella aquatilis bacteremia in a pediatric bone marrow transplant recipient. by Hoppe JE, Herter M, Aleksic S, Klingebiel T, Niethammer D.; 1993 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265657

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Clinical Significance of Expression of Human Cytomegalovirus pp67 Late Transcript in Heart, Lung, and Bone Marrow Transplant Recipients as Determined by Nucleic Acid Sequence-Based Amplification. by Gerna G, Baldanti F, Middeldorp JM, Furione M, Zavattoni M, Lilleri D, Revello MG.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88622

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Coaggregation of oral Candida isolates with bacteria from bone marrow transplant recipients. by Hsu LY, Minah GE, Peterson DE, Wingard JR, Merz WG, Altomonte V, Tylenda CA.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268245

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Colon biopsies for evaluation of acute graft-versus-host disease (A-GVHD) in allogeneic bone marrow transplant patients. by Shidham VB, Chang CC, Shidham G, Ghazala F, Lindholm PF, Kampalath B, George V, Komorowski R.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153523

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Comparison of plasma PCR and bronchoalveolar lavage fluid culture for detection of cytomegalovirus infection in adult bone marrow transplant recipients. by Aspin MM, Gallez-Hawkins GM, Giugni TD, Tegtmeier B, Lang DJ, Schmidt GM, Forman SJ, Zaia JA.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263979

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Detection of Pseudomonas mesophilica as a source of nosocomial infections in a bone marrow transplant unit. by Gilchrist MJ, Kraft JA, Hammond JG, Connelly BL, Myers MG.; 1986 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268792

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Direct isolation and characterization of JC virus from urine samples of renal and bone marrow transplant patients. by Myers C, Frisque RJ, Arthur RR.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251067

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Disseminated Microascus cirrosus infection in pediatric bone marrow transplant recipient. by Krisher KK, Holdridge NB, Mustafa MM, Rinaldi MG, McGough DA.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228024

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Do double-beta-lactam combinations prolong neutropenia in patients undergoing chemotherapy or bone marrow transplantation for hematological disease? by Kibbler CC, Prentice HG, Sage RJ, Hoffbrand AV, Brenner MK, Noone P.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172468

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Early detection of human cytomegalovirus viremia in bone marrow transplant recipients by DNA amplification. by Nolte FS, Emmens RK, Thurmond C, Mitchell PS, Pascuzzi C, Devine SM, Saral R, Wingard JR.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228142

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Effects of Retroviral Vector Design on Expression of Human Adenosine Deaminase in Murine Bone Marrow Transplant Recipients Engrafted with Genetically Modified Cells. by Riviere I, Brose K, Mulligan RC.; 1995 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41403

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Effects on oral and intestinal microfloras of norfloxacin and pefloxacin for selective decontamination in bone marrow transplant patients. by Giuliano M, Pantosti A, Gentile G, Venditti M, Arcese W, Martino P.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172742

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Efficacy of Low-Dose Dopamine in Preventing Amphotericin B Nephrotoxicity in Bone Marrow Transplant Patients and Leukemia Patients. by Camp MJ, Wingard JR, Gilmore CE, Lin LS, Dix SP, Davidson TG, Geller RB.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106006

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Empirical antibacterial therapy in febrile, granulocytopenic bone marrow transplant patients. by Peterson PK, McGlave P, Ramsay NK, Rhame F, Goldman AI, Kersey J.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284106

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Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency. by Gratama JW, Oosterveer MA, Zwaan FE, Lepoutre J, Klein G, Ernberg I.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282526

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Evaluation of four methods for cytomegalovirus antibody detection for use by a bone marrow transplantation service. by Leland DS, Barth KA, Cunningham EB, Jansen J, Tricot GJ, French ML.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267256

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Fatal Disseminated Trichoderma longibrachiatum Infection in an Adult Bone Marrow Transplant Patient: Species Identification and Review of the Literature. by Richter S, Cormican MG, Pfaller MA, Lee CK, Gingrich R, Rinaldi MG, Sutton DA.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88664

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Genomic variation of adenovirus type 5 isolates recovered from bone marrow transplant recipients. by Webb DH, Shields AF, Fife KH.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265888

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Human Cytomegalovirus Immediate-Early mRNA Detection by Nucleic Acid Sequence-Based Amplification as a New Parameter for Preemptive Therapy in Bone Marrow Transplant Recipients. by Gerna G, Baldanti F, Lilleri D, Parea M, Alessandrino E, Pagani A, Locatelli F, Middeldorp J, Revello MG.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86605

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Infection in the bone marrow transplant recipient and role of the microbiology laboratory in clinical transplantation. by LaRocco MT, Burgert SJ.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172920

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Investigation of potential interaction of ciprofloxacin with cyclosporine in bone marrow transplant recipients. by Kruger HU, Schuler U, Proksch B, Gobel M, Ehninger G.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171756

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Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation. by Ikehara S, Yasumizu R, Inaba M, Izui S, Hayakawa K, Sekita K, Toki J, Sugiura K, Iwai H, Nakamura T, et al.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287120

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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. by Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, von Moers A, Morris GE, den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K.; 2002 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151133

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Microascus cinereus (Anamorph Scopulariopsis) Brain Abscess in a Bone Marrow Transplant Recipient. by Baddley JW, Moser SA, Sutton DA, Pappas PG.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88731

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Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. by Wada R, Tifft CJ, Proia RL.; 2000 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27130

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Molecular Epidemiological Study of Aspergillus fumigatus in a Bone Marrow Transplantation Unit by PCR Amplification of Ribosomal Intergenic Spacer Sequences. by Radford SA, Johnson EM, Leeming JP, Millar MR, Cornish JM, Foot AB, Warnock DW.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104817

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Molecular Epidemiology of Outbreak of Respiratory Syncytial Virus within Bone Marrow Transplantation Unit. by Taylor GS, Vipond IB, Caul EO.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87826

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Molecular Epidemiology of Two Consecutive Outbreaks of Parainfluenza 3 in a Bone Marrow Transplant Unit. by Zambon M, Bull T, Sadler CJ, Goldman JM, Ward KN.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105033

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Molecular Methods for Cytomegalovirus Surveillance in Bone Marrow Transplant Recipients. by Weinberg A, Schissel D, Giller R.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139700

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Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction. by Sawyers CL, Timson L, Kawasaki ES, Clark SS, Witte ON, Champlin R.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53305

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Monitoring Cytomegalovirus Infection in Adult and Pediatric Bone Marrow Transplant Recipients by a Real-Time PCR Assay Performed with Blood Plasma. by Leruez-Ville M, Ouachee M, Delarue R, Sauget AS, Blanche S, Buzyn A, Rouzioux C.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154722

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Monitoring of leukocyte cytomegalovirus DNA in bone marrow transplant recipients by nested PCR. by Yuen KY, Lo SK, Chiu EK, Wong SS, Lau YL, Liang R, Chan TK, Ng MH.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228523

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Murine Model of Interstitial Cytomegalovirus Pneumonia in Syngeneic Bone Marrow Transplantation: Persistence of Protective Pulmonary CD8-T-Cell Infiltrates after Clearance of Acute Infection. by Podlech J, Holtappels R, Pahl-Seibert MF, Steffens HP, Reddehase MJ.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112270

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Necrotizing cerebritis in an allogeneic bone marrow transplant recipient due to Cladophialophora bantiana. by Emmens RK, Richardson D, Thomas W, Hunter S, Hennigar RA, Wingard JR, Nolte FS.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229013

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Optimizing hematopoietic recovery following bone marrow transplantation. by Paquette R, Dorshkind K.; 2002 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151019

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Oral Antimicrobial Prophylaxis in Bone Marrow Transplant Recipients: Randomized Trial of Ciprofloxacin versus Ciprofloxacin-Vancomycin. by Ford CD, Reilly W, Wood J, Classen DC, Burke JP.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105612

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PCR Detection of Adenovirus in a Bone Marrow Transplant Recipient: Hemorrhagic Cystitis as a Presenting Manifestation of Disseminated Disease. by Echavarria MS, Ray SC, Ambinder R, Dumler JS, Charache P.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84519

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Persistent Legionella Infection in a Patient after Bone Marrow Transplantation. by Schindel C, Siepmann U, Han SR, Ullmann AJ, Mayer E, Fischer T, Maeurer M.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87590

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Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow transplant recipients. by El-Yazigi A, Ellis M, Ernst P, Spence D, Hussain R, Baillie FJ.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163824

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Population pharmacokinetics and renal function-sparing effects of amphotericin B colloidal dispersion in patients receiving bone marrow transplants. by Amantea MA, Bowden RA, Forrest A, Working PK, Newman MS, Mamelok RD.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162878

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Prevalence of human herpesvirus 6 variant A and B infections in bone marrow transplant recipients as determined by polymerase chain reaction and sequencespecific oligonucleotide probe hybridization. by Drobyski WR, Eberle M, Majewski D, Baxter-Lowe LA.; 1993 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265570

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Prevention of development of autoimmune disease in BXSB mice by mixed bone marrow transplantation. by Wang BY, El-Badri CN, Good RA.; 1997 Oct 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23703

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Procalcitonin Does Not Discriminate Infection from Inflammation after Allogeneic Bone Marrow Transplantation. by Blijlevens NM, Donnelly JP, Meis JF, De Keizer MH, De Pauw BE.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95980

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Protection of Killer Antiidiotypic Antibodies against Early Invasive Aspergillosis in a Murine Model of Allogeneic T-Cell-Depleted Bone Marrow Transplantation. by Cenci E, Mencacci A, Spreca A, Montagnoli C, Bacci A, Perruccio K, Velardi A, Magliani W, Conti S, Polonelli L, Romani L.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127930

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Pseudoepidemic of aspergillosis after development of pulmonary infiltrates in a group of bone marrow transplant patients. by Weems JJ Jr, Andremont A, Davis BJ, Tancrede CH, Guiguet M, Padhye AA, Squinazi F, Martone WJ.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269248

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Quantification of Human Cytomegalovirus DNA in Bone Marrow Transplant Recipients by Real-Time PCR. by Griscelli F, Barrois M, Chauvin S, Lastere S, Bellet D, Bourhis JH.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88550

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Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation. by Broun ER, Wheat JL, Kneebone PH, Sundblad K, Hromas RA, Tricot G.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284500

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Rapid Quantification and Differentiation of Human Polyomavirus DNA in Undiluted Urine from Patients after Bone Marrow Transplantation. by Biel SS, Held TK, Landt O, Niedrig M, Gelderblom HR, Siegert W, Nitsche A.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87458

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Rat cytomegalovirus-induced pneumonitis after allogeneic bone marrow transplantation: effective treatment with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. by Stals FS, Zeytinoglu A, Havenith M, de Clercq E, Bruggeman CA.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187642

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Real-Time Automated PCR for Early Diagnosis and Monitoring of Cytomegalovirus Infection after Bone Marrow Transplantation. by Machida U, Kami M, Fukui T, Kazuyama Y, Kinoshita M, Tanaka Y, Kanda Y, Ogawa S, Honda H, Chiba S, Mitani K, Muto Y, Osumi K, Kimura S, Hirai H.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86962

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Reconstruction of the immune system after unrelated or partially matched T-celldepleted bone marrow transplantation in children: functional analyses of lymphocytes and correlation with immunophenotypic recovery following transplantation. by Kook H, Goldman F, Giller R, Goeken N, Peters C, Comito M, Rumelhart S, Holida M, Lee N, Trigg M.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170484

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Regression of adjuvant-induced arthritis in rats following bone marrow transplantation. by van Bekkum DW, Bohre EP, Houben PF, Knaan-Shanzer S.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298650

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Safety and tolerance of recombinant leukocyte A interferon in bone marrow transplant recipients. by Winston DJ, Ho WG, Schroff RW, Champlin RE, Gale RP.; 1983 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184981

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Selection of Unrelated Donors for Bone Marrow Transplantation is Improved by HLA Class II Genotyping with Oligonucleotide Hybridization. by Tiercy J, Morel C, Freidel AC, Zwahlen F, Gebuhrer L, Betuel H, Jeannet M, Mach B.; 1991 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52245

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Thymus: A Direct Target Tissue in Graft-Versus-Host Reaction After Allogeneic Bone Marrow Transplantation that Results in Abrogation of Induction of Self-Tolerance. by Fukushi N, Arase H, Wang B, Ogasawara K, Gotohda T, Good RA, Onoe K.; 1990 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54521

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Tumor Control in a Model of Bone Marrow Transplantation and Acute LiverInfiltrating B-Cell Lymphoma: an Unpredicted Novel Function of Cytomegalovirus. by Erlach KC, Podlech J, Rojan A, Reddehase MJ.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135996

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

A 32-year-old man with hepatitis C who developed progressive liver failure after a bone marrow transplant. Author(s): Lyra AC, Brunt EM, Pincus S, Di Bisceglie AM. Source: Seminars in Liver Disease. 2002 February; 22(1): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11928083&dopt=Abstract

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

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A fatal case of West Nile virus infection in a bone marrow transplant recipient. Author(s): Hiatt B, DesJardin L, Carter T, Gingrich R, Thompson C, de MagalhaesSilverman M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 November 1; 37(9): E129-31. Epub 2003 October 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557983&dopt=Abstract

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A graft-versus-tumor effect in a patient with ependymoma who received an allogenic bone marrow transplant for therapy-related leukemia. Case report. Author(s): Tanaka M, Shibui S, Kobayashi Y, Nomura K, Nakanishi Y. Source: Journal of Neurosurgery. 2002 August; 97(2): 474-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186480&dopt=Abstract

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A pilot study on the role of cytomegalovirus & human herpesvirus-6 infections in Indian bone marrow transplant recipients. Author(s): Finny GJ, Mathews V, Abraham P, Abraham M, Chandy M, Srivastava A, Nitsche A, Siegert W, Sridharan G. Source: The Indian Journal of Medical Research. 2001 August; 114: 39-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785448&dopt=Abstract

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A retrospective investigation of advanced periodontal disease as a risk factor for septicemia in hematopoietic stem cell and bone marrow transplant recipients. Author(s): Akintoye SO, Brennan MT, Graber CJ, McKinney BE, Rams TE, Barrett AJ, Atkinson JC. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2002 November; 94(5): 581-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424452&dopt=Abstract

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A second unrelated bone marrow transplant with an unrelated donor marrow: treatment of a patient with relapsed leukemia. Author(s): Basara N, Bischoff M, Blau IW, Hermann D, Romer E, Rudolphi M, Kirsten D, Sanchez H, Fauser AA. Source: Bone Marrow Transplantation. 1998 February; 21(3): 291-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9489653&dopt=Abstract

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ACE inhibitors and AII receptor antagonists in the treatment and prevention of bone marrow transplant nephropathy. Author(s): Moulder JE, Fish BL, Cohen EP. Source: Current Pharmaceutical Design. 2003; 9(9): 737-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570791&dopt=Abstract

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Acute renal failure in bone marrow transplant patients admitted to the intensive care unit. Author(s): Letourneau I, Dorval M, Belanger R, Legare M, Fortier L, Leblanc M. Source: Nephron. 2002 April; 90(4): 408-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961399&dopt=Abstract

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Adenovirus: an increasingly important pathogen in paediatric bone marrow transplant patients. Author(s): Walls T, Shankar AG, Shingadia D. Source: The Lancet Infectious Diseases. 2003 February; 3(2): 79-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560192&dopt=Abstract

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Admission of bone marrow transplant recipients to the intensive care unit: outcome, survival and prognostic factors. Author(s): Jackson SR, Tweeddale MG, Barnett MJ, Spinelli JJ, Sutherland HJ, Reece DE, Klingemann HG, Nantel SH, Fung HC, Toze CL, Phillips GL, Shepherd JD. Source: Bone Marrow Transplantation. 1998 April; 21(7): 697-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9578310&dopt=Abstract

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Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia. Author(s): Maguire AM, Vowels MR, Russell S, Cohn RJ, Cole C, Saxon B, Alvaro F, Marshall GM. Source: Journal of Paediatrics and Child Health. 2002 April; 38(2): 166-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030999&dopt=Abstract

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An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation. Author(s): Schots R, Van Riet I, Othman TB, Trullemans F, De Waele M, Van Camp B, Kaufman L. Source: Bone Marrow Transplantation. 2002 October; 30(7): 441-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368956&dopt=Abstract

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Analysis of sepsis in allogeneic bone marrow transplant recipients: a single-center study. Author(s): Mitsui H, Karasuno T, Santo T, Fukushima K, Matsunaga H, Nakamura H, Hiraoka A. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 September; 9(3): 238-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513392&dopt=Abstract

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Antibody responses to vaccinations given within the first two years after transplant are similar between autologous peripheral blood stem cell and bone marrow transplant recipients. Author(s): Gandhi MK, Egner W, Sizer L, Inman I, Zambon M, Craig JI, Marcus RE. Source: Bone Marrow Transplantation. 2001 October; 28(8): 775-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781630&dopt=Abstract

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Antiviral prophylaxis may prevent human herpesvirus-6 reactivation in bone marrow transplant recipients. Author(s): Rapaport D, Engelhard D, Tagger G, Or R, Frenkel N. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2002 March; 4(1): 10-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123421&dopt=Abstract

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Aspergillus galactomannan antigen in the cerebrospinal fluid of bone marrow transplant recipients with probable cerebral aspergillosis. Author(s): Viscoli C, Machetti M, Gazzola P, De Maria A, Paola D, Van Lint MT, Gualandi F, Truini M, Bacigalupo A. Source: Journal of Clinical Microbiology. 2002 April; 40(4): 1496-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923380&dopt=Abstract

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Assessment of psychological distress in prospective bone marrow transplant patients. Author(s): Trask PC, Paterson A, Riba M, Brines B, Griffith K, Parker P, Weick J, Steele P, Kyro K, Ferrara J. Source: Bone Marrow Transplantation. 2002 June; 29(11): 917-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12080358&dopt=Abstract

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Atypical cells in bronchoalveolar lavage specimens from bone marrow transplant recipients. A potential pitfall. Author(s): Gulbahce HE, Baker KS, Kumar P, Kjeldahl K, Pambuccian SE. Source: American Journal of Clinical Pathology. 2003 July; 120(1): 101-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866379&dopt=Abstract

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Atypical presentation of bone marrow transplant retinopathy. Author(s): Demirci H, Shields JA, Shields CL, Maguire AM. Source: Journal of Pediatric Ophthalmology and Strabismus. 2003 November-December; 40(6): 361-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14655986&dopt=Abstract

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Automated nucleotide sequencing reveals substantial disparity between the HLA-A2 genes of bone marrow transplant recipients and donors. Author(s): Szmania S, Keever-Taylor C, Baxter-Lowe LA. Source: Human Immunology. 1997 August-September; 56(1-2): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9455496&dopt=Abstract

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Baboon bone marrow transplant suggests new directions for AIDS research. Author(s): Lein B. Source: Pi Perspect. 1996 April; (No 18): 15-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11363509&dopt=Abstract

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B-cell-autonomous somatic mutation deficit following bone marrow transplant. Author(s): Glas AM, van Montfort EH, Storek J, Green EG, Drissen RP, Bechtold VJ, Reilly JZ, Dawson MA, Milner EC. Source: Blood. 2000 August 1; 96(3): 1064-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910923&dopt=Abstract

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Bedside leukoreduction of cellular blood components in preventing cytomegalovirus transmission in allogeneic bone marrow transplant recipients: a retrospective study. Author(s): Narvios AB, Lichtiger B. Source: Haematologica. 2001 July; 86(7): 749-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454531&dopt=Abstract

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Blood tacrolimus concentrations in bone marrow transplant patients undergoing plasmapheresis. Author(s): Hale GA, Reece DE, Munn RK, Kniska AB, Phillips GL. Source: Bone Marrow Transplantation. 2000 February; 25(4): 449-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10723590&dopt=Abstract

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Bone marrow transplant and toxoplasmosis. Author(s): Miles AI. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 May; 13(5): 824. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10374890&dopt=Abstract

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Bone marrow transplant engraftment analysis with loss of an informative allele. Author(s): Schichman SA, Lin P, Gilbrech LJ, Gray PS, Wilson CS, Sawyer JR. Source: The Journal of Molecular Diagnostics : Jmd. 2002 November; 4(4): 230-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411591&dopt=Abstract

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Bone marrow transplant for breast cancer is questioned on basis of incomplete data. Author(s): White K. Source: Journal of Women's Health & Gender-Based Medicine. 1999 June; 8(5): 577-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10839639&dopt=Abstract

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Bone marrow transplant for dyskeratosis congenita. Author(s): Lau YL, Ha SY, Chan CF, Lee AC, Liang RH, Yuen HL. Source: British Journal of Haematology. 1999 May; 105(2): 571. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10233444&dopt=Abstract

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Bone marrow transplant for lymphoma: where is the field going? Author(s): Gribben JG. Source: Biochimica Et Biophysica Acta. 1999 May 31; 1423(3): C31-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382538&dopt=Abstract

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Bone marrow transplant in Diamond-Blackfan anemia. Author(s): Alter BP. Source: Bone Marrow Transplantation. 1998 May; 21(9): 965-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613795&dopt=Abstract

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Bone marrow transplant in Pakistan: indications and economics. Author(s): Anwar M. Source: J Coll Physicians Surg Pak. 2003 September; 13(9): 549-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971886&dopt=Abstract

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Bone marrow transplant in Ph+ ALL patients. Author(s): Avivi I, Goldstone AH. Source: Bone Marrow Transplantation. 2003 April; 31(8): 623-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692601&dopt=Abstract

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Bone marrow transplant in thalassemia. A role for radiation? Author(s): Lee YS, Kristovich KM, Ducore JM, Vichinsky E, Crouse VL, Glader BE, Amylon MD. Source: Annals of the New York Academy of Sciences. 1998 June 30; 850: 503-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668596&dopt=Abstract

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Bone marrow transplant nurses' knowledge, beliefs, and attitudes regarding pain management. Author(s): Pederson C, Parran L. Source: Oncology Nursing Forum. 1997 October; 24(9): 1563-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9348597&dopt=Abstract

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Bone marrow transplant patients with life-threatening organ failure: when should treatment stop? Author(s): Perry AR, Rivlin MM, Goldstone AH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 January; 17(1): 298-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458246&dopt=Abstract

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Bone marrow transplant raises issues of privacy. Author(s): Davies S. Source: Bmj (Clinical Research Ed.). 1997 May 3; 314(7090): 1356. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11644925&dopt=Abstract

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Bone marrow transplant teaching rounds: promoting excellence in nursing care. Author(s): Keller CA, Carolin K, Fedoronko K. Source: Oncology Nursing Forum. 2001 April; 28(3): 457-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11338754&dopt=Abstract

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Breakthrough trichosporonosis in a bone marrow transplant recipient receiving caspofungin acetate. Author(s): Goodman D, Pamer E, Jakubowski A, Morris C, Sepkowitz K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 August 1; 35(3): E35-6. Epub 2002 June 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115115&dopt=Abstract

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Bronchoalveolar lavage cell composition in allogeneic bone marrow transplant patients without symptomatic lung complications. Author(s): de la Camara R, Giron R, Marron C, Martinez C, Ancochea J, FernandezRanada JM, Aspa J. Source: Bone Marrow Transplantation. 1997 December; 20(12): 1087-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9466283&dopt=Abstract

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Bronchoalveolar lavage in the diagnosis of pulmonary complications of bone marrow transplant patients. Author(s): Huaringa AJ, Leyva FJ, Signes-Costa J, Morice RC, Raad I, Darwish AA, Champlin RE. Source: Bone Marrow Transplantation. 2000 May; 25(9): 975-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10800066&dopt=Abstract

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Candida lusitaniae chorioamnionitis in a bone marrow transplant patient. Author(s): DiLorenzo DJ, Wong G, Ludmir J. Source: Obstetrics and Gynecology. 1997 October; 90(4 Pt 2): 702-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770607&dopt=Abstract

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Caregiver responses and needs. An ambulatory bone marrow transplant model. Author(s): Grimm PM, Zawacki KL, Mock V, Krumm S, Frink BB. Source: Cancer Practice. 2000 May-June; 8(3): 120-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898136&dopt=Abstract

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Case report: Kinetics of Epstein-Barr virus load in a bone marrow transplant patient with no sign of lymphoproliferative disease. Author(s): Biasolo MA, Calistri A, Cesaro S, Gentile G, Mengoli C, Palu G. Source: Journal of Medical Virology. 2003 February; 69(2): 220-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683411&dopt=Abstract

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Cataract surgery in allogeneic bone marrow transplant recipients with graft-versushost disease(1). Author(s): Penn EA, Soong HK. Source: Journal of Cataract and Refractive Surgery. 2002 March; 28(3): 417-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973086&dopt=Abstract

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Cauda equina syndrome in a 65-year-old man, status post-bone marrow transplant for chronic myeloid leukemia. Author(s): Dalton SR, Ririe DW, Neuhauser TS. Source: Archives of Pathology & Laboratory Medicine. 2001 October; 125(10): 1385-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11570925&dopt=Abstract

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Changes in the pattern of TCR V beta repertoire expression after bone marrow transplant is linked to the HLA haplotype in humans. Author(s): Lonial S, Bomberger C, Waller EK. Source: British Journal of Haematology. 2001 April; 113(1): 224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328305&dopt=Abstract

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Chryseobacterium indologenes bacteremia in a bone marrow transplant recipient with chronic graft-versus-host disease. Author(s): Lin JT, Wang WS, Yen CC, Liu JH, Chiou TJ, Yang MH, Chao TC, Chen PM. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(11-12): 882-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14723368&dopt=Abstract

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Clinical significance of alimentary tract microbes in bone marrow transplant recipients. Author(s): Yuen KY, Woo PC, Liang RH, Chiu EK, Chen FF, Wong SS, Lau YL, Ha SY, Peiris JS, Siau H, Chan TK. Source: Diagnostic Microbiology and Infectious Disease. 1998 February; 30(2): 75-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9554172&dopt=Abstract

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Community respiratory virus infections in bone marrow transplant recipients: the M.D. Anderson Cancer Center experience. Author(s): Champlin RE, Whimbey E. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2001; 7 Suppl: 8S-10S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777103&dopt=Abstract

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Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients. Author(s): Machetti M, Feasi M, Mordini N, Van Lint MT, Bacigalupo A, Latge JP, Sarfati J, Viscoli C. Source: Bone Marrow Transplantation. 1998 May; 21(9): 917-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613784&dopt=Abstract

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Comparison of bone marrow transplant and chemotherapy for relapsed childhood acute lymphoblastic leukaemia: the MRC UKALL X experience. Medical Research Council Working Party on Childhood Leukaemia. Author(s): Wheeler K, Richards S, Bailey C, Chessells J. Source: British Journal of Haematology. 1998 April; 101(1): 94-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9576189&dopt=Abstract

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Comparison of DNA amplification, mRNA amplification, and DNA hybridization techniques for detection of cytomegalovirus in bone marrow transplant recipients. Author(s): Diaz-Mitoma F, Leger C, Miller H, Giulivi A, Frost R, Shaw L, Huebsch L. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5159-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14605153&dopt=Abstract

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Comparison of PCR, enzyme immunoassay and conventional culture for adenovirus detection in bone marrow transplant patients with hemorrhagic cystitis. Author(s): Raboni SM, Siqueira MM, Portes SR, Pasquini R. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 August; 27(3): 270-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878091&dopt=Abstract

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Comparison of short tandem repeat and variable number tandem repeat genetic markers for quantitative determination of allogeneic bone marrow transplant engraftment. Author(s): Schichman SA, Suess P, Vertino AM, Gray PS. Source: Bone Marrow Transplantation. 2002 February; 29(3): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859397&dopt=Abstract

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Complete remission of tumour with interleukin 2 therapy in a patient with nonHodgkin's lymphoma post allogeneic bone marrow transplant associated with polyclonal T-cell bone marrow lymphocytosis. Author(s): Kiss TL, Spaner D, Daly AS, Hasegawa WS, Lipton JH, Messner HA, Chang H. Source: British Journal of Haematology. 2003 February; 120(3): 523-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580972&dopt=Abstract

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Contamination of bone marrow products with an actinomycete resembling Microbacterium species and reinfusion into autologous stem cell and bone marrow transplant recipients. Author(s): Hirji Z, Saragosa R, Dedier H, Crump M, Franke N, Burrows L, Jamieson F, Brown S, Gardam MA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 May 15; 36(10): E115-21. Epub 2003 May 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746790&dopt=Abstract

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CT assessment of bone marrow transplant patients with rhinocerebral aspergillosis. Author(s): Saah D, Sichel JY, Schwartz A, Nagler A, Eliashar R. Source: American Journal of Otolaryngology. 2002 November-December; 23(6): 328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430122&dopt=Abstract

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Cunninghamella bertholletiae infection in a bone marrow transplant patient: amphotericin lung penetration, MIC determinations, and review of the literature. Author(s): Garey KW, Pendland SL, Huynh VT, Bunch TH, Jensen GM, Pursell KJ. Source: Pharmacotherapy. 2001 July; 21(7): 855-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444582&dopt=Abstract

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Cytomegalovirus glycoprotein B sequence variation among Japanese bone marrow transplant recipients. Author(s): Wada K, Mizuno S, Kato K, Kamiya T, Ozawa K. Source: Intervirology. 1997; 40(4): 215-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9612721&dopt=Abstract

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Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance. Author(s): Seo SK, Regan A, Cihlar T, Lin DC, Boulad F, George D, Prasad VK, Kiehn TE, Polsky B. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 November 1; 33(9): E105-8. Epub 2001 September 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577375&dopt=Abstract

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Death, dying and emotional labour: problematic dimensions of the bone marrow transplant nursing role? Author(s): Kelly D, Ross S, Gray B, Smith P. Source: Journal of Advanced Nursing. 2000 October; 32(4): 952-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095235&dopt=Abstract

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Delayed non-infectious lung disease in allogeneic bone marrow transplant recipients. Author(s): Trisolini R, Stanzani M, Agli LL, Colangelo A, Bonifazi F, Falcioni S, Patelli M, Falcone F, Bandini G, Tura S, Poletti V. Source: Sarcoidosis Vasc Diffuse Lung Dis. 2001 March; 18(1): 75-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11354551&dopt=Abstract

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Dermatologic changes associated with roquinimex immunotherapy after autologous bone marrow transplant. Author(s): Ohsuga Y, Rowe JM, Liesveld J, Burns RP, Gaspari AA. Source: Journal of the American Academy of Dermatology. 2000 September; 43(3): 43741. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10954654&dopt=Abstract

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Detection of human polyomaviruses in urine from bone marrow transplant patients: comparison of electron microscopy with PCR. Author(s): Biel SS, Nitsche A, Kurth A, Siegert W, Ozel M, Gelderblom HR. Source: Clinical Chemistry. 2004 February; 50(2): 306-12. Epub 2003 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684621&dopt=Abstract

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Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. Author(s): Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, Dhedin N, Vernant JP, Agut H. Source: Journal of Virological Methods. 2002 February; 100(1-2): 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742650&dopt=Abstract

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Development of psoriasis after syngeneic bone marrow transplant from psoriatic donor: further evidence for adoptive autoimmunity. Author(s): Snowden JA, Heaton DC. Source: The British Journal of Dermatology. 1997 July; 137(1): 130-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9274640&dopt=Abstract

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Development of systemic lupus erythematosus following autologous bone marrow transplant for acute lymphocytic leukemia. Author(s): Steinbach WJ, Sandborg CI. Source: The Journal of Rheumatology. 2001 June; 28(6): 1467-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11409148&dopt=Abstract

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Diagnosis of invasive aspergillosis in bone marrow transplant recipients by polymerase chain reaction. Author(s): Williamson EC, Leeming JP, Palmer HM, Steward CG, Warnock D, Marks DI, Millar MR. Source: British Journal of Haematology. 2000 January; 108(1): 132-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10651736&dopt=Abstract

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Diagnosis of post-bone marrow transplant pulmonary lymphoproliferative disorder by bronchoalveolar lavage. Author(s): Schellhase DE, Jones SM, Saylors RL, Tryka AF. Source: Pediatric Pulmonology. 1998 January; 25(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475334&dopt=Abstract

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Diagnosis of toxoplasmosis in bone marrow transplant recipients: comparison of PCR-based results and immunohistochemistry. Author(s): Held TK, Kruger D, Switala AR, Beyer J, Kingreen D, Busemann C, Janitschke K, Siegert W. Source: Bone Marrow Transplantation. 2000 June; 25(12): 1257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10871730&dopt=Abstract

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Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. Author(s): Kanamori H, Maruta A, Sasaki S, Yamazaki E, Ueda S, Katoh K, Tamura T, Otsuka-Aoba M, Taguchi J, Harano H, Ogawa K, Mohri H, Okubo T, Matsuzaki M, Watanabe S, Koharazawa H, Fujita H, Kodama F. Source: Bone Marrow Transplantation. 1998 April; 21(7): 705-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9578311&dopt=Abstract

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Discontinuation of immunosuppression for prevention of kidney graft rejection after receiving a bone marrow transplant from the same HLA identical sibling donor. Author(s): Gajewski JL, Ippoliti C, Ma Y, Champlin R. Source: American Journal of Hematology. 2002 December; 71(4): 311-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447962&dopt=Abstract

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Disparate lympho-erythroid donor to recipient chimaerism in a beta(0)-thalassaemia bone marrow transplant recipient with red cell indices indicative of apparent full engraftment. Author(s): Weinberg RS, Vlachos A, Najfeld V, Galperin Y, Scalise A, Fruchtman S, Lipton JM. Source: British Journal of Haematology. 1997 October; 99(1): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9359504&dopt=Abstract

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Disseminated nocardiosis in a bone marrow transplant recipient with chronic GVHD. Author(s): Bhave AA, Thirunavukkarasu K, Gottlieb DJ, Bradstock K. Source: Bone Marrow Transplantation. 1999 March; 23(5): 519-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10100569&dopt=Abstract

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Disseminated toxoplasmosis in marrow recipients: a report of three cases and a review of the literature. Bone Marrow Transplant Team. Author(s): Chandrasekar PH, Momin F. Source: Bone Marrow Transplantation. 1997 April; 19(7): 685-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9156245&dopt=Abstract

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Does isochromosome 7q mandate bone marrow transplant in children with Shwachman-Diamond syndrome? Author(s): Cunningham J, Sales M, Pearce A, Howard J, Stallings R, Telford N, Wilkie R, Huntly B, Thomas A, O'Marcaigh A, Will A, Pratt N. Source: British Journal of Haematology. 2002 December; 119(4): 1062-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472589&dopt=Abstract

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Donor leukocyte infusion for treatment of graft rejection post partially mismatched related donor bone marrow transplant. Author(s): Godder KT, Abhyankar SH, Lamb LS, Best RG, Geier SS, Pati AR, Gee AP, Henslee-Downey PJ. Source: Bone Marrow Transplantation. 1998 July; 22(1): 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9678806&dopt=Abstract

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Dramatic improvement of BMD following vitamin D therapy in a bone marrow transplant recipient. Author(s): Arekat MR, And G, Lemke S, Moses AM. Source: Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry. 2002 Fall; 5(3): 267-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357064&dopt=Abstract

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Duodenal hematoma as a complication of endoscopic biopsy in pediatric bone marrow transplant recipients. Author(s): Ramakrishna J, Treem WR. Source: Journal of Pediatric Gastroenterology and Nutrition. 1997 October; 25(4): 426-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9327375&dopt=Abstract

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Dynamics of Enterococcus faecalis colonization of bone marrow transplant patients. Author(s): Pasquarella C, Morrison D, Savino A, Cookson BD. Source: Advances in Experimental Medicine and Biology. 1997; 418: 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9331652&dopt=Abstract

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Early detection of cytomegalovirus (CMV) infection in bone marrow transplant patients by reverse transcription-PCR for CMV spliced late gene UL21.5: a two site evaluation. Author(s): Boriskin YS, Fuller K, Powles RL, Vipond IB, Rice PS, Booth JC, Caul EO, Butcher PD. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2002 February; 24(1-2): 13-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744424&dopt=Abstract

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Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study. Author(s): Antonini G, Ceschin V, Morino S, Fiorelli M, Gragnani F, Mengarelli A, Iori AP, Arcese W. Source: Neurology. 1998 May; 50(5): 1441-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9596002&dopt=Abstract

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Effect of clinical outcomes data on intensive care unit utilization by bone marrow transplant patients. Author(s): Paz HL, Garland A, Weinar M, Crilley P, Brodsky I. Source: Critical Care Medicine. 1998 January; 26(1): 66-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9428545&dopt=Abstract

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Effect of extended immunosuppressive drug treatment on B cell vs T cell reconstitution in pediatric bone marrow transplant recipients. Author(s): D'Costa S, Slobod KS, Benaim E, Bowman L, Cunningham J, Holladay M, Howlett N, Srivastava DK, Hurwitz JL. Source: Bone Marrow Transplantation. 2001 September; 28(6): 573-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11607770&dopt=Abstract

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Effect of repeated dosing on the pharmacokinetics of oral fluconazole in bone marrow transplant patients. Author(s): el-Yazigi A, Ellis M, Ernst P, Hussein R, Baillie FJ. Source: Journal of Clinical Pharmacology. 1997 November; 37(11): 1031-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9505996&dopt=Abstract

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Effects of clarithromycin on oral mucositis in bone marrow transplant recipients. Author(s): Yuen KY, Woo PC, Tai JW, Lie AK, Luk J, Liang R. Source: Haematologica. 2001 May; 86(5): 554-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410428&dopt=Abstract

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Effects of cyclosporin A on hepatitis C virus infection in bone marrow transplant patients. Bone Marrow Transplantation Team. Author(s): Akiyama H, Yoshinaga H, Tanaka T, Hiruma K, Tanikawa S, Sakamaki H, Onozawa Y, Wakita T, Kohara M. Source: Bone Marrow Transplantation. 1997 December; 20(11): 993-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9422481&dopt=Abstract

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Efficacy of amlodipine in pediatric bone marrow transplant patients. Author(s): Khattak S, Rogan JW, Saunders EF, Theis JG, Arbus GS, Koren G. Source: Clinical Pediatrics. 1998 January; 37(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475697&dopt=Abstract

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Emergence of cotrimoxazole- and quinolone-resistant Campylobacter infections in bone marrow transplant recipients. Author(s): Lau SK, Woo PC, Leung KW, Yuen KY. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 February; 21(2): 1279. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939393&dopt=Abstract

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Empiric carbapenem monotherapy in pediatric bone marrow transplant recipients. Author(s): Nelson WK, Rayback PA, Quinones R, Giller RH. Source: The Annals of Pharmacotherapy. 2002 September; 36(9): 1360-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196052&dopt=Abstract

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Endocrine late effects after bone marrow transplant. Author(s): Brennan BM, Shalet SM. Source: British Journal of Haematology. 2002 July; 118(1): 58-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100128&dopt=Abstract

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Endothelial dysfunction after bone marrow transplantation: increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications. Author(s): Nurnberger W, Michelmann I, Burdach S, Gobel U. Source: Annals of Hematology. 1998 February; 76(2): 61-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9540759&dopt=Abstract

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EORTC QLQ-C30 and FACT-BMT for the measurement of quality of life in bone marrow transplant recipients: a comparison. Author(s): Kopp M, Schweigkofler H, Holzner B, Nachbaur D, Niederwieser D, Fleischhacker WW, Kemmler G, Sperner-Unterweger B. Source: European Journal of Haematology. 2000 August; 65(2): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10966168&dopt=Abstract

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Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells. Author(s): Gustafsson A, Levitsky V, Zou JZ, Frisan T, Dalianis T, Ljungman P, Ringden O, Winiarski J, Ernberg I, Masucci MG. Source: Blood. 2000 February 1; 95(3): 807-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10648390&dopt=Abstract

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Epstein-Barr virus dacryoadenitis as a complication of bone marrow transplant in a child with combined immunodeficiency. Author(s): Thomson J, Vassiliou G, Veys P, Redmill B, Edelsten C. Source: Eye (London, England). 2001 December; 15(Pt 6): 815-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827022&dopt=Abstract

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Epstein-Barr virus-associated post-transplant lymphoproliferative disease after bone marrow transplantation mimicking graft-versus-host disease. Author(s): Claviez A, Tiemann M, Wagner HJ, Dreger P, Suttorp M. Source: Pediatric Transplantation. 2000 May; 4(2): 151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272609&dopt=Abstract

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Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Registry and the American Society of Blood and Marrow Transplantation. Author(s): Antin JH, Childs R, Filipovich AH, Giralt S, Mackinnon S, Spitzer T, Weisdorf D. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2001; 7(9): 473-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669214&dopt=Abstract

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Evans syndrome after autologous bone marrow transplant for recurrent Hodgkin's disease. Author(s): Keung YK, Cobos E, Bolanos-Meade J, Issarachai S, Brideau A, Morgan D. Source: Bone Marrow Transplantation. 1997 December; 20(12): 1099-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9466285&dopt=Abstract

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Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Author(s): Collin BA, Leather HL, Wingard JR, Ramphal R. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 October 1; 33(7): 947-53. Epub 2001 September 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528564&dopt=Abstract

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Ex vivo generation of cytotoxic T lymphocytes specific for one or two distinct viruses for the prophylaxis of patients receiving an allogeneic bone marrow transplant. Author(s): Regn S, Raffegerst S, Chen X, Schendel D, Kolb HJ, Roskrow M. Source: Bone Marrow Transplantation. 2001 January; 27(1): 53-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244438&dopt=Abstract

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Factor analysis and validity of the Transplant Evaluation Rating Scale in a large bone marrow transplant sample. Author(s): Hoodin F, Kalbfleisch KR. Source: Journal of Psychosomatic Research. 2003 May; 54(5): 465-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12726904&dopt=Abstract

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Failure of the administration of donor mononuclear cells for the treatment of relapse after bone marrow transplant for leukemia. Author(s): Borbolla JR, Lopez-Hernandez MA, Trueba E, Gonzalez-Avante M, DeDiego J, Alvarado M, Jimenez RM. Source: Journal of Hematotherapy & Stem Cell Research. 2000 August; 9(4): 415-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10982238&dopt=Abstract

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Fatal Chaetomium cerebritis in a bone marrow transplant patient. Author(s): Thomas C, Mileusnic D, Carey RB, Kampert M, Anderson D. Source: Human Pathology. 1999 July; 30(7): 874-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10414510&dopt=Abstract

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Fatal disseminated Trichoderma longibrachiatum infection in an adult bone marrow transplant patient: species identification and review of the literature. Author(s): Richter S, Cormican MG, Pfaller MA, Lee CK, Gingrich R, Rinaldi MG, Sutton DA. Source: Journal of Clinical Microbiology. 1999 April; 37(4): 1154-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10074541&dopt=Abstract

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Fatal donor-derived Epstein-Barr virus-associated post-transplant lymphoproliferative disorder following reduced intensity volunteer-unrelated bone marrow transplant for myelodysplastic syndrome. Author(s): Ho AY, Adams S, Shaikh H, Pagliuca A, Devereux S, Mufti GJ. Source: Bone Marrow Transplantation. 2002 May; 29(10): 867-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058237&dopt=Abstract

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Fatal herpesvirus 6 encephalitis after unrelated bone marrow transplant. Author(s): Bosi A, Zazzi M, Amantini A, Cellerini M, Vannucchi AM, De Milito A, Guidi S, Saccardi R, Lombardini L, Laszlo D, Rossi Ferrini P. Source: Bone Marrow Transplantation. 1998 August; 22(3): 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9720744&dopt=Abstract

90

Bone Marrow Transplant

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Fatal infection caused by Francisella tularensisin a neutropenic bone marrow transplant recipient. Author(s): Sarria JC, Vidal AM, Kimbrough RC, Figueroa JE. Source: Annals of Hematology. 2003 January; 82(1): 41-3. Epub 2002 November 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574964&dopt=Abstract

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Fatal post-transplant lymphoproliferative disorder following allogeneic bone marrow transplantation for aplastic anemia. Author(s): Rudzki Z, Werda L, Piatkowska-Jakubas B, Mensah P, Zazula M, Bialas M, Skotnicki AB, Stachura J. Source: Pol J Pathol. 2002; 53(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014224&dopt=Abstract

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Fatal Salmonella group G enteritis mimicking intestinal graft-versus-host disease in a bone marrow transplant recipient. Author(s): Shaikh ZH, Ueno NT, Kontoyiannis DP. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2001 March; 3(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11429037&dopt=Abstract

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FDA approves baboon bone marrow transplant for AIDS patient. Food and Drug Administration. Author(s): Baker R. Source: Beta. 1995 September; : 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11362897&dopt=Abstract

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Fixing the intestinal mucosa in the bone marrow transplant patient: lessons from other intestinal immunodeficiencies and inflammatory disorders. Author(s): Proujansky R. Source: Pediatric Transplantation. 1999; 3 Suppl 1: 9-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10587965&dopt=Abstract

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Flow cytometric assessment of bone marrow transplant patient. Author(s): Auer I, Luider J. Source: Przegl Lek. 2000; 57 Suppl 1: 33-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10822994&dopt=Abstract

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FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model. Author(s): Kelly LM, Liu Q, Kutok JL, Williams IR, Boulton CL, Gilliland DG. Source: Blood. 2002 January 1; 99(1): 310-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756186&dopt=Abstract

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Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group. Author(s): Wolff SN, Fay J, Stevens D, Herzig RH, Pohlman B, Bolwell B, Lynch J, Ericson S, Freytes CO, LeMaistre F, Collins R, Pineiro L, Greer J, Stein R, Goodman SA, Dummer S. Source: Bone Marrow Transplantation. 2000 April; 25(8): 853-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10808206&dopt=Abstract

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Fluctuating lymphocyte chimerism, tolerance and anti-tumor response in a patient with refractory lymphoma receiving nonmyeloablative conditioning and a haploidentical related allogeneic bone marrow transplant. Author(s): Toh HC, Spitzer TR, Preffer F, Alexander SI, McAfee S, Dombkowski D, Clark JS, Colby C, Saidman S, Sackstein R, Sykes M. Source: Cytokines, Cellular & Molecular Therapy. 2002 December; 7(2): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607794&dopt=Abstract

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Foscarnet-induced electrolyte abnormalities in a bone marrow transplant patient receiving parenteral nutrition. Author(s): Matarese LE, Speerhas R, Seidner DL, Steiger E. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 May-June; 24(3): 170-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850943&dopt=Abstract

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Functional analysis of the CD8+CD57+ cell population in normal healthy individuals and matched unrelated T-cell-depleted bone marrow transplant recipients. Author(s): Rowbottom AW, Garland RJ, Lepper MW, Kaneria SS, Goulden NJ, Oakhill A, Steward CG. Source: British Journal of Haematology. 2000 August; 110(2): 315-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971387&dopt=Abstract

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Fungal infections after bone marrow transplant. Author(s): Wingard JR. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 1999; 5(2): 55-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371357&dopt=Abstract

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Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients. Author(s): Tollemar J, Gross N, Dolgiras N, Jarstrand C, Ringden O, Hammarstrom L. Source: Bone Marrow Transplantation. 1999 February; 23(3): 283-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084261&dopt=Abstract

92

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Further evaluation of a scale to screen for risk of emotional difficulties in bone marrow transplant recipients. Author(s): Molassiotis A. Source: Journal of Advanced Nursing. 1999 April; 29(4): 922-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215984&dopt=Abstract

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Gallbladder sludge formation after bone marrow transplant: sonographic observations. Author(s): Teefey SA, Hollister MS, Lee SP, Jacobson AF, Higano CS, Bianco JA, Colacurcio CJ. Source: Abdominal Imaging. 1994 January-February; 19(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8161906&dopt=Abstract

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Gamma knife radiosurgery in patients with advanced breast cancer undergoing bone marrow transplant. Author(s): Levin KJ, Youssef EF, Sloan AE, Patel R, Zabad RK, Zamorano L. Source: Journal of Neurosurgery. 2002 December; 97(5 Suppl): 663-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507116&dopt=Abstract

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Ganciclovir prophylaxis for cytomegalovirus infection in pediatric allogeneic bone marrow transplant recipients. Author(s): Canpolat C, Culbert S, Gardner M, Whimbey E, Tarrand J, Chan KW. Source: Bone Marrow Transplantation. 1996 April; 17(4): 589-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8722360&dopt=Abstract

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Ganciclovir-induced encephalopathy in a bone marrow transplant recipient. Author(s): Sharathkumar A, Shaw P. Source: Bone Marrow Transplantation. 1999 August; 24(4): 421-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467333&dopt=Abstract

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Ganciclovir-resistant cytomegalovirus encephalitis in a bone marrow transplant recipient. Author(s): Julin JE, van Burik JH, Krivit W, Webb C, Holman CJ, Clark HB, Balfour HH Jr. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2002 December; 4(4): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535263&dopt=Abstract

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Gastrointestinal complications in bone marrow transplant patients. Author(s): May GR, Urbanski SJ. Source: Przegl Lek. 2000; 57 Suppl 1: 45-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10822997&dopt=Abstract

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Genetic characterization of thymidine kinase from acyclovir-resistant and susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients. Author(s): Morfin F, Souillet G, Bilger K, Ooka T, Aymard M, Thouvenot D. Source: The Journal of Infectious Diseases. 2000 July; 182(1): 290-3. Epub 2000 June 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10882609&dopt=Abstract

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Genotyping of adenoviruses isolated in an outbreak in a bone marrow transplant unit shows that diverse strains are involved. Author(s): Venard V, Carret A, Corsaro D, Bordigoni P, Le Faou A. Source: The Journal of Hospital Infection. 2000 January; 44(1): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10633057&dopt=Abstract

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Gentamicin and tobramycin pharmacokinetics in pediatric bone marrow transplant patients. Author(s): Jacobson PA, West NJ, Price J, Hutchinson RJ. Source: The Annals of Pharmacotherapy. 1997 October; 31(10): 1127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9337435&dopt=Abstract

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Global meaning and psychological adjustment among survivors of bone marrow transplant. Author(s): Johnson Vickberg SM, Duhamel KN, Smith MY, Manne SL, Winkel G, Papadopoulos EB, Redd WH. Source: Psycho-Oncology. 2001 January-February; 10(1): 29-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180575&dopt=Abstract

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Glomerular and extraglomerular immune complex deposits in a bone marrow transplant recipient. Author(s): Ohsawa I, Ohi H, Fujita T, Endo M, Ito T, Sawada U, Yamaguchi Y. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2000 July; 36(1): E3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873902&dopt=Abstract

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Graft rejection and second bone marrow transplants for acquired aplastic anaemia: a report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group. Author(s): McCann SR, Bacigalupo A, Gluckman E, Hinterberger W, Hows J, Ljungman P, Marin P, Nissen C, van't Veer Kerthof E, Raghavachar A, et al. Source: Bone Marrow Transplantation. 1994 March; 13(3): 233-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8199566&dopt=Abstract

94

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Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. Author(s): Rocha V, Wagner JE Jr, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM, Gluckman E. Source: The New England Journal of Medicine. 2000 June 22; 342(25): 1846-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10861319&dopt=Abstract

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Graft-vs-host-disease-associated conjunctival chemosis and central serous chorioretinopathy after bone marrow transplant. Author(s): Cheng LL, Kwok AK, Wat NM, Neoh EL, Jon HC, Lam DS. Source: American Journal of Ophthalmology. 2002 August; 134(2): 293-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140049&dopt=Abstract

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Granisetron (Kytril) plus dexamethasone for antiemetic control in bone marrow transplant patients receiving highly emetogenic chemotherapy with or without total body irradiation. Author(s): Abbott B, Ippoliti C, Hecth D, Bruton J, Whaley B, Champlin R. Source: Bone Marrow Transplantation. 2000 June; 25(12): 1279-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10871733&dopt=Abstract

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Granulocyte colony-stimulating factor-combined marrow-ablative chemotherapy and autologous blood cell transplantation for the treatment of patients with acute myelogenous leukemia in first remission. The Fukouka Bone Marrow Transplant Group. Author(s): Harada M, Akashi K, Hayashi S, Eto T, Takamatsu Y, Teshima T, Hirota Y, Taniguchi S, Nagafuji K, Mizuno S, Gondo H, Niho Y. Source: International Journal of Hematology. 1997 October; 66(3): 297-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9401275&dopt=Abstract

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Growth and growth hormone status after a bone marrow transplant. Author(s): Shalet SM, Brennan BM. Source: Hormone Research. 2002; 58 Suppl 1: 86-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373020&dopt=Abstract

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Growth in patients after allogeneic bone marrow transplant for hematological diseases in childhood. Author(s): Cohen A, van Lint MT, Uderzo C, Rovelli A, Lavagetto A, Vitale V, Morchio A, Locasciulli A, Bacigalupo A, Romano C. Source: Bone Marrow Transplantation. 1995 March; 15(3): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7599557&dopt=Abstract

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Guidelines for prophylaxis of cytomegalovirus disease in bone marrow transplant patients. Author(s): Badas A, Stoukides CA. Source: The Annals of Pharmacotherapy. 1996 December; 30(12): 1483-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8968462&dopt=Abstract

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Guillain-Barre syndrome in organ and bone marrow transplant patients. Author(s): Bulsara KR, Baron PW, Tuttle-Newhall JE, Clavien PA, Morgenlander J. Source: Transplantation. 2001 April 27; 71(8): 1169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11374420&dopt=Abstract

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Haemopoietic stem cell transplantation in Australia, 1992-95: a report from the Australian Bone Marrow Transplant Recipient Registry. Author(s): Atkinson K, Nivison-Smith I, Hawkins T. Source: Aust N Z J Med. 1997 August; 27(4): 408-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9448882&dopt=Abstract

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Health-related quality of life in pediatric bone marrow transplant survivors: according to whom? Author(s): Parsons SK, Barlow SE, Levy SL, Supran SE, Kaplan SH. Source: Int J Cancer Suppl. 1999; 12: 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10679870&dopt=Abstract

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High busulfan concentrations are associated with increased transplant-related mortality in allogeneic bone marrow transplant patients. Author(s): Ljungman P, Hassan M, Bekassy AN, Ringden O, Oberg G. Source: Bone Marrow Transplantation. 1997 December; 20(11): 909-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9422468&dopt=Abstract

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High spontaneous IL-10 production in unrelated bone marrow transplant recipients is associated with fewer transplant-related complications and early deaths. Author(s): Baker KS, Roncarolo MG, Peters C, Bigler M, DeFor T, Blazar BR. Source: Bone Marrow Transplantation. 1999 June; 23(11): 1123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382951&dopt=Abstract

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High-dose carboplatin and regimen-related toxicity following autologous bone marrow transplant. Author(s): Colby C, Koziol S, McAfee SL, Yeap B, Spitzer TR. Source: Bone Marrow Transplantation. 2002 March; 29(6): 467-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960264&dopt=Abstract

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High-dose therapy and autologous stem-cell support for chemosensitive transformed low-grade follicular non-Hodgkin's lymphoma: a case-matched study from the European Bone Marrow Transplant Registry. Author(s): Williams CD, Harrison CN, Lister TA, Norton AJ, Blystad AK, Coiffier B, Taghipour G, Schmitz N, Goldstone AH; European Bone Marrow Transplant Lymphoma Working Party. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 February 1; 19(3): 727-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157024&dopt=Abstract

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HLA and bone marrow transplant donor search strategies. Author(s): Agrawal S, Bhardwaj U. Source: J Assoc Physicians India. 2002 July; 50: 937-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126352&dopt=Abstract

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Hospital capacity and post-transplant survival after allogeneic bone marrow transplantation: analysis of data from the Japan Society for Hematopoietic Cell Transplantation. Author(s): Matsuo K, Hamajima N, Morishima Y, Harada M. Source: Bone Marrow Transplantation. 2000 November; 26(10): 1061-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108304&dopt=Abstract

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How psychometrically sound is the transplant evaluation rating scale for bone marrow transplant recipients? Author(s): Hoodin F, Kalbfleisch KR. Source: Psychosomatics. 2001 November-December; 42(6): 490-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815684&dopt=Abstract

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Human bone marrow transplant rejection is associated with telomere cleavage. Author(s): Multani AS, Worth LL, Jeha S, Chan KW, Pathak S. Source: International Journal of Molecular Medicine. 2001 December; 8(6): 607-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712073&dopt=Abstract

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Human cytomegalovirus immediate-early mRNA detection by nucleic acid sequencebased amplification as a new parameter for preemptive therapy in bone marrow transplant recipients. Author(s): Gerna G, Baldanti F, Lilleri D, Parea M, Alessandrino E, Pagani A, Locatelli F, Middeldorp J, Revello MG. Source: Journal of Clinical Microbiology. 2000 May; 38(5): 1845-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790111&dopt=Abstract

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Human herpes virus 8 (HHV8) serology in allogeneic bone marrow transplant recipients. Author(s): Rosenzwajg M, Fery N, Bons V, Damaj G, Gluckman E, Gluckman J. Source: Bone Marrow Transplantation. 1999 August; 24(4): 351-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467321&dopt=Abstract

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Human herpesvirus 6 infection in autologous bone marrow transplant recipients: a prospective study. Author(s): Moschettini D, Galieni P, Valensin PE, Laszlo D, Scalia G, Tozzi M, Lauria F, Donati D. Source: Journal of Medical Virology. 2000 January; 60(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10568761&dopt=Abstract

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Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients. Author(s): Zerr DM, Gooley TA, Yeung L, Huang ML, Carpenter P, Wade JC, Corey L, Anasetti C. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 September 15; 33(6): 763-71. Epub 2001 August 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11512080&dopt=Abstract

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Human herpesvirus 6 viremia in bone marrow transplant recipients: clinical features and risk factors. Author(s): Yoshikawa T, Asano Y, Ihira M, Suzuki K, Ohashi M, Suga S, Kudo K, Horibe K, Kojima S, Kato K, Matsuyama T, Nishiyama Y. Source: The Journal of Infectious Diseases. 2002 April 1; 185(7): 847-53. Epub 2002 March 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920307&dopt=Abstract

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Human herpesvirus-6 (HHV-6) and HHV-7 infections in bone marrow transplant recipients. Author(s): Peiris M. Source: Critical Reviews in Oncology/Hematology. 1999 December; 32(3): 187-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10633848&dopt=Abstract

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Human mesenchymal stem cells are not of donor origin in patients with severe aplastic anemia who underwent sex-mismatched allogeneic bone marrow transplant. Author(s): Stute N, Fehse B, Schroder J, Arps S, Adamietz P, Held KR, Zander AR. Source: Journal of Hematotherapy & Stem Cell Research. 2002 December; 11(6): 977-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590713&dopt=Abstract

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Human papillomavirus infection and anogenital condyloma in bone marrow transplant recipients. Author(s): Daneshpouy M, Socie G, Clavel C, Devergie A, Rivet J, Cartier I, Brousse N, Birembaut P, Gluckman E, Janin A. Source: Transplantation. 2001 January 15; 71(1): 167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11211188&dopt=Abstract

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Hyponatremia during administration of tacrolimus in an allogeneic bone marrow transplant recipient. Author(s): Azuma T, Narumi H, Kojima K, Nawa Y, Hara M. Source: International Journal of Hematology. 2003 October; 78(3): 268-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604289&dopt=Abstract

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Hypophosphatemia and hypouricemia in pediatric allogeneic bone marrow transplant recipients. Author(s): Uckan D, Cetin M, Dida A, Batu A, Tuncer M, Tezcan I. Source: Pediatric Transplantation. 2003 April; 7(2): 98-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654049&dopt=Abstract

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Identification by 16S ribosomal RNA gene sequencing of an Enterobacteriaceae species from a bone marrow transplant recipient. Author(s): Woo PC, Leung PK, Leung KW, Yuen KY. Source: Molecular Pathology : Mp. 2000 August; 53(4): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040945&dopt=Abstract

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Idiopathic pneumonia syndrome after bone marrow transplantation: the role of pretransplant radiation conditioning and local cytokine dysregulation in promoting lung inflammation and fibrosis. Author(s): Shankar G, Cohen DA. Source: International Journal of Experimental Pathology. 2001 April; 82(2): 101-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454101&dopt=Abstract

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IgG response to pneumococcal polysaccharide-protein conjugate appears similar to IgG response to polysaccharide in bone marrow transplant recipients and healthy adults. Author(s): Storek J, Mendelman PM, Witherspoon RP, McGregor BA, Storb R. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 November; 25(5): 1253-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9402399&dopt=Abstract

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Immune response to polio vaccination in bone marrow transplant recipients. Author(s): Engelhard D, Handsher R, Naparstek E, Hardan I, Strauss N, Aker M, Or R, Baciu H, Slavin S. Source: Bone Marrow Transplantation. 1991 October; 8(4): 295-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1661633&dopt=Abstract

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Immunopathology of early graft-versus-host disease--a prospective study of skin, rectum, and peripheral blood in allogeneic and autologous bone marrow transplant recipients. Author(s): Sviland L, Pearson AD, Green MA, Baker BD, Eastham EJ, Reid MM, Hamilton PJ, Proctor SJ, Malcolm AJ. Source: Transplantation. 1991 December; 52(6): 1029-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1836284&dopt=Abstract

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Immunosuppressive therapy vs. bone marrow transplant for severe aplastic anemia. Author(s): Abella E, Ravindranth Y. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1997 November-December; 19(6): 533-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9407941&dopt=Abstract

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Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Author(s): Filipovich AH, Stone JV, Tomany SC, Ireland M, Kollman C, Pelz CJ, Casper JT, Cowan MJ, Edwards JR, Fasth A, Gale RP, Junker A, Kamani NR, Loechelt BJ, Pietryga DW, Ringden O, Vowels M, Hegland J, Williams AV, Klein JP, Sobocinski KA, Rowlings PA, Horowitz MM. Source: Blood. 2001 March 15; 97(6): 1598-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238097&dopt=Abstract

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Incidence of histoplasmosis following allogeneic bone marrow transplant or solid organ transplant in a hyperendemic area. Author(s): Vail GM, Young RS, Wheat LJ, Filo RS, Cornetta K, Goldman M. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2002 September; 4(3): 148-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421460&dopt=Abstract

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Incidence of imipenem hypersensitivity reactions in febrile neutropenic bone marrow transplant patients with a history of penicillin allergy. Author(s): McConnell SA, Penzak SR, Warmack TS, Anaissie EJ, Gubbins PO. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 December; 31(6): 1512-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11096026&dopt=Abstract

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Increased soluble Fas-ligand in sera of bone marrow transplant recipients with acute graft-versus-host disease. Author(s): Kanda Y, Tanaka Y, Shirakawa K, Yatomi T, Nakamura N, Kami M, Saito T, Izutsu K, Asai T, Yuji K, Ogawa S, Honda H, Mitani K, Chiba S, Yazaki Y, Hirai H. Source: Bone Marrow Transplantation. 1998 October; 22(8): 751-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9827971&dopt=Abstract

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Influence of intestinal decontamination using metronidazole on the detection of methanogenic Archaea in bone marrow transplant recipients. Author(s): Ansorg R, Rath PM, Runde V, Beelen DW. Source: Bone Marrow Transplantation. 2003 January; 31(2): 117-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621493&dopt=Abstract

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Intramural duodenal haematoma following endoscopic biopsy in a bone marrow transplant patient. Author(s): Worynski A, Zimmerman M, Herrmann RP, Forbes GM. Source: Aust N Z J Med. 1998 December; 28(6): 843-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972424&dopt=Abstract

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Intravenous cyclosporine and tacrolimus caused anaphylaxis but oral cyclosporine capsules were tolerated in an allogeneic bone marrow transplant recipient. Author(s): Takamatsu Y, Ishizu M, Ichinose I, Ogata K, Onoue M, Kumagawa M, Suzumiya J, Tamura K. Source: Bone Marrow Transplantation. 2001 August; 28(4): 421-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571519&dopt=Abstract

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Intravenous cyclosporine-rifampin interaction in a pediatric bone marrow transplant recipient. Author(s): Zelunka EJ. Source: Pharmacotherapy. 2002 March; 22(3): 387-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898895&dopt=Abstract

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Intravesical rhGM-CSF for the treatment of late onset hemorrhagic cystitis after bone marrow transplant. Author(s): Vela-Ojeda J, Tripp-Villanueva F, Sanchez-Cortes E, Ayala-Sanchez M, Garcia-Ruiz Esparza MA, Rosas-Cabral A, Gonzalez-Llaven J. Source: Bone Marrow Transplantation. 1999 December; 24(12): 1307-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10627639&dopt=Abstract

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Invasive fungal infections in pediatric bone marrow transplant recipients: single center experience of 10 years. Author(s): Hovi L, Saarinen-Pihkala UM, Vettenranta K, Saxen H. Source: Bone Marrow Transplantation. 2000 November; 26(9): 999-1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11100280&dopt=Abstract

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Invasive mold infections in allogeneic bone marrow transplant recipients. Author(s): Baddley JW, Stroud TP, Salzman D, Pappas PG. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 May 1; 32(9): 1319-24. Epub 2001 April 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303267&dopt=Abstract

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Iron overload in bone marrow transplant recipients. Author(s): Strasser SI, Kowdley KV, Sale GE, McDonald GB. Source: Bone Marrow Transplantation. 1998 July; 22(2): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9707025&dopt=Abstract

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Is autologous bone marrow transplant (ABMT) and high-dose chemotherapy an approach that can rescue some children with advanced cancer disease? Author(s): Rivera-Luna R, Olaya-Vargas A, Meza-Coria C, Cardenas-Cardos R, LealLeal C, Amador-Zarco J. Source: Pediatric Hematology and Oncology. 2001 October-November; 18(7): 443-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594707&dopt=Abstract

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Isolated testicular relapse after bone marrow transplant with total body irradiation and testicular boost in acute lymphoblastic leukemia. Author(s): Li CK, Shing MM, Chik KW, Kwan WH, Lai DH, Leung TF, Yuen PM. Source: Bone Marrow Transplantation. 1998 August; 22(4): 397-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9722077&dopt=Abstract

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Kinetics of anti-CMV antibodies after administration of intravenous immunoglobulins to bone marrow transplant recipients. Author(s): Bosi A, De Majo E, Guidi S, Parri F, Saccardi R, Vannucchi AM, Fanci R, Ferrini PR. Source: Haematologica. 1990 March-April; 75(2): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2162799&dopt=Abstract

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Kinetics of the antibody response against human cytomegalovirus-specific proteins in allogeneic bone marrow transplant recipients. Author(s): Schoppel K, Schmidt C, Einsele H, Hebart H, Mach M. Source: The Journal of Infectious Diseases. 1998 November; 178(5): 1233-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9780241&dopt=Abstract

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Late onset Epstein-Barr virus-associated lymphoproliferative disease after allogeneic bone marrow transplant presenting as breast masses. Author(s): Abhyankar SH, Chiang KY, McGuirk JP, Pati AR, Godder KT, Welsh JA, Waldron RL, McElveen JL, Henslee-Downey PJ. Source: Bone Marrow Transplantation. 1998 February; 21(3): 295-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9489654&dopt=Abstract

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Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital. Author(s): Grow WB, Moreb JS, Roque D, Manion K, Leather H, Reddy V, Khan SA, Finiewicz KJ, Nguyen H, Clancy CJ, Mehta PS, Wingard JR. Source: Bone Marrow Transplantation. 2002 January; 29(1): 15-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840139&dopt=Abstract

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Late outcomes after bone marrow transplant for aplastic anaemia. Author(s): Eapen M, Ramsay NK, Mertens AC, Robison LL, DeFor T, Davies SM. Source: British Journal of Haematology. 2000 December; 111(3): 754-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11122134&dopt=Abstract

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Leukaemic transformation of donor cells in a patient receiving a second allogeneic bone marrow transplant for severe aplastic anaemia. Author(s): Lawler M, Locasciulli A, Longoni D, Schiro R, McCann SR. Source: Bone Marrow Transplantation. 2002 March; 29(5): 453-6. Review. Erratum In: Bone Marrow Transplant. 2002 May; 29(9): 805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11919737&dopt=Abstract

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Liver disease during the first post-transplant year in bone marrow transplantation recipients: retrospective study. Author(s): Kim BK, Chung KW, Sun HS, Suh JG, Min WS, Kang CS, Sim SI, Shin WS, Kim CC. Source: Bone Marrow Transplantation. 2000 July; 26(2): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918430&dopt=Abstract

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Living The Discipline on a stem cell transplant unit: spiritual care outcomes among bone marrow transplant survivors. Author(s): Berger JA. Source: Journal of Health Care Chaplaincy. 2001; 11(1): 83-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398538&dopt=Abstract

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Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease. Author(s): Gor D, Sabin C, Prentice HG, Vyas N, Man S, Griffiths PD, Emery VC. Source: Bone Marrow Transplantation. 1998 March; 21(6): 597-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9543064&dopt=Abstract

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Long-term follow-up of human herpes virus 6 infection in autologous bone marrow transplant recipients. Author(s): Galieni P, Moschettini D, Donati D, Tozzi M, Valensin PE, Lauria F. Source: Haematologica. 2001 July; 86(7): 782-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454544&dopt=Abstract

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Low transplant mortality in allogeneic bone marrow transplantation for acute myeloid leukemia: a randomized study of low-dose cyclosporin versus low-dose cyclosporin and low-dose methotrexate. Author(s): Zikos P, Van Lint MT, Frassoni F, Lamparelli T, Gualandi F, Occhini D, Mordini N, Berisso G, Bregante S, De Stefano F, Soracco M, Vitale V, Bacigalupo A. Source: Blood. 1998 May 1; 91(9): 3503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9558411&dopt=Abstract

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Low-dose fractionated total body irradiation (TBI) adversely affects prognosis of patients with leukemia receiving an HLA-matched allogeneic bone marrow transplant from an unrelated donor (UD-BMT). Author(s): Corvo R, Lamparelli T, Bruno B, Barra S, Van Lint MT, Vitale V, Bacigalupo A. Source: Bone Marrow Transplantation. 2002 December; 30(11): 717-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439693&dopt=Abstract

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Lymphoid blast crisis of chronic myelogenous leukemia occurring more than 11 years after receiving an allogeneic bone marrow transplant for chronic myelogenous leukemia in myeloid blast crisis at onset. Author(s): Fukuno K, Tsurumi H, Yamada T, Oyama M, Matsuyama T, Terakura S, Kodera Y, Moriwaki H. Source: Bone Marrow Transplantation. 2003 February; 31(3): 211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621483&dopt=Abstract

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Measles in bone marrow transplant recipients during an outbreak in Sao Paulo, Brazil. Author(s): Machado CM, Goncalves FB, Pannuti CS, Dulley FL, de Souza VA. Source: Blood. 2002 January 1; 99(1): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756156&dopt=Abstract

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Measles in bone marrow transplant recipients. Author(s): Storek J. Source: Blood. 2002 April 15; 99(8): 3070. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949628&dopt=Abstract

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Mechanical ventilation for bone marrow transplant patients: when does it become futile? Author(s): Klingemann HG. Source: Critical Care Medicine. 2000 March; 28(3): 899-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10752858&dopt=Abstract

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Meeting Report. Bone Marrow Transplant Scientists' Association of Australia. Author(s): Trickett A. Source: Cytotherapy. 2002; 4(2): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434780&dopt=Abstract

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Molecular methods for cytomegalovirus surveillance in bone marrow transplant recipients. Author(s): Weinberg A, Schissel D, Giller R. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409398&dopt=Abstract

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Monitoring cytomegalovirus infection in adult and pediatric bone marrow transplant recipients by a real-time PCR assay performed with blood plasma. Author(s): Leruez-Ville M, Ouachee M, Delarue R, Sauget AS, Blanche S, Buzyn A, Rouzioux C. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2040-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734246&dopt=Abstract

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Monitoring of active HHV-6 infection in bone marrow transplant recipients by real time PCR; comparison to detection of viral DNA in plasma by qualitative PCR. Author(s): Ihira M, Yoshikawa T, Suzuki K, Ohashi M, Suga S, Horibe K, Tanaka N, Kimura H, Kojima S, Kato K, Matsuyama T, Nishiyama Y, Asano Y. Source: Microbiology and Immunology. 2002; 46(10): 701-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477249&dopt=Abstract

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Monitoring vital signs in a bone marrow transplant unit: are they needed in the middle of the night? Author(s): Sharda S, Carter J, Wingard JR, Mehta P. Source: Bone Marrow Transplantation. 2001 June; 27(11): 1197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11551031&dopt=Abstract

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Multiple pulmonary nodules caused by B-cell post-transplant lymphoproliferative disorder after bone marrow transplantation: monitoring Epstein-Barr virus viral load. Author(s): Shoji N, Ohyashiki JH, Suzuki A, Kubota N, Kimura Y, Matsubayashi J, Mukai K, Ohyashiki K. Source: Japanese Journal of Clinical Oncology. 2003 August; 33(8): 408-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523062&dopt=Abstract

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Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Author(s): Hachem RY, Hicks K, Huen A, Raad I. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): E8-11. Epub 2003 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830431&dopt=Abstract

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NASA light-emitting diodes for the prevention of oral mucositis in pediatric bone marrow transplant patients. Author(s): Whelan HT, Connelly JF, Hodgson BD, Barbeau L, Post AC, Bullard G, Buchmann EV, Kane M, Whelan NT, Warwick A, Margolis D. Source: Journal of Clinical Laser Medicine & Surgery. 2002 December; 20(6): 319-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513918&dopt=Abstract

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Naso-jejunal feeding in allogeneic bone marrow transplant recipients: results of a pilot study. Author(s): Sefcick A, Anderton D, Byrne JL, Teahon K, Russell NH. Source: Bone Marrow Transplantation. 2001 December; 28(12): 1135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803355&dopt=Abstract

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Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant. Author(s): Otaibi AA, Barker C, Anderson R, Sigalet DL. Source: Journal of Pediatric Surgery. 2002 May; 37(5): 770-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987097&dopt=Abstract

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New approach to administrative medical decision-making: evidence-based medicine using high dose chemotherapy/bone marrow transplant for breast cancer. Author(s): Lucey C, Westphal JR. Source: Southern Medical Journal. 1998 February; 91(2): 196-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9496875&dopt=Abstract

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No effect of nadroparin prophylaxis in the prevention of central venous catheter (CVC)-associated thrombosis in bone marrow transplant recipients. Author(s): Lagro SW, Verdonck LF, Borel Rinkes IH, Dekker AW. Source: Bone Marrow Transplantation. 2000 November; 26(10): 1103-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108310&dopt=Abstract

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Nodular granulomatous Pneumocystis carinii pneumonia in a bone marrow transplant recipient. Case report. Author(s): Leroy X, Copin MC, Ramon P, Jouet JP, Gosselin B. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2000 May; 108(5): 363-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10937774&dopt=Abstract

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Nosocomial colonization, septicemia, and Hickman/Broviac catheter-related infections in bone marrow transplant recipients. A 5-year prospective study. Author(s): Elishoov H, Or R, Strauss N, Engelhard D. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 1998 March; 77(2): 83-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556701&dopt=Abstract

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Nosocomial outbreak of Legionella pneumophila serogroup 3 pneumonia in a new bone marrow transplant unit: evaluation, treatment and control. Author(s): Oren I, Zuckerman T, Avivi I, Finkelstein R, Yigla M, Rowe JM. Source: Bone Marrow Transplantation. 2002 August; 30(3): 175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189536&dopt=Abstract

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Nosocomial transmission of Saccharomyces cerevisiae in bone marrow transplant patients. Author(s): Olver WJ, James SA, Lennard A, Galloway A, Roberts IN, Boswell TC, Russell NH. Source: The Journal of Hospital Infection. 2002 December; 52(4): 268-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473471&dopt=Abstract

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Nutrition support for bone marrow transplant patients. Author(s): Murray SM, Pindoria S. Source: Cochrane Database Syst Rev. 2002; (2): Cd002920. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076459&dopt=Abstract

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One antigen mismatched related donor bone marrow transplant in a patient with acute lymphoblastic leukaemia and beta-thalassaemia major: potential cure of both marrow disorders. Author(s): Kottaridis PD, Peggs K, Lawrence A, Verfuerth S, Chatterjee R, Telfer P, Porter JB, Mackinnon S, Goldstone AH. Source: Bone Marrow Transplantation. 2000 March; 25(6): 677-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734304&dopt=Abstract

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Open lung biopsy in bone marrow transplant recipients has a poor diagnostic yield for a specific diagnosis. Author(s): Shaikh ZH, Torres HA, Walsh GL, Champlin RE, Kontoyiannis DP. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2002 June; 4(2): 80-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220244&dopt=Abstract

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Open lung biopsy in pediatric bone marrow transplant patients. Author(s): Hayes-Jordan A, Benaim E, Richardson S, Joglar J, Srivastava DK, Bowman L, Shochat SJ. Source: Journal of Pediatric Surgery. 2002 March; 37(3): 446-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11877664&dopt=Abstract

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Optimum dental radiography in bone marrow transplant patients. Author(s): Bishay N, Petrikowski CG, Maxymiw WG, Lee L, Wood RE. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 1999 March; 87(3): 375-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10102604&dopt=Abstract

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Oral antimicrobial prophylaxis in bone marrow transplant recipients: randomized trial of ciprofloxacin versus ciprofloxacin-vancomycin. Author(s): Ford CD, Reilly W, Wood J, Classen DC, Burke JP. Source: Antimicrobial Agents and Chemotherapy. 1998 June; 42(6): 1402-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624484&dopt=Abstract

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Oral presentation of a novel variant of herpes simplex infection in a group of bone marrow transplant patients: a report of five cases. Author(s): Brooke AE, Eveson JW, Luker J, Oakhill A. Source: The British Journal of Dermatology. 1999 August; 141(2): 381-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468838&dopt=Abstract

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Origins of Staphylococcus epidermidis and Streptococcus oralis causing bacteraemia in a bone marrow transplant patient. Author(s): Kennedy HF, Morrison D, Kaufmann ME, Jackson MS, Bagg J, Gibson BE, Gemmell CG, Michie JR. Source: Journal of Medical Microbiology. 2000 April; 49(4): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755632&dopt=Abstract

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Outbreak of Stenotrophomonas maltophilia bacteremia in allogenic bone marrow transplant patients: role of severe neutropenia and mucositis. Author(s): Labarca JA, Leber AL, Kern VL, Territo MC, Brankovic LE, Bruckner DA, Pegues DA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 January; 30(1): 195-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619754&dopt=Abstract

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Outcome of autologous transplantation for mantle cell lymphoma: a study by the European Blood and Bone Marrow Transplant and Autologous Blood and Marrow Transplant Registries. Author(s): Vandenberghe E, Ruiz de Elvira C, Loberiza FR, Conde E, Lopez-Guillermo A, Gisselbrecht C, Guilhot F, Vose JM, van Biesen K, Rizzo JD, Weisenburger DD, Isaacson P, Horowitz MM, Goldstone AH, Lazarus HM, Schmitz N. Source: British Journal of Haematology. 2003 March; 120(5): 793-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614212&dopt=Abstract

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Outcomes of touch therapies during bone marrow transplant. Author(s): Smith MC, Reeder F, Daniel L, Baramee J, Hagman J. Source: Alternative Therapies in Health and Medicine. 2003 January-February; 9(1): 40-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564350&dopt=Abstract

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Papillary endothelial hyperplasia in a bone marrow transplant recipient with extensive chronic graft-versus-host disease. Author(s): Yoshihara T, Chiyonobu T, Tatebe A, Morimoto A, Imashuku S. Source: British Journal of Haematology. 2002 December; 119(3): 584. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437630&dopt=Abstract

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Pathogenesis and treatment of graft-versus-host disease after bone marrow transplant. Author(s): Vogelsang GB, Lee L, Bensen-Kennedy DM. Source: Annual Review of Medicine. 2003; 54: 29-52. Epub 2001 December 03. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359826&dopt=Abstract

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Pathologic quiz case: renal impairment after bone marrow transplantation. Bone marrow transplant nephropathy. Author(s): Chan GS, Lam MF, Au WY, Chan KW. Source: Archives of Pathology & Laboratory Medicine. 2004 February; 128(2): 233-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14736275&dopt=Abstract

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Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplant-related toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications. Author(s): Ferra C, de Sanjose S, Lastra CF, Marti F, Marino EL, Sureda A, Brunet S, Gallardo D, Berlanga JJ, Garcia J, Granena A. Source: Bone Marrow Transplantation. 1997 December; 20(12): 1075-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9466281&dopt=Abstract

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Polyomavirus viruria in bone marrow transplant recipients: lack of correlation with clinical symptoms. Author(s): Rabenau HF, Preiser W, Franck S, Schwerdtfeger S, Doerr HW. Source: Infection. 2002 April; 30(2): 91-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018476&dopt=Abstract

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Proinflammatory cytokines and their role in the development of major transplantrelated complications in the early phase after allogeneic bone marrow transplantation. Author(s): Schots R, Kaufman L, Van Riet I, Ben Othman T, De Waele M, Van Camp B, Demanet C. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 June; 17(6): 1150-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764383&dopt=Abstract

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Prolonged selective neutropenia after allogeneic bone marrow transplantation: possible effect of presensitization by donor lymphocytes prior to transplant. Author(s): Towatari M, Miyamura K, Akatsuka Y, Yamamoto K, Minami S, Kodera Y. Source: International Journal of Hematology. 1997 December; 66(4): 513-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9479877&dopt=Abstract

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Psychological support to an autologous bone marrow transplant unit in a community hospital: a pilot experience. Author(s): Amato JJ, Williams M, Greenberg C, Bar M, Lo S, Tepler I. Source: Psycho-Oncology. 1998 March-April; 7(2): 121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9589510&dopt=Abstract

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Pulmonary alveolar proteinosis: lung transplant or bone marrow transplant? Author(s): Gaine SP, O'Marcaigh AS. Source: Chest. 1998 February; 113(2): 563-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9498994&dopt=Abstract

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Pulmonary veno-occlusive disease after autologous bone marrow transplant in a child with stage IV neuroblastoma: case report and literature review. Author(s): Trobaugh-Lotrario AD, Greffe B, Deterding R, Deutsch G, Quinones R. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 May; 25(5): 405-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759629&dopt=Abstract

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Quality of life and psychological distress of bone marrow transplant recipients: the 'time trajectory' to recovery over the first year. Author(s): McQuellon RP, Russell GB, Rambo TD, Craven BL, Radford J, Perry JJ, Cruz J, Hurd DD. Source: Bone Marrow Transplantation. 1998 March; 21(5): 477-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9535040&dopt=Abstract

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Quality of life following bone marrow transplant. Author(s): Molassiotis A. Source: Nurs Times. 1995 October 11-17; 91(41): 38-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7479134&dopt=Abstract

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Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Author(s): McQuellon RP, Russell GB, Cella DF, Craven BL, Brady M, Bonomi A, Hurd DD. Source: Bone Marrow Transplantation. 1997 February; 19(4): 357-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9051246&dopt=Abstract

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Quality of life one year following bone marrow transplantation: psychometric evaluation of the quality of life in bone marrow transplant survivors tool. Author(s): Saleh US, Brockopp DY. Source: Oncology Nursing Forum. 2001 October; 28(9): 1457-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683315&dopt=Abstract

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Quantification of human cytomegalovirus DNA in bone marrow transplant recipients by real-time PCR. Author(s): Griscelli F, Barrois M, Chauvin S, Lastere S, Bellet D, Bourhis JH. Source: Journal of Clinical Microbiology. 2001 December; 39(12): 4362-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724846&dopt=Abstract

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Quantitation of hepatitis G virus RNA in allogeneic bone marrow transplant recipients. Stem Cell Transplantation Team. Author(s): Kanda Y, Chiba S, Kami M, Asai T, Tanaka Y, Saito T, Yazaki Y, Hirai H. Source: British Journal of Haematology. 1998 March; 100(4): 798-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9531353&dopt=Abstract

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Quantitation of human cytomegalovirus DNA in bone marrow transplant recipients. Author(s): Gerna G, Furione M, Baldanti F, Percivalle E, Comoli P, Locatelli F. Source: British Journal of Haematology. 1995 November; 91(3): 674-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8555075&dopt=Abstract

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Quantitative evaluation of post-bone marrow transplant engraftment status using fluorescent-labeled variable number of tandem repeats. Author(s): Luhm RA, Bellissimo DB, Uzgiris AJ, Drobyski WR, Hessner MJ. Source: Molecular Diagnosis : a Journal Devoted to the Understanding of Human Disease Through the Clinical Application of Molecular Biology. 2000 June; 5(2): 129-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11066014&dopt=Abstract

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Quantitative measurement of quality of life in adult patients undergoing bone marrow transplant or peripheral blood stem cell transplant: a decade in review. Author(s): Hacker ED. Source: Oncology Nursing Forum. 2003 July-August; 30(4): 613-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861322&dopt=Abstract

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Question: Bone marrow transplant for fibrodysplasia ossificans progressiva: has the hour arrived? Author(s): Altschuler EL. Source: Clinical Orthopaedics and Related Research. 2001 November; (392): 450-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11716421&dopt=Abstract

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Reactivation of hepatitis B e antigen-negative chronic hepatitis B in a bone marrow transplant recipient following lamivudine withdrawal. Author(s): Myers RP, Swain MG, Urbanski SJ, Lee SS. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2001 September; 15(9): 599-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573103&dopt=Abstract

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Recurrence of allergic rhinitis, previously alleviated with allergen immunotherapy, after autologous bone marrow transplant. Author(s): Kelso JM. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 September; 89(3): 316-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269654&dopt=Abstract

112

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Reduction of distress associated with paediatric bone marrow transplant: complementary health promotion interventions. Author(s): Phipps S. Source: Pediatric Rehabilitation. 2002 October-December; 5(4): 223-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745902&dopt=Abstract

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Residual leukaemia after bone marrow transplant in children with acute lymphoblastic leukaemia after first haematological relapse or with poor initial presenting features. Author(s): Bunin N, Johnston DA, Roberts WM, Ouspenskaia MV, Papusha VZ, Brandt MA, Zipf TF. Source: British Journal of Haematology. 2003 February; 120(4): 711-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588362&dopt=Abstract

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Respiratory syncytial virus infection in the late bone marrow transplant period: report of three cases and review. Author(s): Khushalani NI, Bakri FG, Wentling D, Brown K, Mohr A, Anderson B, Keesler C, Ball D, Bernstein ZP, Bernstein SH, Czuczman MS, Segal BH, McCarthy PL Jr. Source: Bone Marrow Transplantation. 2001 May; 27(10): 1071-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438823&dopt=Abstract

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Respiratory syncytial virus pneumonitis-induced diffuse alveolar damage in an autologous bone marrow transplant recipient. Author(s): Markovic SN, Adlakha A, Smith TF, Walker RC. Source: Mayo Clinic Proceedings. 1998 February; 73(2): 153-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9472999&dopt=Abstract

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Respiratory tract viral infections in bone marrow transplant patients. Author(s): Raboni SM, Nogueira MB, Tsuchiya LR, Takahashi GA, Pereira LA, Pasquini R, Siqueira MM. Source: Transplantation. 2003 July 15; 76(1): 142-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865800&dopt=Abstract

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Rhizopus presenting as an endobronchial obstruction following bone marrow transplant. Author(s): Maddox L, Long GD, Vredenburgh JJ, Folz RJ. Source: Bone Marrow Transplantation. 2001 September; 28(6): 634-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11607783&dopt=Abstract

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Risk factors for anaerobic bloodstream infections in bone marrow transplant recipients. Author(s): Lark RL, McNeil SA, VanderHyde K, Noorani Z, Uberti J, Chenoweth C. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 August 1; 33(3): 338-43. Epub 2001 July 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438899&dopt=Abstract

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Risk factors in bone marrow transplant recipients with leukaemia. Increased relapse risk in patients treated with ciprofloxacin for gut decontamination. Author(s): Carlens S, Ringden O, Aschan J, Hagglund H, Ljungman P, Mattsson J, Remberger M. Source: Clinical Transplantation. 1998 April; 12(2): 84-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9575394&dopt=Abstract

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Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant. Author(s): Laughlin MJ, McGaughey DS, Crews JR, Chao NJ, Rizzieri D, Ross M, Gockerman J, Cirrincione C, Berry D, Mills L, Defusco P, LeGrand S, Peters WP, Vredenburgh JJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 March; 16(3): 1008-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9508184&dopt=Abstract

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Severe hemolytic anemia due to multiple red cell alloantibodies after an ABOincompatible allogeneic bone marrow transplant. Author(s): Lopez A, de la Rubia J, Arriaga F, Jimenez C, Sanz GF, Carpio N, Marty ML. Source: Transfusion. 1998 March; 38(3): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9563404&dopt=Abstract

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Static electric charge may contribute to infections in bone marrow transplant wards. Author(s): Allen JE, Henshaw DL, Wynne H, Ross F, Oakhill A. Source: The Journal of Hospital Infection. 2003 May; 54(1): 80-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767852&dopt=Abstract

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Subcutaneous plasmacytomas with tropism to sites of previous trauma in a multiple myeloma patient treated with an autologous bone marrow transplant. Author(s): Rosenblum MD, Bredeson CN, Chang CC, Rizzo JD. Source: American Journal of Hematology. 2003 April; 72(4): 274-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666140&dopt=Abstract

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Successful allogeneic bone marrow transplant for chronic myeloid leukaemia despite previous interferon-induced cardiomyopathy. Author(s): Broady R, Hawkins T, Browett P, Palmer S. Source: Bone Marrow Transplantation. 1998 April; 21(8): 833-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9603410&dopt=Abstract

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Successful cidofovir treatment of adenovirus-associated hemorrhagic cystitis and renal dysfunction after allogenic bone marrow transplant. Author(s): Hatakeyama N, Suzuki N, Kudoh T, Hori T, Mizue N, Tsutsumi H. Source: The Pediatric Infectious Disease Journal. 2003 October; 22(10): 928-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14579818&dopt=Abstract

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Successful management of impending late graft failure in a thalassemic bone marrow transplant recipient. Author(s): Zakrzewski JL. Source: Haematologica. 2002 October; 87(10): Ecr32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368175&dopt=Abstract

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Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient. Author(s): Okamoto T, Okada M, Mori A, Saheki K, Takatsuka H, Wada H, Tamura A, Fujimori Y, Takemoto Y, Kanamaru A, Kakishita E. Source: Bone Marrow Transplantation. 1997 November; 20(9): 801-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384487&dopt=Abstract

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Syngeneic hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma: a comparison with allogeneic and autologous transplantation--The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. Author(s): Bierman PJ, Sweetenham JW, Loberiza FR Jr, Taghipour G, Lazarus HM, Rizzo JD, Schmitz N, van Besien K, Vose JM, Horowitz M, Goldstone A; Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 October 15; 21(20): 3744-53. Epub 2003 September 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963703&dopt=Abstract

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Syngeneic peripheral blood stem cell transplantation for severe aplastic anaemia. South Island Bone Marrow Transplant Team. Author(s): Manley R, Fearnley D, Patton WN, Newhook C, Spearing RL, Hart DN. Source: Bone Marrow Transplantation. 1997 December; 20(11): 1009-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9422486&dopt=Abstract

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T cell immunotherapeutic populations control viral infections in bone marrow transplant recipients. Author(s): Slobod KS, Benaim E, Woodruff L, Nooner S, Houston J, Holladay M, Lockey T, Hurwitz JL. Source: Immunologic Research. 2001; 24(3): 289-301. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817326&dopt=Abstract

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The effect of oral mucositis on morbidity and mortality in bone marrow transplant. Author(s): Gabriel DA, Shea T, Olajida O, Serody JS, Comeau T. Source: Seminars in Oncology. 2003 December; 30(6 Suppl 18): 76-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14727245&dopt=Abstract

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The effect of T cell depletion with Campath-1M on immune reconstitution after chemotherapy and allogeneic bone marrow transplant as treatment for leukaemia. Author(s): Lowdell MW, Craston R, Ray N, Koh M, Galatowicz G, Prentice HG. Source: Bone Marrow Transplantation. 1998 April; 21(7): 679-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9578307&dopt=Abstract

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The experience of leukaemia and bone marrow transplant: searching for meaning and agency. Author(s): Xuereb MC, Dunlop R. Source: Psycho-Oncology. 2003 July-August; 12(5): 397-409. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833554&dopt=Abstract

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The international bone marrow transplant registry. Author(s): Goldman JM, Horowitz MM. Source: International Journal of Hematology. 2002 August; 76 Suppl 1: 393-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430889&dopt=Abstract

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The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Author(s): Burnett AK, Wheatley K, Goldstone AH, Stevens RF, Hann IM, Rees JH, Harrison G; Medical Research Council Adult and Paediatric Working Parties. Source: British Journal of Haematology. 2002 August; 118(2): 385-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139722&dopt=Abstract

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Total parenteral nutrition in bone marrow transplant: what is the appropriate energy level? Author(s): Forchielli ML, Azzi N, Cadranel S, Paolucci G. Source: Oncology. 2003; 64(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457025&dopt=Abstract

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Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4 quality of life instrument into traditional Chinese. Author(s): Lau AK, Chang CH, Tai JW, Eremenco S, Liang R, Lie AK, Fong DY, Lau CM. Source: Bone Marrow Transplantation. 2002 January; 29(1): 41-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840143&dopt=Abstract

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Treatment of diffuse alveolar hemorrhage after allogeneic bone marrow transplant with recombinant factor VIIa. Author(s): Hicks K, Peng D, Gajewski JL. Source: Bone Marrow Transplantation. 2002 December; 30(12): 975-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476294&dopt=Abstract

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Treatment of relapsing refractory diffuse large cell lymphoma after matched unrelated donor bone marrow transplant with immunosuppression withdrawal and rituximab. Author(s): Wong R, de Lima M, Couriel D, Giralt S, Hosing C, Shahjahan M, Cheng YC, Bruton J, Champlin R, Khouri I. Source: Leukemia & Lymphoma. 2003 May; 44(5): 829-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802922&dopt=Abstract

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Unexpected late graft failure 9 months after HLA-identical bone marrow transplant (BMT) for chronic myeloid leukemia (CML): treatment with a second BMT. Author(s): Gil-Fernandez JJ, Arranz R, Camara R, Alegre A, Figuera A, FernandezRanada JM. Source: Haematologica. 1998 March; 83(3): 285-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9580418&dopt=Abstract

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Unmanipulated bone marrow transplantation from one-HLA locus mismatched siblings carries high transplant-related mortality in Chinese patients. Author(s): Leung AY, Lie AK, Au WY, Hawkins BR, Kwong YL, Liang R. Source: Haematologica. 2001 May; 86(5): 518-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410416&dopt=Abstract

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Unrelated allogeneic bone marrow transplant in adrenoleukodystrophy using CD34+ stem cell selection. Author(s): Borker A, Yu LC. Source: Metabolic Brain Disease. 2002 September; 17(3): 139-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322784&dopt=Abstract

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Unrelated bone marrow transplantation in thalassemia. The experience of the Italian Bone Marrow Transplant Group (GITMO). Author(s): La Nasa G, Giardini C, Locatelli F, Argiolu F, Vassallo E, Prete A, Caocci G, Floris R, Garau P, Littera R, Mantovani D, Oppi S, Piras E, De Stefano P, Sanna MA, Mulargia M, Carcassi C, Contu L; Italian Bone Marrow Transplant Group (GITMO). Source: Haematologica. 2002 August; 87(8 Suppl): 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412392&dopt=Abstract

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Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Transplant Group (GITMO). Author(s): Dini G, Cancedda R, Locatelli F, Bosi A, Bandini G, Alessandrino EP, Porta F, Uderzo C, Messina C, Fagioli F, Arcese W, Marenco P, Fanin R, Falda M, Soligo D, La Nasa G, Giardini C, Pession A, Scime R, Di Bartolomeo P, Bruno B, Garbarino L, Lamparelli T, Giorgiani G, Lanino E, Manzitti C, Bacigalupo A; Italian Bone Marrow Transplant Group (GITMO). Source: Haematologica. 2000 November; 85(11 Suppl): 30-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268321&dopt=Abstract

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Unrelated donors selected prospectively by block-matching have superior bone marrow transplant outcome. Author(s): Witt C, Sayer D, Trimboli F, Saw M, Herrmann R, Cannell P, Baker D, Christiansen F. Source: Human Immunology. 2000 February; 61(2): 85-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10717799&dopt=Abstract

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Unsuspected Toxoplasma gondii empyema in a bone marrow transplant recipient. Author(s): Dawis MA, Bottone EJ, Vlachos A, Burroughs MH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 May 1; 34(9): E37-9. Epub 2002 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11941570&dopt=Abstract

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Use of fiberoptic bronchoscopy in bone marrow transplant recipients. Author(s): Glazer M, Breuer R, Berkman N, Lossos IS, Kapelushnik J, Nagler A, Naparstek E, Kramer MR, Lafair J, Engelhard D, Or R. Source: Acta Haematologica. 1998; 99(1): 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9490561&dopt=Abstract

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Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients: a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious Diseases Working Party of the EBMT. Author(s): Ljungman P, Cordonnier C, Einsele H, Bender-Gotze C, Bosi A, Dekker A, De la Camara R, Gmur J, Newland AC, Prentice HG, Robinson AJ, Rovira M, Rosler W, Veil D. Source: Bone Marrow Transplantation. 1998 March; 21(5): 473-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9535039&dopt=Abstract

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Utility of fiberoptic bronchoscopy in bone marrow transplant patients. Author(s): White P, Bonacum JT, Miller CB. Source: Bone Marrow Transplantation. 1997 October; 20(8): 681-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383232&dopt=Abstract

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Validation of the nursing diagnosis anxiety in adult patients undergoing bone marrow transplant. Author(s): Young LK, Polzin J, Todd S, Simuncak SL. Source: International Journal of Nursing Terminologies and Classifications : the Official Journal of Nanda International. 2002 July-September; 13(3): 88-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12599511&dopt=Abstract

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Value of PCR analysis for long term survivors after allogeneic bone marrow transplant for chronic myelogenous leukemia: a comparative study. Author(s): Costello RT, Kirk J, Gabert J. Source: Leukemia & Lymphoma. 1996 January; 20(3-4): 239-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624462&dopt=Abstract

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Value of the pretransplant evaluation in predicting toxic day-100 mortality among blood stem-cell and bone marrow transplant recipients. Author(s): Goldberg SL, Klumpp TR, Magdalinski AJ, Mangan KF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 December; 16(12): 3796-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9850024&dopt=Abstract

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Vancomycin-resistant enterococcal infections in bone marrow transplant recipients. Author(s): Koc Y, Snydman DR, Schenkein DS, Miller KB. Source: Bone Marrow Transplantation. 1998 July; 22(2): 207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9707033&dopt=Abstract

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Varicella zoster gastritis in a bone marrow transplant recipient. Author(s): McCluggage WG, Fox JD, Baillie KE, Coyle PV, Jones FG, O'Hara MD. Source: Journal of Clinical Pathology. 1994 November; 47(11): 1054-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7829687&dopt=Abstract

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Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. Author(s): Little R, Wittes RE, Longo DL, Wilson WH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 February; 16(2): 584-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9469345&dopt=Abstract

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Viral infections in pediatric bone marrow transplant patients. Author(s): Wasserman R, August CS, Plotkin SA. Source: The Pediatric Infectious Disease Journal. 1988 February; 7(2): 109-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2830586&dopt=Abstract

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Virus-specific cytotoxic T lymphocytes as prophylaxis for Epstein-Barr virus lymphoproliferative disease in pediatric bone marrow transplant recipients. Author(s): Norville R, Nance D, Cheshire S. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1997 October; 14(4): 194-201. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9322393&dopt=Abstract

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Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient. Author(s): Rosebraugh CJ, Flockhart DA, Yasuda SU, Woosley RL. Source: Journal of Clinical Pharmacology. 2001 February; 41(2): 224-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11210406&dopt=Abstract

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Von Willebrand factor-cleaving protease activity and proteolysis of von Willebrand factor in bone marrow transplant-associated thrombotic microangiopathy. Author(s): Arai S, Allan C, Streiff M, Hutchins GM, Vogelsang GB, Tsai HM. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2001; 2(5): 292-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920264&dopt=Abstract

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Walking with fan through BMT. Bone Marrow Transplant. Author(s): Chen SY. Source: J Christ Nurs. 2002 Spring; 19(2): 22-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908046&dopt=Abstract

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What is the merit of an alternative bone marrow transplant? Author(s): Trigg ME. Source: Bone Marrow Transplantation. 1996 December; 18 Suppl 3: S28-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971404&dopt=Abstract

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Which bone marrow transplant recipients are at risk of acquiring life-threatening fungal infections? Author(s): Tollemar J, Ringden O, Aschan J, Sundberg B. Source: Transplantation Proceedings. 1990 February; 22(1): 208-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2309316&dopt=Abstract

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Which children do benefit from bone marrow transplant? The EBMT Paediatric Diseases Working Party. Author(s): Niethammer D, Klingebiel T, Ebell W, Henze G, Paolucci P, Riehm H. Source: Bone Marrow Transplantation. 1996 November; 18 Suppl 2: 43-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8932798&dopt=Abstract

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White matter dysfunction and its neuropsychological correlates: a longitudinal study of a case of metachromatic leukodystrophy treated with bone marrow transplant. Author(s): Shapiro EG, Lipton ME, Krivit W. Source: J Clin Exp Neuropsychol. 1992 July; 14(4): 610-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1356997&dopt=Abstract

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Work related stresses of pediatric bone marrow transplant nurses. Author(s): Stutzer CA. Source: J Assoc Pediatr Oncol Nurses. 1989; 6(2): 16. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2661805&dopt=Abstract

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Work-related stresses of pediatric bone marrow transplant nurses. Author(s): Stutzer CA. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1989 July; 6(3): 70-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2604927&dopt=Abstract

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Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and bone marrow transplant.

Finding Nutrition Studies on Bone Marrow Transplant 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 “bone marrow transplant” (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 “bone marrow transplant” (or a synonym): •

A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. Source: MacBurney, M. Young, L.S. Ziegler, T.R. Wilmore, D.W. J-Am-Diet-Assoc. Chicago : the Association, 1925-. November 1994. volume 94 (11) page 1263-1266. 00028223

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A national survey of infection prevention practices on bone marrow transplant units. Author(s): Johns Hopkins Hospital, Baltimore, MD. Source: Poe, S S Larson, E McGuire, D Krumm, S Oncol-Nurs-Forum. 1994 NovDecember; 21(10): 1687-94 0190-535X

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A randomized placebo-controlled trial of lisofylline in HLA-identical, sibling-donor, allogeneic bone marrow transplant recipients. The Lisofylline Marrow Transplant Study Group. Author(s): Arizona Cancer Center, University of Arizona, Tucson, AZ 85724-0524, USA. Source: List, A F Maziarz, R Stiff, P Jansen, J Liesveld, J Andrews, F Schuster, M Wolff, S Litzow, M Karanes, C Dahlberg, S Kirkhart, B Bianco, J A Singer, J W Bone-MarrowTransplant. 2000 February; 25(3): 283-91 0268-3369

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A survey of the use of low income microbial diets in pediatric bone marrow transplant programs. Source: French, M.R. Levy Milne, R. Zibrik, D. J-Am-Diet-Assoc. Chicago, IL : The American Dietetic Association. October 2001. volume 101 (10) page 1194-1198. 0002-8223

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Acquiescence to adjunctive experimental therapies may relate to psychological distress: pilot data from a bone marrow transplant center. Author(s): University of Florida College of Medicine, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA. Source: Mehta, P Rodrigue, J Nejame, C Gaa, R Wingard, J R Bone-Marrow-Transplant. 2000 Mar; 25(6): 673-6 0268-3369

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Asthma as a consequence of bone marrow transplantation. Author(s): Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. Source: Rietz, Heather Plummer, Alan L Gal, Anthony A Chest. 2002 July; 122(1): 369-70 0012-3692

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Autologous bone marrow transplant using 4-HC, VP-16 purged bone marrow for acute non-lymphoblastic leukemia. Author(s): Memorial Sloan Kettering Cancer Center, New York, NY. Source: Gulati, S C Shank, B Sarris, A Berman, E Gee, T Cunningham, I Flomenberg, N O'Reilly, R J Clarkson, B Bone-Marrow-Transplant. 1989 January; 4 Suppl 1116-8 02683369

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Bone marrow transplantation in the People's Republic of China. Chinese Bone Marrow Transplant Registry. Author(s): Institute of Hematology, Beijing Medical University, People's Republic of China. Source: Lu, D P Bone-Marrow-Transplant. 1994 June; 13(6): 703-4 0268-3369

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Constrictive pericarditis post allogeneic bone marrow transplant for Philadelphiapositive acute lymphoblastic leukaemia. Author(s): Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

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Source: Cavet, J Lennard, A Gascoigne, A Finney, R D Lucraft, H H Richardson, C Taylor, P R Proctor, S J Jackson, G H Bone-Marrow-Transplant. 2000 Mar; 25(5): 571-3 0268-3369 •

Continuous intravenous administration of rmGM-CSF enhances immune as well as hematopoietic reconstitution following syngeneic bone marrow transplantation in mice. Author(s): Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel. Source: Naparstek, E Ohana, M Greenberger, J S Slavin, S Exp-Hematol. 1993 January; 21(1): 131-7 0301-472X

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De novo chronic graft-versus-host disease presenting as hemolytic anemia following partially mismatched related donor bone marrow transplant. Author(s): University of South Carolina, Columbia, USA. Source: Godder, K Pati, A R Abhyankar, S H Lamb, L S Armstrong, W Henslee Downey, P J Bone-Marrow-Transplant. 1997 April; 19(8): 813-7 0268-3369

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Declining lymphocyte counts following cytomegalovirus (CMV) infection are associated with fatal CMV disease in bone marrow transplant patients. Author(s): Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092. Source: Fries, B C Khaira, D Pepe, M S Torok Storb, B Exp-Hematol. 1993 September; 21(10): 1387-92 0301-472X

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Disseminated nocardiosis in a bone marrow transplant recipient with chronic GVHD. Author(s): Department of Haematology, Westmead Hospital, NSW, Australia. Source: Bhave, A A Thirunavukkarasu, K Gottlieb, D J Bradstock, K Bone-MarrowTransplant. 1999 Mar; 23(5): 519-21 0268-3369

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Dramatic improvement of BMD following vitamin D therapy in a bone marrow transplant recipient. Author(s): Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA. Source: Arekat, M R And, G Lemke, S Moses, A M J-Clin-Densitom. 2002 Fall; 5(3): 26771 1094-6950

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Effect of extended immunosuppressive drug treatment on B cell vs T cell reconstitution in pediatric bone marrow transplant recipients. Author(s): Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. Source: D'Costa, S Slobod, K S Benaim, E Bowman, L Cunningham, J Holladay, M Howlett, N Srivastava, D K Hurwitz, J L Bone-Marrow-Transplant. 2001 September; 28(6): 573-80 0268-3369

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Efficacy and safety of mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant recipient. Author(s): Clinic for Bone Marrow Transplantation and Hematology/Oncology, IdarOberstein, Germany. Source: Basara, N Blau, W I Kiehl, M G Romer, E Rudolphi, M Bischoff, M Kirsten, D Sanchez, H Gunzelmann, S Fauser, A A Transplant-Proc. 1998 December; 30(8): 4087-9 0041-1345

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Empiric carbapenem monotherapy in pediatric bone marrow transplant recipients. Author(s): Department of Pharmacy, The Children's Hospital, Denver, CO, USA. [email protected]

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Source: Nelson, W K Rayback, P A Quinones, R Giller, R H Ann-Pharmacother. 2002 September; 36(9): 1360-5 1060-0280 •

Gallbladder sludge formation after bone marrow transplant: sonographic observations. Author(s): Department of Radiology, University of Washington School of Medicine, Seattle. Source: Teefey, S A Hollister, M S Lee, S P Jacobson, A F Higano, C S Bianco, J A Colacurcio, C J Abdom-Imaging. 1994 Jan-February; 19(1): 57-60 0942-8925

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Glutamine supplementation in bone marrow transplantation. Author(s): Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. [email protected] Source: Ziegler, Thomas R Br-J-Nutr. 2002 January; 87 Suppl 1: S9-15 0007-1145

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Growth hormone function and treatment following bone marrow transplant for neuroblastoma. Author(s): Division of Pediatric Endocrinology, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia 19104. Source: Olshan, J S Willi, S M Gruccio, D Moshang, T Bone-Marrow-Transplant. 1993 October; 12(4): 381-5 0268-3369

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Hematopoietic growth factors after HLA-identical allogeneic bone marrow transplantation in patients treated with methotrexate-containing graft-vs.-host disease prophylaxis. Author(s): Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-3330, USA. Source: Martin Algarra, S Bishop, M R Tarantolo, S Cowles, M K Reed, E Anderson, J R Vose, J M Bierman, P Armitage, J O Kessinger, A Exp-Hematol. 1995 December; 23(14): 1503-8 0301-472X

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High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant. Author(s): University of Toronto Autologous Bone Marrow Transplant Program, Canada. Source: Crump, M Smith, A M Brandwein, J Couture, F Sherret, H Sutton, D M Scott, J G McCrae, J Murray, C Pantalony, D et al. J-Clin-Oncol. 1993 April; 11(4): 704-11 0732-183X

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Hodgkin's disease, recurrent disease, salvage therapy, mini-BEAM, bone marrow transplantation. Author(s): Department of Hematology, Hospital La Paz, Universidad Autonoma de Madrid, Spain. [email protected] Source: Fernandez Jimenez, M C Canales, M A Ojeda, E de Bustos, J G Aguado, M J Hernandez Navarro, F Haematologica. 1999 November; 84(11): 1007-11 0390-6078

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Hormonal and psychologic assessment in LLA patients after bone marrow transplant. Author(s): Pediatric Department, Scientific Institute H San Raffaele, University of Milan, Italy. Source: Nizzoli, G Bregani, P Braggion, F Fasolato, V Chiumello, G Bone-MarrowTransplant. 1991; 8 Suppl 136-8 0268-3369

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Idiopathic pneumonia syndrome after syngeneic bone marrow transplant in mice. Author(s): Department of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

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Source: Bhalla, K S Folz, R J Am-J-Respir-Crit-Care-Med. 2002 December 15; 166(12 Pt 1): 1579-89 1073-449X •

Intravenous pentoxifylline failed to prevent transplant-related toxicities in allogeneic bone marrow transplant recipients. Author(s): BMT Unit, University Hospital Eppendorf, Hamburg, Germany. Source: Stockschlader, M Kalhs, P Peters, S Zeller, W Kruger, W Kabisch, H Lechner, K Zander, A Bone-Marrow-Transplant. 1993 October; 12(4): 357-62 0268-3369

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Myasthenia gravis after allogeneic bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX40+ CD4+ T cells. Author(s): Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Source: Kotani, A Takahashi, A Koga, H Morita, R Fukuyama, H Ichinohe, T Ishikawa, T Hori, T Uchiyama, T Eur-J-Haematol. 2002 Nov-December; 69(5-6): 318-20 0902-4441

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Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients. Author(s): Clinic for Bone Marrow Transplantation and Hematology/Oncology, IdarOberstein, Germany. [email protected] Source: Basara, N Blau, W I Kiehl, M G Schmetzer, B Bischoff, M Kirsten, D Gunzelmann, S Fauser, A A Clin-Transplant. 2000 April; 14(2): 121-6 0902-0063

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Myeloablative therapy and bone marrow rescue in advanced neuroblastoma. Report from the Italian Bone Marrow Transplant Registry. Italian Association of Pediatric Hematology-Oncology, BMT Group. Author(s): Department of Hematology-Oncology, Giannina Gaslini Children's Hospital, Genova, Italy. Source: Garaventa, A Rondelli, R Lanino, E Dallorso, S Dini, G Bonetti, F Arrighini, A Santoro, N Rossetti, F Miniero, R Andolina, M Amici, A Indolfi, P Lo Curto, M Favre, C Paolucci, P Pession, A De Bernardi, B Bone-Marrow-Transplant. 1996 July; 18(1): 125-30 0268-3369

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Naso-jejunal feeding in allogeneic bone marrow transplant recipients: results of a pilot study. Author(s): Department of Haematology, The Nottingham City Hospital NHS Trust, Hucknall Road, Nottingham NG5 1PB, UK. Source: Sefcick, A Anderton, D Byrne, J L Teahon, K Russell, N H Bone-MarrowTransplant. 2001 December; 28(12): 1135-9 0268-3369

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Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin. Author(s): Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver General Hospital, Canada. Source: Reece, D E Frei Lahr, D A Shepherd, J D Dorovini Zis, K Gascoyne, R D Graeb, D A Spinelli, J J Barnett, M J Klingemann, H G Herzig, G P et al. Bone-Marrow-Transplant. 1991 November; 8(5): 393-401 0268-3369

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Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of experimental bone marrow transplant nephropathy. Author(s): Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA. Source: Moulder, J E Fish, B L Cohen, E P Bone-Marrow-Transplant. 1997 April; 19(7): 729-35 0268-3369

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Nutrition support for bone marrow transplant patients. Author(s): c/o Cochrane Pain, Palliative and Supportive Care Group, Churchill Hospital, Old Road, Oxford, UK, OX3 7LJ. [email protected] Source: Murray, S M Pindoria, S Cochrane-Database-Syst-Revolume 2002; (2): CD002920 1469-493X

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Nutritional support of the bone marrow transplant patient. Author(s): Rush-Presbyterian-St. Luke's Medical Center, Rush College of Nursing, Chicago, Illinois. Source: Keenan, A M Nurs-Clin-North-Am. 1989 June; 24(2): 383-93 0029-6465

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Outcomes of touch therapies during bone marrow transplant. Author(s): University of Colorado Health Sciences Center School of Nursing, Denver, USA. Source: Smith, M C Reeder, F Daniel, L Baramee, J Hagman, J Altern-Ther-Health-Med. 2003 Jan-February; 9(1): 40-9 1078-6791

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Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplant-related toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications. Author(s): Department of Clinical Hematology, Institut Catala d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain. Source: Ferra, C de Sanjose, S Lastra, C F Marti, F Marino, E L Sureda, A Brunet, S Gallardo, D Berlanga, J J Garcia, J Granena, A Bone-Marrow-Transplant. 1997 December; 20(12): 1075-80 0268-3369

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Pilot study of high dose ICE (ifosfamide, carboplatin, etoposide) chemotherapy and autologous bone marrow transplant (ABMT) with neoR-transduced bone marrow and peripheral blood stem cells in patients with metastatic breast cancer. Source: O'Shaughnessy, J A Cowan, K H Wilson, W Bryant, G Goldspiel, B Gress, R Nienhuis, A W Dunbar, C Sorrentino, B Stewart, F M et al. Hum-Gene-Ther. 1993 June; 4(3): 331-54 1043-0342

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Possible association of retinoic acid with bone marrow transplant nephropathy. Author(s): Section of Nephrology, Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA. [email protected] Source: Turman, M A Hammond, S Grovas, A Rauck, A M Pediatr-Nephrol. 1999 November; 13(9): 755-8 0931-041X

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Prevention of radiation-induced nephropathy and fibrosis in a model of bone marrow transplant by an angiotensin II receptor blocker. Author(s): Department of Pathology, University of Missouri at Kansas City, Kansas City, Missouri 64106, USA. [email protected] Source: Molteni, A Moulder, J E Cohen, E P Fish, B L Taylor, J M Veno, P A Wolfe, L F Ward, W F Exp-Biol-Med-(Maywood). 2001 December; 226(11): 1016-23 1535-3702

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Randomized trial comparing netilmicin plus imipenem-cilastatin versus netilmicin plus ceftazidime as empiric therapy for febrile neutropenic bone marrow transplant recipients. Author(s): Bone Marrow Transplant Unit, University of Florence, Careggi Hospital, Florence, Italy. Source: Laszlo, D Bacci, S Bosi, A Fanci, R Guidi, S Saccardi, R Vannucchi, A M Rossi Ferrini, P J-Chemother. 1997 April; 9(2): 95-101 1120-009X

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Relationships between oral mucositis and treatment variables in bone marrow transplant patients. Author(s): Georgetown University School of Nursing, Washington, D.C. 20007. Source: Zerbe, M B Parkerson, S G Ortlieb, M L Spitzer, T Cancer-Nurs. 1992 June; 15(3): 196-205 0162-220X

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Salvage of relapsed malignant histiocytosis by autologous bone marrow transplant. Author(s): Department of Medicine, Tom Baker Cancer Center, Calgary, Alberta, Canada. Source: Berry, J Russell, J A Bone-Marrow-Transplant. 1989 January; 4(1): 123-4 02683369

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Severe osteopenia with recurrent fractures after bone marrow transplant for WiskottAldrich syndrome: a case report. Author(s): Department of Orthopaedics, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland. Source: Talkhani, I S Reidy, D Fogarty, E E O'Meara, A J-Pediatr-Orthopage 2000 MayJune; 20(3): 402-4 0271-6798

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Surveillance cultures in bone marrow transplant recipients: worthwhile or wasteful? Author(s): Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City 84132, USA. Source: Riley, D K Pavia, A T Beatty, P G Denton, D Carroll, K C Bone-MarrowTransplant. 1995 Mar; 15(3): 469-73 0268-3369

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The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding. Author(s): Department of Pathology and Laboratory Medicine, University of South Florida College of Medicine, Tampa 33612-4799. Source: Benson, K Fields, K Hiemenz, J Zorsky, P Ballester, O Perkins, J Elfenbein, G Semin-Oncol. 1993 October; 20(5 Suppl 6): 102-9 0093-7754

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The prognostic significance of autologous bone marrow transplant in advanced neuroblastoma. Author(s): Pediatric Oncology Group, St Louis, MO 63108. Source: Shuster, J J Cantor, A B McWilliams, N Pole, J G Castleberry, R P Marcus, R Pick, T Smith, E I Hayes, F A J-Clin-Oncol. 1991 June; 9(6): 1045-9 0732-183X

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Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. Author(s): Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Source: Little, R Wittes, R E Longo, D L Wilson, W H J-Clin-Oncol. 1998 February; 16(2): 584-8 0732-183X

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to bone marrow transplant; 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: •

Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Integrative Medicine Communications; www.drkoop.com

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CHAPTER 3. ALTERNATIVE MARROW TRANSPLANT

MEDICINE

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BONE

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to bone marrow transplant. 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 bone marrow transplant 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 “bone marrow transplant” (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 bone marrow transplant: •

A case of hemophagocytic lymphohistiocytosis with prolonged remission after syngeneic bone marrow transplantation. Author(s): Hasegawa D, Sano K, Kosaka Y, Hayakawa A, Nakamura H. Source: Bone Marrow Transplantation. 1999 August; 24(4): 425-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467334&dopt=Abstract

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A conceptual model of adaptation to illness and quality of life for cancer patients treated with bone marrow transplants. Author(s): Molassiotis A. Source: Journal of Advanced Nursing. 1997 September; 26(3): 572-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9378879&dopt=Abstract

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A phase I study of interleukin-6 after autologous bone marrow transplantation for patients with poor prognosis Hodgkin's disease. Author(s): Imrie KR, Sheridan B, Colwill R, Crump M, Stewart AK, McCrae J, Danish R, Sutton D, Romeyer F, Keating A. Source: Leukemia & Lymphoma. 1997 May; 25(5-6): 555-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9250827&dopt=Abstract

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A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin. Author(s): Valimaki MJ, Kinnunen K, Volin L, Tahtela R, Loyttyniemi E, Laitinen K, Makela P, Keto P, Ruutu T. Source: Bone Marrow Transplantation. 1999 February; 23(4): 355-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10100579&dopt=Abstract

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A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. Author(s): Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. Source: The New England Journal of Medicine. 1996 July 11; 335(2): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8649495&dopt=Abstract

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A single-center study of 11 patients with intraocular lymphoma treated with conventional chemotherapy followed by high-dose chemotherapy and autologous bone marrow transplantation in 5 cases. Author(s): Soussain C, Merle-Beral H, Reux I, Sutton L, Fardeau C, Gerber S, Ben Othman T, Binet JL, Lehoang P, Leblond V. Source: Leukemia & Lymphoma. 1996 October; 23(3-4): 339-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9031115&dopt=Abstract

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A study of thiotepa, etoposide and fractionated total body irradiation as a preparative regimen prior to bone marrow transplantation for poor prognosis patients with neuroblastoma. Author(s): Kamani N, August CS, Bunin N, Leahey A, Bayever E, Goldwein J, Zusman J, Evans AE, Angio GD. Source: Bone Marrow Transplantation. 1996 June; 17(6): 911-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8807093&dopt=Abstract

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Acquiescence to adjunctive experimental therapies may relate to psychological distress: pilot data from a bone marrow transplant center. Author(s): Mehta P, Rodrigue J, Nejame C, Gaa R, Wingard JR. Source: Bone Marrow Transplantation. 2000 March; 25(6): 673-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734303&dopt=Abstract

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Activated allogeneic cell therapy (allo-ACT) for relapsed chronic myelogenous leukemia (CML) refractory to buffy coat transfusions post-allogeneic bone marrow transplantation. Author(s): Kapelushnik J, Nagler A, Or R, Naparstek E, Ackerstein A, Samuel S, Morecki S, Nabet C, Slavin S. Source: Bone Marrow Transplantation. 1996 December; 18(6): 1153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971387&dopt=Abstract

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Acute ischaemic cerebrovascular accident after autologous bone marrow transplantation. Author(s): van der Lelie J, Louwerse ES, Thomas LL, van Oers MH, von dem Borne AE. Source: European Journal of Haematology. 1996 January-February; 56(1-2): 95-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8600004&dopt=Abstract

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Additional stem cell therapy for graft failure after allogeneic bone marrow transplantation. Author(s): Min CK, Kim DW, Lee JW, Min WS, Kim CC. Source: Acta Haematologica. 2000; 104(4): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279309&dopt=Abstract

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Adoptive immunotherapy following allogeneic bone marrow transplantation. Author(s): Dazzi F, Goldman JM. Source: Annual Review of Medicine. 1998; 49: 329-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9509267&dopt=Abstract

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Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow transplantation (BMT): evidence for a graft-versus-myeloma effect. Author(s): Bertz H, Burger JA, Kunzmann R, Mertelsmann R, Finke J. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 February; 11(2): 281-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9009093&dopt=Abstract

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Allogeneic bone marrow transplant in pediatric patients with high-risk hematopoietic malignancies early in the course of their disease. Author(s): Amylon MD, Co JP, Snyder DS, Donaldson SS, Blume KG, Forman SJ. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1997 January-February; 19(1): 54-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9065720&dopt=Abstract

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Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide. Author(s): Duerst RE, Horan JT, Liesveld JL, Abboud CN, Zwetsch LM, Senf ES, Constine LS, Raubertas RF, Passarell JA, DiPersio JF.

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Source: Bone Marrow Transplantation. 2000 March; 25(5): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10713624&dopt=Abstract •

Allogeneic bone marrow transplantation for low-grade lymphoma and chronic lymphocytic leukemia. Author(s): Toze CL, Shepherd JD, Connors JM, Voss NJ, Gascoyne RD, Hogge DE, Klingemann HG, Nantel SH, Nevill TJ, Phillips GL, Reece DE, Sutherland HJ, Barnett MJ. Source: Bone Marrow Transplantation. 2000 March; 25(6): 605-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10734294&dopt=Abstract

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Allogeneic bone marrow transplantation: cure for familial Mediterranean fever. Author(s): Milledge J, Shaw PJ, Mansour A, Williamson S, Bennetts B, Roscioli T, Curtin J, Christodoulou J. Source: Blood. 2002 August 1; 100(3): 774-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130485&dopt=Abstract

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Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. Author(s): Slavin S, Naparstek E, Nagler A, Ackerstein A, Kapelushnik J, Or R. Source: Experimental Hematology. 1995 December; 23(14): 1553-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8542946&dopt=Abstract

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Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Author(s): Slavin S, Naparstek E, Nagler A, Ackerstein A, Samuel S, Kapelushnik J, Brautbar C, Or R. Source: Blood. 1996 March 15; 87(6): 2195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8630379&dopt=Abstract

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Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation. Author(s): Morris JD, Harris RE, Hashmi R, Sambrano JE, Gruppo RA, Becker AT, Morris CL. Source: Bone Marrow Transplantation. 1997 November; 20(10): 871-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9404929&dopt=Abstract

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Art therapy with adult bone marrow transplant patients in isolation: a pilot study. Author(s): Gabriel B, Bromberg E, Vandenbovenkamp J, Walka P, Kornblith AB, Luzzatto P. Source: Psycho-Oncology. 2001 March-April; 10(2): 114-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268138&dopt=Abstract

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Association of CD34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation. Author(s): Bittencourt H, Rocha V, Chevret S, Socie G, Esperou H, Devergie A, Dal Cortivo L, Marolleau JP, Garnier F, Ribaud P, Gluckman E. Source: Blood. 2002 April 15; 99(8): 2726-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929759&dopt=Abstract

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Autologous bone marrow transplant in a patient with sickle cell disease and diffuse large B-cell lymphoma. Author(s): Onitilo AA, Lazarchick J, Brunson CY, Frei-Lahr D, Stuart RK. Source: Transplantation Proceedings. 2003 December; 35(8): 3089-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14697986&dopt=Abstract

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Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. Author(s): Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Source: The New England Journal of Medicine. 1995 December 7; 333(23): 1540-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7477169&dopt=Abstract

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Autologous bone marrow transplantation for acute myeloid leukemia using 4hydroperoxycyclophosphamide-purged bone marrow and the busulfan/etoposide preparative regimen: a follow-up report. Author(s): Linker CA, Ries CA, Damon LE, Rugo HS, Wolf JL. Source: Bone Marrow Transplantation. 1998 November; 22(9): 865-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9827814&dopt=Abstract

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Autologous bone marrow transplantation for aggressive non-Hodgkin's lymphoma: lessons learned and challenges remaining. Author(s): Fisher RI. Source: Journal of the National Cancer Institute. 2001 January 3; 93(1): 4-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11136829&dopt=Abstract

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Autologous bone marrow transplantation for patients with acute myeloblastic leukemia in relapse after autologous blood stem cell transplantation. Author(s): de la Rubia J, Sanz GF, Martin G, Sempere A, Picon I, Carral A, Larrea L, Martinez J, Soler MA, Bonanad S, Lopez F, Jarque I, Sanz MA. Source: Bone Marrow Transplantation. 1996 December; 18(6): 1167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971390&dopt=Abstract

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Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial.

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Author(s): Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 January; 16(1): 48-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9440722&dopt=Abstract •

Autologous bone marrow transplantation in late first complete remission improves outcome in acute myelogenous leukemia. Author(s): Miggiano MC, Gherlinzoni F, Rosti G, Bandini G, Visani G, Fiacchini M, Ricci P, Testoni N, Motta MR, Geromin A, Rizzi S, Belardinelli A, Mangianti S, Manfroi S, Tura S. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 March; 10(3): 402-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8642854&dopt=Abstract

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Autologous bone marrow transplantation in non-Hodgkin's lymphoma patients: effect of a brief course of G-CSF on harvest and recovery. Author(s): Damiani D, Grimaz S, Infanti L, Sperotto A, Silvestri F, Geromin A, Cerno M, Savignano C, Michieli M, Skert C, Fanin R, Baccarani M. Source: Bone Marrow Transplantation. 1999 October; 24(7): 757-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516679&dopt=Abstract

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Autologous bone marrow transplantation in non-Hodgkin's lymphomas: prediction of mononuclear cell yield in bone marrow harvests. Author(s): Rinaldi C, Savignano C, Silvestri F, Geromin A, Cerno M, Fanin R, Biffoni F, Baccarani M. Source: Haematologica. 1995 September-October; 80(5): 443-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8566888&dopt=Abstract

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Autologous bone marrow transplantation in relapsed HIV-related non-Hodgkin's lymphoma. Author(s): Gabarre J, Leblond V, Sutton L, Azar N, Jouan M, Boccaccio C, Gonzalez H, Charlotte F, Gentilini M, Binet JL. Source: Bone Marrow Transplantation. 1996 December; 18(6): 1195-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971396&dopt=Abstract

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Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study. Author(s): Vellenga E, van Agthoven M, Croockewit AJ, Verdonck LF, Wijermans PJ, van Oers MH, Volkers CP, van Imhoff GW, Kingma T, Uyl-de Groot CA, Fibbe WE. Source: British Journal of Haematology. 2001 August; 114(2): 319-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529850&dopt=Abstract

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Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte. Author(s): Haioun C, Lepage E, Gisselbrecht C, Bastion Y, Coiffier B, Brice P, Bosly A, Dupriez B, Nouvel C, Tilly H, Lederlin P, Biron P, Briere J, Gaulard P, Reyes F. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1997 March; 15(3): 1131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9060555&dopt=Abstract

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Blast crisis of chronic myelogenous leukemia in long-lasting systemic lupus erythematosus: regression of both diseases after autologous bone marrow transplantation. Author(s): Meloni G, Capria S, Vignetti M, Mandelli F, Modena V. Source: Blood. 1997 June 15; 89(12): 4659. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192793&dopt=Abstract

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Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent. Author(s): Li CF, Zhang YM, Wu XD, He YL, Sun J, Chen SJ, Li CK, Tsang KS. Source: Journal of Paediatrics and Child Health. 2002 June; 38(3): 308-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047703&dopt=Abstract

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Bone marrow transplantation for therapy-induced acute myeloid leukemia in children with previous lymphoid malignancies. Author(s): Hale GA, Heslop HE, Bowman LC, Rochester RA, Pui CH, Brenner MK, Krance RA. Source: Bone Marrow Transplantation. 1999 October; 24(7): 735-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516676&dopt=Abstract

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Bone marrow transplantation in chronic GvHD and autoimmune diseases. Author(s): Andolina M, Maximova N, Rabusin M, Parco S, Colovic M, Jankovic G. Source: Bone Marrow Transplantation. 1996 November; 18 Suppl 2: 145-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8932817&dopt=Abstract

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Bone marrow transplantation through standard central venous catheters. Author(s): Gallardo D, Alonso E, Riu C, Ponce C, Salar A, Ferra C, Berlanga JJ, Granena A. Source: Transplantation Proceedings. 1995 August; 27(4): 2354. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7652839&dopt=Abstract

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Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma. Author(s): Fielding AK, Pearce RM, Goldstone AH.

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Source: The New England Journal of Medicine. 1995 September 14; 333(11): 729; Author Reply 730. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7637758&dopt=Abstract •

Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma. Author(s): Mross K. Source: The New England Journal of Medicine. 1995 September 14; 333(11): 728; Author Reply 730. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7637757&dopt=Abstract

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Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma. Author(s): Burke HB. Source: The New England Journal of Medicine. 1995 September 14; 333(11): 728; Author Reply 730. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7637756&dopt=Abstract

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Bone marrow transplantation versus chemotherapy in non-Hodgkin's lymphoma. Author(s): Nimer SD, Zelenetz A, Portlock C. Source: The New England Journal of Medicine. 1995 September 14; 333(11): 728-9; Author Reply 730. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7503899&dopt=Abstract

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Bone marrow transplantation: it's not just about blood anymore! Author(s): Horwitz EM. Source: Pediatric Transplantation. 2003; 7 Suppl 3: 56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603694&dopt=Abstract

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Changes in the pattern of TCR V beta repertoire expression after bone marrow transplant is linked to the HLA haplotype in humans. Author(s): Lonial S, Bomberger C, Waller EK. Source: British Journal of Haematology. 2001 April; 113(1): 224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328305&dopt=Abstract

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Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Author(s): Robinson SP, Goldstone AH, Mackinnon S, Carella A, Russell N, de Elvira CR, Taghipour G, Schmitz N; Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Source: Blood. 2002 December 15; 100(13): 4310-6. Epub 2002 August 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393626&dopt=Abstract

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Chemotherapy and donor peripheral blood progenitor cells for acute leukemia in early relapse after allogeneic bone marrow transplantation. Author(s): Alessandrino EP, Bernasconi P, Caldera D, Colombo A, Malcovati L, Martinelli G, Bonfichi M, Pagnucco G, Salvaneschi L, Bernasconi C. Source: Bone Marrow Transplantation. 1999 March; 23(6): 607-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217192&dopt=Abstract

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Clinical significance of bone marrow metastases as detected using the polymerase chain reaction in patients with breast cancer undergoing high-dose chemotherapy and autologous bone marrow transplantation. Author(s): Fields KK, Elfenbein GJ, Trudeau WL, Perkins JB, Janssen WE, Moscinski LC. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1996 June; 14(6): 1868-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8656255&dopt=Abstract

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Cognitive behavioral pain and anxiety interventions in pediatric oncology centers and bone marrow transplant units. Author(s): McCarthy AM, Cool VA, Petersen M, Bruene DA. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1996 January; 13(1): 3-12; Discussion 13-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8904461&dopt=Abstract

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Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation. Author(s): Lee JH, Lee KH, Kim S, Seol M, Kim SH, Kim WK, Lee JS. Source: Leukemia Research. 2001 April; 25(4): 305-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248327&dopt=Abstract

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Compound heterozygosity for haemochromatosis gene mutations and hepatic iron overload in allogeneic bone marrow transplant recipients. Author(s): Grigg AP, Bhathal PS. Source: Pathology. 2001 February; 33(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280607&dopt=Abstract

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Coping patterns among bone marrow transplant patients: a hermeneutical inquiry. Author(s): Shuster GF, Steeves RH, Onega L, Richardson B. Source: Cancer Nursing. 1996 August; 19(4): 290-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8768687&dopt=Abstract

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Correlation between enhancement of graft-versus-leukemia effects following allogeneic bone marrow transplantation by rIL-2 and increased frequency of cytotoxic T-lymphocyte precursors in murine myeloid leukemia. Author(s): Leshem B, Vourka-Karussis U, Slavin S.

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Source: Cytokines, Cellular & Molecular Therapy. 2000 September; 6(3): 141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11140883&dopt=Abstract •

Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation. Author(s): Freedman A, Neuberg D, Mauch P, Gribben J, Soiffer R, Anderson K, Robertson M, Fisher DC, Schlossman R, Kroon M, Rhuda C, Kuhlman C, Ritz J, Nadler L. Source: Blood. 1997 December 15; 90(12): 4996-5001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9389719&dopt=Abstract

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Cytokine network in peripheral blood mononuclear cells after allogeneic bone marrow transplantation. Author(s): Tanaka J, Imamura M, Kasai M, Hashino S, Kobayashi S, Noto S, Sakurada K, Asaka M. Source: Transplantation Proceedings. 1996 June; 28(3): 1746-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8658865&dopt=Abstract

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Detection of CMV DNA in bone marrow transplant recipients: plasma versus leucocyte polymerase chain reaction. Author(s): Woo PC, Lo SK, Yuen KY, Peiris JS, Siau H, Chiu EK, Liang RH, Chan TK. Source: Journal of Clinical Pathology. 1997 March; 50(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9155674&dopt=Abstract

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Development of secondary anaplastic oligoastrocytoma after matched unrelated bone marrow transplantation in a child with acute myeloid leukemia. Author(s): Panigrahi S, Das M, Stagler D, Konstantini S, Gmori M, Slavin S, Nagler A. Source: Acta Haematologica. 2003; 109(4): 196-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853693&dopt=Abstract

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Early toxicity of intensified conditioning with etoposide combined with total body irradiation/cyclophosphamide or busulfan/cyclophosphamide in children undergoing autologous or allogeneic bone marrow transplantation. Author(s): Horstmann M, Kroschke G, Stockschlader M, Betker R, Kruger W, Erttmann R, Kabisch H, Zander A. Source: Pediatric Hematology and Oncology. 1996 January-February; 13(1): 45-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8718502&dopt=Abstract

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Effect of oral glutamine supplementation during bone marrow transplantation. Author(s): Coghlin Dickson TM, Wong RM, offrin RS, Shizuru JA, Johnston LJ, Hu WW, Blume KG, Stockerl-Goldstein KE.

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Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 March-April; 24(2): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772184&dopt=Abstract •

Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Author(s): Ziegler TR, Bye RL, Persinger RL, Young LS, Antin JH, Wilmore DW. Source: The American Journal of the Medical Sciences. 1998 January; 315(1): 4-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9427568&dopt=Abstract

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Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas. Author(s): Bouffet E, Mottolese C, Jouvet A, Philip I, Frappaz D, Carrie C, BrunatMentigny M. Source: European Journal of Cancer (Oxford, England : 1990). 1997 January; 33(1): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9071906&dopt=Abstract

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Etoposide with/without G-CSF with busulfan and cyclophosphamide as conditioning for bone marrow transplantation. The BMT Team. Author(s): Kanda Y, Akiyama H, Tanikawa S, Sakamaki H, Sasaki T, Takamoto S, Onozawa Y. Source: American Journal of Hematology. 1996 April; 51(4): 265-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8602625&dopt=Abstract

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Etoposide-containing regimens with autologous bone marrow transplantation in children with malignant brain tumors. Author(s): Busca A, Miniero R, Besenzon L, Cordero di Montezemolo L, Cenni M, Fagioli F, Sandri A, Vassallo E, Ricardi U, Madon E. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1997 November-December; 13(11-12): 572-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9454971&dopt=Abstract

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Expression of CD134 (0X-40) on T cells during the first 100 days following allogeneic bone marrow transplantation as a marker for lymphocyte activation and therapyresistant graft-versus-host disease. Author(s): Lamb LS Jr, Abhyankar SA, Hazlett L, O'Neal W, Folk RS, Vogt S, Parrish RS, Bridges K, Henslee-Downey PJ, Gee AP. Source: Cytometry : the Journal of the Society for Analytical Cytology. 1999 October 15; 38(5): 238-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10516610&dopt=Abstract

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Follicular cell carcinoma of the thyroid in a child after bone marrow transplantation for acute lymphoblastic leukemia. Author(s): Rovelli A, Cohen A, Uderzo C, Dodero P, Brisigotti M, Castellani MR, Romano C.

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Source: Acta Haematologica. 1997; 97(4): 225-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9158666&dopt=Abstract •

Fractionated total-body irradiation, etoposide, and cyclophosphamide followed by allogeneic bone marrow transplantation for patients with high-risk or advanced-stage hematological malignancies. Author(s): Long GD, Amylon MD, Stockerl-Goldstein KE, Negrin RS, Chao NJ, Hu WW, Nademanee AP, Snyder DS, Hoppe RT, Vora N, Wong R, Niland J, Reichardt VL, Forman SJ, Blume KG. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 1997 December; 3(6): 324-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9502300&dopt=Abstract

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Functional hyperactivity of monocytes after bone marrow transplantation: possible relevance for the development of post-transplant complications or relapse. Author(s): Castenskiold EC, Kelsey SM, Collins PW, Coldwell RD, Allen PD, Side LE, Makin HL, Goldstone AH, Newland AC. Source: Bone Marrow Transplantation. 1995 June; 15(6): 879-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581085&dopt=Abstract

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Gastro-intestinal toxicity related to bone marrow transplantation: disruption of the intestinal barrier precedes clinical findings. Author(s): Johansson JE, Ekman T. Source: Bone Marrow Transplantation. 1997 May; 19(9): 921-5. Erratum In: Bone Marrow Transplant 2001 February; 27(4): 462. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9156267&dopt=Abstract

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Glutamine supplementation in bone marrow transplantation. Author(s): Ziegler TR. Source: The British Journal of Nutrition. 2002 January; 87 Suppl 1: S9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895159&dopt=Abstract

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Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. Author(s): Ziegler TR. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2578S-84S; Discussion 2590S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533316&dopt=Abstract

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Graft rejection and recovery of host-derived hematopoiesis after allogeneic bone marrow transplantation: relation to conditioning with high dose etoposide and total body irradiation. Author(s): Hara M, Shinagawa K, Omoto E, Sunami K, Deguchi S, Narumi H, Kojima K, Azuma T, Takamatsu H, Nakao S, Harada M.

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Source: International Journal of Hematology. 1998 July; 68(1): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713173&dopt=Abstract •

Grover's-like disease in the setting of bone marrow transplantation and autologous peripheral blood stem cell infusion. Author(s): Harvell JD, Hashem C, Williford PL, White WL. Source: The American Journal of Dermatopathology. 1998 April; 20(2): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9557789&dopt=Abstract

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Growth in children with poor-risk neuroblastoma after regimens with or without total body irradiation in preparation for autologous bone marrow transplantation. Author(s): Hovi L, Saarinen-Pihkala UM, Vettenranta K, Lipsanen M, Tapanainen P. Source: Bone Marrow Transplantation. 1999 November; 24(10): 1131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10578163&dopt=Abstract

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Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: a randomised pilot study. Author(s): Johansson JE, Ekman T. Source: Bone Marrow Transplantation. 1999 July; 24(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10435732&dopt=Abstract

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Hematopoietic growth factors after HLA-identical allogeneic bone marrow transplantation in patients treated with methotrexate-containing graft-vs.-host disease prophylaxis. Author(s): Martin-Algarra S, Bishop MR, Tarantolo S, Cowles MK, Reed E, Anderson JR, Vose JM, Bierman P, Armitage JO, Kessinger A. Source: Experimental Hematology. 1995 December; 23(14): 1503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8542938&dopt=Abstract

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Hepatic mucormycosis in a bone marrow transplant recipient who ingested naturopathic medicine. Author(s): Oliver MR, Van Voorhis WC, Boeckh M, Mattson D, Bowden RA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 March; 22(3): 521-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8852973&dopt=Abstract

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High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission. Author(s): Zander AR, Berger C, Kroger N, Stockshlader M, Kruger W, Horstmann M, Grimm J, Zeller W, Kabisch H, Erttmann R, Schonrock P, Kuse R, Braumann D, Illiger HJ, Fiedler W, de Witt M, Hossfeld KD, Weh HJ.

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Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1997 December; 3(12 Pt 2): 2671-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10068272&dopt=Abstract •

High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults. Author(s): Droz JP, Biron P. Source: Cancer. 1995 July 1; 76(1): 154-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8630870&dopt=Abstract

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High-dose carboplatin, etoposide and cyclophosphamide with autologous bone marrow transplantation for the treatment of advanced malignancies: a phase I study. Author(s): Saez RA, Slease RB, Strnad C, Selby GB, Confer DL, Epstein RB. Source: Bone Marrow Transplantation. 1995 October; 16(4): 507-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8528165&dopt=Abstract

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High-dose carboplatin, etoposide, and cyclophosphamide with autologous bone marrow transplantation in first-line therapy for patients with poor-risk germ cell tumors. Author(s): Motzer RJ, Mazumdar M, Bajorin DF, Bosl GJ, Lyn P, Vlamis V. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1997 July; 15(7): 2546-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9215823&dopt=Abstract

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High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission. Author(s): Freedman AS, Neuberg D, Gribben JG, Mauch P, Soiffer RJ, Fisher DC, Anderson KC, Andersen N, Schlossman R, Kroon M, Ritz J, Aster J, Nadler LM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 January; 16(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9440717&dopt=Abstract

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High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. Author(s): Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G. Source: The New England Journal of Medicine. 1997 May 1; 336(18): 1290-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9113932&dopt=Abstract

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High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective

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randomized italian multicenter study. Author(s): Martelli M, Vignetti M, Zinzani PL, Gherlinzoni F, Meloni G, Fiacchini M, De Sanctis V, Papa G, Martelli MF, Calabresi F, Tura S, Mandelli F. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1996 February; 14(2): 534-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8636768&dopt=Abstract •

High-dose chemotherapy with autologous bone marrow transplantation for refractory metastatic gestational trophoblastic disease. Author(s): Giacalone PL, Benos P, Donnadio D, Laffargue F. Source: Gynecologic Oncology. 1995 September; 58(3): 383-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7672706&dopt=Abstract

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High-dose cytosine arabinoside and fractionated total body irradiation as a preparative regimen for the treatment of children with acute lymphoblastic leukemia and Down syndrome by allogeneic bone marrow transplantation. Author(s): Conter V, D'Angelo P, Rizzari C, Jankovic M, Dampier C, Masera G, Johnson FL. Source: Bone Marrow Transplantation. 1996 February; 17(2): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8640182&dopt=Abstract

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High-dose etoposide, cyclophosphamide and total body irradiation with allogeneic bone marrow transplantation for resistant acute myeloid leukemia: a study by the North American Marrow Transplant Group. Author(s): Brown RA, Wolff SN, Fay JW, Pineiro L, Collins RH Jr, Lynch JP, Stevens D, Greer J, Herzig RH, Herzig GP. Source: Leukemia & Lymphoma. 1996 July; 22(3-4): 271-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8819076&dopt=Abstract

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High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: results of a phase II clinical trial. Author(s): Horning SJ, Negrin RS, Hoppe RT, Rosenberg SA, Chao NJ, Long GD, Brown BW, Blume KG. Source: Blood. 2001 January 15; 97(2): 404-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11154216&dopt=Abstract

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High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission. Author(s): Freedman AS, Gribben JG, Neuberg D, Mauch P, Soiffer RJ, Anderson KC, Pandite L, Robertson MJ, Kroon M, Ritz J, Nadler LM. Source: Blood. 1996 October 1; 88(7): 2780-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8839876&dopt=Abstract

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Holism in the care of the allogeneic bone marrow transplant population: role of the nurse practitioner. Author(s): Griffith KA. Source: Holistic Nursing Practice. 1999 January; 13(2): 20-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10196899&dopt=Abstract

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Human herpes virus-6 encephalitis after bone marrow transplantation: successful treatment with ganciclovir. Author(s): Mookerjee BP, Vogelsang G. Source: Bone Marrow Transplantation. 1997 November; 20(10): 905-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9404935&dopt=Abstract

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Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii. III. Suppression of graft-versus-host disease in murine allogeneic bone marrow transplantation by the PG27 extract. Author(s): Fidler JM, Ku GY, Piazza D, Xu R, Jin R, Chen Z. Source: Transplantation. 2002 August 27; 74(4): 445-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352901&dopt=Abstract

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Impaired plasma antioxidative defense and increased nontransferrin-bound iron during high-dose chemotherapy and radiochemotherapy preceding bone marrow transplantation. Author(s): Durken M, Herrnring C, Finckh B, Nagel S, Nielsen P, Fischer R, Berger HM, Moison RM, Pichlmeier U, Kohlschutter B, Zander AR, Kohlschutter A. Source: Free Radical Biology & Medicine. 2000 March 15; 28(6): 887-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802219&dopt=Abstract

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Improved outcome with T-cell-depleted bone marrow transplantation for acute leukemia. Author(s): Aversa F, Terenzi A, Carotti A, Felicini R, Jacucci R, Zei T, Latini P, Aristei C, Santucci A, Martelli MP, Cunningham I, Reisner Y, Martelli MF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 May; 17(5): 1545-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10334542&dopt=Abstract

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Increased soluble Fas-ligand in sera of bone marrow transplant recipients with acute graft-versus-host disease. Author(s): Kanda Y, Tanaka Y, Shirakawa K, Yatomi T, Nakamura N, Kami M, Saito T, Izutsu K, Asai T, Yuji K, Ogawa S, Honda H, Mitani K, Chiba S, Yazaki Y, Hirai H. Source: Bone Marrow Transplantation. 1998 October; 22(8): 751-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9827971&dopt=Abstract

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Induction of graft versus leukemia effects by cell-mediated lymphokine-activated immunotherapy after syngeneic bone marrow transplantation in murine B cell

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leukemia. Author(s): Weiss L, Nusair S, Reich S, Sidi H, Slavin S. Source: Cancer Immunology, Immunotherapy : Cii. 1996 October; 43(2): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8954144&dopt=Abstract •

Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Author(s): Kroger N, Kruger W, Wacker-Backhaus G, Hegewisch-Becker S, Stockschlader M, Fuchs N, Russmann B, Renges H, Durken M, Bielack S, de Wit M, Schuch G, Bartels H, Braumann D, Kuse R, Kabisch H, Erttmann R, Zander AR. Source: Bone Marrow Transplantation. 1998 December; 22(11): 1029-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9877263&dopt=Abstract

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Intensive remission induction therapy for chronic myeloid leukemia in blast phase with a goal of post-remission bone marrow transplant--a pilot study. Author(s): Lipton JH, Messner HA, Curtis JE, Atkins HL, Minden MD. Source: European Journal of Haematology. 1996 July; 57(1): 42-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8698130&dopt=Abstract

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Intrathecal prophylaxis following autologous bone marrow transplantation for nonHodgkin's lymphoma. Author(s): Varadi G, Lossos A, Nagler A. Source: Acta Oncologica (Stockholm, Sweden). 1997; 36(3): 349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9208912&dopt=Abstract

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Kaposi's sarcoma after autologous bone marrow transplantation for multiple myeloma. Author(s): Vivancos P, Sarra J, Palou J, Valls A, Garcia J, Granena A. Source: Bone Marrow Transplantation. 1996 April; 17(4): 669-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8722373&dopt=Abstract

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Late renal damage after total body irradiation and bone marrow transplantation in a mouse model: effect of radiation fractionation. Author(s): Safwat A, Nielsen OS, el-Badawy S, Overgaard J. Source: European Journal of Cancer (Oxford, England : 1990). 1995 June; 31A(6): 987-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7646934&dopt=Abstract

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Living The Discipline on a stem cell transplant unit: spiritual care outcomes among bone marrow transplant survivors. Author(s): Berger JA. Source: Journal of Health Care Chaplaincy. 2001; 11(1): 83-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11398538&dopt=Abstract

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Low levels of serum soluble c-kit relates to delayed engraftment after bone marrow transplantation. Author(s): Hashino S, Imamura M, Tanaka J, Kobayashi S, Kasai M, Sakurada K, Asaka M. Source: Leukemia & Lymphoma. 1997 April; 25(3-4): 327-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9168443&dopt=Abstract

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Lymphoproliferative disorders following allogeneic bone marrow transplantation: the Vancouver experience. Author(s): Micallef IN, Chhanabhai M, Gascoyne RD, Shepherd JD, Fung HC, Nantel SH, Toze CL, Klingemann HG, Sutherland HJ, Hogge DE, Nevill TJ, Le A, Barnett MJ. Source: Bone Marrow Transplantation. 1998 November; 22(10): 981-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849695&dopt=Abstract

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Massage therapy for patients undergoing autologous bone marrow transplantation. Author(s): Ahles TA, Tope DM, Pinkson B, Walch S, Hann D, Whedon M, Dain B, Weiss JE, Mills L, Silberfarb PM. Source: Journal of Pain and Symptom Management. 1999 September; 18(3): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517036&dopt=Abstract

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Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model. Author(s): Chen BJ, Chen Y, Cui X, Fidler JM, Chao NJ. Source: Transplantation. 2002 January 15; 73(1): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792990&dopt=Abstract

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Minimizing graft rejection in allogeneic T cell-depleted bone marrow transplantation. Author(s): Rigden JP, Cornetta K, Srour EF, Hanna M, Broun ER, Hromas R, Baute J, Hilton J, Cox E, Rubin L, Gonin R, Tricot G. Source: Bone Marrow Transplantation. 1996 November; 18(5): 913-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8932845&dopt=Abstract

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MR and proton spectroscopy of white matter disease induced by high-dose chemotherapy with bone marrow transplant in advanced breast carcinoma. Author(s): Brown MS, Simon JH, Stemmer SM, Stears JC, Scherzinger A, Cagnoni PJ, Jones RB. Source: Ajnr. American Journal of Neuroradiology. 1995 November-December; 16(10): 2013-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8585489&dopt=Abstract

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Multiplex amplification and fluorimetric detection of short tandem repeats for mixed chimerism after bone marrow transplant. Author(s): Madeo D, Cappellari A, Castaman G, Raimondi R, Rodeghiero F.

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Source: Leukemia & Lymphoma. 2003 August; 44(8): 1395-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952234&dopt=Abstract •

Myeloablative therapy and bone marrow rescue in advanced neuroblastoma. Report from the Italian Bone Marrow Transplant Registry. Italian Association of Pediatric Hematology-Oncology, BMT Group. Author(s): Garaventa A, Rondelli R, Lanino E, Dallorso S, Dini G, Bonetti F, Arrighini A, Santoro N, Rossetti F, Miniero R, Andolina M, Amici A, Indolfi P, Lo Curto M, Favre C, Paolucci P, Pession A, De Bernardi B. Source: Bone Marrow Transplantation. 1996 July; 18(1): 125-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8832005&dopt=Abstract

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New clonal karyotypic abnormalities acquired following autologous bone marrow transplantation for acute myeloid leukemia do not appear to confer an adverse prognosis. Author(s): Imrie KR, Dube I, Prince HM, Girouard C, Crump M, Keating A. Source: Bone Marrow Transplantation. 1998 February; 21(4): 395-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9509975&dopt=Abstract

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Nodal gamma/delta T cell lymphoma in complete remission following allogeneic bone marrow transplantation from an HLA-matched unrelated donor. Author(s): Aoyama Y, Yamane T, Hino M, Ota K, Hasegawa T, Sakamoto C, Nakamae H, Yamamura R, Koh KR, Takubo T, Inoue T, Tsubaki K, Tatsumi N. Source: Acta Haematologica. 2001; 105(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340254&dopt=Abstract

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Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Author(s): Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Source: Blood. 1998 February 1; 91(3): 756-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9446633&dopt=Abstract

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Oral eicosapentaenoic acid for complications of bone marrow transplantation. Author(s): Takatsuka H, Takemoto Y, Iwata N, Suehiro A, Hamano T, Okamoto T, Kanamaru A, Kakishita E. Source: Bone Marrow Transplantation. 2001 October; 28(8): 769-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781629&dopt=Abstract

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Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Author(s): Cockerham MB, Weinberger BB, Lerchie SB.

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Source: The Annals of Pharmacotherapy. 2000 March; 34(3): 300-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917373&dopt=Abstract •

Outcome of a multicenter treatment program including autologous or allogeneic bone marrow transplantation for de novo acute myeloid leukemia. Author(s): Wahlin A, Brinch L, Hornsten P, Evensen SA, Oberg G, Simonsson B, Hedenus M. Source: European Journal of Haematology. 1997 April; 58(4): 233-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9186533&dopt=Abstract

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Outcomes of touch therapies during bone marrow transplant. Author(s): Smith MC, Reeder F, Daniel L, Baramee J, Hagman J. Source: Alternative Therapies in Health and Medicine. 2003 January-February; 9(1): 40-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564350&dopt=Abstract

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Pain language of bone marrow transplantation patients. Author(s): Ho SM, Horne DJ, Szer J. Source: Psychological Reports. 2001 August; 89(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729547&dopt=Abstract

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Patient reports of complications of bone marrow transplantation. Author(s): Bellm LA, Epstein JB, Rose-Ped A, Martin P, Fuchs HJ. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2000 January; 8(1): 33-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10650895&dopt=Abstract

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PG27, an extract of Tripterygium wilfordii hook f, induces antigen-specific tolerance in bone marrow transplantation in mice. Author(s): Chen Y, Zeng D, Schlegel PG, Fidler J, Chao NJ. Source: Blood. 2000 January 15; 95(2): 705-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10627483&dopt=Abstract

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Phase I study of high-dose continuous intravenous infusion of VP-16 in combination with high-dose melphalan followed by autologous bone marrow transplantation in children with stage IV neuroblastoma. Author(s): Valteau-Couanet D, Vassal G, Pondarre C, Bonnay M, Benhamou E, Couanet D, Plantaz D, Hartmann O. Source: Bone Marrow Transplantation. 1996 April; 17(4): 485-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8722343&dopt=Abstract

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Phlebotomy to reduce iron overload in patients cured of thalassemia by bone marrow transplantation. Italian Cooperative Group for Phlebotomy Treatment of Transplanted Thalassemia Patients.

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Author(s): Angelucci E, Muretto P, Lucarelli G, Ripalti M, Baronciani D, Erer B, Galimberti M, Giardini C, Gaziev D, Polchi P. Source: Blood. 1997 August 1; 90(3): 994-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9242528&dopt=Abstract •

Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients. Author(s): Jonas CR, Puckett AB, Jones DP, Griffith DP, Szeszycki EE, Bergman GF, Furr CE, Tyre C, Carlson JL, Galloway JR, Blumberg JB, Ziegler TR. Source: The American Journal of Clinical Nutrition. 2000 July; 72(1): 181-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10871578&dopt=Abstract

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Plasma levels of granulocyte colony-stimulating factor in patients after allogeneic bone marrow transplantation for chronic myeloid leukemia correlate with engraftment of transplanted marrow. Author(s): Busch FW, Pilgrim TB, Kramer A, Ehninger G. Source: Bone Marrow Transplantation. 1997 April; 19(7): 653-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9156241&dopt=Abstract

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Primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma of the adult: sequential intensive treatment with the F-MACHOP regimen (+/- radiotherapy) and autologous bone marrow transplantation. Author(s): Fanin R, Silvestri F, Geromin A, Cerno M, Infanti L, Zaja F, Barillari G, Savignano C, Rinaldi C, Damiani D, Buffoli A, Biffoni F, Baccarini M. Source: Blood. 1996 February 15; 87(4): 1243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8608211&dopt=Abstract

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Prognostic factors in bone marrow transplantation for beta thalassemia major: experiences from Iran. Author(s): Ghavamzadeh A, Nasseri P, Eshraghian MR, Jahani M, Baybordi I, Nateghi J, Khodabandeh A, Sadjadi AR, Mohyeddin M, Khademi Y. Source: Bone Marrow Transplantation. 1998 December; 22(12): 1167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9894719&dopt=Abstract

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Progression of natural immunity during one-year treatment of residual disease in neuroblastoma patients with high doses of interleukin-2 after autologous bone marrow transplantation. Author(s): Marti F, Pardo N, Peiro M, Bertran E, Amill B, Garcia J, Cubells J, Rueda F. Source: Experimental Hematology. 1995 December; 23(14): 1445-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8542930&dopt=Abstract

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Progressive multifocal leukoencephalopathy after autologous bone marrow transplantation and alpha-interferon immunotherapy. Author(s): Re D, Bamborschke S, Feiden W, Schroder R, Lehrke R, Diehl V, Tesch H.

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Source: Bone Marrow Transplantation. 1999 February; 23(3): 295-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084263&dopt=Abstract •

Prolonged impairment of hematopoiesis after high-dose therapy followed by autologous bone marrow transplantation. Author(s): Domenech J, Linassier C, Gihana E, Dayan A, Truglio D, Bout M, Petitdidier C, Delain M, Petit A, Bremond JL, et al. Source: Blood. 1995 June 1; 85(11): 3320-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7756665&dopt=Abstract

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Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission. Groupe d'Etude les Lymphomes de l'Adulte (GELA). Author(s): Mounier N, Haioun C, Cole BF, Gisselbrecht C, Sebban C, Morel P, Marit G, Bouabdallah R, Ravoet C, Salles G, Reyes F, Lepage E. Source: Blood. 2000 June 15; 95(12): 3687-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10845898&dopt=Abstract

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Randomized trial showing equivalent efficacy of filgrastim 5 micrograms/kg/d and 10 micrograms/kg/d following high-dose chemotherapy and autologous bone marrow transplantation in high-risk lymphomas. Author(s): Stahel RA, Jost LM, Honegger H, Betts E, Goebel ME, Nagler A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1997 May; 15(5): 1730-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9164179&dopt=Abstract

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Reduced-intensity bone marrow transplantation from an alternative unrelated donor for myelodysplastic syndrome of first-donor origin. Author(s): Komeno Y, Kanda Y, Kandabashi K, Kawazu M, Goyama S, Takeshita M, Nannya Y, Niino M, Nakamoto T, Kurokawa M, Tsujino S, Ogawa S, Aoki K, Chiba S, Motokura T, Hirai H. Source: American Journal of Hematology. 2003 March; 72(3): 220-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605397&dopt=Abstract

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Reduction of distress associated with paediatric bone marrow transplant: complementary health promotion interventions. Author(s): Phipps S. Source: Pediatric Rehabilitation. 2002 October-December; 5(4): 223-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745902&dopt=Abstract

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Repetitious appearance and disappearance of different kinds of clonal cytogenetic abnormalities after allogeneic bone marrow transplantation.

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Author(s): Lin YW, Hamahata K, Watanabe K, Adachi S, Akiyama Y, Kubota M, Nakahata T. Source: International Journal of Hematology. 2001 July; 74(1): 86-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530811&dopt=Abstract •

Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkin's lymphoma prior to autologous bone marrow transplantation. Author(s): Girouard C, Dufresne J, Imrie K, Stewart AK, Brandwein J, Prince HM, Pantolony D, Keating A, Crump M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1997 July; 8(7): 675-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9296221&dopt=Abstract

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Songwriting and digital video production interventions for pediatric patients undergoing bone marrow transplantation, part I: an analysis of depression and anxiety levels according to phase of treatment. Author(s): Robb SL, Ebberts AG. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2003 January-February; 20(1): 2-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569430&dopt=Abstract

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Songwriting and digital video production interventions for pediatric patients undergoing bone marrow transplantation, part II: an analysis of patient-generated songs and patient perceptions regarding intervention efficacy. Author(s): Robb SL, Ebberts AG. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 2003 January-February; 20(1): 16-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569431&dopt=Abstract

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Substance abuse and bone marrow transplant. Author(s): Chang G, Antin JH, Orav EJ, Randall U, McGarigle C, Behr HM. Source: The American Journal of Drug and Alcohol Abuse. 1997 May; 23(2): 301-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9143640&dopt=Abstract

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Successful correction of hemophagocytic lymphohistiocytosis with related or unrelated bone marrow transplantation. Author(s): Baker KS, DeLaat CA, Steinbuch M, Gross TG, Shapiro RS, Loechelt B, Harris R, Filipovich AH. Source: Blood. 1997 May 15; 89(10): 3857-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9160694&dopt=Abstract

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Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation.

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Author(s): Hattori K, Yabe M, Matsumoto M, Kudo Y, Yasuda Y, Inoue H, Minami S, Miyakita H, Kawamura N, Komori K, Yamamoto I, Yabe H. Source: Bone Marrow Transplantation. 2001 June; 27(12): 1315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11548852&dopt=Abstract •

Successful mobilisation of blood stem cells following previous autologous bone marrow transplantation. Author(s): McQuaker IG, Haynes AP, Iqbal A, Russell NH. Source: Bone Marrow Transplantation. 1996 July; 18(1): 263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8832036&dopt=Abstract

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Successful pregnancy after bone marrow transplantation for thalassaemia. Author(s): Borgna-Pignatti C, Marradi P, Rugolotto S, Marcolongo A. Source: Bone Marrow Transplantation. 1996 July; 18(1): 235-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8832025&dopt=Abstract

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Successful treatment of HTLV-1-associated acute adult T-cell leukaemia lymphoma by allogeneic bone marrow transplantation. Author(s): Borg A, Yin JA, Johnson PR, Tosswill J, Saunders M, Morris D. Source: British Journal of Haematology. 1996 September; 94(4): 713-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8826899&dopt=Abstract

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Supplementation with antioxidants prior to bone marrow transplantation. Author(s): Clemens MR, Waladkhani AR, Bublitz K, Ehninger G, Gey KF. Source: Wiener Klinische Wochenschrift. 1997 October 17; 109(19): 771-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9370141&dopt=Abstract

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T cell depleted haploidentical bone marrow transplantation for the treatment of children with severe combined immunodeficiency. Author(s): Smogorzewska EM, Brooks J, Annett G, Kapoor N, Crooks GM, Kohn DB, Parkman R, Weinberg KI. Source: Arch Immunol Ther Exp (Warsz). 2000; 48(2): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10807052&dopt=Abstract

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t(9;13)(q34;q12) chromosomal translocation persisting 4 years post autologous bone marrow transplantation for secondary AML despite morphological remission. Author(s): Mahendra P, Richards EM, Sinclair P, Nacheva E, Marcus RE. Source: Clinical and Laboratory Haematology. 1996 June; 18(2): 121-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8866147&dopt=Abstract

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Tandem high dose chemotherapy with autologous bone marrow transplantation for initial relapse of testicular germ cell cancer.

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Author(s): Broun ER, Nichols CR, Gize G, Cornetta K, Hromas RA, Schacht B, Einhorn LH. Source: Cancer. 1997 April 15; 79(8): 1605-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9118046&dopt=Abstract •

The effect of using music therapy with relaxation imagery in the management of patients undergoing bone marrow transplantation: a pilot feasibility study. Author(s): Sahler OJ, Hunter BC, Liesveld JL. Source: Alternative Therapies in Health and Medicine. 2003 November-December; 9(6): 70-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14618861&dopt=Abstract

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The effectiveness of the comprehensive coping strategy program on clinical outcomes in breast cancer autologous bone marrow transplantation. Author(s): Gaston-Johansson F, Fall-Dickson JM, Nanda J, Ohly KV, Stillman S, Krumm S, Kennedy MJ. Source: Cancer Nursing. 2000 August; 23(4): 277-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10939175&dopt=Abstract

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The organization of a counselling service for the families of patients undergoing bone marrow transplant. Author(s): Invernizzi G, Broich G, Bressi C, Guggeri G, Caparrelli S, Deliliers GL. Source: Anticancer Res. 1999 May-June; 19(3B): 2293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10472347&dopt=Abstract

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The pharmacokinetics and toxicity of two application schedules with high-dose VP16 in patients receiving an allogeneic bone marrow transplantation. Author(s): Mross K, Reifke J, Bewermeier P, Kruger W, Hossfeld DK, Zander A. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1996 January; 7(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9081397&dopt=Abstract

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The role of VP-16 in autologous bone marrow transplantation for acute myeloblastic leukemia. Author(s): Parikh PM, Gelfand R, Gulati SC. Source: J Assoc Physicians India. 1996 April; 44(4): 252-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9251396&dopt=Abstract

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The true cost of bone marrow transplantation. Author(s): Weeks FM, Yee GC, Bartfield AA, Wingard JR.

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Source: The American Journal of the Medical Sciences. 1997 August; 314(2): 101-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9258212&dopt=Abstract •

The utility of plasma polymerase chain reaction for human herpes virus-6 among pediatric bone marrow transplant recipients: results of a pilot study. Author(s): Allen UD, Tellier R, Doyle J, Petric M, Wasfy S, Kumar P, Calderwood S, Freedman M, Saunders F. Source: Bone Marrow Transplantation. 2001 September; 28(5): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593320&dopt=Abstract

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Therapeutic play and bone marrow transplantation. Author(s): Kuntz N, Adams JA, Zahr L, Killen R, Cameron K, Wasson H. Source: Journal of Pediatric Nursing. 1996 December; 11(6): 359-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8991336&dopt=Abstract

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Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group. Author(s): Tsang RW, Gospodarowicz MK, Sutcliffe SB, Crump M, Keating A. Source: European Journal of Cancer (Oxford, England : 1990). 1999 January; 35(1): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211091&dopt=Abstract

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Time course analysis of semi-quantitative PCR and antigenaemia assay for prevention of cytomegalovirus disease after bone marrow transplantation. Author(s): Kanda Y, Chiba S, Suzuki T, Kami M, Yazaki Y, Hirai H. Source: British Journal of Haematology. 1998 January; 100(1): 222-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9450815&dopt=Abstract

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Total body irradiation before allogeneic bone marrow transplantation: is more dose better? Author(s): Bieri S, Helg C, Chapuis B, Miralbell R. Source: International Journal of Radiation Oncology, Biology, Physics. 2001 March 15; 49(4): 1071-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240249&dopt=Abstract

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Treatment of a delayed graft failure after allogeneic bone marrow transplantation with IL-3 and GM-CSF. Author(s): Vannucchi AM, Bosi A, Laszlo D, Guidi S, Saccardi R, Rossi-Ferrini P. Source: Haematologica. 1995 July-August; 80(4): 341-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7590505&dopt=Abstract

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Treatment of deep vein thrombosis using temporary vena caval filters after allogeneic bone marrow transplantation. Author(s): Kanda Y, Yamamoto R, Chizuka A, Suguro M, Hamaki T, Matsuyama T, Takezako N, Miwa A, Togawa A, Kume M, Tsukuda M, Hasuo K. Source: Leukemia & Lymphoma. 2000 July; 38(3-4): 429-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830752&dopt=Abstract

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Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Author(s): Henter JI, Samuelsson-Horne A, Arico M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G; Histocyte Society. Source: Blood. 2002 October 1; 100(7): 2367-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239144&dopt=Abstract

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TT virus in bone marrow transplant recipients. Author(s): Kanda Y, Tanaka Y, Kami M, Saito T, Asai T, Izutsu K, Yuji K, Ogawa S, Honda H, Mitani K, Chiba S, Yazaki Y, Hirai H. Source: Blood. 1999 April 15; 93(8): 2485-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194426&dopt=Abstract

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TT virus in hematological disorders and bone marrow transplant recipients. Author(s): Kanda Y, Hirai H. Source: Leukemia & Lymphoma. 2001 February; 40(5-6): 483-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426521&dopt=Abstract

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VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. Author(s): Santini G, Salvagno L, Leoni P, Chisesi T, De Souza C, Sertoli MR, Rubagotti A, Congiu AM, Centurioni R, Olivieri A, Tedeschi L, Vespignani M, Nati S, Soracco M, Porcellini A, Contu A, Guarnaccia C, Pescosta N, Majolino I, Spriano M, Vimercati R, Rossi E, Zambaldi G, Mangoni L, Rizzoli V, et al. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 August; 16(8): 2796-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9704732&dopt=Abstract

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Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. Author(s): Little R, Wittes RE, Longo DL, Wilson WH. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 February; 16(2): 584-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9469345&dopt=Abstract

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Walking with fan through BMT. Bone Marrow Transplant. Author(s): Chen SY. Source: J Christ Nurs. 2002 Spring; 19(2): 22-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908046&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to bone marrow transplant; 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 Amyloidosis 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 Chronic Myelogenous Leukemia Source: Integrative Medicine Communications; www.drkoop.com

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Leukemia Source: Integrative Medicine Communications; www.drkoop.com Lymphoma Source: Integrative Medicine Communications; www.drkoop.com Myelofibrosis Source: Integrative Medicine Communications; www.drkoop.com Myeloproliferative Disorders Source: Integrative Medicine Communications; www.drkoop.com Polycythemia Vera Source: Integrative Medicine Communications; www.drkoop.com Sickle Cell Anemia Source: Healthnotes, Inc.; www.healthnotes.com Thrombocytosis Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Cell Therapy Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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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. TRANSPLANT

DISSERTATIONS

ON

BONE

MARROW

Overview In this chapter, we will give you a bibliography on recent dissertations relating to bone marrow transplant. 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 “bone marrow transplant” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bone marrow transplant, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Bone Marrow Transplant 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 bone marrow transplant. 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: •

An Analysis of the Effects of Pastoral Care on the Spiritual Health of Bone Marrow Transplant Patients by Quiett, Jeffrey Scott; PhD from New Orleans Baptist Theological Seminary, 1999, 114 pages http://wwwlib.umi.com/dissertations/fullcit/9962139

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Coping with Life-Threatening Medical Treatment: Families and the Bone Marrow Transplantation Experience by Farrall, Michael Geronimo, PhD from University of Kentucky, 1988, 202 pages http://wwwlib.umi.com/dissertations/fullcit/8914902

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Finding the Comfort Zone: Physicians' Perspectives on Addressing Infertility with Adolescent Bone Marrow Transplant Patients and Their Parents by Lakhani, Shaheen Uddin, PsyD from Massachusetts School of Professional Psychology, 2003, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3088238

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Locus of Control, Coping, Anxiety and Depression in a Bone Marrow Transplant Population by Mertlich, Gary Brent, PhD from Case Western Reserve University, 1996, 163 pages http://wwwlib.umi.com/dissertations/fullcit/9720436

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Neuropsychological Functioning: Pre- and Post-Bone Marrow Transplant by Cool, Valerie Ann, PhD from The University of Iowa, 1991, 115 pages http://wwwlib.umi.com/dissertations/fullcit/9136911

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The Impact of Bone Marrow Transplantation on the Quality of Life of Cancer Patients and Their Families: a Longitudinal Study by Case, Patricia Fay; PhD from Wayne State University, 1999, 253 pages http://wwwlib.umi.com/dissertations/fullcit/9954495

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The Psychosocial Consequences of Bone Marrow Transplantation for Adult Patients (Clinical Social Work) by Freund, Barbara Lee, PhD from New York University, 1991, 339 pages http://wwwlib.umi.com/dissertations/fullcit/9212725

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

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CHAPTER 5. CLINICAL TRIALS AND BONE MARROW TRANSPLANT Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning bone marrow transplant.

Recent Trials on Bone Marrow Transplant The following is a list of recent trials dedicated to bone marrow transplant.8 Further information on a trial is available at the Web site indicated. •

Bone Marrow Transplantation and Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia Condition(s): adult acute lymphoblastic leukemia in remission; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI); Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomizedphase III trial to compare the effectiveness of bone marrow transplantation with standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002514

8

These are listed at www.ClinicalTrials.gov.

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Bone Marrow Transplantation in Treating Children With Sickle Cell Disease Condition(s): Sickle Cell Anemia Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Sickle cell disease is an inherited disorder in which abnormal, crescent-shaped red blood cells interfere with the ability of the blood to carry oxygen through the body and can cause severe pain, stroke, and organ damage. Bone marrow transplantation, is a procedure in which the soft, sponge-like tissue in the center of bones producing white blood cells, red blood cells, and platelets is replaced by bone marrow from a another person. Bone marrow transplantation may be an effective treatment in relieving the symptoms of sickle cell disease. PURPOSE: Phase I/II trial to study the effectiveness of bone marrow transplantation in treating children who have sickle cell disease. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004485

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Bone Marrow Transplantation in Treating Patients With Hematologic Cancers Condition(s): acute leukemia; atypical chronic myeloid leukemia; chronic leukemia; chronic myeloproliferative disorders; myelodysplastic and myeloproliferative disease; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): H. Lee Moffitt Cancer Center and Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of donor bone marrow transplantation in treating patients who have hematologic cancers. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005797

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Bone Marrow Transplantation in Treating Patients With Multiple Myeloma, Chronic Phase Chronic Myelogenous Leukemia, or Agnogenic Myeloid Metaplasia Condition(s): chronic idiopathic myelofibrosis; Chronic Myelogenous Leukemia; Multiple Myeloma; refractory plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy that was used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of allogeneic

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bone marrow transplantation in treating patients who have multiple myeloma, chronic phase chronic myelogenous leukemia, or agnogenic myeloidmetaplasia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004181 •

Bone Marrow Transplantation Plus Cyclophosphamide and Radiation Therapy in Treating Patients With Hematologic Cancer Condition(s): Acute Lymphocytic Leukemia; Acute Myeloid Leukemia; atypical chronic myeloid leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Fox Chase Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Radiation therapy uses high-energy xrays to damage cancer cells. PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation from an unrelated donor plus cyclophosphamide and radiation therapy in treating patients who have hematologic cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002809

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Busulfan and Cyclophosphamide Followed by Bone Marrow Transplantation in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome Condition(s): adult acute monocytic leukemia; adult acute myeloid leukemia; atypical chronic myeloid leukemia; childhood acute myeloid leukemia and other myeloid malignancies; Chronic Myelomonocytic Leukemia; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of busulfan and cyclophosphamide followed by bone marrow transplantation in treating patients who have acute myelogenous leukemia or myelodysplastic syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00004896 •

Chemotherapy Followed by Peripheral Stem Cell or Bone Marrow Transplantation Compared With Chemotherapy Alone in Treating Patients With Small Cell Lung Cancer Condition(s): limited stage small cell lung cancer; extensive stage small cell lung cancer Study Status: This study is currently recruiting patients. Sponsor(s): EBMT Solid Tumors Working Party Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known whether high-dose chemotherapy plus peripheral stem cell or bone marrow transplantation is more effective than chemotherapy alone for treating small cell lung cancer. PURPOSE: Randomizedphase III trial to compare the effectiveness of chemotherapy followed by peripheral stem cell or bone marrow transplantation with that of chemotherapy alone in treating patients who have limited-stage or extensivestage small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011921

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Chemotherapy Plus Bone Marrow Transplantation and Filgrastim in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome Condition(s): Acute Myeloid Leukemia; adult acute monocytic leukemia; atypical chronic myeloid leukemia; childhood acute monocytic leukemia; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Robert H. Lurie Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing and die. Bone marrow transplantation may be able to replace cells that were destroyed by chemotherapy. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of chemotherapy plus bone marrow transplantation and filgrastim in treating patients who have acute myelogenous leukemia or myelodysplastic syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004899

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Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia Condition(s): untreated adult acute lymphoblastic leukemia; stage I adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; contiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II adult lymphoblastic lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): EORTC Leukemia Cooperative Group; Leucemies Aigues et Lymphomes de l'Adulte Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. Bone marrow transplantation can replace immune cells that were destroyed by chemotherapy. PURPOSE: Randomizedphase III trial to study the effectiveness of chemotherapy compared with or without bone marrow transplantation in treating patients with acute lymphoblastic leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002700

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Combination Chemotherapy and Bone Marrow Transplantation in Treating Patients With Aplastic Anemia or Hematologic Cancer Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known which regimen of combination chemotherapy followed by bone marrow transplantation is most effective for aplastic anemia or hematologic cancer. PURPOSE: Phase II/III trial to determine the effectiveness of different regimens of combination chemotherapy followed by bone marrow transplantation in treating patients who have aplastic anemia or hematologic cancer. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003816

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Combination Chemotherapy and Bone Marrow Transplantation in Treating Patients With Refractory or Recurrent Ovarian Cancer Condition(s): recurrent ovarian epithelial cancer Study Status: This study is currently recruiting patients.

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Bone Marrow Transplant

Sponsor(s): Loyola University Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous bone marrow transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with cyclophosphamide, carboplatin, mitoxantrone and autologous bone marrow transplantation in treating patients with refractory or recurrent ovarian cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002474 •

Combination Chemotherapy and Total-Body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia Condition(s): adult acute lymphoblastic leukemia in remission; childhood acute lymphoblastic leukemia in remission Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and donor white blood cells may prevent this from happening. PURPOSE: Phase I/II trial to determine the effectiveness of combination chemotherapy and total-body irradiation followed by peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027547

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Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Advanced Hematologic Cancer Condition(s): acute leukemia; atypical chronic myeloid leukemia; chronic leukemia; Graft Versus Host Disease; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of busulfan and melphalan followed by donor bone marrow transplantation in treating patients who have advanced hematologic cancer.

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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014469 •

Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer Condition(s): bone marrow ablation; Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with thiotepa, carboplatin, and topotecan followed by bone marrow transplantation in treating patients who have metastatic or progressive rare cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002515

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Combination Chemotherapy Followed by Donor Bone Marrow Transplantation or Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer or Genetic Disorders Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; Leukemia; Lymphoma; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Peripheral stem cell transplantation or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by donor bone marrow transplantation or peripheral stem cell transplantation in treating patients who have hematologic cancer or genetic disorders. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008307

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Bone Marrow Transplant

Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Brain Cancer Condition(s): adult brain tumor; childhood central nervous system germ cell tumor; childhood ependymoma; Childhood Medulloblastoma; childhood supratentorial primitive neuroectodermal tumors Study Status: This study is currently recruiting patients. Sponsor(s): Kaplan Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining temozolomide, thiotepa, and carboplatin followed by peripheral stem cell transplantation or bone marrow transplantation in treating patients who have brain cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025558

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Combination Chemotherapy Followed by Surgery and Peripheral Stem Cell or Bone Marrow Transplantation in Treating Infants With Newly Diagnosed Neuroblastoma Condition(s): localized resectable neuroblastoma; regional neuroblastoma; disseminated neuroblastoma; stage 4S neuroblastoma; localized unresectable neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): European Infant Neuroblastoma Study Group - 1999 Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy given before surgery followed by peripheral stem cell or bone marrow transplantation in treating infants who have newly diagnosed neuroblastoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025649

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Combining Chemotherapy, Tacrolimus, Mycophenolate Mofetil, and Radiation Therapy with Donor Bone Marrow Transplantation in Treating Patients with Hematologic Cancer Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; Leukemia; Lymphoma; myelodysplastic and myeloproliferative diseases; plasma cell neoplasm Study Status: This study is currently recruiting patients.

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Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Tacrolimus and mycophenolate mofetil may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy, tacrolimus, mycophenolate mofetil, and radiation therapy with allogeneic bone marrow transplantation in treating patients who have hematologic cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049504 •

Cyclophosphamide Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancer Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; Leukemia; Lymphoma; myelodysplastic and myeloproliferative diseases; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): Sidney Kimmel Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. PURPOSE: Phase I trial to study the effectiveness of cyclophosphamide plus bone marrow transplantation in treating patients who have hematologic cancer. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006042

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Donor Bone Marrow Transplantation in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders Condition(s): acute leukemia; atypical chronic myeloid leukemia; chronic leukemia; chronic myeloproliferative disorders; myelodysplastic and myeloproliferative disease; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): H. Lee Moffitt Cancer Center and Research Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or total-body irradiation used to kill leukemia and lymphoma cells. Bone marrow transplantation using donated bone marrow may be an effective treatment for malignant or nonmalignant hematologic disorders. PURPOSE: Phase II trial to study the effectiveness of donor bone marrow

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Bone Marrow Transplant

transplantation in treating patients who have leukemia, lymphoma, or nonmalignant hematologic disorders. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005622 •

Filgrastim-Mobilized Peripheral Stem Cell Transplantation Compared With Bone Marrow Transplantation From Compatible Unrelated Donors in Treating Patients With Hematologic Malignancies Condition(s): acute leukemia; chronic leukemia; chronic myeloproliferative disorders; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Blood and Marrow Transplant Clinical Trials Network; National Heart, Lung, and Blood Institute (NHLBI); National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Colony-stimulating factors, such as filgrastim, stimulate the production of blood cells. Peripheral stem cell transplantation or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. Giving filgrastim to stimulate peripheral stem cells that can be collected for peripheral stem cell transplant may result in fewer side effects after the transplant. Sometimes the transplanted cells from a donor can be rejected by the body's tissues. Methotrexate and cyclosporine or tacrolimus may prevent this from happening. It is not yet known whether filgrastim-mobilized donor peripheral stem cell transplantation is more effective than donor bone marrow transplantation in treating hematologic malignancies. PURPOSE: Randomizedphase III trial to compare the effectiveness of filgrastim-mobilized donor peripheral stem cell transplantation with that of donor bone marrow transplantation in treating patients who have hematologic cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00075816

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High-Dose Chemotherapy, Total-Body Irradiation, and Autologous Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Hematologic Cancer or Solid Tumors Condition(s): Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation or autologous bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of high-dose chemotherapy regimens with or without

Clinical Trials 171

total-body irradiation followed by autologous stem cell transplantation or autologous bone marrow transplantation in treating patients who have hematologic malignancies or solid tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060255 •

Monoclonal Antibody Therapy Plus Combination Chemotherapy and Bone Marrow Transplantation in Treating Patients With Acute Myelogenous Leukemia Condition(s): adult acute myeloid leukemia in remission Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy plus combination chemotherapy and bone marrow transplantation in treating patients who have acute myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005940

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Monoclonal Antibody, Cyclophosphamide, and Radiation Therapy Followed by Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome Condition(s): adult acute myeloid leukemia; childhood acute myeloid leukemia; Chronic Myelomonocytic Leukemia; juvenile myelomonocytic leukemia; Myelodysplastic Syndromes; secondary acute myeloid leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining monoclonal antibody therapy with chemotherapy and radiation therapy may kill more cancer cells. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody, cyclophosphamide, total-body irradiation, and bone marrow transplant in treating patients who have advanced acute myeloid leukemia or myelodysplastic syndrome. Phase(s): Phase II

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Bone Marrow Transplant

Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003868 •

Prevention of Graft-Versus-Host Disease in Patients Undergoing Bone Marrow Transplantation Condition(s): Leukemia; Lymphoma; Plasma Cell Neoplasm; Aplstic Anemia; Solid Tumor; Graft Versus Host Disease Study Status: This study is currently recruiting patients. Sponsor(s): Sidney Kimmel Cancer Center Purpose - Excerpt: RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Stem cells that have been treated in the laboratory to remove lymphocytes may prevent this from happening. PURPOSE: Clinical trial to prevent graft-versus-host disease in patients undergoing bone marrow transplantation. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003538

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Pyrazoloacridine and Stem Cell or Bone Marrow Transplantation in Treating Young Patients With Recurrent or Refractory Neuroblastoma Condition(s): recurrent neuroblastoma; disseminated neuroblastoma Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining pyrazoloacridine with peripheral stem cell or bone marrow transplantation in treating young patients who have recurrent or refractoryneuroblastoma. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053950

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Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant Condition(s): Kidney Failure; Bone Marrow Transplantation; Kidney Transplantation; Kidney Failure, Chronic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Immune Tolerance Network

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Purpose - Excerpt: This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body's immune system. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063817 •

Relationship Between Personality and Coping Styles in Bone Marrow Transplant Candidates Condition(s): Bone Marrow Transplantation; Neoplasms Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will look at how people cope with an upcoming bone marrow transplant and how personality characteristics influence coping styles in stressful medical situations. Personality traits, such as extraversion, optimism and selfesteem have been related to active, problem-focused coping styles, whereas neuroticism has been related to increased psychological distress and denial as a way of coping. Coping styles, in turn, have been related to disease outcome. For example, a fighting spirit and avoidance have been correlated with longer survival, whereas fatalism, anxious preoccupation and feelings of helplessness and hopelessness were related to a poor disease outcome. A better understanding of the relationship between coping styles and personality may help improve supportive care for people undergoing bone marrow transplants. This study will: - Explore the relationship between personality traits, coping styles and psychological stress in patients awaiting bone marrow transplantation Identify what coping styles people use to prepare for bone marrow transplantation Identify what personality traits are related to particular coping styles in patients awaiting bone marrow transplantation - Identify the relationship between personality factors and level of psychological distress in patients awaiting bone marrow transplantation Cancer patients 18 years of age and older who are scheduled for bone marrow transplant are eligible for this study. Participants will fill out pencil-and-paper questionnaires providing demographic information (such as age, gender, marital status, ethnicity, and so forth) and answering questions about their opinions and preferences. The information will be used to assess the participants' personality characteristics, coping styles, and psychological distress. The questionnaires take about 45 to 50 minutes to complete. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048256

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Sargramostim Following Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia Condition(s): relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; Philadelphia

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Bone Marrow Transplant

chromosome positive chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia; atypical chronic myeloid leukemia Study Status: This study is currently recruiting patients. Sponsor(s): Sidney Kimmel Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood, and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of allogeneic bone marrow transplantation followed by sargramostim in treating patients who have chronic myelogenous leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002778 •

Thiotepa Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Malignant Glioma Condition(s): adult brain tumor; childhood brain tumor; childhood cerebellar astrocytoma; childhood cerebral astrocytoma and malignant glioma; childhood ependymoma; Childhood Oligodendroglioma Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of thiotepa followed by peripheral stem cell or bone marrow transplantation in treating patients who have malignantglioma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008008

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Total-Body Irradiation Plus Chemotherapy Followed By Donor Bone Marrow Transplantation in Treating Children With Hematologic Cancer Condition(s): childhood non-Hodgkin's lymphoma; Leukemia; myelodysplastic and myeloproliferative diseases Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI)

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Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening. PURPOSE: Phase II trial to study the effectiveness of total-body irradiation and chemotherapy followed by T-cell depleted donor bone marrow transplantation in treating children who have hematologic cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028730 •

Bone Marrow Transplantation in Treating Patients With Hematologic Cancer Condition(s): Leukemia; Lymphoma; Multiple Myeloma; Eye Cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Fred Hutchinson Cancer Research Center Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have hematologic cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005804

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Chemotherapy and Radiation Therapy Plus Bone Marrow Transplantation in Treating Patients With Aggressive Non-Hodgkin's Lymphoma Condition(s): adult non-Hodgkin's lymphoma Study Status: This study is no longer recruiting patients. Sponsor(s): Scotland and Newcastle Lymphoma Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy and radiation therapy plus bone marrow transplantation in treating patients who have aggressive non-Hodgkin's lymphoma. Phase(s): Phase III Study Type: Interventional

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Bone Marrow Transplant

Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003815 •

Chemotherapy Plus Bone Marrow Transplantation in Treating Patients With Metastatic Melanoma Condition(s): Recurrent Melanoma Study Status: This study is no longer recruiting patients. Sponsor(s): Louisiana State University Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Clinical trial to study the effectiveness of chemotherapy plus bone marrow transplantation in treating patients with metastatic melanoma that has not responded to previous therapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003060

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Chemotherapy, Interferon, and Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia Condition(s): chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; Philadelphia chromosome negative chronic myelogenous leukemia Study Status: This study is no longer recruiting patients. Sponsor(s): German CML Study Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens or bone marrow transplantation in treating patients with chronic myelogenous leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002771

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Combination Chemotherapy With Bone Marrow Transplantation in Treating Men With Germ Cell Tumors Condition(s): recurrent testicular cancer; extragonadal germ cell tumor Study Status: This study is no longer recruiting patients. Sponsor(s): Federation Nationale des Centres de Lutte Contre le Cancer

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Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not known whether combining chemotherapy with bone marrow transplantation is a more effective treatment for men with germ cell tumors. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with bone marrow transplantation in treating men with relapsed germ cell tumors. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002566 •

Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome Condition(s): Myeloid Leukemia; Refractory Anemia Study Status: This study is no longer recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia or myelodysplastic syndrome. PURPOSE: Randomized phase III trial to compare the effectiveness of different chemotherapy regimens with or without bone marrow transplantation in treating children who have acute myelogenous leukemia or myelodysplastic syndrome. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002798

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Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia Condition(s): refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; childhood acute promyelocytic leukemia (M3); secondary myelodysplastic syndromes; de novo myelodysplastic syndromes; secondary acute myeloid leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies Study Status: This study is no longer recruiting patients. Sponsor(s): Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow doctors to give higher doses of chemotherapy and kill more cancer cells. It is not yet known whether chemotherapy is more effective with or without bone marrow transplantation for acute myeloid leukemia. PURPOSE: Randomized phase III trial to compare the effectiveness of

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chemotherapy with or without bone marrow transplantation in treating children who have acute myeloid leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003436 •

Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Acute Promyelocytic Leukemia Condition(s): untreated adult acute myeloid leukemia; adult acute promyelocytic leukemia (M3) Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Leukemia Cooperative Group; Gruppo Italiano di Malattie Ematologiche Maligne de l'Aduklto-Associazione Italiana de Ematologia e Oncologia Pediatric Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy to kill tumor cells. It is not yet known which regimen of combination chemotherapy with or without bone marrow transplantation is more effective in treating promyelocytic leukemia PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens with or without bone marrow transplantation in treating patients who have promyelocytic leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002701

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Combination Chemotherapy With or Without Donor Bone Marrow Transplantation in Treating Infants With Previously Untreated Acute Lymphoblastic Leukemia Condition(s): untreated childhood acute lymphoblastic leukemia; L1 childhood acute lymphoblastic leukemia; L2 childhood acute lymphoblastic leukemia; acute undifferentiated leukemia Study Status: This study is no longer recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Bone marrow transplantation allows the doctor to give higher doses of chemotherapy and kill more cancer cells. PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without donor bone marrow transplantation in treating infants who have previously untreated acute lymphoblastic leukemia. Phase(s): Phase II Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022126 •

Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia Condition(s): Myeloid Leukemia; Neutropenia Study Status: This study is no longer recruiting patients. Sponsor(s): Medical Research Council Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to compare the effectiveness of different treatment regimens in treating patients who have acute myeloid leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002658

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Combination Chemotherapy, Radiation Therapy, and Bone Marrow Transplantation in Treating Patients With Retinoblastoma Condition(s): extraocular retinoblastoma

retinoblastoma;

recurrent

retinoblastoma;

intraocular

Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); St. Jude Children's Research Hospital Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus radiation therapy followed by bone marrow transplantation in treating patients who have retinoblastoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004006 •

High Dose Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Intermediate- or High-Grade Non-Hodgkin's Lymphoma Condition(s): stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV grade III follicular large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell

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lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; stage III grade III follicular large cell lymphoma Study Status: This study is no longer recruiting patients. Sponsor(s): British National Lymphoma Investigation Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known whether high dose chemotherapy plus bone marrow transplantation is more effective than high dose chemotherapy alone for intermediate- or high-grade non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of high dose chemotherapy with or without bone marrow transplantation in treating patients who have intermediate- or high-grade nonHodgkin's lymphoma. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003578 •

Total-Body Irradiation, Tacrolimus, and Mycophenolate Mofetil Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancers Condition(s): Leukemia; Lymphoma; Multiple Myeloma Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Johns Hopkins Oncology Center Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Bone marrow transplantation may be able to replace immune cells that have been destroyed by radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Mycophenolate mofetil and tacrolimus may be an effective treatment for graft-versushost disease caused by bone marrow transplantation. PURPOSE: Phase II trial to study the effectiveness of total-body irradiation, tacrolimus, and mycophenolate mofetil plus bone marrow transplantation in treating patients with hematologic cancers. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003572

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A Study of Azidothymidine (AZT) in the Treatment of HIV Infection in Patients Receiving a Bone Marrow Transplant Condition(s): Lymphoma, Non-Hodgkin; HIV Infections Study Status: This study is completed. Sponsor(s): Glaxo Wellcome Purpose - Excerpt: To determine whether zidovudine (AZT) in conjunction with bone marrow transplantation prevents the reinfection of donor hematopoietic/lymphoid cells

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in patients with positive HTLV III antibody and large cell/diffuse histiocytic lymphoma. Patients who are candidates will be evaluated for HTLV III activity and drug levels. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002284 •

Carboplatin, Etoposide, Cyclophosphamide, and Autologous Transplantation in Patients With Relapsed or Refractory Cancer

Bone

Marrow

Condition(s): adult solid tumor; extragonadal germ cell tumor; ovarian germ cell tumor; Testicular Cancer Study Status: This study is suspended. Sponsor(s): Comprehensive Cancer Center of Wake Forest University; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous bone marrow transplantation may help the body kill more tumor cells. PURPOSE: Phase II trial to study the effects of high doses of carboplatin, etoposide, and cyclophosphamide followed by autologous bone marrow transplantation in patients with relapsed or refractory germ cell cancer and other chemotherapy-sensitive solid tumors. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002943 •

Combination Chemotherapy and Bone Marrow Transplantation in Treating Infants With Newly Diagnosed Acute Lymphocytic Leukemia Condition(s): untreated childhood acute lymphoblastic leukemia; acute undifferentiated leukemia Study Status: This study is suspended. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining bone marrow transplantation with chemotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and bone marrow transplantation in treating infants with newly diagnosed acute lymphocytic leukemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002756

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Reduced-Intensity Regimen Before Bone Marrow Transplantation in Treating Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma Condition(s): adult Hodgkin's lymphoma; adult non-Hodgkin's lymphoma Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Photopheresis allows patient white blood cells to be treated with ultraviolet light and drugs outside the body to inactivate T cells. Pentostatin may suppress the immune system and reduce the chance of developing graft-versus-host disease following bone marrow transplantation. Combining photopheresis with pentostatin and total-body irradiation may be effective in killing cancer cells before bone marrow transplantation. PURPOSE: Phase II trial to study the effectiveness of photophoresis, pentostatin, and total-body irradiation as a reducedintensity regimen before allogeneic bone marrow transplantation in treating patients who have relapsednon-Hodgkin's or Hodgkin's lymphoma. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057954

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Reduced-Intensity Regimen Before Donor Bone Marrow Transplantation in Treating Patients With Myelodysplastic Syndromes Condition(s): atypical chronic myeloid leukemia; Chronic Myelomonocytic Leukemia; myelodysplastic and myeloproliferative disease; Myelodysplastic Syndromes Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Photopheresis allows patient white blood cells to be treated with ultraviolet light and drugs outside the body to inactivate T cells. Pentostatin may suppress the immune system and reduce the chance of developing graft-versus-host disease following donor bone marrow transplantation. Combining photopheresis with pentostatin and total-body irradiation may be effective in killing cancer cells before donor bone marrow transplantation. PURPOSE: Phase II trial to study the effectiveness of photophoresis, pentostatin, and total-body irradiation before donor bone marrow transplantation in treating patients who have myelodysplastic syndromes. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045305

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Treatment of Bone Marrow to Prevent Graft-Versus-Host Disease in Patients With Acute or Chronic Leukemia Undergoing Bone Marrow Transplantation Condition(s): Leukemia Study Status: This study is completed. Sponsor(s): Chimeric Therapies

Clinical Trials 183

Purpose - Excerpt: RATIONALE: Bone marrow that has been treated to remove certain white blood cells may reduce the chance of developing graft-versus-host disease following bone marrow transplantation. PURPOSE: Randomized phase II/III trial to compare the effectiveness of treated bone marrow with that of untreated bone marrow in preventing graft-versus-host disease in patients with acute or chronic leukemia who are undergoing bone marrow transplantation. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004255

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

185

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

Patents on Bone Marrow Transplant By performing a patent search focusing on bone marrow transplant, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on bone marrow transplant: •

Bone marrow transplant method and apparatus Inventor(s): Altshuler; John H. (Englewood, CO), Farrish; Dean T. (Parker, CO) Assignee(s): Applied Medical Devices, Inc. (englewood, Co) Patent Number: 4,486,188 Date filed: April 8, 1982 Abstract: A bone marrow transplant method and apparatus has been devised for the efficient recovery of bone marrow from a donor or patient by inserting a pair of aspiration needles at the intended site of removal and, through connection with a pair of syringes, the pressure is regulated to bring about selective removal of bone marrow and sinusoidal blood through one of the aspiration needles while positively forcing an intravenous solution through the other of the aspiration needles to replace the bone marrow removed from the site. The bone marrow and sinusoidal blood are drawn into a chamber for mixture with another intravenous solution and thereafter forced into a collection bag. A disposable assembly is provided for ready interchangeable use in association with a fluid flow and valve control unit in carrying out the method and principles of the present invention. Excerpt(s): This invention relates to a novel and improved method and apparatus adaptable for use in medical transplant procedures; and more particularly to a method and apparatus for efficiently recovering bone marrow in bone marrow transplant operations. In the past, bone marrow transplants have been performed with success but have involved considerable pain due mainly to the number of bone marrow aspirations which must be performed. Bone marrow is comprised of bone marrow cells and large volumes of sinusoidal blood. For instance, it is not uncommon to have to insert a needle on the order of fifteen to seventy times into different sites or locations in order to recover acceptable quantities of bone marrow. Moreover, the bone marrow which is extracted is not separated from the sinusoidal blood, and in transfusing substantial volumes of material into the recipient, the bone marrow cavity is so finite and limited in capacity that it cannot readily accommodate huge volumes of blood and bone marrow. Thus, it is customary to inject the mass of material into the vein and depend upon the bone marrow present to find its way back into the marrow of the patient so as to function as normal marrow and undergo normal growth. A typical case requiring bone marrow transplantation is one in which healthy bone marrow is removed from a cancer patient prior to chemotherapy and the same bone marrow reinfused into the patient after chemotherapy. Another example is the need for bone marrow transplantation into a patient with decreased bone marror function as in aplastic anemia or bone marrow failure due to drugs. In this latter situation, healthy bone marrow must be removed from a healthy donor with the healthy marrow being infused into the recipient patient. It is therefore desirable to provide for a method and apparatus by means of which bone marrow may be harvested from a patient with a minimal number of needle placements which are capable of being performed under local anethesia over a relatively short period of time. Moreover, it is desirable that the procedure be virtually painless once the needles are inserted into the patient so as to avoid activation of stretch receptors in the marrow cavity. Web site: http://www.delphion.com/details?pn=US04486188__

Patents 187

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Method of mobilizing pluripotential hematopoietic stem cells with IL-7 Inventor(s): Grzegorzewski; Krzysztof (Montgomery Village, MD), Keller; Jonathan (Frederick, MD), Komschlies-McConville; Kristin L. (Westminister, MD), Ruscetti; Francis (New Market, MD), Wiltrout; Robert H. (Frederick, MD) Assignee(s): The United States of America AS Represented by the Department of Health (washington, Dc) Patent Number: 5,637,323 Date filed: November 16, 1994 Abstract: This invention provides a method of isolating an increased number of hematopoietic stem cells from a subject comprising a) administering interleukin-7 to the subject in an amount that mobilizes the hematopoietic stem cells to the peripheral blood; and, b) isolating a population of leukocytes enriched for hematopoietic stem cells from the peripheral blood. Also provided is a method of transplanting an increased number of hematopoietic stem cells from a donor to a recipient to enhance repopulation of the recipient's hematopoietic and immune cells comprising a) administering interleukin-7 to the donor in an amount that mobilizes the hematopoietic stem cells to the peripheral blood; b) isolating a population of leukocytes enriched for hematopoietic stem cells from the donor's peripheral blood; and, c) transplanting the isolated population of leukocytes enriched for hematopoietic stem cells to the recipient, thereby enhancing the repopulation of the recipient's hematopoietic and immune cells. Finally, the invention provides a method of improving engraftment of a bone marrow transplant or a peripheral blood leukocyte transplant from a donor to a recipient comprising administering interleukin-7 to the recipient following transplantation in an amount that enhances engraftment. Excerpt(s): The present invention relates to the field of hematopoietic cell mobilization. In particular, IL-7 has been found to mobilize hematopoietic stem cells, which can be used to augment peripheral blood transfusions and bone marrow transplantations. Autologous bone marrow transplantation (BMT) has been used for the support of high dose chemotherapy in the treatment of various neoplastic diseases (1). Under steadystate conditions, the majority of primitive hematopoietic stem and progenitor cells reside in the bone marrow, and only a low number of these cells can be isolated from the peripheral blood. However, additional peripheral blood progenitor cells (PBPC) and peripheral blood stem cells (PBSC) can be mobilized by treatment with myelosuppressive agents (2), and/or certain growth factors (3, 4). Recent studies have shown that PBPC and PBSC exhibit enhanced potential for engraftment as compared to BMT (4, 5). The differentiation of cells of the various hemopoietic lineages involves a complex and, as yet, incompletely understood series of events. In recent years, advances have been made in isolating and expressing cytokines known to be involved in hematopoiesis. Granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin-3 (IL-3), granulocyte-CSF, CSF-1 and IL-6 have been shown to be directly stimulatory to myeloid progenitor cells (25, 26). In contrast, the factors which regulate lymphopoiesis at the progenitor cell level are largely unknown despite a large body of evidence showing significant effects of various interleukins on mature T-cells and Bcells. Web site: http://www.delphion.com/details?pn=US05637323__

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Rapid expansion method ("REM") for in vitro propagation of T lymphocytes Inventor(s): Greenberg; Philip D. (Mercer Island, WA), Riddell; Stanley R. (Bothell, WA) Assignee(s): Fred Hutchinson Cancer Research Center (seattle, Wa) Patent Number: 5,827,642 Date filed: October 3, 1994 Abstract: The present invention provides a rapid expansion method (termed "REM"), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes. REM involves culturing the T cells in association with a disproportionately large concentration of nondividing feeder cells, preferably.gamma.irradiated peripheral blood mononuclear cells ("PBMC") present at an excess of at least 40-fold (relative to the number of target T cells), more preferably at an excess of at least about 200-fold. Cultures grown under REM exhibit dramatically enhanced expansion rates that can be even further elevated by the use of appropriate concentrations of an additional feeder cell, an anti-CD3 monoclonal antibody and IL-2, as described herein. Clonal expansions in the range of 500-fold to 3000-fold can be achieved within a single stimulation cycle of about 10-13 days, which is more than 100-fold more efficient than currently employed methods of culturing human T cell clones. Genetic transduction efficiencies were also enhanced using REM-expanded T lymphocytes. Several examples involving human bone marrow transplant recipients illustrate the effective use of REMexpanded antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy in humans. Excerpt(s): This invention relates to improved methods for culturing T lymphocytes, including human antigen-specific cytolytic and helper T lymphocytes. The method of the present invention results in the very rapid and efficient expansion of T cells which are useful, for example, in adoptive immunotherapy. T lymphocytes are formed in the bone marrow, migrate to and mature in the thymus and then enter the peripheral blood and lymphatic circulation. T lymphocytes are subdivided into three distinct types of cells: helper T cells, suppressor T cells, and cytotoxic T cells. T lymphocytes, unlike B lymphocytes, do not produce antibody molecules, but express a heterodimeric cell surface receptor that recognizes peptide fragments of antigenic proteins that are attached to proteins of the major histocompatibility complex (MHC) and expressed on the surfaces of target cells; see, e.g., Abbas, A. K., Lichtman, A. H., and Pober, J. S., Cellular and Molecular Immunology, 1991, esp. pages 15-16. Cytotoxic T lymphocytes (CTLs) are typically of the CD3+, CD8+, CD4- phenotype and lyse cells that display fragments of foreign antigens associated with class I MHC molecules on their cell surfaces. Target cells for CTL recognition include normal cells expressing antigens after infection by viruses or other pathogens; and tumor cells that have undergone transformation and are expressing mutated proteins or are over-expressing normal proteins. Web site: http://www.delphion.com/details?pn=US05827642__

Patents 189

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Treatment of aluimmunization and refractoriness to platelet transfusion by protein A column therapy Inventor(s): Christie; Douglas J. (St. Paul, MN), Howe; Robert B. (Wayzata, MN) Assignee(s): Regents of the University of Minnesota (minneapolis, Mn) Patent Number: 5,277,701 Date filed: November 15, 1991 Abstract: The invention provides a therapeutic method for treating refractoriness to platelet transfusion by isolating blood serum from an alloimmunized patient undergoing platelet transfusion therapy, passing the serum through a bed comprising staphococcal protein A coupled to a solid support and returning the treated plasma to the patient. The method can be conducted by batch-type procedure or by continuously conducting the steps so that blood is withdrawn, passed through the bed, and returned to the patient as a continuous stream. The method is useful to treat alloimmunized patients suffering from leukemia, aplastic anemia, myelofibrosis, myelodysplastic syndrome, or in a bone marrow transplant patient. Excerpt(s): Refractoriness to platelet transfusion (RPT) is a serious complication of leukemia therapy, bone marrow transplantation, and other disorders where multiple infusions of platelets are required to prevent bleeding. Alloimmunization to HLA class I antigens is an important cause of RPT, with some estimates as high as 50-70% of patients receiving multiple platelet transfusions becoming alloimmunized to HLA antigens. (P. Daly et al., JAMA, 253:435 (1980); D. Hogge et al., Am. J. Hematol., 14:363 (1983); R. Kakaiya et al., Transfusion, 24:35 (1984); J. Eernisse et al., Exp. Hematol., 9:77 (1981); M. Murphy et al., Brit. J. Haematol., 60:409 (1985); and M. Murphy et al., Brit. J. Haematol., 62:529 (1986).) Additionally, antibodies directed against platelet-specific antigens, such as HPA-1a(=P1.sup.A1)*, HPA-1b(=P1.sup.A2) and HPA-3a(=Bak.sup.a), HPA2b(=Sib.sup.a), Nak.sup.a, and Gov.sup.a /Gov.sup.b have also been implicated in platelet transfusion failure. (R. Kickler et al., Transfusion, 30:622 (1990); F. Langenscheidt et al., Transfusion, 28:597 (1988); H. Saji et al., Vox Sang, 56:283 (1989), H. Ikeda et al., Vox Sang, 57:213 (1989); and J. Kelton et al., Blood, 75:2172 (1990).) Moreover, drug-dependent antibodies induced by vancomycin were recently found in association with RPT in two patients with leukemia. (D. Christie et al., Blood, 75:518 (1990).) Thus, it is apparent that a wide variety of different antibodies may contribute to shortened survival of transfused platelets. Standard transfusion strategies generally recommend that patients first receive pooled random donor platelets, followed by random single donor and HLA-matched single donor platelets once alloimmunization occurs. (J. Herman et al., Am. J. Ped. Hematol./Oncol., 9:272 (1987)). Although steroids, splenectomy, immunosuppressive therapy, IV IgG, and plasmapheresis have often proved successful in treating autoimmune thrombocytopenia (ATP), they have for the most part been ineffective in reducing RPT due to alloimmunization. (J. Herman et al., Am. J. Ped. Hematol./Oncol., 9:272 (1987); D. Hogge et al., Blood, 64:253 (1984); C. Schiffer et al., Blood, 64:937 (1984); and W. Bensinger et al., Transplantation, 41:602 (1986).) Several reports have shown marked increases in platelet counts in patients with ATP following reinfusion of autologous plasma that had been absorbed by immobilized protein A. (T. Guthrie et al, Sem. Hematol., 26(Suppl 1):3 (1989); K. Muroi et al., Sem. Hematol., 26(Suppl 1):10 (1989); A. Mittleman et al., Sem. Hematol., 26(Suppl 1):15 (1989); and H. Snyder, Jr. et al., Artif. Organ, 13:71 (1989).) In the present study, we investigated the effectiveness of protein A column therapy for improving platelet counts and transfusion refractoriness in 12 thrombocytopenic patients with histories of being unresponsive to platelet transfusion therapy. A therapeutic method is provided for

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treating refractoriness to platelet transfusion (RTP) in alloimmunized patients undergoing platelet transfusion therapy which permits the patients to sustain higher average daily platelet counts (2-10X higher than pretreatment) and to exhibit improved responsiveness to both random and HLA-matched platelet transfusion. The present method also decreases circulating platelet antibodies, which are responsible for alloimmunization. Web site: http://www.delphion.com/details?pn=US05277701__ •

Vectors encoding a modified low affinity nerve growth factor receptor Inventor(s): Bordignon; Claudio (Milan, IT), Mavilio; Fulvio (Milan, IT) Assignee(s): Roche Diagnostics Gmbh (mannheim, De) Patent Number: 6,268,214 Date filed: June 12, 1998 Abstract: In the course of therapy following an allogeneic bone marrow transplant (alloBMT) in which lymphocytes were removed from the transplant, donor lymphocytes are introduced after a delay to reconstitute immunity in the patient. According to the invention, these donor lymphocytes are transduced with a detectable cell surface marker and a suicide gene prior to introducing them into the patient. Introduction of these transduced lymphocytes after allo-BMT, serves to treat or prevent complications from the BMT, including disease relapse, reactivation of viral infection and Graft versus Host disease. Excerpt(s): Bone marrow transplant represents hope for survival for many patients who suffer from blood, lymphatic and bone-related disorders, and from depleted marrow cells resulting from intensive chemo- and/or radiotherapy. In an "allogeneic" bone marrow transplantation ("allo-BMT"), bone marrow is transplanted from a donor other than the patient (autologous transplant) or the patient's identical sibling (syngeneic transplant). Allogeneic BMT is the treatment of choice for many hematologic malignancies, such as leukemia, lymphoma and multiple myolema (1, 2). It is the only curative therapy for chronic myeloid leukemia. Transplantation of allogeneic bone marrow, particularly when employed together with high-dose chemoradiotherapy, has been shown to produce superior results compared to autologous or syngeneic transplants (3). The advantages associated with allogeneic BMT are limited by the risk of a potentially life-threatening complication, graft versus host disease (GvHD). In performing allogeneic BMT, the patient initially undergoes an immunosuppressive regimen to minimize rejection of the graft. Severe GvHD following allo-BMT can be controlled by: (i) treating the patient to eliminate residual recipient alloreactive T cells, and (ii) treating the graft to remove mature alloreactive T lymphocytes (2). Web site: http://www.delphion.com/details?pn=US06268214__

Patent Applications on Bone Marrow Transplant As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take 10

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

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several years.) The following patent applications have been filed since December 2000 relating to bone marrow transplant: •

Bcr-Abl directed compositions and uses for inhibiting Philadelphia chromosome stimulated cell growth Inventor(s): Arlinghaus, Ralph B.; (Bellaire, TX), Liu, Jiaxin; (Bellaire, TX), LopezBerestein, Gabriel; (Bellaire, TX), Lu, Dai; (Pearland, TX), Wu, Yun; (Houston, TX) Correspondence: Fulbright & Jaworski L.L.P.; 600 Congress AVE.; Suite 2400; Austin; TX; 78701; US Patent Application Number: 20040022772 Date filed: March 25, 2003 Abstract: Compositions comprising or encoding one or more peptides that inhibit the Bcr--Abl oncoprotein and that bind to molecules involved in Bcr--Abl function are disclosed. The peptides and polypeptides inhibit the growth of, and induce cell death of, Philadelphia chromosome-positive leukemia cells expressing the Bcr--Abl oncoprotein. Methods for treating leukemias (e.g., CML, ALL and AML), including autologous bone marrow transplant therapy, using the peptide and polypeptide compositions of the invention are also provided. Excerpt(s): The present invention relates generally to the field of malignant cell proliferation. More particularly, it provides compositions and methods to limit Bcr--Abl oncoprotein-driven malignant cell proliferation. Peptide and protein molecules are provided that inhibit various Bcr--Abl signal transduction pathways, e.g., activation of the Ras protein. Methods for reducing Philadelphia chromosome-positive cells in cell populations, including bone marrow culture, and methods of treating various leukemias are also provided. The Philadelphia chromosome (Ph.sup.1) is associated with the bulk of chronic myelogenous leukemia (CML) patients (more than 95%), 10-25% of acute lymphocytic leukemia (ALL) patients, and about 2-3% of acute myelogenous leukemias (AML). This abnormal chromosome fuses most of the ABL gene to the 5' two-thirds of the BCR gene. A number of different kinds of evidence support the contention that Bcr-Abl oncoproteins, such as p210 and p185 BCR--ABL, are causative factors in these leukemias (Campbell et al., 1991). The malignant activity is due in large part to the Bcr-Abl protein's highly activated protein tyrosine kinase activity and its abnormal interaction with protein substrates (Campbell er al., 1991, Arlinghaus et al., 1990). The Bcr--Abl oncoprotein p210 Bcr--Abl is associated with both CML and ALL, whereas the smaller oncoprotein, p185 BCR--ABL, is associated with ALL patients, although some CML patients also express p185 (Campbell et al., 1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Control of NK cell function and survival by modulation of ship activity Inventor(s): Ghansah, Tomar; (Sarasota, FL), Kerr, William G.; (Tampa, FL) Correspondence: Jeff Lloyd, ESQ.; Saliwanchik, Lloyd & Saliwanchik; 2421 N. W. 41st Street, Suite A-1; Gainesville; FL; 32606-6669; US Patent Application Number: 20020165192 Date filed: March 14, 2002 Abstract: Inhibition of dendritic cell function in solid organ grafts or allogeneic bone marrow transplants prior to or during engraftment by blocking SH2-containing inositol

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phosphatase (SHIP) expression or function is taught as a method of abrogating immune rejection and thereby increasing the efficacy of engraftment of an allogeneic bone marrow transplant or solid organ allograft or xenograft. Also disclosed is a transgenic mouse having the genotype SHIP.sup.-/- which exhibits enhanced survival following mismatched allogeneic marrow grafts. Excerpt(s): This application claims priority to U.S. application Ser. No. 09/955,174, which claims priority to U.S. Provisional Application 60/233,661, filed Sep. 19, 2000, and to a U.S. Provisional Application filed on Aug. 23, 2001, under PEPPER HAMILTON LLP Docket Number 114205.2401, entitled "Control of NK Cell Function and Survival by Modulation of SHIP Activity," the disclosure of which is hereby incorporated in its entirety by reference. This invention relates to the hematopoietic-specific SH2containing Inositol Polyphosphatase (SHIP) and its effect in modulating Natural Killer (NK) cell function and survival. Specifically, genetic and pharmaceutical methods are disclosed for the modulation of SHIP activity in order to influence NK cell function. The invention further relates to methods for decreasing immune rejection of histoincompatible bone marrow grafts and solid organ allografts or xenografts, and methods for screening substances or genetic constructs for their ability to modulate SHIP activity. Activation of phosphatidylinositol 3'-kinase (PI 3-kinase) by growth factors and oncogenes has been implicated as a critical step in mitogenic signaling, cellular transformation and in the prevention of cell death (apoptosis), as described in Cantley et al, Cell 64:281-302 (1991), Kapeller and Cantley. Bioessays 16:565-76 (1994), and Stephens et al, Biochim BiophysActa 1179:27-75 (1993). PI3-kinase consists of 85 kDa and 110 kDa subunits which associate with receptor tyrosine kinases, other receptors and intracellular signaling molecules in response to survival signals, treatment with growth factors or in normal or transformed cells. Blockade of PI 3-kinase function either by mutagenesis or with pharmacological inhibitors prevents mitogenic signaling and can enhance apoptosis by blocking the activation of Akt/Protein Kinase B. Further, two products of PI 3-kinase, Ptdlns(3,4,5)P.sub.3 (PIP3) and Ptdlns(3,4)P.sub.2, increase in cells treated with mitogenic stimuli, as shown by Hawkins, et al. Nature 358:157-910, (1992) and Klippel et al, Molecular and Cellular Biology 16:41174127 (1996). The products of PI 3-kinase are presumed to act as second messengers, as regulators of protein-protein interactions, or recruit other kinases that phosphorylate downstream effectors of PI3K signaling. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

L-leucyl-L-leucine methyl ester treatment of donor lypmhocyte infusions in bone marrow transplant patients Inventor(s): Flomenberg, Neal; (Cherry Hill, NJ), Hsieh, Michael; (Philadelphia, PA), Korngold, Robert; (Cherry Hill, NJ) Correspondence: Thomas Jefferson University; Intellectual Property Division; 1020 Walnut Street; Suite 620; Philadelphia; PA; 19107; US Patent Application Number: 20010036664 Date filed: March 9, 2001 Abstract: The present invention relates to a method of inhibiting graft-versus-host disease in allogeneic hematopoietic stem cell transplant (HSCT) patients by using Lleucyl-L-leucine methyl ester (LLME) to eliminate selective cytotoxic T cells in donor lymphocyte infusions (DLI). LLME has been shown to inhibit GVHD in animal models by selectively inducing apoptosis in natural killer cells and cytotoxic T cells. The

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application of LLME to the human clinical HSCT situation, however, has been hampered by HSC toxicity when unseparated marrow is treated at the concentrations necessary to purge GVHD-inducing T cells prior to infusion. In the present invention, this problem is circumvented by the LLME ex vivo treatment of DLI administered following transplantation of T cell-depleted HSC. In this setting, the effects of LLME on HSC contained within the DLI are irrelevant for clinical outcome. In another embodiment, the risk of toxicity to the stem cell population is avoided by ex vivo LLME treatment of donor lymphocytes after separation of CD34.sup.+ stem cells and then coadministration of the LLME-treated donor CD34.sup.- fraction and the untreated CD34.sup.+ stem cells. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119 based upon U.S. Provisional Application No. 60/188,391 filed Mar. 10, 2000. The present invention generally relates to the fields of medicine and immunology and to a method of using Lleucyl-L-leucine methyl ester (LLME) to selectively eliminate cytotoxic T-cells in donor lymphocyte infusions (DLI) simultaneously with, as part of, or following allogeneic hematopoietic stem cell transplantation (HSCT) and, more particularly, to inhibiting the development of graft-versus-host-disease in mammals. Allogeneic hematopoietic stem cell transplantation (HSCT) is a unique modality in cancer therapy. While, in some settings, this treatment may be the only currently curative approach and may produce very low relapse rates, its high early mortality often dampens enthusiasm for its use. The consequences of graft versus host disease (GVHD) prophylaxis and treatment and, in particular, the immunoincompetence and vulnerability to secondary opportunistic infections of allogeneic HSCT recipients are the major reasons for the higher mortality in these patients. The hallmark of this immunodeficiency is a prolonged CD4.sup.+ T cell cytopenia. Current approaches for conditioning patients and T cell-depleting HSCT can secure consistent engraftment without any GVHD, but clinical outcome is still unsatisfactory because of immunoincompetence and secondary infections. Since GVHD can be prevented without the need for ongoing immune suppression, if immunoincompetence, particularly CD4.sup.+ cytopenia, can be rapidly reversed, then the mortality of allogeneic HSCT will drop to levels more comparable to those of autologous HSCT, producing an improved therapeutic index. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treatment of acute lymphocytic leukemia Inventor(s): Brown, Valerie I.; (Philadelphia, PA), Grupp, Stephan A.; (Havertown, PA) Correspondence: Dann, Dorfman, Herrell & Skillman; 1601 Market Street; Suite 2400; Philadelphia; PA; 19103-2307; US Patent Application Number: 20040039010 Date filed: May 30, 2003 Abstract: Methods for treating patients having an early B cell derived acute lymphoblastic leukemia with rapamycin or a derivative thereof are provided. Also provided are methods for treating patients having an early B cell derived acute lymphoblastic leukemia with rapamycin or a derivative thereof in combination with an IL-7 inhibitor. Finally methods for preventing GVHD in ALL patients following a bone marrow transplant are disclosed. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) to U.S. Provisional Patent Application No. 60/384,245 filed on May 30, 2002, the entire disclosure of which

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is incorporated by reference herein. Methods for using rapamycin or derivatives thereof, in the treatment of a patient with early B cell derived acute lymphoblastic leukemia (ALL) are disclosed. Methods are also provided for the treatment of a patient afflicted by an early B cell-derived ALL with rapamycin or a derivative thereof in combination with an IL-7 inhibitor. Also provided are methods for preventing GVHD in ALL patients following bone marrow transplantation. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical composition, a method of preparing it and a method of treatment by use thereof Inventor(s): Hassan, Moustapha; (Huddinge, SE), Hassan, Zuzana; (Huddinge, SE) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, N.W.; Washington; DC; 20001; US Patent Application Number: 20040022841 Date filed: April 30, 2003 Abstract: Pharmaceutically acceptable liposome-encapsulated busulphan formulations for parenteral administration are provided, as well as such formulations furthermore comprising glutathione and/or at least one glutathione precursor and a process for manufacture of the preparations. The formulations are stable, have improved biodistribution and significantly reduced side effects over those produced by oral administration or parenteral administration of free drug. The formulations are useful as part of stem cell and/or bone marrow transplant conditioning regimens. A method of treatment of a mammal by use of such formulations. Excerpt(s): The present application is a continuation-in-part of application Ser. No. 09/719,840, filed Dec. 18, 2000, which was a 371 of PCT of PCT/SE99/01093, filed Jun. 18, 1999, and claims priority from U.S. provisional applications Ser. No. 60/376,533, filed May 1, 2002, and Ser. No. 60/089,759, filed Jun. 18, 1998, all of which are hereby incorporated by reference herein. This invention relates to the fields of biochemistry and medicine, and in particular to a pharmaceutical composition of busulphan having enhanced therapeutic efficiency coupled to decreased negative side effects and to a method of therapeutic treatment of a mammal by use of such composition. Busulphan (1,4-bis-(methanesulphonyloxy)butan) is a bifunctional alkylating agent with potent antitumor effects. It has been widely used for treatment of malignant diseases, especially hematological malignancies and myeloproliferative disorders. Its use was for a long time restricted to low dose oral therapy, with recorded side effects such as busulphaninduced pulmonary fibrosis (Oakhill et al. 1981. J. Clin. Pathol. 34(5):495-500.) and irreversible myelo-suppression (Canellos 1985. Chronic Leukemias In: Cancer: Principles and Practice of Oncology, pp 1739-1752). In 1983, high-dose combination chemotherapy based on oral busulphan for pretransplant-conditioning of patients undergoing both autologous and allogeneic bone marrow transplantation (Santos, G. W. et al. 1983. N. Engl. J. Med. 309:1347-1353; Lu, C. et al. 1984. Cancer Treatm. Repts. 68:711-717) was introduced. Since then, high dose busulphan replaces total body irradiation (TBI), most commonly in combination with cyclophosphamide, and has proven to be a most effective anti-leukemic regimen when used in conjunction with autologous or allogeneic hematopoietic stem cell support. The main advantage of highdose busulphan therapy for use in marrow ablation treatment is that total body

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irradiation regimen is avoided, which is especially advantageous for young children and adults who received TBI as part of their initial therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of autoimmune diseases Inventor(s): Skurkovich, Boris; (Pawtucket, RI), Skurkovich, Simon; (Rockville, MD) Correspondence: Morgan, Lewis & Bockius Llp; 1701 Market Street; Philadelphia; PA; 19103-2921; US Patent Application Number: 20030059428 Date filed: March 8, 2002 Abstract: The invention includes methods of treating skin-related autoimmune disease in a patient, graft-versus-host disease, and bone marrow transplant rejection, where the method includes administration of antibody to gamma interferon to the patient. Excerpt(s): This application is a continuation-in-part application of co-pending U.S. patent application Ser. No. 09/419,053, filed Oct. 15, 1999, which is a divisional of U.S. patent application Ser. No. 08/995,730, filed Dec. 22, 1997, now issued as U.S. Pat. No. 6,333,032 BI, which is a continuation of U.S. application Ser. No. 08/771,831, filed Dec. 23, 1996, now issued U.S. Pat. No. 5,888,511, which is a continuation-in-part of U.S. patent application Ser. No. 08/025,408, filed Feb. 26, 1993. The ability of the immune system to discriminate between "self" and "non-self" antigens is vital to the functioning of the immune system as a specific defense against invading microorganisms. "Non-self" antigens are those antigens on substances entering or present in the body which are detectably different or foreign from the animal's own constituents, whereas "self" antigens are those which, in the healthy animal, are not detectably different or foreign from its own constituents. However, under certain conditions, including in certain disease states, an individual's immune system will identify its own constituents as "nonself," and initiate an immune response against "self" material, at times causing more damage or discomfort as from an invading microbe or foreign material, and often producing serious illness in an individual. Autoimmune disease results when an individual's immune system attacks his own organs or tissues, producing a clinical condition associated with the destruction of that organ or tissue, as exemplified by diseases such as rheumatoid arthritis, insulin-dependent diabetes mellitus, acquired immunodeficiency syndrome ("AIDS"), hemolytic anemias, rheumatic fever, Crohn's disease, Guillain-Barre syndrome, psoriasis, thyroiditis, Graves' disease, myasthenia gravis, glomerulonephritis, autoimmune hepatitis, multiple sclerosis, systemic lupus erythematosus, etc. Blocking, neutralizing or inhibiting the immune response or removing its cause in these cases is, therefore, desirable. Autoimmune disease may be the result of a genetic predisposition alone or as the result of the influence of certain exogenous agents such as, viruses, bacteria, or chemical agents, or as the result of the action of both. Some forms of autoimmunity arise as the result of trauma to an area usually not exposed to lymphocytes, such as neural tissue or the lens of the eye. When the tissues in these areas become exposed to lymphocytes, their surface proteins can act as antigens and trigger the production of antibodies and cellular immune responses which then begin to destroy those tissues. Other autoimmune diseases develop after exposure of the individual to antigens which are antigenically similar to, that is crossreactive with, the individual's own tissue. For example, in rheumatic fever an antigen of the streptococcal bacterium, which causes rheumatic fever, is cross-reactive with parts of the human heart. The antibodies cannot differentiate between the bacterial antigens and

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the heart muscle antigens, consequently cells with either of those antigens can be destroyed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Vector encoding suicide and marker constructs Inventor(s): Lewis, Victor; (Calgary, CA), Orchard, Paul; (Eden Prairie, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030121068 Date filed: November 4, 2002 Abstract: The present invention provides a vector encoding a detectable cell surface marker and a suicide construct, and cells and a non-human mammal transduced with this vector. Introduction of lymphocytes transduced with this vector, after allogeneic bone marrow transplantation, serves to treat or prevent complications from the bone marrow transplant, including graft versus host disease. Excerpt(s): This application claims the benefit of the filing dates of U.S. Provisional Applications Serial No. 60/334,795, filed Nov. 30, 2001, and No. 60/369,507, filed Apr. 3, 2002, under 35 U.S.C.sctn.119(e), which are herein incorporated by reference. The present invention provides a vector including a nucleic acid sequence encoding a detectable cell surface marker and a suicide construct, and cells, e.g. lymphocytes, transduced with this vector. Introduction of lymphocytes transduced with this vector, after allogeneic bone marrow transplantation, serves to treat or prevent complications from the bone marrow transplant, including graft versus host disease. Patients having blood, lymphatic or bone-related disorders may receive a bone marrow transplant (BMT). Bone marrow taken from the patient is "autologous " marrow, and bone marrow from an identical sibling (twin) is "syngenic" marrow. Unfortunately, in many circumstances, bone marrow from these sources is unavailable or not appropriate. Donor bone marrow must then be taken from a donor other than the patient or an identical sibling. This type of marrow is termed "allogeneic" bone marrow. Allogeneic BMT is used to treat many hematologic malignancies, such as leukemia, lymphoma and multiple myeloma, as well as to treat genetic disorders. It is the only curative therapy for chronic myeloid leukemia (CML). Allogeneic BMT (allo-BMT) is an important modality in the treatment of hematologic malignancies. In cases of relapsed leukemia, the infusion of matched or alternate donor hematopoietic stem cells after high dose conditioning chemotherapy, with or without radiation, may offer the best chance for permanent cure. Major contributors to non-relapse mortality include infections and the presence of graftversus-host disease (GVHD). The morbidity associated with GVHD is high, and the mortality observed in cases of severe (grade III/IV) GVHD is greater than 50%. The risk of grade III-IV GVHD is higher in alternative donor transplantation. 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 bone marrow transplant, you can access the U.S. Patent Office archive via the Internet at the following

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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 “bone marrow transplant” (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 bone marrow transplant. You can also use this procedure to view pending patent applications concerning bone marrow transplant. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON BONE MARROW TRANSPLANT Overview This chapter provides bibliographic book references relating to bone marrow transplant. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bone marrow transplant 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 “bone marrow transplant” (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 bone marrow transplant: •

Cutaneous and Oral Manifestations of Reactions to Anti-infective Drugs: A Monograph Source: Research Triangle Park, NC: Glaxo, Inc. 1993. 31 p. Contact: Available from Glaxo-Wellcome Education Resource Center. 5 Moore Drive, Research Triangle Park, NC 27709. (800) 824-2896. PRICE: Single copy free. Stock Number GVL290. Summary: As patients receive multiple drugs, identifying drug-induced reactions becomes increasingly complex and pinpointing a specific drug as the cause is even more challenging. This professional education monograph focuses on the dermatologic signs that can be used to identify the anti-infective agents, primary antibacterial and antifungal drugs, responsible for skin and oral reactions. Topics include the role of the medication history, clinical assessment, epidemiology, pathophysiology, and diagnostic

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tests. The monograph then presents six case scenarios covering toxic epidermal necrolysis in HIV infection, erythema multiform in a young woman, tetracyclineinduced photosensitivity reaction, erythema nodosum in a young woman, ampicillininduced eruption in mononucleosis, and a bone marrow transplant recipient with papular urticarial eruptions. The monograph concludes with a list of educational objectives, a list of references, and a self-test and directions for registering for continuing medical education credits. 12 figures. 6 tables. 11 references. (AA-M). •

Oral Health in Cancer Therapy Source: Austin, TX: Texas Cancer Council. 1999. 48 p. Contact: Available from Dental Oncology Education Program. 1106 Clayton Lane, Suite 216E, Austin, TX 78723. (888) 443-2439. Fax (512) 443-0953. Website: www.doep.org. PRICE: Single copy free. Also available on the web at http://www.doep.org/OHCT.pdf. Summary: With the increasing trend in outpatient management, including cancer therapy, every health care professional is a potential and integral part of the cancer treatment team that once existed solely within the hospital environment. This guide helps health care providers to assist patients in maintaining their oral health prior to, during, and following the treatment of cancer. The guide includes seven sections: an introduction, different types of cancer therapies, pretreatment, during cancer therapy, following cancer therapy, oral care in pediatric oncology (cancer care for children), and reimbursement for cancer related oral care. Specific topics include the cancer treatment team, stages of cancer therapy, head and neck radiation, chemotherapy, bone marrow transplant, head and neck surgery, pretreatment dental assessment, the role of oral hygiene, fluoride therapy, hematologic guidelines, antibiotic protocols, oral hygiene, mouth rinses, mucositis management, topical anesthetics, infections, fungal medications, antiviral agents, neurotoxicity, growth factors, handling of secretions during chemotherapy, nutrition concerns, xerostomia (dry mouth) management, drugs that may make xerostomia worse, postoperative rehabilitation, and sources of payment for costs of cancer related oral care. Much of the information is presented in table or outline format, for ease of reference. The guide concludes with a list of selected references (organized by topic) and information about the Dental Oncology Education Program (www.doep.org). 51 references.

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

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""B"" Is for Bone Marrow: Bone Marrow Transplant by Elizabeth Bussey Sowdal; ISBN: 0929173392; http://www.amazon.com/exec/obidos/ASIN/0929173392/icongroupinterna

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A Reason for Optimism: Treating Cancer With a Bone Marrow Transplant by Barbara J. Munson, Connie Marshall (Illustrator); ISBN: 0964875403; http://www.amazon.com/exec/obidos/ASIN/0964875403/icongroupinterna

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Bone marrow transplants national program has greatly increased pool of potential donors : report to congressional committees (SuDoc GA 1.13:HRD-93-11) by U.S. General Accounting Office; ISBN: B00010G2GA; http://www.amazon.com/exec/obidos/ASIN/B00010G2GA/icongroupinterna

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Bone Marrow Transplants: A Book of Basics by Susan K. Stewart; ISBN: 0964735202; http://www.amazon.com/exec/obidos/ASIN/0964735202/icongroupinterna

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Bone Marrow Transplants: A Guide for Cancer Patients and Their Families by Marianne L. Shaffer, George W. Santos (Designer); ISBN: 0878338551; http://www.amazon.com/exec/obidos/ASIN/0878338551/icongroupinterna

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Exercise for patients having a bone marrow transplant (SuDoc HE 20.3002:EX 3/2) by U.S. Dept of Health and Human Services; ISBN: B00010QCF6; http://www.amazon.com/exec/obidos/ASIN/B00010QCF6/icongroupinterna

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Homecare Management of the Bone Marrow Transplant Patient by Jean Nelson Lonergan (Editor), et al; ISBN: 0867207442; http://www.amazon.com/exec/obidos/ASIN/0867207442/icongroupinterna

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Organ and Bone Marrow Transplant Program Reauthorization Act of 1995 : report (to accompany S. 1324) (SuDoc Y 1.1/5:104-256) by U.S. Congressional Budget Office; ISBN: B00010QYT0; http://www.amazon.com/exec/obidos/ASIN/B00010QYT0/icongroupinterna

Chapters on Bone Marrow Transplant In order to find chapters that specifically relate to bone marrow transplant, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and bone marrow transplant 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 “bone marrow transplant” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on bone marrow transplant: •

Antimicrobial Therapy for Immunocompromised Patients Source: in Newman, M.G. and van Winkelhoff, A.J., eds. Antibiotic and Antimicrobial Use in Dental Practice. 2nd ed. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 227-233. 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: $32.00 plus shipping and handling. ISBN: 0867153970.

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Summary: Oral infections can seriously affect morbidity (illness) and mortality (death) in immunocompromised patients, and the number of these patients who present for care in the dental office continues to increase. This chapter on antimicrobial therapy for immunocompromised patients is from a textbook that integrates basic facts and principles of antibiotic therapy with recently-emerged concepts of care. The authors cover antimicrobial treatment for prophylaxis (prevention) and secondary infections in HIV, cancer chemotherapy, and bone marrow or organ transplant patients. Specific topics include periodontal lesions, oral candidiasis, odontogenic infection, oral changes during cancer chemotherapy, and bone marrow transplantation. Important principles, key facts, and clinical insights are highlighted and the chapter concludes with a list of references. 2 figures. 20 references. •

Gastrointestinal Complications in Stem Cell Transplantation Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 649-654. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Stem cell transplantation (SCT) is the standard of care for the treatment of many hematologic (blood) malignancies, pediatric solid tumors, inherited disorders, and aplastic anemia (a deficiency of all the formed elements of blood). SCT also is being used to treat many autoimmune disorders in experimental situations. This chapter on gastrointestinal complications in SCT is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). Several patients with CD and leukemia have remitted or remained in remission after bone marrow transplantation. Complications related to SCT are becoming more widely recognized. Gastrointestinal complications of SCT result from preparative regimen toxicity, infection, and acute and chronic graft-versus-host (GVH) disease, which may be difficult to diagnostically separate and are therefore addressed in this chapter. Diarrhea related to toxicity induced by the preoperative regimen may last until day 15 after SCT. Infectious causes of diarrhea must be considered and can include bacterial and viral pathogens. Once infectious causes are ruled out, antidiarrheal agents (such as loperamide) may be initiated. Nausea, vomiting, and anorexia occur commonly during the preparative regimen; if they are severe, total parenteral (outside the GI tract) nutrition (TPN) must be used. At its simplest level, GVH disease arises from the recipient's immune recognition of minor antigenic differences between donor and recipient. Patients with gut GVH disease present with abdominal pain, nausea, and vomiting or diarrhea. The physical examination and history may include a rash on the hands, feet, and ears. In addition, significant GI bleeding may occur post transplant and contribute to higher mortality associated with SCT. 4 figures. 10 references.

•

Mucositis Source: in Groenwald, S.L., eds., et al. Cancer Symptom Management. Sudbury, MA: Jones and Bartlett Publishers. 1996. p. 308-318. Contact: Available from Jones and Bartlett Publishers. 40 Tall Pine Drive, Sudbury, MA 01776. (978) 443-5000; Fax (978) 443-8000; E-mail: [email protected]; http://www.jbpub.com. PRICE: $90.00 plus shipping and handling. ISBN: 0867207329.

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Summary: This chapter on mucositis is from a book on cancer symptom management. Oral mucositis, sometimes called stomatitis, is one of the most common and troublesome forms of mucositis in individuals with cancer. This inflammatory and ulcerative response of the oral mucosa results from the physiologic effects of multiple stressors including cancer and its treatment. Topics include the incidence of mucositis in people with cancer, its impact on quality of life, the etiology of oral mucositis, risk factors, radiation therapy, biological response modifiers, bone marrow transplant therapy, multimodal therapy, assessment of the mouth and oral mucosa, diagnostic evaluation, degrees of toxicity, symptom management, the role of effective oral hygiene, protective interventions, management of the complications of mucositis (including pain, infection, and bleeding), dental management, and patient education. The authors stress that a systematic approach to oral assessment will help with early detection of mucositis and ongoing evaluation of oral complications. Prevention and management require a comprehensive and customized plan of care that involves the individual and caregiver in maintaining oral hygiene and managing problems such as xerostomia (dry mouth), infection, bleeding, and pain. 5 figures. 4 tables. 45 references. •

Chapter 47: Pityriasis Rosea Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 541-546. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail: [email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on the epidemiology, etiology, pathogenesis, clinical manifestations, pathology, diagnosis, and treatment of pityriasis rosea (PR). This acute, self limiting skin eruption has a distinctive and constant course. PR is equally common in both sexes, is rare in the very young and the very old, and is prevalent throughout the world. Probable causes of PR include infection and certain drugs. PR has also been shown to be more common in people with atopy and in people who have had a bone marrow transplant. The primary plaque in PR is oval or round, with a central, wrinkled, salmon colored area and a darker red peripheral zone separated by a collarette of fine scaling. The secondary eruption appears 2 days to 2 months after the primary lesion in crops at intervals of a few days. The duration of the secondary eruption varies between 2 and 10 weeks. The differential diagnosis of PR includes erythema dyschromicum perstans, lichen planus, lichenoid reactions, pityriasis lichenoides, Kaposi's sarcoma, pityriasis alba, nummular eczema, seborrheic dermatitis, superficial tinea, drug eruptions, erythema multiforme, Gianotti Crosti syndrome, guttate psoriasis, and secondary syphilis. Active treatment is not needed in uncomplicated cases because of the self limiting nature of PR. Glucocorticoids may be used to treat widespread, severe forms. 7 figures and 31 references.

•

Malignant Disease and its Treatment Source: in Griffiths, J. and Boyle, S. Colour Guide to Holistic Oral Care: A Practical Approach. Mosby-Year Book Europe. 1993. p. 205-216. Contact: Available from Mosby-Year Book Europe. Lynton House, 7-12 Tavistock Square, London WC1H 9LB, England. Telephone 0171-391 4471. Fax 0171-391 6598. ISBN: 0723417792.

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Summary: This chapter, from a textbook that outlines the role of the nurse in oral health care, discusses malignant disease and its treatment. Topics covered include leukemia; oral malignancies and maxillofacial surgery; other malignancies; and the oral aspects of treatment options, including chemotherapy, radiotherapy, bone marrow transplantation, and immunosuppression. A final section discusses oral care in this population. The authors conclude with a discussion of the role of nursing in the prevention and palliation of oral complications. 11 tables. 21 references.

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CHAPTER 8. TRANSPLANT

MULTIMEDIA

ON

BONE

MARROW

Overview In this chapter, we show you how to keep current on multimedia sources of information on bone marrow transplant. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “bone marrow transplant” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on bone marrow transplant: •

The Child With Immunodeficiency: Evaluation and Management Contact: InfoMedix, 12800 Garden Grove Blvd, Ste F, Garden Grove, CA, 92643, (714) 530-3454. Summary: This sound recording from the American Academy of Allergy and Immunology's 45th Annual Meeting, held February 24 - March 1, 1989, in San Antonio, TX, presents a session on various treatment modalities of immune deficiencies, such as Human immunodeficiency virus (HIV) infection or Acquired immunodeficiency syndrome (AIDS) in children. It covers responses to antigen immunizations, donor Tand B-cells, treating patients with severe combined immune deficiency (SKID) with halfmatched bone marrow transplants; and T-cell deficiencies, such as De George's syndrome. Examples of the use of recombinant interleukin II and fetal thymus transplant for T-cell deficiencies are cited and discussed. Questions from the audience address anaphylactic reactions, patient and family selection for home therapy, B-cell

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dysfunction, subcutaneous infusion versus intramuscular gamma globulin injection, immunoglobulin G subclass deficiencies, and evaluation of patients.

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CHAPTER 9. PERIODICALS AND NEWS ON BONE MARROW TRANSPLANT Overview In this chapter, we suggest a number of news sources and present various periodicals that cover bone marrow transplant.

News Services and Press Releases One of the simplest ways of tracking press releases on bone marrow transplant 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 “bone marrow transplant” (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 bone marrow transplant. 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 “bone marrow transplant” (or synonyms). The following was recently listed in this archive for bone marrow transplant: •

Non-purged bone marrow transplant improves survival in lymphoma Source: Reuters Industry Breifing Date: November 24, 2003

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•

Valacyclovir an option to prevent CMV disease after bone marrow transplant Source: Reuters Industry Breifing Date: April 18, 2003

•

Cognitive deficits follow bone marrow transplant in long-term adult survivors Source: Reuters Medical News Date: August 02, 2002

•

Cytokine improves immune function after bone marrow transplantation in mice Source: Reuters Medical News Date: July 05, 2002

•

Findings may boost bone marrow transplant success Source: Reuters Health eLine Date: March 15, 2002

•

Alloreactive NK cells may enhance success of bone marrow transplants Source: Reuters Medical News Date: March 14, 2002

•

Peripheral stem cell better than bone marrow transplantation for CML Source: Reuters Medical News Date: March 08, 2002

•

Bone marrow transplantation inhibits osteoblastic differentiation of stromal cells Source: Reuters Medical News Date: February 14, 2002

•

Immunity recovers to nearly normal 20 years after bone marrow transplant Source: Reuters Medical News Date: December 21, 2001

•

Slight mismatches OK for bone marrow transplants Source: Reuters Health eLine Date: December 19, 2001

•

T-cell lymphoma transmitted by allogeneic bone marrow transplantation Source: Reuters Industry Breifing Date: November 16, 2001

•

New bone marrow transplant approach offers hope for multiple myeloma treatment Source: Reuters Medical News Date: August 23, 2001

•

Bone marrow transplantation from unrelated donors gives no disadvantage in childhood ALL Source: Reuters Medical News Date: August 09, 2001

•

New method may improve bone marrow transplant Source: Reuters Health eLine Date: July 03, 2001

•

Glucocorticoid use increases fungal infection risk after bone marrow transplant Source: Reuters Medical News Date: June 01, 2001

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “bone marrow transplant” (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 “bone marrow transplant” (or synonyms). If you know the name of a company that is relevant to bone marrow transplant, 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 “bone marrow transplant” (or synonyms).

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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 “bone marrow transplant” (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 bone marrow transplant: •

CDC Recommends Dental Supervision, Treatment of Stem Cell Patients Source: ADA News. American Dental Association News. 31(20): 40-41. November 6, 2000. Contact: Available from American Dental Association (ADA). Subscription Department, 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Summary: This brief professional newsletter article reports that new Centers for Disease Control and Prevention (CDC) guidelines recommend routine dental supervision and vigorous elimination of oral disease for stem cell transplant patients. Dentists and transplant teams should coordinate care to curb the heightened risk of opportunistic infection among pediatric and adult patients receiving blood and bone marrow transplants. The article reviews some of the details of these guidelines and refers readers to the full text of the guidelines (www.cdc.gov/mmwr). The guidelines stress that likely sources of infection should be eliminated prior to transplant procedures. For example, teeth with moderate to severe caries should be restored; ill fitting dental prostheses (dentures) should be repaired; and teeth compromised by moderate to severe periodontal disease should be extracted. The regimen for transplant patients includes advice on brushing, flossing, and rinsing to maintain safe oral hygiene.

Academic Periodicals covering Bone Marrow Transplant Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to bone marrow transplant. In addition to these sources, you can search for articles covering bone marrow transplant that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for bone marrow transplant. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with bone marrow transplant. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks,

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etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to bone marrow transplant: Colony Stimulating Factors •

Systemic - U.S. Brands: Leukine; Neupogen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202628.html

Cyclosporine •

Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202176.html

Ganciclovir •

Systemic - U.S. Brands: Cytovene; Cytovene-IV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202255.html

Granisetron •

Systemic - U.S. Brands: Kytril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202724.html

Tacrolimus •

Systemic - U.S. Brands: Prograf http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202914.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

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213

Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to bone marrow transplant by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “bone marrow transplant” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for bone marrow transplant: •

Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=10

•

AP1903 http://www.rarediseases.org/nord/search/nodd_full?code=1002

•

Agiotensin 1-7 http://www.rarediseases.org/nord/search/nodd_full?code=1019

•

Monoclonal antibodies PM-81 and AML-2-23 http://www.rarediseases.org/nord/search/nodd_full?code=131

•

Sucralfate suspension http://www.rarediseases.org/nord/search/nodd_full?code=181

•

Trisaccharides A and B (trade name: Biosynject) http://www.rarediseases.org/nord/search/nodd_full?code=197

•

Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=5

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•

Roquinimex (trade name: Linomide) http://www.rarediseases.org/nord/search/nodd_full?code=25

•

ST1-RTA immunotoxin (SR 44163) http://www.rarediseases.org/nord/search/nodd_full?code=27

•

Sargramostim (trade name: Leukine) http://www.rarediseases.org/nord/search/nodd_full?code=33

•

Cytomegalovirus immune globulin intravenous (human http://www.rarediseases.org/nord/search/nodd_full?code=434

•

Anti-thymocyte serum (trade name: Nashville Rabbit Anti-thymocyte Serum) http://www.rarediseases.org/nord/search/nodd_full?code=560

•

Chlorhexidine gluconate mouthrinse (trade name: Peridex) http://www.rarediseases.org/nord/search/nodd_full?code=632

•

Busulfan http://www.rarediseases.org/nord/search/nodd_full?code=685

•

Bulsulfan http://www.rarediseases.org/nord/search/nodd_full?code=686

•

Filgrastim (trade name: Neupogen) http://www.rarediseases.org/nord/search/nodd_full?code=702

•

Humanized anti-tac (trade name: Zenapax) http://www.rarediseases.org/nord/search/nodd_full?code=769

•

Busulfan (trade name: Busulfanex) http://www.rarediseases.org/nord/search/nodd_full?code=880

•

Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=901

•

Liposomal Cyclosporin A (trade name: Cyclospire) http://www.rarediseases.org/nord/search/nodd_full?code=911

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

217

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 Institute11: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

12

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). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “bone marrow transplant” (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 31409 298 1215 162 66 33150

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “bone marrow transplant” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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 Biologists19 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.20 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.21 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/.

19 Adapted 20

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. 21 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 bone marrow transplant 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 bone marrow transplant. 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 bone marrow transplant. 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 “bone marrow transplant”:

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Guides on bone marrow transplant Bone Marrow Transplantation http://www.nlm.nih.gov/medlineplus/bonemarrowtransplantation.html

•

Other guides Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.html Stem Cells and Stem Cell Transplantation http://www.nlm.nih.gov/medlineplus/stemcellsandstemcelltransplantation.html

Within the health topic page dedicated to bone marrow transplant, the following was listed: •

General/Overviews Basics on Bone Marrow and Blood Stem Cell Transplants Source: National Marrow Donor Program http://www.marrow.org/PATIENT/basics.html Blood and Marrow Stem Cell Transplantation Source: Leukemia & Lymphoma Society http://www.leukemia-lymphoma.org/all_mat_toc.adp?item_id=2443 Transplant Source: National Marrow Donor Program http://www.marrow.org/MEDICAL/the_transplant.html Understanding Autologous Bone Marrow and Stem Cell Transplantation: Here's What You Should Know Source: International Myeloma Foundation http://myeloma.org/myeloma/kb_index.jsp?type=detail&id=37

•

Specific Conditions/Aspects Asian & Pacific Islander Donors Can Save Lives Source: National Marrow Donor Program http://www.marrow.org/NMDP/api_english.html Changing Transplant Centers Source: National Marrow Donor Program http://www.marrow.org/PATIENT/changing_transplant_centers.html Considerations for Choosing a Bone Marrow Transplant Provider Source: Health Resources and Services Administration http://www.hrsa.gov/osp/dot/choosebmt.htm Delayed Complications After a Blood Stem Cell Transplant Source: National Marrow Donor Program http://www.marrow.org/MEDICAL/delayed_complications_basic.html Evaluating Your Health Before Transplant Source: National Marrow Donor Program http://www.marrow.org/PATIENT/evaluating_health.html

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Factors Leading to Improved Transplant Outcomes Source: National Marrow Donor Program http://www.marrow.org/MEDICAL/factors_leading_patient_outcomes.html Graft-Versus-Host Disease Source: National Marrow Donor Program http://www.marrow.org/MEDICAL/graft_vs_host_disease.html Health History Guidelines (for Bone Marrow Donors) Source: Health Resources and Services Administration http://www.hrsa.gov/osp/dot/chart.htm Marrow Donation Source: National Marrow Donor Program http://www.marrow.org/FAQS/marrow_faqs.html Non-Myeloablative Transplants (Mini-Transplants) Source: National Marrow Donor Program http://www.marrow.org/MEDICAL/mini_transplants.html Patient Resources http://www.marrow.org/PATIENT/MAZE/maze_glossary.pdf Problems in the Post-Transplant Period Source: American Cancer Society http://www.cancer.org/docroot/ETO/content/ETO_1_4X_What_Are_Some_Of_T he_Problems_In_The_Post-Transplant_Period.asp?sitearea=ETO Stem Cell Transplant Coverage Information Source: National Marrow Donor Program http://www.marrow.org/PATIENT/transplant_coverage.html Steps of Marrow and PBSC (Peripheral Blood Stem Cell) Donation Source: National Marrow Donor Program http://www.marrow.org/DONOR/steps_of_donation.html •

From the National Institutes of Health Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers Source: National Cancer Institute http://cis.nci.nih.gov/fact/7_41.htm

•

Journals/Newsletters Blood & Marrow Transplant Newsletter Source: BMT InfoNet http://www.bmtnews.org/newsletters/

•

Latest News New Drug Fights Graft vs. Host Disease Source: 03/01/2004, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16321 .html

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Organizations Leukemia & Lymphoma Society http://www.leukemia-lymphoma.org/hm_lls National Cancer Institute http://www.cancer.gov/ National Marrow Donor Program http://www.marrow.org/ National Organ and Tissue Donation Initiative Source: Dept. of Health and Human Services, Health Resources and Services Administration http://www.organdonor.gov

•

Research Bone Marrow Cell Transplant Treats Clogged Leg Arteries Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3006682 Transplants of Sibling Stem Cells Show Promise for Immune Disorder Source: National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/mar2001/niaid-21.htm

•

Statistics African American Facts & Figures Source: National Marrow Donor Program http://www.marrow.org/NMDP/aa_facts_figures.html American Indian/Alaska Native Facts & Figures Source: National Marrow Donor Program http://www.marrow.org/NMDP/aian_facts_figures.html Asian & Pacific Islander Facts & Figures Source: National Marrow Donor Program http://www.marrow.org/NMDP/api_facts_figures.html General Facts & Figures Source: National Marrow Donor Program http://www.marrow.org/NMDP/general_facts_figures.html Hispanic Facts & Figures Source: National Marrow Donor Program http://www.marrow.org/NMDP/hispanic_facts_figures.html Understanding Survival Curves Source: National Marrow Donor Program http://www.marrow.org/MEDICAL/understanding_survival_outcomes.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

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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 bone marrow transplant. 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: •

Oral Care for Oncology Patients Source: Rancho Dominguez, CA: Laclede, Inc. 1999. [2 p.]. Contact: Available from Laclede, Inc. 2030 East University Drive, Rancho Dominguez, CA 90220. (800) 922-5856 or (310) 605-4280. Fax (310) 605-4288. E-mail: [email protected]. Website: www.laclede.com. PRICE: Contact publisher. Summary: Oral complications occur in almost all patients receiving radiation for head and neck malignancies, in more than 75 percent of bone marrow transplant recipients, and in nearly 40 percent of patients receiving chemotherapy. This brochure describes some of the oral health problems that people undergoing cancer therapy may encounter (including mucositis, stomatitis, infection, dental decay and demineralization, bleeding, and taste alteration), as well as some Biotene products that are available to treat or prevent those problems. The brochure describes toothpaste, mouthwash, mouth gum, moisturizing gel, and denture adhesive products. A final section offers practical tips for coping with a sore mouth. Readers are encouraged to contact their dentists when certain symptoms are experienced. The brochure includes a brief list of helpful web sites for readers who wish to obtain more information. 9 figures.

•

About Tissue Donation Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1993. 15 p. Contact: Available from Channing L. Bete Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. PRICE: $1 each for 1-24 copies; plus $3.75 shipping and handling. Order Number: 37655. Summary: This brochure provides general information about tissue donation. Written in a question-and-answer format, the brochure covers topics including a definition of tissue donation, why it is important to donate, what kinds of tissues can be donated, what happens to donated tissue, how tissue transplants help people, how to become a tissue donor, and the importance of discussing organ donation with one's family. Other specific topics discussed briefly include how a bone marrow transplant is done, age factors for donation, costs, the donation of eyes by people who have vision problems, religious concerns, a donor driver's license, contracting diseases from donating blood or bone marrow, and required request laws. The booklet is written in clear, easy-tounderstand language and is illustrated with cartoon-like figures. The booklet also includes a blank Uniform Donor Card for the reader to fill out.

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Oncology Reference Guide to Oral Health: Prevention and Management of Oral Complications Source: Bethesda, MD: National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH). 2002. [2 p.]. Contact: Available from National Oral Health Information Clearinghouse (NOHIC). 1 NOHIC Way, Bethesda, MD 20892-3500. (301) 402-7364. Fax (301) 907-8830. E-mail: [email protected]. Website: www.nohic.nidcr.nih.gov. PRICE: Single copy free; bulk orders available. Order Number OCCT-4. Summary: This reference guide offers a handy pocket source for basic information about the prevention and management of oral complications after cancer therapy (radiation therapy, chemotherapy, or bone marrow transplantation). Designed to give oncologists a reminder about oral health, the guide begins by reviewing pretreatment objectives for oral health examinations and treatment. The guide then details specific information for each type of treatment, offering suggestions for pretreatment care, strategies for oral hygiene during treatment, and tips for posttreatment care. One section summarizes the treatment options for common oral complications of cancer treatment, including mucositis (stomatitis), xerostomia (dry mouth, salivary gland dysfunction), mouth pain, damaged tooth enamel, taste changes, and dental demineralization. The guide is laminated and folds up easily to pocket size. 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 “bone marrow transplant” (or synonyms). The following was recently posted: •

An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia Source: American Society of Hematology - Medical Specialty Society; 1999 September 1; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2363&nbr=1589&a mp;string=bone+AND+marrow+AND+transplant Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Diseases Treatable By Bone Marrow Transplant Summary: Bone marrow transplants can treat a range of acute, inherited, and chronic diseases. Source: Office of Special Programs, Health Resources and Services Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=895

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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 bone marrow transplant. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

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

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

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

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

•

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

Associations and Bone Marrow Transplant The following is a list of associations that provide information on and resources relating to bone marrow transplant: •

International Bone Marrow Transplant Registry Telephone: (414) 456-8325 Fax: (414) 456-6530 Email: [email protected] Web Site: http://www.ibmtr.org Background: The International Bone Marrow Transplant Registry (IBMTR) and Autologous Blood and Marrow Transplant Registry (ABMTR) are voluntary research organizations that collect, organize, and collaborate information on blood and bone marrow transplants. Comprised of more than 300 worldwide transplant institutions, IBMTR/ABMTR have worked since 1972 to study transplantation, cancer treatments, and other related issues and medical possibilities. IBMTR/ABMTR also offer educational programs for both the professional and public communities, publish reports

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and a regular newsletter entitled 'IBMTR Newsletter,' as well as a selection of audiovisual aids. •

National Bone Marrow Transplant Link Telephone: (248) 358-1886 Toll-free: (800) 546-5268 Fax: (248) 358-1889 Email: [email protected] Web Site: http://www.mbmtlink.org Background: The National Bone Marrow Transplant Link is a not-for-profit voluntary organization dedicated to improving the quality of life of those undergoing bone marrow transplantation (BMT) and promoting public understanding of BMT through programs of education and research. Established in 1992, its primary goal is to assist individuals involved in the bone marrow transplantation process. However, the National BMT Link also educates the public about bone marrow transplantation; works as an advocate for national recognition of BMT as an effective, insurable procedure; supports the continuation of BMT research; and serves as a clearinghouse for information about transplants, transplant centers, donor centers, and bone marrow collection sites. In addition, the organization acts as a resource center of up-to-date medical and scientific reports on BMT and offers a networking service, which is a person-to-person connection that puts potential patients in touch with experienced and accessible peers. The National BMT Link is funded through private, foundation, and corporate donations.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to bone marrow transplant. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with bone marrow transplant. 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 bone marrow transplant. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines.

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The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “bone marrow transplant” (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 “bone marrow transplant”. 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 “bone marrow transplant” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “bone marrow transplant” (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.22

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

22

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)23: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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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/

•

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/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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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/

•

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

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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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/

•

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

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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 bone marrow transplant: •

Basic Guidelines for Bone Marrow Transplant Bone marrow transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003009.htm

•

Signs & Symptoms for Bone Marrow Transplant Anemias Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Leukemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001299.htm Problems breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm

•

Diagnostics and Tests for Bone Marrow Transplant HLA antigens Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003550.htm

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Platelets Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm •

Background Topics for Bone Marrow Transplant Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Physical activities Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Radiation therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001918.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

241

BONE MARROW TRANSPLANT DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablation: The removal of an organ by surgery. [NIH] Accelerated phase: Refers to chronic myelogenous leukemia that is progressing. The number of immature, abnormal white blood cells in the bone marrow and blood is higher than in the chronic phase, but not as high as in the blast phase. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many

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immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [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] 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 Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] 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] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenoleukodystrophy: A chromosome X-linked disease. [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] 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

Dictionary 243

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]

Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from aging, a physiological process, and time factors which refers only to the passage of time. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH]

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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] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [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] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [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]

Dictionary 245

Anaphylactic: Pertaining to anaphylaxis. [EU] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH] Anaplastic large cell lymphoma: A rare agressive form of lymphoma (cancer that begins in cells of the lymphatic system) that is usually of T-cell origin. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergic: 1. Characterized by abnormal inactivity; inactive. 2. Marked by asthenia or lack of energy. 3. Pertaining to anergy. [EU] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] 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] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anogenital: Pertaining to the anus and external genitals. [EU] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH]

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Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing 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] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are

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highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apheresis: Components plateletpheresis. [NIH]

being

separated

out,

as

leukapheresis,

plasmapheresis,

Aplastic anaemia: A form of anaemia generally unresponsive to specific antianaemia therapy, often accompanied by granulocytopenia and thrombocytopenia, in which the bone marrow may not necessarily be acellular or hypoplastic but fails to produce adequate numbers of peripheral blood elements. The term actually is all-inclusive and most probably encompasses several clinical syndromes. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]

Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] 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] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the

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biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] 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] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiovisual Aids: Auditory and visual instructional materials. [NIH] Authorship: The profession of writing. Also the identity of the writer as the creator of a literary production. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autologous tumor cells: Cancer cells from an individual's own tumor. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there.

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[NIH]

Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteraemia: The presence of bacteria in the blood. [EU] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Translocation: The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] 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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH]

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Biliary Tract: The gallbladder and its ducts. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blast Crisis: Rapid increase in the proportion of blast cells in the blood and bone marrow. [NIH]

Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [NIH] Blasts: Immature blood cells. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH]

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Blood Proteins: Proteins that are present in blood serum, including serum albumin, blood coagulation factors, and many other types of proteins. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone marrow ablation: The destruction of bone marrow using radiation or drugs. [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 Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone marrow metastases: Cancer that has spread from the original (primary) tumor to the bone marrow. [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] 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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [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] 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]

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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] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Busulfan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]

Cadaver: A dead body, usually a human body. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often

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of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Caspofungin acetate: A drug used to prevent or treat infections caused by a fungus (a type of microorganism). It belongs to the family of drugs called antifungal agents. [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] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for Pseudomonas and other gram-negative infections in debilitated patients. [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 Cycle Proteins: Proteins that control the cell division cycle. This family of proteins includes a wide variety of classes, including cyclin-dependent kinases, mitogen-activated kinases, cyclins, and phosphoprotein phosphatases (phosphoprotein phosphatase) as well as their putative substrates such as chromatin-associated proteins, cytoskeletal proteins, and transcription factors. [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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH]

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Cell 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] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephaloridine: A cephalosporin antibiotic. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemosis: Severe edema of the conjunctiva, least marked in the tarsal region. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus.

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[NIH]

Choriocarcinoma: A malignant tumor of trophoblastic epithelium characterized by secretion of large amounts of chorionic gonadotropin. It usually originates from chorionic products of conception (i.e., hydatidiform mole, normal pregnancy, or following abortion), but can originate in a teratoma of the testis, mediastinum, or pineal gland. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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 granulocytic leukemia: A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic leukemia: A slowly progressing cancer of the blood-forming tissues. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic phase chronic myelogenous leukemia: A phase of chronic myelogenous leukemia that may last from several months to several years. Although there may be no symptoms of leukemia, there are too many white blood cells. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its

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effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]

Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] 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 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] 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] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [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

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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] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH]

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Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Condyloma: C. acuminatum; a papilloma with a central core of connective tissue in a treelike structure covered with epithelium, usually occurring on the mucous membrane or skin of the external genitals or in the perianal region. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [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] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or

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groups of muscles, in a complex action or series of actions. [NIH] Coreceptors: Invariant receptor of the helper T-cells. [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] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]

Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

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Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [NIH] Cytomegalovirus Retinitis: Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness. [NIH] Cytopenia: A reduction in the number of blood cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] 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] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of

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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]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Abutments: Natural teeth or teeth roots used as anchorage for a fixed or removable denture or other prosthesis (such as an implant) serving the same purpose. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentists: Individuals licensed to practice dentistry. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] 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]

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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] Dilatation: The act of dilating. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease. [NIH] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] 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] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a

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hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [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] Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. [NIH] Drug Eruptions: Adverse cutaneous reactions caused by ingestion, parenteral use, or local application of a drug. These may assume various morphologic patterns and produce various types of lesions. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyskeratosis Congenita: A disturbance in normal keratinization, resulting, in the eye, in hornification of the epithelial layer of the cornea or conjunctiva. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Elastin: The protein that gives flexibility to tissues. [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

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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] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] 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] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] 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] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small

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intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] 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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [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] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known

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as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Erythroleukemia: Cancer of the blood-forming tissues in which large numbers of immature, abnormal red blood cells are found in the blood and bone marrow. [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] Erythropoiesis: The production of erythrocytes. [EU] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evaluable patients: Patients whose response to a treatment can be measured because enough information has been collected. [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] Exfoliation: A falling off in scales or layers. [EU] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensive-stage small cell lung cancer: Cancer that has spread outside the lung to other tissues in the chest or to other parts of the body. [NIH] 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 Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [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] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH]

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Flexor: Muscles which flex a joint. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicular large cell lymphoma: A rare type of non- Hodgkin's lymphoma (cancer of the lymphatic system) with large cells that look cleaved (split) or non-cleaved under the microscope. It is an indolent (slow-growing) type of lymphoma. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental

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conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH]

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Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational trophoblastic disease: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic tumor, gestational trophoblastic neoplasia, molar pregnancy, or choriocarcinoma. [NIH] Gestational trophoblastic neoplasia: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic disease, gestational trophoblastic tumor, molar pregnancy, or choriocarcinoma. [NIH] Gestational trophoblastic tumor: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic disease, gestational trophoblastic neoplasia, molar pregnancy, or choriocarcinoma. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH]

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Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Graft-versus-tumor: An immune response to a person's tumor cells by immune cells present in a donor's transplanted tissue, such as bone marrow or peripheral blood. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal

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disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulocytopenia: A deficiency in the number of granulocytes, a type of white blood cell. [NIH]

Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]

Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Hematologic Diseases: Disorders of the blood and blood forming tissues. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH]

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Hematologist: A doctor who specializes in treating diseases of the blood. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematopoietic tissue: Tissue in which new blood cells are formed. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU]

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Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH]

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Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Idiopathic myelofibrosis: A progressive disease in which the bone marrow is replaced by fibrous tissue and is unable to produce red blood cells; the cause is unknown. [NIH] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

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Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to

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prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH]

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Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-3: A multilineage cell growth factor secreted by lymphocytes, epithelial cells, and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Also called multi-CSF, it is considered one of the hematopoietic colony stimulating factors. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-7: Hematopoietic growth factor that promotes growth of B-cell precursors and also is co-mitogenic with Interleukin-2 for mature T-cell activation. It is produced by bone

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marrow stromal cells. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intrathecal chemotherapy: Anticancer drugs that are injected into the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Islet: Cell producing insulin in pancreas. [NIH]

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Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]

Kinetic: Pertaining to or producing motion. [EU] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

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Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH]

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Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Lisofylline: A drug that may protect healthy cells from chemotherapy and radiation without inhibiting the effects of these therapies on tumor cells. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells

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that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphomatoid Papulosis: Clinically benign, histologically malignant, recurrent cutaneous eruption characterized by an infiltration of large atypical cells surrounded by inflammatory cells. The atypical cells resemble Reed-Sternberg cells of Hodgkin's disease or the malignant cells of cutaneous T-cell lymphoma. In some cases, lymphomatoid papulosis progresses to lymphomatous conditions including mycosis fungoides, Hodgkin's disease, cutaneous T-cell lymphoma, or Ki-1 lymphoma. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Maculopapular: Both macular and papular, as an eruption consisting of both macules and papules; sometimes erroneously used to designate a papule that is only slightly elevated. [EU]

Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH]

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Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medulloblastoma: A malignant brain tumor that begins in the lower part of the brain and can spread to the spine or to other parts of the body. Medulloblastomas are sometimes called primitive neuroectodermal tumors (PNET). [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is

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termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and

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viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitosporic Fungi: A large and heterogenous group of fungi whose common characteristic is the absence of a sexual state. Many of the pathogenic fungi in humans belong to this group. [NIH]

Mitotic: Cell resulting from mitosis. [NIH] Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molar pregnancy: A rare cancer in women of child-bearing age in which cancer cells grow in the tissues that are formed in the uterus after conception. Also called gestational trophoblastic disease, gestational trophoblastic neoplasia, gestational trophoblastic tumor, or choriocarcinoma. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH]

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Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]

Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are

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characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]

Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloid Progenitor Cells: One of the two stem cells derived from hematopoietic stem cells the other being the lymphoid progenitor cell. Derived from these myeloid progenitor cells are the erythroid progenitor cells and the myeloid cells (monocytes and granulocytes). [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis,

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prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius. [NIH]

Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Netilmicin: Semisynthetic 1-N-ethyl derivative of sisomycin, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroectodermal Tumors: Malignant neoplasms arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon,

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and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonmalignant: Not cancerous. [NIH] Nonmalignant hematologic disorders: Disorders of the blood, some of which lead to leukemia. [NIH] Norfloxacin: Quinoline-derived synthetic antibacterial agent with a very broad spectrum of action. Oral administration yields highly bactericidal plasma, tissue, and urine levels. Norfloxacin inhibits bacterial DNA-gyrase and is used in gastrointestinal, eye, and urinary infections. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nummular: Coin-sized and coin-shaped. [EU] Nursing Assessment: Evaluation of the nature and extent of nursing problems presented by a patient for the purpose of patient care planning. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nursing Diagnosis: Conclusions derived from the nursing assessment that establish a health status profile for the patient and from which nursing interventions may be ordered. [NIH]

Nutritional Status: State of the body in relation to the consumption and utilization of

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nutrients. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian epithelial cancer: Cancer that occurs in the cells lining the ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH]

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Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Parapsoriasis: The term applied to a group of relatively uncommon inflammatory,

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maculopapular, scaly eruptions of unknown etiology and resistant to conventional treatment. Eruptions are both psoriatic and lichenoid in appearance, but the diseases are distinct from psoriasis, lichen planus, or other recognized dermatoses. Proposed nomenclature divides parapsoriasis into two distinct subgroups, pityriasis lichenoides and parapsoriasis en plaques (small- and large-plaque parapsoriasis). [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pefloxacin: An orally administered broad spectrum quinolone antibacterial agent active against most gram-negative and gram-positive bacteria. It is effective against urinary tract infections as well as against many other systemic infections. The drug is well tolerated in adults, but should not be given to children and pregnant women. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentostatin: A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [NIH]

Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a

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substituted amide linkage to a chain of peptides. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Performance status: A measure of how well a patient is able to perform ordinary tasks and carry out daily activities. [NIH] Perianal: Located around the anus. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal Index: A numerical rating scale for classifying the periodontal status of a person or population with a single figure which takes into consideration prevalence as well as severity of the condition. It is based upon probe measurement of periodontal pockets and on gingival tissue status. [NIH] Periodontal Pocket: An abnormal extension of a gingival sulcus accompanied by the apical migration of the epithelial attachment and bone resorption. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH]

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Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoprotein Phosphatase: A group of enzymes removing the serine- or threoninebound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) EC 3.1.3.16. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photopheresis: A process in which peripheral blood is exposed in an extracorporeal flow system to photoactivated 8-methoxypsoralen (methoxsalen) and ultraviolet light - a procedure known as PUVA therapy. Photopheresis is at present a standard therapy for advanced cutaneous T-cell lymphoma; it shows promise in the treatment of autoimmune diseases. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] Pityriasis Lichenoides: A subgroup of parapsoriasis itself divided into acute and chronic forms. The acute form is characterized by the abrupt onset of a generalized, reddish-brown, maculopapular eruption. Lesions may be vesicular, hemorrhagic, crusted, or necrotic. Histologically the disease is characterized by epidermal necrolysis. The chronic form shows milder skin changes with necrosis. An important variant of the chronic form is lymphomatoid papulosis. [NIH] Pityriasis Rosea: A mild exanthematous inflammation of unknown etiology. It is characterized by the presence of salmon-colored maculopapular lesions. The most striking feature is the arrangement of the lesions such that the long axis is parallel to the lines of

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cleavage. The eruptions are usually generalized, affecting chiefly the trunk, and the course is often self-limiting. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the

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mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelet Transfusion: The transfer of blood platelets from a donor to a recipient or reinfusion to the donor. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH]

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Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Care: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary tumor: The original tumor. [NIH] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not

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itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]

Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH]

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Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen

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lack or right heart failure. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyrazoloacridine: An anticancer drug that belongs to the family of drugs called acridines. [NIH]

Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation Oncology: A subspecialty of medical oncology and radiology concerned with the radiotherapy of cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH]

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Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be

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cancer in the body. [NIH] Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level. [NIH] Remission induction therapy: The initial chemotherapy a person receives to bring about a remission. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Research Support: Financial support of research activities. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinae: A congenital notch or cleft of the retina, usually located inferiorly. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule

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it lasts many weeks or even several months. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rod: A reception for vision, located in the retina. [NIH]

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Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second cancer: Refers to a new primary cancer that is caused by previous cancer treatment, or a new primary cancer in a person with a history of cancer. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to

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another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotonin Syndrome: An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to

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reproduction. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation,

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maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]

Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spherocytes: Small, abnormal spherical red blood cells with more than the normal amount of hemoglobin. [NIH] Spherocytosis: A condition in which there are abnormally thick, almost spherical, red blood cells or spherocytes in the blood. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

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Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Steady state: Dynamic equilibrium. [EU] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other

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disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supratentorial: Located in the upper part of the brain. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces

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tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temozolomide: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed). [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment

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of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Time Factors: Elements of limited time intervals, contributing to particular results or situations. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Abnormalities: Congenital absence of or defects in structures of the teeth. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerase. [NIH] Total-body irradiation: Radiation therapy to the entire body. Usually followed by bone marrow or peripheral stem cell transplantation. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test

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substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transplantation Tolerance: An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response. [NIH]

Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH]

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Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together

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to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Viremia: The presence of viruses in the blood. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Virus Shedding: The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Virus shedding is an important means of vertical transmission (disease transmission, vertical). [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vital Statistics: Used for general articles concerning statistics of births, deaths, marriages, etc. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH]

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Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

319

INDEX A Abdominal, 92, 202, 241, 269, 280, 292 Abdominal Pain, 202, 241, 269 Ablation, 14, 19, 21, 42, 44, 48, 49, 63, 194, 241 Accelerated phase, 173, 241 Acceptor, 241, 281, 292, 312 Acetylcholine, 241, 282 Acetylgalactosamine, 241, 271 Acetylglucosamine, 241, 271 Acquired Immunodeficiency Syndrome, 195, 241 Actin, 66, 241 Acute leukemia, 29, 40, 66, 113, 131, 137, 144, 162, 166, 169, 170, 241, 298 Acute lymphoblastic leukemia, 63, 101, 139, 143, 145, 161, 165, 166, 178, 181, 193, 194, 241 Acute lymphocytic leukemia, 83, 181, 191, 193, 241 Acute myelogenous leukemia, 94, 134, 163, 164, 171, 177, 191, 241, 242 Acute nonlymphocytic leukemia, 16, 241 Acute renal, 75, 242, 273 Acyclovir, 93, 242, 269 Adaptability, 242, 253, 254 Adaptation, 24, 129, 242, 287, 296 Adenine, 39, 242 Adenosine, 68, 242, 293, 295 Adenosine Deaminase, 68, 242, 293 Adenovirus, 26, 69, 71, 75, 81, 114, 242 Adjustment, 12, 93, 242 Adjuvant, 15, 39, 72, 242 Adoptive Transfer, 10, 64, 242 Adrenal Cortex, 242, 243, 299 Adrenergic, 242, 265, 282 Adrenoleukodystrophy, 116, 242 Adverse Effect, 242, 307 Aerobic, 242, 275, 286 Affinity, 16, 190, 242, 243, 248, 307 Agar, 243, 257, 296 Age Factors, 227, 243 Agenesis, 7, 243 Agonist, 57, 243 Aldosterone, 25, 243 Algorithms, 243, 250 Alimentary, 80, 243, 264, 293 Alkaline, 243, 244, 252

Alkylating Agents, 243, 252, 311 Alleles, 31, 243, 281 Allergen, 111, 243 Allergic Rhinitis, 111, 243 Allo, 12, 37, 65, 113, 131, 190, 196, 243 Allograft, 8, 20, 32, 62, 65, 192, 243 Alopecia, 244, 259 Alpha Particles, 244, 301 Alternative medicine, 209, 244 Alveoli, 244, 315 Amebiasis, 244, 285 Amino Acid Sequence, 244, 246, 269 Amino Acids, 244, 245, 266, 269, 293, 297, 300, 304, 310, 313, 314 Amlodipine, 87, 244 Ammonia, 242, 244, 271 Amnion, 244, 254 Ampicillin, 200, 244 Amplification, 67, 68, 69, 70, 81, 96, 146, 244 Ampulla, 244, 264 Anaemia, 93, 244, 247 Anaerobic, 113, 244, 275 Anaesthesia, 244, 277 Anal, 13, 244, 282 Analgesic, 244, 256, 281, 292 Analog, 242, 244, 268, 269, 280 Anaphylactic, 16, 205, 245 Anaphylaxis, 100, 245 Anaplastic, 138, 149, 245 Anaplastic large cell lymphoma, 149, 245 Anatomical, 245, 248, 264, 277, 305 Anemia, 18, 34, 37, 38, 78, 113, 123, 157, 162, 165, 172, 177, 245, 268, 287, 311, 317 Anergic, 10, 245 Anergy, 245 Anesthesia, 245, 264 Anesthetics, 200, 245, 265 Angina, 244, 245 Angina Pectoris, 244, 245 Angioplasty, 50, 245 Angiotensin converting enzyme inhibitor, 125, 245 Angiotensinogen, 245, 303 Animal model, 10, 27, 29, 46, 50, 62, 63, 64, 192, 245 Annealing, 245, 297 Anogenital, 98, 245

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Anorexia, 202, 245, 269, 314 Anthracycline, 245, 260, 275 Antibacterial, 69, 199, 246, 253, 275, 290, 293, 308, 315 Antibiotic, 6, 200, 201, 202, 244, 246, 251, 254, 255, 256, 260, 262, 266, 275, 286, 289, 293, 304, 308, 311, 312 Antibiotic Prophylaxis, 6, 246 Antibody therapy, 171, 246 Anticoagulant, 246, 299 Antiemetic, 94, 246 Antifungal, 47, 199, 246, 253, 268 Antifungal Agents, 246, 253 Antigen, 11, 21, 25, 28, 31, 33, 35, 36, 39, 45, 47, 59, 64, 67, 76, 107, 111, 148, 188, 195, 205, 243, 245, 246, 257, 261, 274, 275, 276, 277, 284, 306 Antigen-presenting cell, 246, 261 Anti-infective, 199, 246 Anti-Infective Agents, 199, 246 Anti-inflammatory, 246, 261, 271, 298 Antimetabolite, 242, 246, 268, 304 Antimicrobial, 71, 72, 107, 201, 202, 246, 256 Antineoplastic, 243, 246, 252, 259, 262, 268, 275, 284, 286, 292, 293, 297, 311, 312, 316 Antineoplastic Agents, 243, 246, 293, 316 Antioxidant, 36, 149, 246, 292 Antiviral, 76, 82, 118, 200, 242, 247, 278, 304 Antiviral Agents, 200, 247 Anus, 244, 245, 247, 251, 294 Anxiety, 118, 137, 151, 160, 247 Aorta, 247, 315 Apheresis, 31, 247 Aplastic anaemia, 93, 102, 114, 247 Aplastic anemia, 90, 97, 99, 165, 186, 189, 202, 247 Apolipoproteins, 247, 282 Apoptosis, 9, 16, 18, 22, 35, 53, 63, 192, 247, 253 Aqueous, 247, 249, 260, 280, 282 Arachidonic Acid, 35, 247, 281, 299 Arterial, 52, 247, 254, 275, 299 Arteries, 226, 247, 250, 251, 259, 282, 285, 311, 314 Arterioles, 52, 247, 251, 252 Aseptic, 247, 291, 309 Aspergillosis, 67, 71, 72, 76, 81, 82, 84, 247 Aspergillus, 67, 70, 76, 102, 247 Aspiration, 186, 247

Assay, 17, 18, 22, 26, 47, 70, 83, 104, 154, 247, 276, 304 Asthenia, 245, 248 Astrocytes, 248, 278, 287 Astrocytoma, 174, 248 Asymptomatic, 244, 248, 292 Atmospheric Pressure, 248, 275 Atrium, 248, 315 Atrophy, 248, 265 Atypical, 76, 162, 163, 164, 166, 169, 174, 182, 248, 277, 283 Audiovisual Aids, 230, 248 Authorship, 54, 248 Autoantibodies, 59, 248 Autoantigens, 248 Autodigestion, 248, 292 Autoimmune disease, 10, 20, 69, 71, 135, 195, 248, 287, 295 Autoimmune Hepatitis, 195, 248 Autoimmunity, 83, 195, 248 Autologous tumor cells, 64, 248 Autonomic, 241, 248, 306 Axillary, 46, 248 B Bacillus, 249, 251 Bacteraemia, 108, 249 Bacteremia, 67, 80, 108, 249 Bacteria, 23, 67, 195, 246, 249, 256, 261, 264, 267, 271, 273, 275, 285, 286, 293, 306, 307, 308, 309, 311, 312, 313, 315 Bacterial Physiology, 242, 249 Bacterial Translocation, 23, 249 Bactericidal, 249, 290 Bacteriophage, 249, 296, 313 Bacterium, 195, 249, 273 Base, 16, 242, 249, 260, 261, 269, 280, 311, 314 Basement Membrane, 249, 267 Basophils, 249, 272, 281 Benign, 249, 269, 270, 283, 289, 292, 301 Beta-Lactamases, 249, 275 Bilateral, 249, 265, 303 Bile, 249, 269, 282, 309 Biliary, 249, 250, 292 Biliary Tract, 250, 292 Biochemical, 9, 18, 19, 243, 246, 250, 251, 268, 306 Biogenesis, 38, 250 Biological response modifier, 203, 250, 278 Biological therapy, 250, 272 Biopsy, 46, 85, 100, 107, 250 Biosynthesis, 247, 250

Index 321

Biotechnology, 66, 73, 209, 219, 250 Biotransformation, 250 Bladder, 250, 259, 287, 299, 314, 315 Blast Crisis, 103, 250 Blast phase, 145, 241, 250, 255 Blasts, 177, 250 Blood Coagulation, 250, 251, 252, 304, 311 Blood Coagulation Factors, 250, 251 Blood Glucose, 250, 273, 278 Blood Platelets, 250, 284, 297, 306, 311 Blood pressure, 250, 253, 275, 287, 307 Blood Proteins, 52, 251 Body Fluids, 251, 263, 307, 314 Bone Density, 16, 251 Bone marrow ablation, 167, 251 Bone marrow aspiration, 186, 251 Bone Marrow Cells, 9, 48, 60, 186, 251, 257, 284, 288 Bone marrow metastases, 137, 251 Bone scan, 251, 305 Bowel, 202, 244, 251, 262, 265, 277, 279, 280 Bowel Movement, 251, 262 Brachytherapy, 251, 279, 301, 317 Branch, 127, 237, 251, 272, 276, 283, 293, 308, 311 Broad-spectrum, 244, 251, 253, 312 Bronchi, 251, 252, 265, 313 Bronchiseptica, 67, 251 Bronchoalveolar Lavage, 36, 68, 76, 84, 251 Bronchoalveolar Lavage Fluid, 68, 251 Bronchoscopy, 117, 118, 252 Buccal, 252, 282, 309 Buffers, 252, 308 Busulfan, 20, 95, 133, 138, 139, 141, 163, 166, 214, 228, 252 C Cadaver, 62, 252 Calcium, 66, 130, 244, 252, 257, 300, 307 Calcium channel blocker, 244, 252 Calmodulin, 66, 252 Candidiasis, 202, 252, 268 Candidosis, 252 Capillary, 6, 252, 315 Capsules, 100, 252 Carbohydrate, 64, 252, 297, 306 Carboplatin, 95, 126, 142, 166, 167, 168, 181, 252 Carcinogen, 252, 284, 285, 311 Carcinogenic, 243, 252, 278, 291, 299, 309 Carcinoma, 23, 139, 146, 252

Cardiac, 14, 44, 62, 252, 264, 265, 275, 288, 309 Cardiomyopathy, 114, 252 Cardiopulmonary, 14, 253 Cardiovascular, 20, 253, 281, 306 Cardiovascular disease, 20, 253 Case report, 7, 74, 80, 106, 110, 127, 253 Caspase, 53, 253 Caspofungin acetate, 79, 253 Catheterization, 245, 253 Catheters, 135, 253, 277, 279 Causal, 253, 273, 304 Ceftazidime, 126, 253 Cell Cycle, 17, 23, 35, 54, 253, 256, 259, 266, 300 Cell Cycle Proteins, 35, 253 Cell Death, 22, 57, 191, 192, 247, 253, 266, 289 Cell Differentiation, 22, 253, 307 Cell Division, 249, 253, 266, 272, 286, 296, 306 Cell membrane, 66, 253, 261, 266, 295 Cell proliferation, 57, 61, 191, 253, 279, 307 Cell Size, 254, 268 Cell Survival, 254, 272 Cellulose, 254, 268, 285, 296 Central Nervous System, 4, 42, 67, 168, 241, 254, 269, 271, 281, 282, 287, 291, 306 Cephaloridine, 253, 254 Ceramide, 53, 254 Cerebellar, 174, 254, 314 Cerebellar Diseases, 254, 314 Cerebellum, 254 Cerebral, 67, 76, 174, 254, 265 Cerebrospinal, 67, 76, 254 Cerebrospinal fluid, 76, 254 Cerebrovascular, 131, 253, 254 Cerebrum, 254 Chemical Warfare, 254, 260 Chemical Warfare Agents, 254, 260 Chemosis, 94, 254 Chimera, 49, 254 Cholesterol, 249, 254, 255, 259, 282, 309 Cholesterol Esters, 254, 282 Chorioamnionitis, 79, 254 Choriocarcinoma, 255, 270, 286 Chorion, 254, 255 Chorioretinitis, 255, 303 Choroid, 255, 303 Chromatin, 247, 253, 255, 265 Chromic, 20, 255 Chromium, 255

322

Bone Marrow Transplant

Chromosomal, 29, 152, 244, 255, 304, 311 Chromosome, 63, 145, 174, 176, 191, 242, 255, 281, 306, 311, 313 Chronic Disease, 228, 255, 281 Chronic granulocytic leukemia, 255 Chronic leukemia, 162, 166, 169, 170, 183, 255 Chronic lymphocytic leukemia, 132, 255 Chronic myelogenous leukemia, 40, 70, 103, 118, 131, 135, 173, 174, 176, 191, 241, 250, 255 Chronic phase, 163, 173, 176, 228, 241, 255 Chronic phase chronic myelogenous leukemia, 163, 173, 176, 255 Chylomicrons, 255, 282 Cidofovir, 114, 255 Cilastatin, 126, 255, 275 Ciprofloxacin, 69, 71, 107, 109, 113, 126, 256 CIS, 38, 225, 256, 303 Cisplatin, 128, 142, 256 Clarithromycin, 86, 256 Clear cell carcinoma, 256, 261 Clinical Medicine, 256, 298 Clinical Protocols, 62, 64, 256 Cloning, 38, 250, 256 Coagulation, 250, 256, 273, 296, 312 Coculture, 17, 256 Codeine, 256, 292 Cofactor, 24, 256, 299, 311 Colitis, 256, 277 Collagen, 53, 249, 256, 267, 296, 299 Collapse, 245, 257 Colloidal, 71, 257, 306 Colony-Stimulating Factors, 257, 272 Complement, 257, 269, 283, 296 Complementary and alternative medicine, 129, 158, 257 Complementary medicine, 129, 257 Complete remission, 82, 134, 141, 147, 150, 257, 302 Complete response, 257 Computational Biology, 219, 258 Computed tomography, 251, 258, 305 Computerized axial tomography, 258, 305 Conception, 255, 258, 267, 270, 286, 309 Condyloma, 98, 258 Congestion, 258, 265 Conjunctiva, 254, 258, 263 Connective Tissue, 251, 256, 258, 267, 280, 282, 285, 304, 305, 309, 310 Constitutional, 258, 288, 303

Consultation, 6, 33, 258 Consumption, 258, 269, 290, 303 Contamination, 31, 82, 258 Continuum, 62, 258 Contraindications, ii, 258 Conventional therapy, 48, 258 Conventional treatment, 258, 293 Cooperative group, 31, 42, 258 Coordination, 15, 28, 43, 254, 258, 287 Coreceptors, 24, 259 Cornea, 259, 263, 309, 317 Coronary, 50, 245, 253, 259, 285 Coronary heart disease, 253, 259 Coronary Thrombosis, 259, 285 Corpuscle, 259, 265 Cortex, 61, 259 Cortical, 35, 259 Cortisone, 259, 261, 298 Crossing-over, 259, 302 Crowns, 259, 261 Curative, 17, 18, 27, 31, 34, 47, 50, 190, 193, 196, 259, 311 Cutaneous, 4, 59, 199, 252, 259, 263, 282, 283, 295 Cyclic, 252, 259, 294 Cyclin, 24, 55, 253, 259 Cyclin-Dependent Kinases, 253, 259 Cyclosporine, 31, 37, 44, 69, 100, 170, 212, 259 Cystitis, 71, 81, 100, 114, 151, 259 Cytarabine, 137, 142, 259 Cytokine, 22, 24, 31, 53, 55, 57, 59, 63, 98, 138, 208, 260, 267, 293, 305 Cytomegalovirus Infections, 260, 269 Cytomegalovirus Retinitis, 114, 260 Cytopenia, 193, 260 Cytoplasm, 65, 247, 249, 253, 260, 265, 272, 304 Cytosine, 72, 143, 260 Cytoskeletal Proteins, 253, 260 Cytoskeleton, 66, 260, 286 Cytotoxic, 6, 11, 21, 23, 34, 88, 89, 119, 137, 188, 192, 193, 260, 276, 301, 307 Cytotoxic chemotherapy, 6, 260 Cytotoxicity, 11, 32, 256, 260, 280 D Databases, Bibliographic, 219, 260 Daunorubicin, 260, 263 De novo, 123, 148, 177, 260 Decision Making, 56, 260 Decontamination, 68, 100, 113, 260 Degenerative, 260, 273, 304

Index 323

Deletion, 247, 260 Dementia, 241, 260 Denaturation, 261, 297 Dendrites, 261, 290 Dendritic, 21, 33, 191, 261, 284 Dendritic cell, 21, 33, 191, 261 Density, 251, 261, 268, 282 Dental Abutments, 261 Dental Care, 4, 6, 261 Dental Caries, 7, 261 Dentists, 7, 210, 227, 261 Dentures, 210, 261 Depolarization, 261, 307 Dermal, 261, 281 Dermatitis, 59, 203, 261, 263 DES, 135, 176, 261 Dexamethasone, 94, 142, 261 Diabetes Mellitus, 261, 270, 273 Diagnostic procedure, 185, 209, 261 Diarrhea, 6, 202, 244, 261 Diarrhoea, 261, 269 Diffusion, 261, 277 Digestion, 243, 249, 251, 262, 279, 282, 292, 309, 315 Digestive system, 184, 262, 287 Dilatation, 6, 245, 262, 298 Dimerization, 37, 262 Dimethyl, 39, 262, 282 Direct, iii, 14, 24, 33, 37, 41, 56, 62, 65, 68, 73, 211, 256, 262, 270, 302 Disease Progression, 53, 61, 63, 262, 316 Disease Susceptibility, 20, 262 Disease Transmission, 262, 316 Disease Transmission, Vertical, 262, 316 Disease-Free Survival, 12, 262 Disparity, 41, 77, 262 Dissociation, 243, 262, 279 Distal, 262, 280, 300 Dorsal, 262, 265, 297 Dose-dependent, 262, 317 Double-blinded, 31, 262 Doxorubicin, 138, 262 Drive, ii, vi, 40, 121, 126, 199, 201, 202, 227, 263 Drosophila, 9, 263 Drug Eruptions, 203, 263 Drug Interactions, 212, 263 Drug Resistance, 82, 263 Drug Tolerance, 263, 312 Duct, 244, 253, 263, 266, 305 Duodenum, 249, 263, 264, 292, 309 Dyskeratosis Congenita, 78, 263

Dyspnea, 263, 300 Dystrophy, 69, 263 E Eczema, 203, 263 Edema, 65, 254, 260, 263, 314 Effector, 11, 21, 34, 241, 257, 263, 280, 294 Effector cell, 21, 263, 280 Efficacy, 8, 16, 21, 29, 30, 32, 34, 42, 47, 58, 64, 68, 87, 123, 150, 151, 192, 263, 275 Effusion, 263, 283 Elastin, 257, 263 Electrolyte, 91, 243, 263, 298, 308, 314 Electrons, 247, 249, 263, 279, 292, 301 Emaciation, 241, 264 Embryo, 244, 253, 264, 267, 277, 289, 314 Empiric, 87, 123, 126, 264 Empyema, 117, 264 Enalapril, 44, 264 Enamel, 7, 228, 261, 264, 280 Encapsulated, 194, 264 Encephalitis, 89, 92, 97, 144, 264 Encephalitis, Viral, 264 Encephalopathy, 92, 264 Endarterectomy, 245, 264 Endocarditis, 252, 264 Endoscope, 264 Endoscopic, 85, 100, 252, 264 Endothelial cell, 52, 65, 264, 267, 311 Endotoxin, 264, 314 Enhancer, 51, 264 Enteral Nutrition, 23, 91, 139, 264 Enteritis, 59, 90, 264 Enterocolitis, 105, 265 Environmental Exposure, 265, 291 Environmental Health, 218, 220, 265 Enzymatic, 252, 257, 259, 261, 265, 274, 297, 303 Eosinophils, 265, 272, 281 Epidermal, 200, 265, 280, 281, 284, 295 Epidermis, 265, 280, 281, 298, 301 Epigastric, 265, 292 Epinephrine, 242, 265, 314 Epithelial, 23, 25, 51, 55, 57, 263, 265, 278, 292, 294 Epithelial Cells, 55, 57, 265, 278 Epithelium, 23, 55, 249, 255, 258, 265, 292, 317 Epitope, 41, 64, 265 ERV, 265, 266 Erythema, 200, 203, 265, 315 Erythema Multiforme, 203, 265 Erythema Nodosum, 200, 265

324

Bone Marrow Transplant

Erythrocyte Membrane, 38, 265, 308 Erythrocytes, 244, 245, 251, 266, 273, 302 Erythroid Progenitor Cells, 266, 288 Erythroleukemia, 34, 38, 266 Erythromycin, 256, 266, 305 Erythropoiesis, 38, 266 Esophagus, 262, 266, 294, 309 Ethnic Groups, 46, 266 Etoposide, 124, 126, 130, 131, 133, 137, 138, 139, 140, 141, 142, 143, 181, 266 Eukaryotic Cells, 260, 266, 291 Evaluable patients, 32, 266 Excitation, 266, 268 Exfoliation, 266, 289 Exocrine, 266, 292 Exocytosis, 65, 266 Exogenous, 45, 195, 250, 263, 266 Expiratory, 265, 266 Expiratory Reserve Volume, 265, 266 Extensive-stage small cell lung cancer, 164, 266 Extensor, 266, 300 External-beam radiation, 266, 279, 301, 317 Extracellular, 35, 248, 258, 267, 307 Extracellular Matrix, 35, 258, 267 Extracellular Space, 267 Extracorporeal, 267, 295 Extraocular, 179, 267 Extravasation, 267, 273 Eye Infections, 242, 267 F Facial, 7, 267 Family Planning, 219, 267 Fat, 247, 251, 254, 259, 267, 281, 287, 304, 308 Feasibility Studies, 18, 267 Febrile, 69, 99, 126, 267 Fetal Blood, 254, 267 Fetal Development, 22, 267 Fetus, 254, 267, 296, 298, 314, 315 Fibrin, 6, 52, 250, 267, 296, 311 Fibrinogen, 267, 296, 311 Fibroblast Growth Factor, 36, 267 Fibroblasts, 26, 267, 278 Fibrosis, 25, 35, 98, 126, 267, 300, 305 Filgrastim, 150, 164, 170, 214, 267 Flexor, 266, 268, 281 Flow Cytometry, 19, 48, 62, 268 Fluconazole, 67, 71, 86, 91, 268 Fludarabine, 37, 50, 268 Fluorescence, 45, 268

Fluorescent Dyes, 268 Fluorouracil, 26, 37, 157, 268 Folate, 16, 268 Fold, 188, 268, 285 Folic Acid, 268 Follicular large cell lymphoma, 179, 268 Fractionation, 145, 268 Fungi, 246, 247, 267, 268, 285, 286, 317 Fungus, 252, 253, 268 G Gallbladder, 92, 124, 241, 249, 250, 262, 269 Gamma Rays, 269, 301 Ganciclovir, 60, 92, 114, 144, 212, 269 Ganglion, 269, 291, 317 Gas, 244, 261, 265, 269, 274, 290, 315 Gas exchange, 269, 315 Gastric, 23, 248, 269, 274 Gastrin, 269, 274 Gastritis, 119, 269 Gastroenteritis, 50, 269 Gastrointestinal, 6, 92, 118, 202, 249, 256, 264, 265, 269, 281, 290, 306, 310, 311, 314 Gastrointestinal tract, 249, 269, 281, 306, 314 Gastrostomy, 264, 269 Gene Expression, 9, 23, 25, 43, 45, 51, 269 Genetic Code, 269, 290 Genetic Engineering, 250, 256, 269 Genetic Markers, 81, 269 Genetic testing, 270, 297 Genetics, 16, 44, 242, 263, 270, 276 Genital, 256, 270, 305, 316 Genomics, 32, 270 Genotype, 35, 41, 192, 270, 294 Germ cell tumors, 142, 177, 270 Germ Cells, 270, 291, 308, 311 Germinal Center, 59, 270 Gestational, 143, 270, 286 Gestational trophoblastic disease, 143, 270, 286 Gestational trophoblastic neoplasia, 270, 286 Gestational trophoblastic tumor, 270, 286 Giardiasis, 270, 285 Gland, 228, 242, 255, 259, 270, 282, 292, 295, 299, 306, 309, 312 Glioma, 42, 174, 270 Glomerular, 61, 93, 270, 303 Glomeruli, 270 Glomerulonephritis, 61, 195, 270 Glomerulosclerosis, 35, 61, 270

Index 325

Glomerulus, 61, 270, 289 Glucocorticoid, 208, 261, 271, 298 Glucose, 46, 250, 254, 255, 261, 271, 273, 278, 305 Glutamic Acid, 268, 271, 299 Glutamine, 122, 124, 138, 139, 140, 147, 271 Glycoprotein, 82, 267, 271, 287, 311, 314 Glycosaminoglycans, 16, 271 Glycosidic, 271 Gonad, 271 Gonadal, 50, 271, 309 Governing Board, 271, 298 Grade, 96, 132, 139, 179, 180, 196, 271 Graft Rejection, 31, 49, 60, 84, 85, 146, 271, 277 Grafting, 271, 277 Graft-versus-tumor, 74, 271 Gram-negative, 249, 251, 253, 271, 275, 293, 312 Gram-positive, 72, 271, 275, 293, 309 Granulocyte Colony-Stimulating Factor, 138, 149, 257, 267, 271 Granulocytes, 257, 272, 280, 288, 307, 316 Granulocytopenia, 247, 272 Gravis, 125, 195, 272 Growth factors, 28, 36, 124, 141, 187, 192, 200, 272 Gyrase, 272, 290 H Haematological, 112, 272 Haematoma, 100, 272 Hallucination, 119, 272 Haplotypes, 46, 272 Haptens, 243, 272 Health Promotion, 112, 150, 272 Health Services, iv, 8, 56, 220, 272 Health Status, 272, 290 Heart attack, 253, 272 Heart failure, 272, 301 Heart Transplantation, 62, 272 Hematologic Diseases, 64, 147, 272 Hematologic malignancies, 12, 27, 28, 48, 170, 171, 190, 196, 272 Hematologist, 18, 273 Hematoma, 85, 273 Hematopoiesis, 8, 10, 22, 28, 61, 140, 150, 187, 273 Hematopoietic Stem Cell Transplantation, 14, 19, 21, 40, 42, 44, 48, 56, 57, 63, 193, 273

Hematopoietic Stem Cells, 19, 22, 28, 34, 39, 40, 187, 196, 273, 288 Hematopoietic tissue, 55, 251, 273 Hemodynamics, 61, 273 Hemoglobin, 245, 266, 273, 280, 308, 311 Hemoglobin M, 273 Hemoglobinopathies, 20, 273 Hemolysis, 266, 273 Hemolytic, 6, 38, 113, 123, 195, 273, 311 Hemorrhage, 6, 36, 65, 116, 260, 273, 301, 309 Hemostasis, 30, 65, 273, 306 Hepatic, 26, 36, 137, 141, 273, 287 Hepatitis, 24, 50, 59, 73, 87, 111, 273, 277 Hepatocyte, 26, 273 Hepatomegaly, 273, 277 Hereditary, 38, 273, 304, 311 Heredity, 269, 270, 273 Herpes, 4, 60, 93, 97, 103, 107, 144, 154, 242, 274 Herpes virus, 97, 103, 144, 154, 274 Herpes Zoster, 274 Heterodimer, 25, 274 Heterogeneity, 14, 52, 243, 274 Heterogenic, 274 Heterogenous, 25, 274, 286 Histamine, 274, 282 Histiocytosis, 127, 274 Histocompatibility, 4, 11, 35, 274 Homogeneous, 258, 274 Homologous, 243, 259, 274, 306, 310, 313 Hormone, 94, 124, 243, 259, 261, 265, 269, 274, 278, 284, 299, 304, 307, 312 Humoral, 271, 274, 313 Hybrid, 274 Hybridization, 71, 73, 81, 274 Hybridoma, 59, 274 Hydrogen, 241, 249, 252, 261, 274, 281, 286, 290, 292, 294, 300, 317 Hydrolases, 274, 283 Hydrolysis, 242, 249, 250, 256, 275, 294, 295, 297 Hydrophobic, 275, 282 Hydroxylysine, 257, 275 Hydroxyproline, 257, 275 Hydroxyurea, 228, 275 Hyperbaric, 151, 275 Hyperbaric oxygen, 151, 275 Hyperplasia, 108, 275, 281 Hypersensitivity, 4, 99, 243, 245, 275, 281, 304 Hypertension, 244, 253, 264, 275, 314

326

Bone Marrow Transplant

Hypertrophy, 275 Hypoplasia, 7, 275 I Id, 128, 156, 224, 228, 229, 236, 238, 275 Idarubicin, 137, 275 Idiopathic, 36, 98, 124, 162, 275 Idiopathic myelofibrosis, 162, 275 Ifosfamide, 126, 142, 275 Imaging procedures, 275, 313 Imipenem, 99, 126, 255, 275 Immune function, 29, 57, 60, 208, 275, 276 Immune Sera, 276 Immunity, 28, 35, 51, 64, 149, 190, 208, 241, 276, 313 Immunization, 52, 242, 276 Immunoassay, 81, 276 Immunocompromised, 51, 201, 202, 276 Immunocompromised Host, 52, 276 Immunodeficiency, 4, 88, 152, 193, 205, 241, 276 Immunodeficiency syndrome, 205, 276 Immunofluorescence, 66, 276 Immunogenetics, 41, 276 Immunoglobulin, 40, 206, 246, 276, 287 Immunohistochemistry, 65, 84, 276 Immunologic, 4, 28, 37, 38, 59, 62, 115, 242, 276, 293, 301, 317 Immunology, 11, 24, 77, 104, 111, 117, 123, 145, 188, 193, 205, 242, 243, 268, 276 Immunosuppressant, 243, 268, 276 Immunosuppressive Agents, 20, 62, 276 Immunosuppressive therapy, 4, 99, 189, 276 Immunotherapy, 18, 31, 33, 38, 39, 83, 111, 131, 144, 145, 149, 188, 242, 250, 276 Immunotoxin, 214, 277 Impairment, 109, 150, 267, 277, 285 Implant radiation, 277, 279, 301, 317 Implantation, 17, 258, 277 In vitro, 9, 10, 19, 22, 24, 26, 27, 31, 33, 38, 39, 40, 52, 54, 188, 277, 297, 304, 306, 311, 312 In vivo, 8, 9, 10, 22, 23, 24, 26, 27, 33, 34, 37, 38, 39, 40, 48, 52, 54, 56, 63, 277, 311 Incision, 277, 279 Indicative, 84, 200, 277, 293, 315 Indolent, 268, 277 Induction, 10, 20, 22, 25, 39, 46, 49, 62, 64, 65, 73, 144, 277 Induction therapy, 277 Infarction, 259, 277, 285 Infectious Mononucleosis, 23, 277, 287

Infiltration, 25, 61, 270, 277, 283, 317 Inflammatory bowel disease, 202, 277 Infusion, 10, 17, 25, 31, 85, 88, 137, 141, 148, 193, 196, 206, 277, 313 Ingestion, 263, 278, 297 Initiation, 52, 278, 313 Inlay, 278, 303 Inner ear, 278, 315 Inorganic, 256, 278 Inositol, 191, 192, 278 Insight, 10, 40, 278 Insulator, 278, 287 Insulin, 57, 195, 278, 279, 292 Insulin-dependent diabetes mellitus, 195, 278 Intensive Care, 75, 86, 278 Interferon, 72, 114, 149, 176, 195, 228, 278, 283 Interferon-alpha, 278 Interleukin-2, 132, 149, 278 Interleukin-3, 187, 257, 278 Interleukin-6, 130, 278 Interleukin-7, 187, 278 Interleukins, 187, 276, 279 Internal Medicine, 12, 21, 124, 279, 284 Internal radiation, 279, 301, 317 Interstitial, 25, 36, 70, 251, 267, 279, 289, 303, 317 Intestinal, 6, 23, 68, 90, 100, 140, 249, 265, 279, 316 Intestine, 65, 251, 264, 279, 280 Intoxication, 279, 317 Intracellular, 57, 66, 192, 277, 279, 283, 284, 298, 302, 307 Intramuscular, 206, 279, 293 Intraocular, 114, 130, 179, 279 Intrathecal, 42, 145, 279 Intrathecal chemotherapy, 42, 279 Intravenous, 100, 101, 118, 123, 125, 148, 186, 214, 277, 279, 293 Intrinsic, 9, 25, 243, 249, 279 Invasive, 47, 71, 81, 84, 101, 102, 276, 279, 283 Ionization, 279 Ionizing, 65, 244, 265, 279, 301 Ions, 249, 252, 262, 263, 274, 279, 300 Islet, 20, 57, 279 J Jejunostomy, 264, 280 Joint, 16, 44, 256, 268, 280, 310 K Kb, 218, 224, 280

Index 327

Keratin, 280 Keratinocytes, 59, 280 Keratolytic, 261, 280, 297 Kidney Cortex, 61, 280 Kidney Glomerulus, 280 Killer Cells, 280 Kinetic, 279, 280 L Lamivudine, 111, 280 Large Intestine, 262, 279, 280, 302, 307 Latency, 23, 25, 51, 69, 280 Latent, 12, 23, 280, 298 Lavage, 79, 280 Laxative, 243, 280, 285 Lens, 195, 280 Lesion, 203, 280, 282, 307 Lethal, 21, 47, 57, 61, 147, 249, 280 Leucine, 34, 192, 193, 280 Leucocyte, 138, 280, 281, 283 Leukaemia, 7, 75, 81, 107, 112, 113, 114, 115, 122, 152, 281 Leukapheresis, 247, 281 Leukocytes, 61, 187, 249, 251, 265, 272, 278, 279, 281, 314 Leukoencephalopathy, 149, 281 Leukopenia, 281, 317 Leukotrienes, 247, 281 Levo, 281, 284 Library Services, 236, 281 Lichen Planus, 203, 281, 293 Life cycle, 51, 268, 281 Ligament, 281, 299 Ligands, 11, 32, 57, 281 Ligation, 39, 281 Linkage, 46, 269, 281, 294 Linkage Disequilibrium, 46, 281 Lipid, 26, 47, 247, 278, 281, 282, 287, 292 Lipid Peroxidation, 281, 292 Lipoprotein, 26, 271, 282 Liposome, 194, 282 Lisofylline, 122, 282 Liver, 17, 26, 73, 102, 241, 247, 248, 249, 259, 260, 262, 268, 269, 273, 282, 287, 298, 305 Liver scan, 282, 305 Localization, 59, 276, 282 Localized, 168, 261, 264, 272, 273, 277, 281, 282, 287, 296, 315 Longitudinal study, 120, 282 Loperamide, 202, 282 Low-density lipoprotein, 282 Lumen, 65, 282

Lupus, 282, 310 Lymph, 46, 248, 249, 259, 264, 277, 282, 283 Lymph node, 46, 248, 249, 282, 283 Lymphadenopathy, 277, 282 Lymphatic, 188, 190, 196, 245, 268, 277, 282, 285, 308, 312 Lymphatic system, 245, 268, 282, 308, 312 Lymphoblastic, 81, 107, 112, 122, 161, 165, 166, 178, 193, 283 Lymphoblasts, 241, 283 Lymphocyte, 17, 35, 36, 91, 123, 137, 139, 192, 193, 241, 246, 280, 283, 284 Lymphocyte Count, 123, 241, 283 Lymphocytic, 163, 181, 283 Lymphocytosis, 82, 283 Lymphoid, 9, 22, 29, 32, 49, 63, 103, 135, 165, 180, 246, 270, 280, 283, 288 Lymphokine, 144, 283 Lymphomatoid Papulosis, 283, 295 Lymphoproliferative, 23, 27, 80, 84, 88, 89, 90, 102, 105, 119, 146, 283, 293 Lysosomal Storage Diseases, 16, 283 Lytic, 23, 283, 306 M Macrophage, 24, 25, 26, 35, 187, 257, 283 Macula, 61, 283 Maculopapular, 283, 293, 295 Magnetic Resonance Imaging, 283, 305 Maintenance therapy, 44, 283 Major Histocompatibility Complex, 33, 45, 188, 272, 283 Malignancy, 14, 25, 48, 284, 292 Malignant tumor, 255, 284, 287 Marital Status, 173, 284 Mediate, 39, 53, 280, 284 Mediator, 278, 284, 306 Medical Oncology, 9, 53, 151, 153, 284, 301 Medical Records, 284, 304 Medical Staff, 262, 284 MEDLINE, 219, 284 Medulloblastoma, 42, 168, 284 Megakaryocytes, 251, 284 Melanin, 284, 294, 314 Melanocytes, 284 Melanoma, 39, 176, 284 Melphalan, 124, 147, 148, 166, 284 Membrane Proteins, 284 Memory, 21, 65, 245, 261, 270, 284 Meninges, 254, 284 Meningitis, 268, 284 Mental Disorders, 184, 285, 300

328

Bone Marrow Transplant

Mentors, 41, 285 Mercury, 268, 285 Mesenchymal, 21, 25, 97, 285 Mesenteric, 249, 285 Meta-Analysis, 13, 285 Metabolite, 250, 262, 285, 298 Metastasis, 10, 285 Metastatic, 9, 39, 58, 126, 142, 143, 167, 176, 285, 306 Methionine, 262, 285, 310 Methoxsalen, 285, 295 Methylcellulose, 17, 285 Metronidazole, 100, 285 MI, 240, 285 Microbe, 195, 285, 312 Microbiology, 11, 24, 50, 69, 76, 80, 81, 87, 89, 96, 104, 108, 110, 242, 248, 285 Microorganism, 253, 256, 286, 293, 316 Micro-organism, 261, 286 Microscopy, 52, 66, 83, 249, 286 Microtubules, 286, 292 Migration, 9, 286, 294 Milliliter, 251, 286 Mitochondria, 286, 291 Mitomycin, 45, 286 Mitosis, 247, 286 Mitosporic Fungi, 247, 286 Mitotic, 266, 286 Mitoxantrone, 166, 286 Mobility, 16, 38, 286 Mobilization, 187, 286 Modeling, 12, 286 Modification, 28, 269, 286, 301, 317 Molar pregnancy, 270, 286 Monitor, 16, 35, 42, 58, 64, 287 Monoamine, 287, 306 Monoamine Oxidase, 287, 306 Monoclonal, 39, 51, 59, 62, 142, 171, 188, 213, 279, 287, 301, 304, 317 Monocyte, 36, 287 Mononuclear, 33, 89, 134, 138, 188, 277, 287, 314 Mononucleosis, 200, 287 Monotherapy, 87, 123, 287 Morphological, 152, 264, 268, 284, 287 Morphology, 65, 272, 287 Motility, 287, 306 Motion Sickness, 287, 288 Mucins, 287, 305 Mucolytic, 251, 287 Mucosa, 23, 90, 141, 203, 249, 265, 282, 287, 309

Mucositis, 4, 5, 86, 105, 108, 115, 127, 147, 200, 202, 203, 227, 228, 287, 312 Multicenter study, 143, 287 Multidrug resistance, 44, 287 Multiple Myeloma, 47, 58, 64, 113, 130, 131, 145, 162, 163, 175, 180, 196, 208, 287 Multiple sclerosis, 195, 287 Muscular Dystrophies, 263, 287 Mutagenesis, 38, 44, 192, 288 Mutagens, 288 Myasthenia, 125, 195, 288 Mycophenolate mofetil, 50, 123, 125, 166, 169, 180, 288 Myelin, 287, 288 Myelodysplasia, 28, 113, 288 Myelodysplastic syndrome, 89, 150, 163, 164, 171, 177, 182, 189, 288, 307 Myelofibrosis, 157, 189, 288 Myeloid Cells, 61, 288 Myeloid Progenitor Cells, 61, 187, 288 Myeloma, 48, 58, 131, 224, 274, 288 Myeloproliferative Disorders, 157, 162, 169, 170, 194, 288 Myelosuppression, 47, 105, 288 Myocardium, 245, 285, 288 N Narcotic, 288, 292 Nasogastric, 264, 288 Natural killer cells, 32, 192, 288 Natural selection, 250, 288 Nausea, 202, 246, 269, 288, 314 Nebramycin, 289, 312 Necrolysis, 200, 289, 295 Necrosis, 247, 260, 277, 285, 289, 295 Need, 3, 7, 19, 20, 37, 40, 42, 62, 186, 193, 199, 201, 210, 213, 231, 242, 289, 312, 314 Neonatal, 16, 289 Neoplasia, 289 Neoplasm, 162, 167, 168, 169, 172, 289, 292, 305, 314 Neoplastic, 10, 187, 283, 289, 305 Nephritis, 6, 289 Nephron, 75, 270, 289 Nephropathy, 6, 61, 74, 109, 125, 126, 289 Nephrotoxic, 6, 289 Nerve, 190, 242, 245, 259, 261, 269, 284, 287, 289, 291, 298, 305, 309, 317 Nerve Growth Factor, 190, 289 Nervous System, 139, 254, 284, 289, 290, 310 Netilmicin, 126, 289 Networks, 9, 289

Index 329

Neural, 195, 274, 287, 289 Neuroblastoma, 39, 43, 110, 124, 125, 127, 130, 141, 147, 148, 149, 168, 172, 289 Neuroectodermal Tumors, 289 Neurologic, 86, 125, 289 Neuromuscular, 241, 289, 306, 314 Neuronal, 67, 289 Neurons, 67, 261, 289, 310 Neuroretinitis, 290, 303 Neurotoxicity, 200, 290 Neutrons, 244, 279, 290, 301 Neutropenia, 34, 68, 108, 109, 179, 290 Neutrophil, 28, 290 Nitrogen, 259, 271, 284, 290, 292, 314 Nonmalignant, 36, 147, 169, 290 Nonmalignant hematologic disorders, 169, 290 Norfloxacin, 68, 290 Nosocomial, 68, 106, 290 Nuclei, 69, 244, 264, 269, 283, 286, 290, 291, 300 Nucleic acid, 96, 196, 260, 269, 274, 288, 290, 304, 317 Nucleic Acid Hybridization, 274, 290 Nucleus, 247, 249, 255, 259, 260, 265, 266, 269, 287, 290, 300, 309 Nummular, 203, 290 Nursing Assessment, 290 Nursing Care, 79, 290 Nursing Diagnosis, 118, 290 Nutritional Status, 6, 290 O Occult, 39, 291 Oncogene, 19, 291 Oncogenic, 63, 291, 300 Oncologist, 6, 18, 291 Operon, 291, 303 Opportunistic Infections, 27, 34, 193, 241, 291 Optic Nerve, 290, 291, 303 Oral Health, 5, 6, 200, 204, 227, 228, 291 Oral Hygiene, 200, 203, 210, 228, 291 Organ Culture, 291, 312 Organ Transplantation, 20, 49, 291 Organelles, 66, 260, 284, 291, 296 Oropharynx, 23, 291 Outpatient, 200, 291 Ovarian epithelial cancer, 165, 291 Ovaries, 291, 306 Ovary, 271, 291, 292, 309 Overall survival, 13, 41, 56, 60, 291 Overexpress, 36, 61, 62, 292

Ovum, 281, 292, 299 Oxidation, 241, 247, 250, 273, 281, 292 Oxidative Stress, 36, 45, 292 Oxycodone, 119, 292 P Paclitaxel, 147, 157, 292 Paediatric, 75, 112, 115, 120, 150, 292 Palate, 292, 309 Palliative, 53, 58, 126, 292, 311 Pancreas, 58, 241, 262, 278, 279, 292, 314 Pancreas Transplant, 58, 292 Pancreas Transplantation, 58, 292 Pancreatic, 6, 292 Pancreatic Insufficiency, 6, 292 Pancreatitis, 6, 292 Papilloma, 258, 292 Papillomavirus, 98, 292 Parapsoriasis, 292, 295 Parenteral, 91, 115, 122, 139, 149, 194, 202, 263, 293 Parenteral Nutrition, 91, 115, 122, 149, 293 Partial remission, 143, 293, 302, 303 Partial response, 142, 293 Particle, 282, 293, 313 Pathogen, 75, 293 Pathogenesis, 23, 24, 36, 45, 60, 108, 203, 293 Pathologic, 6, 50, 109, 247, 250, 252, 259, 275, 293, 300 Pathologic Processes, 247, 293 Pathologies, 5, 293 Pathophysiology, 27, 36, 199, 293 Patient Education, 203, 227, 234, 236, 240, 293 Pefloxacin, 68, 293 Pelvic, 293, 299 Penicillin, 99, 244, 293 Pentostatin, 182, 293 Pentoxifylline, 109, 125, 126, 293 Peptide, 25, 32, 33, 38, 59, 65, 188, 191, 256, 267, 274, 280, 293, 294, 297, 299, 300 Peptide Chain Elongation, 256, 293 Peptide Fragments, 188, 294 Perception, 272, 294, 305 Performance status, 48, 294 Perianal, 258, 294 Pericarditis, 122, 294 Pericardium, 294, 310 Periodontal disease, 74, 210, 294 Periodontal Index, 7, 294 Periodontal Pocket, 294

330

Bone Marrow Transplant

Peripheral stem cell transplantation, 164, 166, 167, 168, 170, 294, 312 Peripheral stem cells, 170, 271, 294 PH, 72, 85, 251, 294 Pharmacokinetic, 294 Pharmacologic, 30, 62, 245, 294, 313 Pharynx, 291, 294 Phenotype, 9, 30, 37, 61, 66, 188, 294 Phenylalanine, 294, 314 Phosphodiesterase, 293, 294 Phospholipases, 295, 307 Phospholipids, 267, 278, 282, 295 Phosphoprotein Phosphatase, 253, 295 Phosphorus, 252, 295 Phosphorylate, 192, 295 Phosphorylated, 9, 295 Phosphorylation, 9, 259, 295 Photopheresis, 182, 295 Photosensitivity, 200, 295 Physical Examination, 202, 295 Physiologic, 24, 44, 203, 243, 250, 267, 295, 302, 314 Pigment, 284, 295 Pilot study, 74, 105, 125, 126, 132, 139, 141, 145, 154, 295 Pituitary Gland, 267, 295 Pityriasis, 203, 293, 295 Pityriasis Lichenoides, 203, 293, 295 Pityriasis Rosea, 203, 295 Placenta, 267, 296, 299, 314 Plants, 271, 285, 287, 296, 305, 313, 314 Plaque, 4, 203, 245, 293, 296 Plasma cells, 246, 287, 288, 296 Plasma protein, 296, 300, 306 Plasmapheresis, 77, 189, 247, 296 Plasmin, 296 Plasminogen, 25, 35, 296 Plasminogen Activators, 296 Plasticity, 17, 40, 55, 296 Plastids, 291, 296 Platelet Activation, 296, 307 Platelet Aggregation, 65, 293, 296, 311 Platelet Count, 189, 297 Platelet Transfusion, 189, 297 Plateletpheresis, 247, 297 Platelets, 52, 66, 162, 189, 240, 288, 296, 297, 305, 311 Platinum, 256, 297 Pneumonitis, 36, 50, 72, 112, 297 Podophyllotoxin, 266, 297 Poisoning, 269, 279, 285, 288, 297, 306

Polymerase, 70, 71, 83, 84, 137, 138, 154, 247, 297, 303 Polymerase Chain Reaction, 70, 71, 83, 84, 137, 138, 154, 297 Polymorphic, 45, 297 Polymorphism, 32, 38, 45, 297 Polypeptide, 191, 244, 256, 267, 274, 296, 297, 311, 317 Polysaccharide, 98, 246, 254, 297 Posterior, 244, 254, 255, 262, 292, 297 Postnatal, 297, 309 Postoperative, 200, 297 Postsynaptic, 298, 307 Potassium, 128, 243, 298 Potentiation, 298, 307 Practicability, 267, 298 Practice Guidelines, 220, 228, 298 Preclinical, 10, 34, 60, 64, 298 Precursor, 194, 245, 247, 259, 263, 265, 272, 294, 296, 298, 299, 300, 314 Predisposition, 57, 195, 298 Prednisolone, 298 Prednisone, 31, 109, 126, 138, 298 Preleukemia, 288, 298, 307 Prenatal, 41, 264, 298 Prenatal Care, 41, 298 Prevalence, 5, 71, 294, 298 Prickle, 280, 298 Primary tumor, 46, 298 Primitive neuroectodermal tumors, 168, 284, 298 Probe, 71, 294, 298 Prodrug, 27, 298 Progeny, 34, 55, 299 Progesterone, 299, 309 Prognostic factor, 39, 56, 75, 149, 299, 310 Progression, 9, 58, 64, 149, 245, 259, 299 Progressive disease, 275, 299 Proline, 257, 275, 299 Promoter, 38, 51, 62, 299 Promyelocytic leukemia, 177, 178, 299 Prone, 20, 69, 299 Prospective Studies, 47, 299 Prospective study, 30, 86, 97, 99, 106, 130, 135, 282, 299 Prostaglandins, 247, 299 Prostate, 54, 299, 314 Protease, 119, 299 Protective Agents, 57, 299 Protein C, 98, 244, 247, 249, 280, 282, 299, 308

Index 331

Protein S, 191, 247, 250, 256, 266, 269, 299, 304, 311 Proteinuria, 270, 287, 300 Prothrombin, 30, 300, 311 Protocol, 5, 15, 21, 22, 26, 30, 37, 44, 49, 57, 64, 300 Protons, 244, 274, 279, 300, 301 Proto-Oncogene Proteins, 292, 300 Proto-Oncogene Proteins c-mos, 292, 300 Proximal, 51, 262, 280, 300 Pruritic, 263, 281, 300 Psoriasis, 83, 195, 203, 293, 300 Psychiatric, 41, 285, 300 Psychiatry, 106, 300, 315 Psyllium, 157, 300 Puberty, 57, 300 Public Policy, 219, 300 Publishing, 66, 201, 300 Pulmonary, 4, 36, 67, 70, 72, 79, 84, 105, 110, 124, 194, 250, 251, 258, 281, 300, 315 Pulmonary Artery, 250, 300, 315 Pulmonary Fibrosis, 194, 300 Pulse, 287, 301 Purpura, 30, 301 Pyrazoloacridine, 172, 301 Q Quality of Life, 14, 54, 58, 87, 95, 110, 111, 116, 129, 134, 160, 203, 230, 301, 310 R Race, 284, 286, 301 Radiation oncologist, 291, 301 Radiation Oncology, 15, 54, 65, 125, 154, 301 Radioactive, 251, 260, 274, 277, 279, 282, 291, 301, 305, 317 Radiography, 107, 301 Radioimmunotherapy, 28, 301 Radioisotope, 301, 313 Radiolabeled, 26, 279, 301, 317 Radiology, 46, 74, 107, 124, 301 Radiotherapy, 43, 46, 149, 190, 204, 251, 279, 301, 309, 317 Randomized clinical trial, 58, 302 Randomized Controlled Trials, 12, 302 Reactivation, 76, 97, 111, 190, 302 Receptor, 10, 11, 26, 35, 53, 74, 126, 188, 190, 192, 242, 246, 259, 302, 306, 307 Receptors, Serotonin, 302, 306 Recombinant, 8, 38, 51, 55, 72, 116, 132, 205, 302, 315 Recombination, 46, 269, 302

Reconstitution, 10, 28, 29, 35, 37, 48, 49, 50, 57, 60, 64, 86, 115, 123, 134, 302 Rectum, 99, 247, 251, 262, 269, 277, 280, 299, 302 Recurrence, 28, 46, 111, 302 Red blood cells, 50, 162, 266, 273, 275, 288, 302, 305, 307, 308 Refer, 1, 252, 257, 268, 274, 282, 283, 287, 290, 301, 302 Refraction, 302, 308 Refractory, 20, 30, 42, 91, 116, 127, 131, 133, 143, 151, 154, 162, 165, 166, 172, 177, 181, 302 Regeneration, 40, 55, 267, 302 Registries, 32, 108, 302 Remission, 39, 58, 94, 129, 142, 143, 145, 152, 161, 166, 171, 202, 283, 302, 303 Remission Induction, 145, 303 Remission induction therapy, 145, 303 Renal failure, 6, 303, 314 Renin, 35, 245, 303 Repopulation, 17, 55, 187, 303 Repressor, 51, 291, 303 Research Design, 18, 303 Research Support, 43, 303 Residual disease, 28, 39, 149, 303 Respiration, 286, 287, 303 Respiratory Physiology, 303, 315 Restoration, 18, 20, 25, 259, 302, 303, 317 Retina, 255, 260, 280, 290, 291, 303, 304 Retinae, 283, 303 Retinal, 260, 262, 291, 303 Retinitis, 50, 260, 303, 304 Retinoblastoma, 179, 304 Retinopathy, 76, 304 Retrospective, 13, 18, 39, 56, 74, 77, 102, 304 Retrospective Studies, 13, 304 Retrospective study, 77, 102, 304 Retroviral vector, 17, 40, 304 Retrovirus, 39, 304 Rheology, 293, 304 Rheumatism, 304 Rheumatoid, 53, 195, 304 Rheumatoid arthritis, 53, 195, 304 Rhinitis, 251, 304 Ribavirin, 30, 304 Ribonucleoside Diphosphate Reductase, 275, 304 Ribosome, 304, 313 Risk factor, 14, 36, 74, 75, 97, 113, 203, 299, 304

332

Bone Marrow Transplant

Ristocetin, 304, 315 Rituximab, 116, 304 Rod, 249, 304 Roxithromycin, 66, 305 S Saline, 251, 305 Saliva, 23, 305 Salivary, 5, 228, 260, 262, 305, 317 Salivary glands, 260, 262, 305 Salvage Therapy, 124, 305 Saponins, 305, 309 Sarcoma, 44, 145, 203, 298, 305 Sargramostim, 173, 174, 214, 305 Scans, 46, 305 Schizoid, 305, 317 Schizophrenia, 305, 317 Schizotypal Personality Disorder, 305, 317 Sclerosis, 287, 305 Screening, 41, 45, 54, 192, 256, 305 Second cancer, 14, 305 Secondary tumor, 285, 305 Secretion, 26, 255, 274, 278, 279, 287, 292, 306, 315 Segmental, 58, 270, 306 Segmentation, 306 Segregation, 302, 306 Semen, 299, 306 Semisynthetic, 253, 256, 266, 275, 289, 292, 305, 306 Sepsis, 23, 75, 249, 306 Septicemia, 74, 106, 306 Sequence Analysis, 38, 45, 306 Sequencing, 9, 77, 98, 297, 306 Serologic, 276, 306 Serology, 97, 306 Serotonin, 105, 287, 302, 306, 314 Serotonin Syndrome, 105, 306 Serous, 94, 306 Sertraline, 119, 306 Serum, 75, 146, 189, 214, 242, 251, 257, 276, 282, 302, 306, 314 Serum Albumin, 251, 306 Sex Characteristics, 300, 306 Shedding, 307, 316 Shock, 16, 245, 307, 313 Side effect, 5, 18, 21, 53, 164, 170, 174, 194, 211, 213, 242, 250, 259, 288, 307, 310, 312, 317 Signal Transduction, 9, 18, 29, 32, 53, 63, 66, 191, 278, 307 Signs and Symptoms, 302, 307, 314 Skeletal, 16, 40, 287, 288, 307

Skeleton, 38, 241, 280, 307 Skull, 307, 311 Sludge, 92, 124, 307 Small cell lung cancer, 164, 307 Small intestine, 255, 263, 265, 270, 274, 279, 288, 307 Smoldering leukemia, 288, 307 Smooth muscle, 51, 274, 307, 310 Social Environment, 301, 307 Sodium, 243, 307 Soft tissue, 4, 251, 307, 308 Solid tumor, 39, 63, 171, 181, 202, 263, 308 Soma, 308 Somatic, 77, 274, 286, 308 Specialist, 230, 308 Specificity, 34, 59, 65, 243, 298, 308 Spectrin, 38, 308 Spectrum, 29, 42, 46, 275, 290, 293, 305, 308 Sperm, 255, 270, 308 Spherocytes, 308 Spherocytosis, 38, 308 Spinal cord, 248, 254, 269, 279, 284, 289, 308 Spinous, 265, 280, 308 Spirochete, 308, 310 Spleen, 249, 260, 274, 282, 283, 308 Splenectomy, 189, 308 Splenomegaly, 277, 308 Sporadic, 304, 308 Staging, 16, 46, 305, 308 Standard therapy, 31, 295, 309 Steady state, 9, 309 Stereotactic, 44, 309 Sterility, 16, 259, 309 Steroid, 32, 57, 259, 305, 309 Stimulus, 263, 266, 272, 280, 309 Stomach, 241, 248, 262, 266, 269, 274, 280, 288, 294, 307, 308, 309 Stomatitis, 203, 227, 228, 309 Strand, 297, 309 Streptococcal, 195, 309 Streptococcus, 108, 309 Stress, 4, 5, 7, 9, 57, 173, 203, 210, 269, 288, 292, 298, 304, 309, 315 Stroke, 162, 184, 218, 253, 309 Stroma, 17, 57, 309 Stromal, 208, 251, 279, 309 Stromal Cells, 208, 251, 279, 309 Subacute, 277, 309 Subclinical, 277, 309 Subcutaneous, 113, 206, 263, 293, 310

Index 333

Subspecies, 308, 310 Substance P, 266, 285, 302, 304, 306, 310 Sulfur, 280, 285, 310 Supplementation, 124, 130, 138, 139, 140, 152, 310 Supportive care, 173, 310 Suppression, 49, 144, 193, 194, 310, 317 Supratentorial, 168, 310 Survival Analysis, 150, 310 Survival Rate, 42, 62, 291, 310 Symphysis, 299, 310 Symptomatic, 79, 292, 310 Synaptic, 307, 310 Synergistic, 293, 310 Syphilis, 203, 310 Systemic, 4, 5, 22, 47, 59, 83, 135, 149, 195, 212, 245, 247, 249, 250, 252, 265, 273, 277, 279, 293, 298, 301, 306, 309, 310, 313, 317 Systemic lupus erythematosus, 59, 83, 135, 195, 310 T Tachycardia, 249, 310 Tachypnea, 249, 310 Tacrolimus, 50, 77, 98, 100, 168, 169, 170, 180, 212, 310 Teichoic Acids, 271, 311 Telomere, 96, 311 Temozolomide, 168, 311 Temporal, 51, 59, 311 Terminator, 311, 317 Testicular, 101, 152, 176, 181, 311 Testis, 39, 255, 311 Tetracycline, 200, 311 Thalassemia, 34, 37, 78, 117, 148, 149, 311 Therapeutics, 15, 25, 213, 287, 311 Thermal, 262, 290, 297, 311 Thiotepa, 130, 139, 167, 168, 174, 311 Thrombin, 52, 267, 296, 299, 300, 311 Thrombocytes, 297, 311 Thrombocytopenia, 189, 247, 311 Thrombolytic, 296, 311 Thrombomodulin, 87, 299, 311 Thrombosis, 52, 106, 155, 299, 309, 311 Thromboxanes, 247, 311 Thrombus, 52, 259, 277, 297, 311 Thymidine, 60, 93, 312 Thymidine Kinase, 60, 93, 312 Thymus, 10, 22, 24, 49, 57, 60, 73, 188, 205, 276, 282, 283, 312 Thyroid, 139, 312, 314 Thyroid Gland, 312

Thyroiditis, 195, 312 Time Factors, 243, 312 Tissue Culture, 38, 312 Tobramycin, 93, 312 Tolerance, 10, 20, 32, 49, 50, 62, 64, 65, 72, 73, 91, 146, 148, 172, 242, 312 Tomography, 258, 312 Tooth Abnormalities, 7, 312 Tooth Preparation, 242, 312 Topical, 200, 312 Topotecan, 167, 312 Total-body irradiation, 140, 166, 169, 171, 175, 180, 182, 312 Toxicokinetics, 312 Toxicology, 220, 313 Toxins, 45, 246, 264, 277, 301, 306, 313 Toxoplasmosis, 77, 84, 85, 313 Tracer, 46, 313 Trachea, 251, 294, 312, 313 Transcriptase, 280, 304, 313, 317 Transcription Factors, 253, 313 Transduction, 9, 27, 29, 38, 53, 55, 188, 307, 313 Transfection, 23, 250, 313 Transfer Factor, 276, 313 Transfusion, 8, 30, 113, 189, 313 Transgenes, 55, 59, 313 Translation, 62, 116, 266, 313 Translational, 17, 37, 313 Translocate, 65, 313 Translocating, 249, 313 Translocation, 24, 66, 152, 249, 256, 266, 313 Transplantation Tolerance, 20, 313 Trauma, 113, 195, 289, 292, 313 Tremor, 119, 314 Triage, 58, 314 Trichomoniasis, 285, 314 Tropism, 113, 314 Tryptophan, 257, 306, 314 Tumor marker, 39, 314 Tumor Necrosis Factor, 11, 21, 314 Tumour, 82, 269, 314 Tyrosine, 9, 29, 63, 191, 192, 314 U Umbilical Arteries, 314 Umbilical Cord, 17, 254, 314 Umbilical cord blood, 17, 28, 314 Unconscious, 245, 275, 314 Unresectable, 168, 314 Uraemia, 292, 314 Uremia, 303, 314

334

Bone Marrow Transplant

Urethra, 299, 314, 315 Urinary, 256, 259, 290, 293, 315 Urinary tract, 293, 315 Urinary tract infection, 293, 315 Urine, 68, 70, 72, 83, 250, 257, 290, 300, 314, 315 Urticaria, 245, 315 Uterus, 270, 286, 291, 299, 315 V Vaccination, 64, 99, 315 Vaccine, 64, 242, 300, 315 Vacuoles, 291, 315 Vagina, 252, 261, 315 Vaginitis, 252, 315 Vancomycin, 71, 107, 118, 189, 315 Vascular, 52, 65, 245, 255, 277, 296, 312, 315 Vasculitis, 292, 315 Vector, 18, 34, 64, 68, 196, 313, 315 Vein, 155, 186, 279, 314, 315 Vena, 155, 315 Venereal, 310, 315 Venous, 52, 106, 135, 297, 299, 315 Venous blood, 297, 315 Ventilation, 104, 315 Ventricle, 17, 300, 301, 315 Venules, 52, 251, 252, 315 Vesicular, 274, 295, 316 Veterinary Medicine, 219, 316 Vial, 33, 316 Vinca Alkaloids, 316 Vincristine, 138, 316

Viral Load, 105, 316 Viral vector, 28, 316 Viremia, 68, 97, 316 Virulence, 312, 316 Virus Diseases, 247, 316 Virus Shedding, 23, 316 Viscera, 308, 316 Visceral, 16, 316 Vital Statistics, 14, 316 Vitamin A, 278, 316 Vitro, 24, 27, 33, 37, 40, 50, 55, 316 Vivo, 8, 10, 24, 27, 28, 33, 37, 39, 40, 52, 55, 89, 193, 316 W War, 113, 254, 316 Windpipe, 294, 312, 316 Withdrawal, 62, 111, 116, 317 Wound Healing, 267, 317 X Xenograft, 8, 64, 192, 245, 317 Xerostomia, 4, 5, 200, 203, 228, 317 X-ray, 66, 163, 170, 171, 175, 179, 180, 251, 258, 268, 269, 279, 301, 305, 309, 317 X-ray therapy, 279, 317 Y Yeasts, 252, 268, 294, 317 Z Zalcitabine, 280, 317 Zidovudine, 180, 317 Zoster, 119, 317 Zymogen, 299, 317

Index 335

336

Bone Marrow Transplant

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