SMALLPOX VACCINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Smallpox Vaccine: 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: 0-597-84630-8 1. Smallpox Vaccine-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on smallpox vaccine. 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 SMALLPOX VACCINE ................................................................................ 3 Overview........................................................................................................................................ 3 Federally Funded Research on Smallpox Vaccine.......................................................................... 3 E-Journals: PubMed Central ....................................................................................................... 28 The National Library of Medicine: PubMed ................................................................................ 28 CHAPTER 2. CLINICAL TRIALS AND SMALLPOX VACCINE ............................................................. 43 Overview...................................................................................................................................... 43 Recent Trials on Smallpox Vaccine.............................................................................................. 43 Keeping Current on Clinical Trials ............................................................................................. 47 CHAPTER 3. BOOKS ON SMALLPOX VACCINE................................................................................. 49 Overview...................................................................................................................................... 49 Book Summaries: Online Booksellers........................................................................................... 49 Chapters on Smallpox Vaccine..................................................................................................... 49 CHAPTER 4. PERIODICALS AND NEWS ON SMALLPOX VACCINE ................................................... 51 Overview...................................................................................................................................... 51 News Services and Press Releases................................................................................................ 51 Academic Periodicals covering Smallpox Vaccine ....................................................................... 55 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 59 Overview...................................................................................................................................... 59 NIH Guidelines............................................................................................................................ 59 NIH Databases............................................................................................................................. 61 Other Commercial Databases....................................................................................................... 63 APPENDIX B. PATIENT RESOURCES ................................................................................................. 65 Overview...................................................................................................................................... 65 Patient Guideline Sources............................................................................................................ 65 Finding Associations.................................................................................................................... 68 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 71 Overview...................................................................................................................................... 71 Preparation................................................................................................................................... 71 Finding a Local Medical Library.................................................................................................. 71 Medical Libraries in the U.S. and Canada ................................................................................... 71 ONLINE GLOSSARIES.................................................................................................................. 77 Online Dictionary Directories ..................................................................................................... 77 SMALLPOX VACCINE DICTIONARY ...................................................................................... 79 INDEX .............................................................................................................................................. 105
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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 smallpox vaccine 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 smallpox vaccine, 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 smallpox vaccine, 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 smallpox vaccine. 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 smallpox vaccine, 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 smallpox vaccine. 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 SMALLPOX VACCINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on smallpox vaccine.
Federally Funded Research on Smallpox Vaccine The U.S. Government supports a variety of research studies relating to smallpox vaccine. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to smallpox vaccine. 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 smallpox vaccine. The following is typical of the type of information found when searching the CRISP database for smallpox vaccine: •
Project Title: A SAFER AND MORE EFFICACIOUS SMALLPOX VACCINE Principal Investigator & Institution: Yilma, Tilahun D.; Professor and Director; Interntl Lab Molecular Biology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2006
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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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Summary: (provided by applicant): In the aftermath of the attacks of September 11 and the anthrax scare, we have a heightened awareness of US vulnerability to bioterrorism. One of the most feared infectious agents is variola virus, the causative agent of smallpox. Various strains of vaccinia virus (VV) are highly effective in preventing this disease, but have definite rates of complications. Severe illness or death is rare in people with normal immune responses, but considerably more common in individuals with cell-mediated immune defects. The number of individuals that are at risk from this normally innocuous vaccine has greatly increased with the spread of the human immunodeficiency virus (HIV), and it now becomes important to improve the efficacy and safety of this vaccine. We have worked extensively with VV as a recombinant vaccine for a number of diseases; our rinderpest vaccine was described as one of two outstanding rVVs in a leading journal (G. Ada, Nature 349:369, 1991). We have also developed strategies for attenuating VV while enhancing efficacy, with one of the most effective being the incorporation of the interferon-gamma (IFN-gamma) gene. We have shown that expression of IFN-gamma leads to a TH1 immune response essential against viral infection with no deleterious effects. We have also studied the effects of inactivating VV immunomodulating genes such as B8R, B13R, and B22R that are virulence factors in VV. Based on our past experience, we propose developing a safer and more efficacious vaccine for smallpox based on the New York City Board of Health (Wyeth) strain of VV that is currently used in the US. We will delete the B8R gene and insertionally inactivate the TK virulence gene with the human IFN-gamma gene to increase attenuation of the virus and the protective cell-mediated immune responses. This recombinant VV will be compared to the parental vaccine in both normal and simian immunodeficiency virus-infected macaques (used as a model for HIV-infected humans) to assess efficacy and safety for normal and immunodeficient individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSESSMENT OF IMMUNITY TO VACCINIA AND MVA Principal Investigator & Institution: Dolin, Raphael C.; Maxwell Finland Professor of Medicine; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Despite its extraordinary effectiveness against smallpox infection, the parameters of protective immunity generated by vaccinia remain incompletely understood. Large numbers of individuals are at high risk for serious toxicities if vaccinated with or exposed to vaccinia, and the need to develop safer vaccines against smallpox underscores the importance of understanding the immunologic basis for such protection. This project will undertake a detailed examination of T and B cell responses to immunization with vaccinia and MVA under carefully controlled conditions in normal subjects, and to MVA in patients with atopic dermatitis or patients with hematologic malignancies and immune deficiency after hematopoietic stem cell transplantation. The studies will measure neutralizing and other binding antibodies, lymphoproliferative responses by 3H Thymidine incorporation, cytotoxic T-cell activity by a 51Cr release assay, and T-cell gamma interferon responses by ELISPOT. Normal subjects who were vaccinated with either vaccinia or MVA, will be challenged with vaccinia to determine whether protection against challenge was conferred. Measurements of immune responses will be conducted sequentially at multiple time points, including those before and after challenge. Rates and patterns of responses wilt be compared between vaccinia and MVA recipients, and between normals and the patient cohorts. The specificity of the B and T cell responses will be examined employing bioinformatics approaches and molecular techniques of the Research Resource Technical
Studies
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Development Component of the Center. These studies will measure antibody responses to a panel of recombinant vaccinia-encoded proteins identified by bioinformatics as potentially important in neutralization, including the EGF-like domain of DIL (SPGF). Since all subjects in our initial studies will be HLA-A*0201 positive, we will be able to utilize peptides from the recombinant vaccinia proteins to characterize class I allele specific T-cell responses by ELISPOT, cytokine flow cytometry, and peptide-MHC tetramers. Non-class I allele specific T-cell responses will be examined using whole recombinant proteins. Spectratype analysis will also be used to identify predominant Tcell epitopes. These studies wilt provide a comprehensive picture of the immune responses to vaccination with vaccinia and MVA, and identify epitopes against which important responses are directed. These studies will also demonstrate whether 2 groups of high-risk patients respond to MVA in a similar fashion to normals. The proposed studies in years 1 and 2 focus on MVA, but similar approaches would be utilized to study other candidate vaccines against smallpox, as well as vaccines against other agents important in biodefense. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSESSMENT OF SMALLPOX SPECIFIC IMMUNE RESPONSES Principal Investigator & Institution: Denny, Thomas N.; Assistant Professor of Pathology,; Pediatrics; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: This proposal, in response to RFA-AI-02-002, seeks funding to study longlasting immunity (e.g. immunological memory or recall) to smallpox (variola) in individuals who were previously vaccinated in the United States commercially approved smallpox vaccine (preparation of live Vaccinia virus). In the aftermath of September 11, 2001, it is now critical to better define mechanisms of smallpox protective immunity or disease resistance in the general population and in those who may be classified immune compromised and therefore, considered at a higher risk of infection. Though smallpox was considered a disease of historical interest only, since its earlier eradication, it as been known to be a significant pathogen for potential bioterrorist activities. Investigation of long-lasting immunity using current state-of-the-art techniques or methodologies may help determine which individuals are better prepared to serve as "first-line" responders. In addition, this information may help determine a better strategy for use of limited, non-universally administrable vaccine material available today. Specific Aim 1: To assess smallpox-specific long-lasting immunologic responses and correlate to donor age and time since last vaccination in healthy individuals that have previously received a smallpox vaccination. Hypothesis: Initial childhood vaccine administration will be associated with differing levels of smallpoxspecific host immune responses that will vary with number of immunizations given and the time since last vaccination. Specific Aim 2: To assess smallpox-specific long-lasting immunologic responses in HIV- and HIV+ individuals through collaboration with the NIAID DAIDS ACTG and correlate to age and infection status in individuals previously having smallpox vaccination. Hypothesis: HIV infection, CD4 or viral load status, time since last vaccination and host age will each be associated differing levels of smallpoxspecific host immune responses. Specific Aim 3: To viral epitope map and evaluate the CD4/CD8 immune subset critical memory component of virus-specific cell-mediated responses in healthy and immune comprised study participants. Herd immunity or natural boosting is absent from this model, it represents a unique opportunity to extensively study pathogen specific immunological memory. Hypothesis: Response
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level and/or frequency of CD4 or CD8 cells to various immunodominant viral epitopes will change with age, time since last vaccination or presence of disease (e.g, HIV). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUGMENTING INNATE AND VACCINE IMMUNE RESPONSE WITH DER-G Principal Investigator & Institution: Zimmerman, Daniel H.; Cel-Sci Corporation 8229 Boone Blvd, Ste 802 Vienna, Va 22182 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Concerns regarding the United States' vulnerability to a terrorist attack with smallpox have stimulated development of new vaccines, prophylactics and therapeutics. However, a new and successful smallpox vaccine intervention program, or one to treat exposed individual requires not only an effective vaccine, but also agents to treat the complications arising from a widespread vaccination program. Recently, we found that derG, an N terminal deamidated analogue of the human MHC II beta-chain (aa135-149) showed significant protective activity in infectious disease models of malaria and HSV and adjuvant activity for vaccines. The primary goals of this application are to determine the protective activity of derG for vaccinia infections, identify its mechanism of action to support its' development as an immunotherapeutic and/or prophylactic for vaccinia and smallpox infections as a single agent and as an adjuvant for vaccinia vaccines. The ultimate goal of these Phase I studies is to develop sufficient data to justify studies in a primate model of efficacy and animal safety and toxicology studies to support human clinical trials. In addition to the concern that smallpox may be used as a weapon of mass destruction, recombinant vaccinia viruses (VV) are also used as vaccines or as vectors for immunotherapy resulting in the recommendation that individuals working with VV vectors be vaccinated. However, the present vaccines, when available, are associated with serious complications in approximately 1:10,000 primary vaccinees, and mortality in about 1:10 6 primary vaccinations. Our strategy is to use derG as prophylaxsis and as an adjuvant for a replication incompetent vaccine prime to limit the toxicity by live vaccinia virus and to target mucosal activity. Thus, these studies will deliver derG and the vaccine by intranasal administration and will monitor both systemic and mucosal (pulmonary) immunity. We propose to use derG, together with an infectious, but replication incompetent VV (irradiated) vaccine to examine the hypothesis that immune augmentation with derG will prolong survival and also provide adjuvant activity for a replication incompetent vaccine, thereby providing an additional reduction in viral burden and prolongation of survival for vaccinia-infected mice as a model of smallpox infection. This hypothesis will be tested with the following Specific Aims: 1: Determine the immunoregulatory and adjuvant properties of derG during VV vaccination of mice. 2: Determine the immune augmenting and adjuvant activity of derG in mice sub-lethally infected with vaccinia as a model of smallpox. 3: Determine the therapeutic potential of immune intervention in the treatment of lethal vaccinia virus infections and identify surrogates of therapeutic activity. In these studies we will follow survival and ovarian viral titers after intranasal challenge with VV. The studies will also analyze the mechanism of action to identify immune surrogates for use in clinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
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Project Title: BACTERIAL DEVELOPMENT
ANTIGENS
AND
ANTHRAX
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Principal Investigator & Institution: Hewlette, Erik; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008 Summary: The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE), whose theme is "Defense against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens, tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of F. tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection, as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; diagnostics for detection of these pathogens in water, food, and environmental specimens); 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and 4 Developmental Projects (high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL-MEDIATED IMMUNE RESPONSES TO VACCINIA VIRUSES Principal Investigator & Institution: Crowe, James E.; Associate Professor of Pediatrics; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Detailed analysis of T cell responses from individuals enrolled in vaccinia virus vaccine trials may dramatically improve our understanding of the effects of dilution on vaccine immunogenicity and on the relationship of cell-mediated immunity to protection from adverse events following immunization. Our experiments will begin to address the level of cell-mediated immunity elicited in naive adults following vaccination with the Aventis Pasteur smallpox vaccine. Furthermore, these studies will establish a paradigm in which researchers can begin to incorporate improved measures of cell-mediated immunity in
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clinical environments, generating data that will provide useful surrogate biomarkers of immune responses related to adverse events or protection. Specifically, we will test the hypothesis that the lack of a vigorous response of host T cells to immunodominant cytolytic T cell epitopes following primary immunization is associated with adverse events that are related to failure to clear virus shedding rapidly. Previous work examining cell-mediated immunity to vaccinia virus during clinical vaccine trials is very limited. Small studies have examined the effects of smallpox vaccination and identified that human CTL memory responses to vaccinia virus do occur. Much of the work performed to date examining CM1 responses in humans to specific antigens/viruses have been performed using bulk culture proliferation techniques and standard cytotoxicity assays. While these assay provide a measure of T cell responsiveness to specific antigens, they fail to delineate which of the subsets of T cells are involved in protective memory responses or are associated with adverse events. We will examine many of these questions by taking advantage of new technology that allows for examination of T cell responses at the single cell level, and in an immunodominant epitope specific manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR IMMUNITY TO CATEGORY A-C VIRUSES IN HUMANS Principal Investigator & Institution: Ennis, Francis A.; Professor; None; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The proposed UMASS Center for Translational Research on Human Immunology and Biodefense is a comprehensive, interdepartmental collaboration to address, as its overall scientific theme, the role of human T lymphocyte responses in the immunopathogenesis of and protection from category A-C viral pathogens. The Center encompasses senior and junior investigators with significant prior expertise in human immunology and research on biodefense pathogens, including translation to clinical studies, and is organized around the following components: Project 1 (Poxviruses) will define immunodominant human T cell epitopes of vaccinia virus as markers of vaccine efficacy and advance knowledge toward the development of improved smallpox vaccines. Project 2 (Hantaviruses) will define human immune responses associated with immunopathogenesis of hemorrhagic fever with renal syndrome. Project 3 (Flaviviruses) will define protective and immunopathological cross-reactive human T cell responses to sequential virus infections. The Technical Development Component (TDC) will develop novel solidphase array and proteomics technologies for application in T cell epitope identification, detection and enumeration of virus-specific T cells, and identification of biomarkers of protective or pathological T cell responses. Core facilities will provide flow cytometry, MHC class I production, MHC class II production, and program administration services for use by the research projects and TDC. A Pilot Projects component will support pilot funding of promising novel research concepts proposed by UMMS faculty. An Education component will support short-term training of non-Center investigators. The proposed Center will address important NIAID research priorities related to these biodefense pathogens as well as career development for young investigators. The Center will facilitate synergistic interactions between the various investigators, to be assessed by periodic internal and external review that will greatly enhance the overall research productivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CUTANEOUS IMMUNITY AND VACCINIA Principal Investigator & Institution: Kupper, Thomas S.; Professor and Chair; DanaFarber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: The overarching goal of this project is to understand the mechanisms by which transepidermal inoculation of human skin with vaccinia (scarification) leads to a protective immune response to smallpox, and to use this knowledge to help develop vaccination strategies that are both safe and effective, particularly for patients who currently are not vaccination candidates (e.g., patients with atopic dermatitis). Studies will be performed using both human and murine model systems. The potential for vaccinia to productively infect both normal and atopic skin tissue, cells, and artificial skin constructs, will be assessed by vanous techniques. In collaboration with investigators from Project 1, both skin and blood will be sampled at various time points from vaccinated normal volunteers. We will test the validity of our paradigm of cutaneous immune response, wherein Langerhans cells containing virus fragments from infected epidermis migrate to draining lymph nodes and differentiate into potent mature dendritic cells and activate naive T cells. These T cells expand clonally and differentiate into central memory and skin-homing effector memory T cells. Effector memory T cells extravasate from dermal vessels at the vaccine site and enter the papillary dermis and epidermis. Central memory cells traffic into secondary lymphoid tissues and provide long-term immunologic memory. We will characterize key cellular and humoral elements of the protective immune response to variola generated as a result of these events. We will test the extent to which atopic dermatitis patients and normal volunteers vaccinated with MVA develop similar key elements of this protective response. In murine models, we will manipulate the cutaneous microenvironment with biological response modifiers and determine whether these maneuvers improve the immune response to vaccinia. Transgenic mice with targeted epidermal expression of cytokines and chemokines that influence dendritic cell migration and function will also be studied. The efficacy of vaccination will be assessed by testing resistance to vaccinia challenge in these mice after prior vaccination with MVA or vaccinia, with a major goal being to enhance vaccination efficiency. The Harvard Skin Disease Research Center has studied both innate and acquired immune response mechanisms in skin for more than 15 years. The resources of the HSDRC will provide a rich environment for these studies and will enhance collaborative interactions with investigators leading projects 1, 2, and 4. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEFENSE AGAINST BIOWARFARE AND EMERGING INFECTION AGENTS Principal Investigator & Institution: Levine, Myron Max.; Director; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) whose theme is "Defense Against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; and development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and
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Smallpox Vaccine
other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg viruses); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of Francisella tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; and attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; and diagnostics for detection of these pathogens in water, food, and environmental specimens); and 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; and innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and four Developmental Projects (high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF A SAFER SMALLPOX VACCINE Principal Investigator & Institution: Cho, Michael W.; Assistant Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Smallpox, which is caused by variola virus, is a highly contagious disease with a high fatality rate. A successful, worldwide vaccination campaign during the 1950s-l970s, using live vaccinia virus, resulted in eradication of smallpox. However, there remains a remote, but distinct possibility that large stockpiles of the virus may have been produced and stored as a part of bioweapons program in some countries or by terrorist organizations that are presently hostile to the United States. Smallpox poses a grave danger as an agent of biological weapon because of its highly contagious nature. Since vaccination against the disease stopped during early 1970s in the U.S., a large number of the young generation is unvaccinated and vulnerable to possible bioterrorist attacks. Although existing smallpox vaccine is relatively safe, it is not without serious medical complications including eczema vaccinatum, vaccinia necrosum, and encephalitis. Given the high frequency of AIDS patients who are immunodeficient, use of the current vaccine could result in a serious public health disaster. Therefore, it is imperative to consider developing a secondgeneration smallpox vaccine that is safer, yet as effective as the existing vaccine. Presently, variola virus is not available to perform additional research and the immune correlate of protection against either variola or vaccinia virus is largely unknown. Given these circumstances, a study is proposed with a long-term goal of developing a safer smallpox vaccine, with the following specific aims: (1) to characterize humoral and cellular immune responses against vaccinia virus in macaques previously immunized
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with the virus; (2) to evaluate immunogenicity and degree of attenuation of three recombinant vaccinia viruses derived from two different vaccinia strains (Western Reserve and Wyeth) in mice; and (3) to compare immunogenicity and safety of the newly generated vaccinia virus(es) with those of currently licensed smallpox vaccine strain in macaques previously infected with chimeric SlV/HIV -1 (SHIV). A successful completion of the proposed projects would allow better understanding of immune correlates of protection against vaccinia virus and could facilitate development of a safer smallpox vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL RESEARCH PROJECTS Principal Investigator & Institution: Schlievert, Patrick M.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 31-AUG-2005 Summary: Ten projects were submitted by the applicant. The principal strengths identified by reviewers include: 1) the scientific merit and wide scope of research project topics and approaches, 2) a comprehensive timetable for the evaluation of productivity of the projects, 3) a reasonable plan for soliciting projects and awarding funds, 4) the relevance of most of the proposed projects to the overall program plans, 5) the potential of several projects to become full-fledged research projects for the RCE application, and 6) the highly qualified investigators. Principal weaknesses include: 1) the lack of detail regarding the selection, evaluation and management of primary research projects for the RCE application, 2) some developmental research projects, especially those involving viral agents, require strengthening, 3) the insufficient detail regarding the recruitment of women and under-represented minorities, and 4) lack of information about establishment of long-term research partnerships within and outside the region. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISCOVERY OF SUBUNIT VACCINES FOR SMALLPOX Principal Investigator & Institution: Sykes, Kathryn F.; Director of Vaccine Research; Macrogenics, Inc. 1500 E Gude Dr, Ste B Rockville, Md 20850 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: Eradication of smallpox as a natural pathogen happened 20 years ago. Eradication of smallpox as a biothreat is now our objective. New stockpiles of safe and efficacious smallpox vaccine are needed to protect both the civilian and military populations against deliberate release of the smallpox virus. Currently there is no commercially available vaccine, and the previously approved one is a live vaccinia inoculum associated with more adverse events than any other approved vaccine. Recent work has focused on improving the manufacturing process of the original vaccinia vaccine strain and testing other live attenuated viruses. We propose to discover new vaccine candidates from viral components. A subunit design would be safer and more easily controlled during manufacture. Since we anticipate obtaining multiple protective subunits, these can be mixed and matched to effectively defend against wild type, natural variants, and bioengineered smallpox isolates. To identify antigens of smallpox that carry vaccine potential, the goal of our proposed project is to screen all the genes of the closely related cowpox virus for their ability to protect against disease in its natural murine host. This genome-level approach is feasible because the viral genome databases are available and we have developed the platform technologies that make a comprehensive screen fast and efficient. We will establish the electronic and molecular
12
Smallpox Vaccine
protocols to synthetically generate a thousand codon-optimized gene sequences. It will be used to produce a library of high quality cowpox subgenes. An advanced library screening method employing multiplex arrays will enable us to screen all the subgenes for protection in one experiment. Vaccine candidates will be confirmed and immune characterized. Both the cowpox candidates and their variola homologs will be formatted three ways and evaluated in immune and cowpox protection assays. This project will uncover new subunit vaccine candidates against variola and prepare them for final validation in a primate challenge experiment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA DENGUE/VACCINIA
VACCINE
DELIVERY
FOR
BIODEFENSE
WITH
Principal Investigator & Institution: King, Alan D.; Chief Scientific Officer; Cyto Pulse Sciences, Inc. 7513 Connelley Dr, Ste C Hanover, Md 21076 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-JAN-2004 Summary: (provided by applicant): The long-term project objective is the commercialization of a safe, effective, easy to use, and painless polynucleotide vaccine delivery system that can be used in polynucleotide vaccines for biodefense against NIAID Category A, B and C Pathogens. Polynucleotide vaccines are on the forefront of vaccine development. They are important because of the fast development times possible and because cell mediated immune responses can be induced. The delivery system proposed here will be effective for most polynucleotide vaccines. This delivery system specifically addresses the requirement as presented in the NIAID Strategic Plan for Biodefense Research, February 2002, page 8. In addition to Biodefense, this system will provide effective polynucleotide vaccine delivery for less lethal viruses, some cancers and some third world diseases. The defense and commercial applications are extensive. The polynucleotide vaccine delivery system described here uses a microneedle array with the polynucleotide coated right on the needle in the array. There are hundreds of needles each about 0.15 mm long. This array in inserted into the skin with the needle penetrating to about the basal lamina. After insertion the polynucleotide leaves the needle surface and an electric field is used to permeabilize dendritic and epithelial cell membranes to permit the polynucleotide to enter the cell. The system will be tested with the WRAIR/Cyto Pulse dengue DNA vaccine which will be used as a model for hemorrhagic fever viruses and the USAMRIID vaccinia DNA plasmid which is the primary vaccine for small pox. The specific aims of this project are to design and develop to FDA QSR Standards the vaccine delivery system prototype and to test the prototype in a human trial. This is a fast-track application. In Phase I, a system design will be completed including the hand-piece, microneedle array and miniature waveform generator. The coating chemistry and specific waveforms will be optimized in mice. In Phase II, a prototype of the final design will be completed. Safety and efficacy will be demonstrated in mice and safety will be demonstrated in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOMINANCE VACCINATION
IN
T
CELL
RESPONSES
TO
SMALLPOX
Principal Investigator & Institution: Sette, Alessandro B.; Head and Member; La Jolla Institute for Allergy/Immunolgy 10355 Science Center Dr San Diego, Ca 921211118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2006
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Summary: (provided by applicant): Vaccination against variola virus (the causative agent of smallpox) is currently accomplished by vaccinia virus. Little is known about 1) the antigens and epitopes targeted by the cellular responses in humans immunized with vaccinia virus, and 2) which responses are crossreactive with variola virus and hence would be expected to contribute to the protection engendered by the vaccine. In the first part of the studies proposed herein, we will 1) determine immunodominant antigens recognized by Class I and Class II restricted responses in humans immunized with vaccinia virus, 2) map the epitopes recognized within each antigen, and 3) determine their degree of crossreactivity with homologous variola virus-derived sequences. We anticipate that these studies will lead to the definition of a broad range of epitopes, facilitate a rigorous definition of correlates of protection against smallpox infection in humans, and also enable the evaluation of the performance of different vaccine candidates. Vaccinia virus is also actively investigated as a potential vaccine delivery vehicle, either alone or in prime/boost regimens, for disease indications such as HIV, malaria and cancer. Thus, it should be noted that identification and characterization of the determinants recognized by humans infected/vaccinated by vaccinia virus would also enable the characterization and optimization of experimental vaccines utilizing vaccinia virus-derived vectors as a delivery system. The vaccinia-based vaccines currently available, while effective, are associated with significant and serious, albeit rare, side effects. Because of these side effects, and because of the worldwide eradication of variola virus, vaccination of the general population was deemed as no longer desirable. Recent renewed concerns have been raised over bioterrorist use of the virus. In the context of the studies proposed herein, a concern could be raised that if the vaccinia-induced protection is mediated by relatively few immunodominant and crossreactive antigens, a modified smallpox virus could be engineered that lacks those crossreactive epitopes. Under this terrifying scenario, the protection elicited by the vaccinia would be ineffective against the biological weapon. In the second part of the grant, we propose to counter this risk through the identification of variola virus-specific determinants derived from immunodominant antigens in the context of the vaccinia virus responses, but not crossreactive with the homologous variola virus sequences. These variola virus-derived epitopes would be incorporated in an optimized multideterminant vaccine construct, inserted in the currently available vaccinia vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HETEROPOLYMER COMPLICATIONS
SYSTEM
TO
TREAT
VACCINIA
Principal Investigator & Institution: Pincus, Steven E.; Elusys Therapeutics 10 Bloomfield Ave Pine Brook, Nj 07058 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 28-FEB-2005 Summary: (provided by applicant): Smallpox is a particularly dangerous biological weapon because it can be manufactured in large quantities, stored for an extended period of time, and delivered as an infectious aerosol. It is highly infectious and has a death rate as high as 25%. The only approved smallpox vaccine (live vaccinia virus) is available in very limited quantities (15.4 million doses) and is decades old. Current efforts are underway to produce enough vaccine to vaccinate the entire US population. A problem with this vaccination strategy is that a large segment of the population is susceptible to severe adverse reactions associated with the vaccine, including bloodborne dissemination of the vaccinia virus and even death. This threat is even greater now than when smallpox vaccinations were routine (prior to 1974) due to the growing population of immunosuppressed individuals. The broad long-term objective
14
Smallpox Vaccine
of the project is to develop bispecific antibodies (Heteropolymers, HPs) for treatment of complications associated with the administration of smallpox vaccine. In the present work, we hypothesize that vaccinia virus, the active component of smallpox vaccine, can be bound to erythrocytes (Es) via HPs, cleared to acceptor macrophages, and destroyed without killing the target cells. The HPs will consist of one monoclonal antibody (MAb) against a vaccinia protein expressed on the surface of extracellular (EEV) or intracellular (IMV) virus, cross-linked to a second MAb specific for E Complement Receptor Type I (CR1). The goal of the present work is to identify at least one anti-vaccinia HP that will be a candidate for use in future primate studies to establish efficacy against vaccinia complications following administration to immunocompromised animals. To achieve that goal, we will screen the anti-vaccinia MAb panel to identify the high affinity antibodies that bind EEV or IMV forms in solution phase and, preferably, neutralize the virus. The selected MAbs will be used to prepare HPs by cross-Iinking to a MAb specific for human E CR1. The ability of these HPs to bind EEV or IMV forms of vaccinia and transfer it to acceptor macrophages will be tested. We will also determine whether HP bound vaccinia is infectious. We will determine whether these HPs can prevent vaccinia virus spread and pathology in immunocompromised transgenic mice (expressing human CR1). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH TITER VIG FOR THE TREATMENT OF SMALLPOX Principal Investigator & Institution: Nur, Israel; Omrix Biopharmaceuticals Science Park Bldg 14 Nes-Ziona, Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Long-term objectives Based on preliminary studies on Israeli volunteers, it was concluded that only 60% of the population revaccinated against Smallpox reacted to the vaccine, of whom only 10% did so at very high titers. The aim of this R&D project is to develop and produce a high-titer, small volume Vaccinia Immune Globulin (HT-VIG) as an effective countermeasure to Smallpox and the side effects of the Vaccinia vaccine, which can be administered by intra-muscular or intra-venous mutes, including self-injection. The resulting product will be at least ten times more concentrated than existing VIG preparations that are based on immunoglobulin preparations from non-selected, pooled plasma, and it will have greater efficacy. Importantly, it will be a safe and effective prophylactic treatment against Smallpox for people excluded from the Vaccinia vaccination due to immunodeficiency or other risk factors. Given the heightened risk of a Smallpox outbreak due to bio-terrorism, the project's importance and health relevance cannot be underestimated. Specific Aims Omrix' existing ELISA test will be validated, establishing the correlation between it and the standard Vaccinia neutralization assay. The validated ELISA test will be used to determine the level of anti-Vaccinia immunoglobulins in human plasma samples. Following that, the ELISA will be used to screen USA plasma derived from re-vaccinated donors and select high titer anti Vaccinia plasma samples. These samples will be used to produce a limited number of batches of High-Titer VIG, which will then be characterized by use of the ELISA test and the standard Vaccinia Neutralization Bioassay. Development of a concentrated HT-VIG formulation for either small volume IV or IM administration. Research Design & Methods As well as employing standard operating procedures for plasma collection and fractionation, innovative methodology will be employed in two areas of the program: 1) a new validated ELISA screening test will enable selection of very high titer plasma samples resulting in a high potency, small volume HT-VIG product; 2) the development of the
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HT-VIG product will include the new viral removal steps developed by Omrix, such as nano-filtration and solvent detergent treatment, which exhibit high margins of viral inactivation of all known viruses, including Parvo-viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN IMMUNITY TO VACCINIA VIRUS Principal Investigator & Institution: Kazura, James W.; Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Current policy to protect Americans against smallpox mandates immunization of naive and previously vaccinated adults with live vaccinla virus (VV). Knowledge of adaptive immunity to VV is limited to descriptions of neutralizing antibodies, cytotoxic T lymphocyte (CTL) activity, and lymphocyte proliferation responses, largely because widespread vaccination ceased before the current era of molecular immunology. Research in this project will examine the evolution of VVspecific memory T cells in newly vaccinated and re-vaccinated (boosted) adults. The relationship of VV-specific adaptive immunity to viral load and innate immunity will be determined in conjunction with projects by Storch and Stanley. The specific aims are to: 1. Identify immunodominant VV epitopes that induce CD8+ T cell memory. Artificial neural networks and computational algorithms will initially be used to select peptide epitopes, followed by evaluation of peptide binding to HLA class I alleles and assessment of the ability of peptides to stimulate IFN-gamma and IL-2 responses by HLA-matched and HLA-mismatched primary vaccinees and adults given booster doses of VV. 2. Determine the functional phenotype of CD8+ cells during the inductive and memory phases of adaptive immunity to VV. HLA class I tetramer-peptide complexes will be used to identify and quantify CD8+ cells bearing TCR specific for VV epitopes before vaccination and 9 days, 6, 12, and 24 months post-vaccination. Lymphocytes producing putative mediators of immunity (IFN-gamma, perforin, MIP-1alpha) and bearing memory markers (CD45RO, CD45RA, CCR7) will be evaluated prospectively in primary vaccinees and boosted adults. 3. Evaluate the clonotypic repertoire of VVspecific CD8+ cells following primary vaccination and boosting of previously vaccinated adults. TCR Vbeta usage and CDR3 length and sequence polymorphism will be evaluated prospectively in selected HLA-A2+ and HLA-A11+ individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: HUMAN MONOCLONAL ANTIBODIES TO REPLACE VIG FOR THERAPY Principal Investigator & Institution: Cavacini, Lisa A.; Assistant Professor of Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 27-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Prior to Edward Jenner's demonstration in 1796 that immunization with cowpox protected against smallpox infection, virtually everyone contracted smallpox with mortality as high or higher than 30%. A global campaign using vaccinia immunization for protection from smallpox infection resulted in the eradication of smallpox in 1977. Subsequently the WHO recommended that all countries cease vaccination and laboratory stocks be destroyed or transferred to one of two repositories at the CDC in the United States or the Institute of Virus Preparations in Moscow, Russia. Routine vaccination in the United States has not occurred for more than thirty years. Therefore, the vast majority of the population is at risk of smallpox
16
Smallpox Vaccine
infection. Just as smallpox was used as a bioweapon prior to the development of vaccination, it currently represents a potential biological weapon with the majority of the world population at risk. Vaccination within the first few days after exposure is effective at preventing infection in some with a significant decrease in mortality. However, there are rare and serious complications in some vaccinated individuals. The vaccination is contraindicated in a number of groups of people. Vaccinia immune globulin (VIG) has been used as prophylaxis for treating individuals for which contra indications exist for smallpox vaccine and for treatment of those with complications of vaccinations. With the threat of smallpox being used as an agent of bioterrorism, it is prudent to develop alternatives for the use of VIG for prophylaxis and treatment. Supplies of VIG are scarce given that individuals have not been systematically vaccinated for more than 30 years. Furthermore, the validation and safety of VIG remains an issue. Therefore, we propose to generate human monoclonal antibodies as a replacement for VIG. Monoclonal antibodies can be produced with exquisite specificity and can be modified to enhance functional activity. The use of fully human monoclonal antibodies eliminates problems associated with xenogeneic, chimeric or humanized antibodies which include immunogenicity, biological half-life, and inefficient effector function. The development of a cocktail of human monoclonal antibodies that neutralize virus and/or mediate antibody-dependent cellular cytotoxicity can serve as a safe, effective replacement for VIG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN T CELL RESPONSES TO VACCINIA VACCINE Principal Investigator & Institution: Flomenberg, Phyllis R.; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): There is an urgent need to develop safer smallpox vaccines. One approach is the use of modified vaccinia virus Ankara (MVA), a highly attenuated vaccinia virus that does not replicate in human cells. In comparison to vaccinia virus, however, MVA is less immunogenic and may require higher doses and more frequent boosts. There also remain safety concerns about the use of a live attenuated virus and the potential presence of adventitious pathogens. Alternative approaches include the development of inactivated virus or recombinant protein vaccines. However, vaccine development is hampered because little is known about what proteins play an important role in the generation of protective immune responses to smallpox. Recently, 4 envelope proteins that induce neutralizing antibodies were identified, and DNA vaccination with a combination of all 4 genes protected mice from a lethal vaccinia infection. Although a vaccine will need to induce strong T cell responses, in addition to neutralizing antibodies, no information is available about the vaccinia protein targets recognized by T cells. In particular, CD4 T cells are required to enhance B cell, T cell, and innate immune responses to lytic viruses. As a first step, peripheral blood mononuclear cells from healthy adults previously immunized with vaccinia virus will be tested for virus-specific T cell responses. The goals of this study are: 1) to measure the frequencies of human T cell responses to vaccinia structural proteins; 2) to identify major CD4 and CD8 T cell epitopes within the above 4 envelope proteins; and 3) to analyze the frequencies of the T cell responses to these epitopes postvaccination. It is anticipated that this work will provide new tools for the detection and monitoring of vaccinia-specific T cell responses from most individuals and will help develop new strategies for smallpox vaccine development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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17
Project Title: IMMUNODOMINANT EPITOPES OF A SMALLPOX VACCINE IN HUMANS Principal Investigator & Institution: Buller, Mark R.; Professor; Molecular Microbiol and Immun; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2003; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The zenith of the disease smallpox and its eradication in 1977 from human populations occurred prior to the modern era of immunology and molecular biology. Consequently there is little knowledge concerning the immune correlates for recovery from smallpox or the cross-reactive proteins expressed by baccinia virus that were responsible for its success as the smallpox vaccine. The only vaccination indicator that correlated with protection from severe smallpox was the scar. In response to the threat of bioterrorism, the U.S. government has redoubled its efforts to provide strategies that will protect the American public from an outbreak of smallpox or human monkeypox. As part of a comprehensive, multi-faceted plan, the U.S. government has contracted with Acambis Inc. and Baxter Healthcare Corp. to produce approximately 209 million doses of a new tissue culture smallpox vaccine. In addition, proposals are being considered for the next generation of smallpox vaccine that will have an enhanced safety profile, causing fewer vaccine-related complications, especially in immunosuppressed individuals. Evaluating the efficacy of the new Acambis and Baxter vaccine or other second-generation vaccines with enhanced safety profiles will be problematic without detailed knowledge of the immunogenicity of vaccines proven to be efficacious in the smallpox eradication program. Detailed studies on human B and T cell immune responses to proteins encoded by vaccinia virus should help fill this gap in knowledge, and may also identify targets of neutralizing, complement-fixation or ADCC (antibody-dependent cell cytotoxity) antibodies, which may facilitate the development of an efficacious replacement for VIG. We propose to characterize the vaccinia virus-encoded proteins recognized by B and T cell responses during the vaccination of volunteers with the DryVax vaccine. The Specific Aims are to: 1. Characterize the antibody responses to immunodominant vaccinia virus proteins and 2. Identify the epitope specificity of representative vaccinia virus-specific T cell clones. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNOGENETICS OF SMALLPOX VACCINATION Principal Investigator & Institution: Stanley, Samuel L.; Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The goal of this project is to identify genes that are involved in susceptibility and resistance to human vaccinia infection, and, consequently, in some of the adverse effects seen with smallpox vaccination. We (R.B.B.) recently led a multi-center prospective study on the clinical response to vaccinia immunization in 680 naive individuals. Among the 665 individuals responding to the vaccine, 84 (13%) developed fever, muscle aches and lymphadenopathy giving rise to what we have called Acute Vaccinia Syndrome (AVS) in approximately 30% of vaccines. The timing of the onset of these symptoms matched the timing of the highest levels of viral shedding, indicating that fever, and the other components of AVS appear to be secondary to the virus. We hypothesize that individuals developing AVS (and especially fever) have diseasepredisposing alleles that are associated with abnormal innate immune or delayed adaptive immune responses to vaccinia. These individuals may be more susceptible to poxviruses in general, and could constitute a group at increased risk for mortality if
18
Smallpox Vaccine
exposed to smallpox. We propose to identify genes that are expressed in response to vaccinia infection at the site of inoculation and systemically using a transcriptional analysis. We will compare responses between individuals that develop AVS, and those individuals who develop no adverse reactions to immunization. These studies will provide us with a transcriptional profile of the host response to vaccinia infection, identify key molecules in the host response, and, establish parameters for protective immune responses that could be used to test the efficacy of new vaccines. We will also identify alleles associated with adverse effects to vaccinia immunization and abnormal innate immune responses to the virus through the analysis of haplotypes based on single nucleotide polymorphisms in candidate genes. The identify of these alleles may provide clues to the critical elements of the host response to poxvirus, and could provide a method to identify individuals at increased risk for adverse effects to the vaccine, or more severe disease with poxvirus infection. The design of the study, with the inclusion of transcriptional profiling of individuals receiving vaccinia immunization coupled with a detailed virologic and immunologic profile, ensures that we will obtain valuable information on the host response to vaccinia immunization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NORTHEAST BIODEFENSE CENTER Principal Investigator & Institution: Lipkin, W Ian.; Professor; Wadsworth Center Empire State Plaza Albany, Ny 12237 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: (provided by applicant): The northeastern United States is highly vulnerable to emerging infectious diseases and terrorism. With the outbreak of West Nile virus, the World Trade Center tragedy, and subsequent anthrax attacks, Region II has the experience and resolve to mobilize its rich resources in biomedical research to advance the nation's biodefense agenda. Region II institutions will establish a Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Disease Research. This consortium, the Northeast Biodefense Center (NBC), will comprise investigators at more than 25 academic and research institutions in New York, New Jersey, Connecticut, Massachusetts and Puerto Rico. The NBC will have strong links to state, federal and local government agencies and laboratories, as well as biotech and pharmaceutical companies. Major basic and translational research programs will be pursued in six thematic areas: 1) B-Cell Related Prophylaxis and Therapeutics; 2) Bacterial Pathogenesis and Therapeutics; 3) Vaccine Platforms; 4) Viral Pathogenesis and Therapeutics; 5) Smallpox Vaccine: Clinical, Immune, and Viral Outcomes; 6) Pathogen Detection and Diagnostics. These programs will intersect with cores that provide support in Informatics, Proteomics, Protein Expression, Monoclonal Antibodies, Animal Models, as well as Administration. Each research program will integrate and intensify the work of several accomplished investigators and will focus on select agents and toxins including Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, Staphylococcus enterotoxin B, pox viruses, and viruses that cause hemorrhagic fever or encephalitis. Zoonotic diseases will be emphasized due to significance in this region, expertise of NBC members, and access to unique resources such as Plum Island Animal Disease Center and networks of investigators and clinicians in comparative medicine. Streamlined technology transfer procedures will be established to facilitate delivery to industry of vaccines, therapeutics, and diagnostics. The translational arm of the NBC has begun with a study of smallpox vaccination and will develop the region's infrastructure for human vaccine trials. Training programs will be established to promote biodefense research objectives by supporting new investigators, senior
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investigators, and support personnel. An emergency response plan has been developed to rapidly realign the NBC's activities and provide facilities, including cores and scientific support, to first line responders in the event of a biodefense emergency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL VACCINES FOR SMALLPOX Principal Investigator & Institution: Weiner, David B.; Associate Professor of Pathology and Lab; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The current bioterrorism threat has refocused our nation on the issue of our population's susceptibility to a smallpox attack. As a precaution, deployment of dilution of the current stock of vaccine and deployment of a tissue culture version of the VACV vaccine have been requisitioned. This vaccine and likely the new stocks carried a risk of Significant Adverse Events of 1 per 10,000 vaccinated individuals. However, that vaccine was last used in a very different environment. The high-risk groups for AE's include the elderly, the very young, immunocompromised individuals and others. The percentage and absolute numbers of the US population that falls within these categories has risen dramatically in the past 30 years. The greater than 750,000 persons living in the US that are HIV-positive is one clear example. This suggests that the AE risk of the VACV may be unacceptable and can only be deployed as a last resort. However, the option of abandoning this approach and developing new approaches leaves us at risk for a possibly unknown period of time. The hypothesis to be tested in this application is that there is a third option, to develop a strategy that uses the current vaccine yet limits its pathogenesis while improving its potency. It is our hypothesis that priming with enhanced expressing plasmid vaccines that induce nonneutralizing cellular immune responses will prime for successful and even enhanced boosting with the current vaccine, yet limit its associated pathogenesis. This application will use quantitative T cell assays including Elispot and ICC and tetramer analysis, and novel human HLA+DR positive transgenic mice that we have developed to pursue the three specific aims. Novel cellular reagents including MHC class I tetramers will be developed that will have significant value in following VACV challenge in humans as they may be useful as cellular surrogates for the current site reaction take. Together these studies will establish if this simple and novel approach can bridge the current situation and produce a safer more effective smallpox vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ORTHOPOXVIRUS VACCINE DEVELOPMENT Principal Investigator & Institution: Feinberg, Mark A.; Associate Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The long-term objectives of this project are to produce novel vaccines and immunotherapeutics designed to abrogate the activities of poxvirus-encoded extracellular accessory proteins (XAPs). We will focus on the XAPs that interfere with host responses, particularly immune responses, against poxvirus infections. We will test the hypothesis that preexisting immunity to the XAPs will abrogate the in vivo replicative advantages that poxviruses gain from expressing these XAPs, and reduce viral virulence in the immunized host. The specific aims of this project are as follows: 1. Construct Venezuelan Equine Encephalitis (VEE) virus replicons expressing mutationally
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Smallpox Vaccine
inactivated XAPs of cowpox virus (CPXV). Initially, we will focus on the extra-cellular viral inhibitors of complement and interferon. Subsequently, we will target the other orthopoxvirus XAPs, each of which is encoded by CPXV. 2. Assemble and test prototype VEE replicon particle (VRP) vaccines for CPXV-XAPs: VRPs will be assembled containing replicons expressing the genetically inactivated XAPs. We will determine the immunological responses of mice vaccinated with the VRP-CPXV-XAP vaccines. We will determine the abilities of antisera from immunized mice to neutralize the in vitro activities of the target XAPs, as well as cross-protective properties of the VRP-CPXVXAP-induced antibodies against accessory proteins encoded by other orthopoxviruses, including variola virus. 3. Evaluate the efficacy of prophylactic VRP-CPXV-XAP vaccines in the mouse model: We will determine if vaccination with the VRP-CPXVXAP vaccines can reduce CPXV replication and pathogenesis following challenge with CPXV in the mouse. We will also examine the effects of these VRP vaccines on infections with vaccinia viruses, and we will determine the efficacy of prime boost regimens involving primary immunization with VRP-CPXV-XAP vaccines followed by vaccination with vaccinia virus vaccines. 4. Evaluate the efficacy of therapeutic VRPCPXV-XAP vaccines and anti-XAP antibodies in the mouse model: We will determine if post-infection vaccination with VRP-CPXV-XAP vaccines or post-infection treatment with monoclonal antibodies against XAPs encoded by cowpox virus can attenuate cowpox and vaccinia virus infections in the mouse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POX VIRUS IMMUNOLOGY AND VACCINE DEVELOPMENT Principal Investigator & Institution: Ahmed, Rafi; Director; Microbiology and Immunology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-DEC-2007 Summary: (provided by applicant): There is a serious need for a smallpox vaccine alternative because of the significant incidence of adverse events to the current vaccine (Dryvax). Large groups in the American population are not qualified to receive the current smallpox vaccine due to immunodeficiency (from genetic causes, HIV, or immunosuppressive drugs), old age, skin disorders, young age (< 1 yr), or pregnancy. These groups are major populations and must be accounted for in any reasonable national smallpox vaccination strategy. Therefore, assessment of the immunogenicity of alternative smallpox vaccines such as modified vaccinia Ankara (MVA) must be done accurately and expeditiously. Our access to samples from ongoing clinical trials of Dryvax and MVA, our expertise in quantitating both cellular and humoral immunity, and our immunologic proteomics approach places our research group in a unique position to address this important issue. Long term protective immunity to smallpox is likely provided by three arms of the immune system: circulating neutralizing antibodies, memory B cells, and memory T cells. Virtually none of the vaccinia protein targets responsible for these T cell, B cell, and neutralizing antibody responses have been identified. The experiments in this proposal are designed to determine the dominant anti-smallpox immune responses and to compare the magnitude and breadth of the T and B cell responses induced by Dryvax versus MVA. This valuable information will not only allow an accurate assessment of the quality of the immune responses elicited by the alternative smallpox vaccine MVA but can also then be immediately parlayed into additional areas of proposed research such as: 1) diagnostic tools for measuring long term smallpox immunity in vaccinees; 2) development of simple, rapid, and sensitive immunological tools for assessing recent smallpox (variola major) exposure/infection; and 3) development of therapeutic anti-smallpox neutralizing monoclonal human
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antibodies. Finally, the knowledge acquired from the detailed studies described herein regarding the immunodominant protein targets of human vaccinia-specific T and B cells will lay the foundation for developing a safe and effective smallpox subunit vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POXVIRUS ADVERSE EFFECTS ON CARDIAC CELLS AND THE HEART Principal Investigator & Institution: Sherry, Barbara A.; Professor; Molecular Biomedical Sciences; North Carolina State University Raleigh 2230 Stinson Drive Raleigh, Nc 27695 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): In response to concerns that bioterrorists may release smallpox virus in the United States, the government has implemented a multistage vaccination program. However, the observation of cardiac adverse events following vaccination has resulted in the Centers for Disease Control recommending that people at risk for heart disease should be excluded from the vaccination program. Notably, myocarditis has been diagnosed in 18 recent smallpox vaccinees in the USA. Despite this recent temporal association between myocarditis and smallpox vaccination as well as a similar historic association, there have been no studies of the effects of poxviruses on cardiac cells, or the development of any animal models to study poxvirus-induced myocarditis. For other viruses, myocarditis can reflect a direct cytopathogenic effect of the virus on cardiac myocytes, or can be mediated by immune cells, cytokines, or other soluble factors. Poxviruses can be directly cytopathogenic, but also encode a number of modulators of cytokine responses. Cowpox virus contains the full complement of known orthopoxvirus accessory genes that affect immune responses, while DryVax (the current vaccine strain of vaccinia virus) encodes fewer accessory genes, and modified vaccinia Ankara virus (MVA, which is replication-defective in human cells) contains even fewer accessory genes. Our preliminary data demonstrate that cowpox virus and DryVax replicate in murine primary cardiac myocyte cultures (PCMCs) whereas MVA does not. Moreover, cowpox, DryVax, and MVA are each cytopathogenic to these cultures, though the type of cytopathogenicity is virus strainspecific. We hypothesize that poxviruses have virus strain-specific adverse effects on cardiac cells, either directly or indirectly, resulting in damage to cardiac myocytes and the heart. In Specific Aim 1, we will determine the effect of these three poxviruses (cowpox, DryVax, and MVA) on murine primary cardiac myocyte cultures (PCMCs) and control cultures, analyzing viral infection and gene expression, and induction of cytopathogenicity. In Specific Aim 2, we will determine the association between cytokines and poxvirus infection on cytopathogenicity to PCMCs and control cultures. In Specific Aim 3, we will determine whether these poxviruses induce myocarditis in a variety of mouse strains. Studies proposed in this R21 application will provide the foundation for future in-depth studies with the goal of Improving current and future smallpox vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POXVIRUS IMMUNITY AND DNA/MVA HIV VACCINES Principal Investigator & Institution: Amara, Rama R.; None; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-OCT-2007 Summary: (provided by applicant): We recently demonstrated the ability of an AIDS vaccine consisting of DNA priming and recombinant modified vaccinia Ankara (MVA)
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booster immunizations (DNA/MVA SHIV vaccine) to control a pathogenic SHIV 89.6P challenge that was administered seven months after the final immunization in macaques. The prototype HIV-1 clade B version of our DNA/MVA vaccine (DNA/MVA HIV vaccine) is entering phase I safety trials in humans in January of 2003. Due to the recent bioterrorism threat the US government is prepared to vaccinate at least a subset of people with the current smallpox vaccine (Dryvax/New York Board of Health strain of vaccinia). The anti-vaccinia virus immunity generated by Dryvax may limit the boosting ability of MVA, hence the efficacy of DNA/MVA HIV vaccines. This is a very important question that needs to be addressed as DNA/MVA vaccines go forward in human trials. There is a serious need for a smallpox vaccine alternative because of the high incidence of adverse events to the current vaccine. Also, many people are not qualified to receive the current smallpox vaccine due to immunodeficiency, skin disorders, old age, young age (< 1 yr), or pregnancy. These groups are major populations and must be accounted for in any reasonable national smallpox vaccination strategy. MVA was developed towards the end of smallpox eradication for use in immunocompromised individuals and was used to vaccinate about 120,000 individuals. However, because smallpox had been controlled in first world countries by the time that MVA was developed, individuals who were vaccinated with MVA were not exposed to variola, and the efficacy of MVA as a smallpox vaccine was not determined. In this proposal we wish to address 1) the effect of preexisting immunity to smallpox on the ability of DNA/MVA vaccine to control pathogenic SHIV challenge, 2) the ability of vaccinia-specific immune responses raised by DNA/MVA vaccine to protect from a lethal monkeypox challenge and 3) the ability of a candidate DNA/MVA vaccine to control both SHIV and monkeypox challenges that are administered sequentially in the presence and absence of preexisting immunity to smallpox. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POXVIRUS VACCINE RESEARCH Principal Investigator & Institution: Isaacs, Stuart N.; Assistant Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Bioterrorism with variola virus is of immense concern because (a) virtually the entire world population is susceptible since routine vaccination was discontinued; (b) there are no treatments; (c) the virus in aerosol form is stable; (d) the virus is transmissible person-to-person; and (e) infection results in high morbidity and mortality. Vaccination with vaccinia virus (VV) was a key factor in eradicating smallpox. The necessity to vaccinate an at-risk population with W is central to preparing for the potential threat of smallpox bioterrorism. However recognized complications of vaccinia vaccination, especially in immunocompromised hosts, pregnant women, and infants impose serious limitations of this strategy. In past vaccination efforts, such complications were treated in the U.S. with human vaccinia immune globulin (VIG) obtained from W immunized people. Current stocks of VIG are low, and while new stocks are being generated, there are still serious drawbacks to relying on a blood product. Consequently, there is a critical need to develop therapeutic interventions to counter complications from the current vaccine and to develop a safer vaccine. As part of the mid-Atlantic Regional Center of Excellence in Biodefense & Emerging Infectious Diseases, our poxvirus research project's hypothesis is that vaccine candidates and new therapies can be developed by understanding and targeting poxvirus proteins recognized by the humoral and innate immune system. To do this we will: 1. Develop a
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subunit vaccine against smallpox (variola) virus (Cohen/Eisenberg/Friedman, U. Penn) 2. Identify new targets of neutralizing antibody (Isaacs, U. Penn) 3. Identify the targets of VIG using a proteomics approach (Lambris, U. Penn) 4. Develop an ectromelia virus challenge system in the mouse as a model of smallpox pathogenesis and prevention (Braciale, U. Virginia) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POXVIRUSES: DEFINING EPITOPE IMMUNODOMINANCE Principal Investigator & Institution: Terajima, Masanori; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 01-OCT-2003; Project End 30-SEP-2008 Summary: Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. This was accomplished without a detailed understanding of human T cell responses to poxviruses. Due to concerns about the use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Considering the relatively high incidence of side effects, developing a safer, but effective vaccine is very important. Vaccinia virus elicits strong cellular as well as humoral immune responses. Cellular immunity seems to be more important for recovery from infection. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia. The presence of neutralizing antibody alone did not prevent the development of progressive vaccinia if cell-mediated immunity was defective. In order to analyze human T cell responses to licensed and experimental smallpox vaccines at the single cell level, it is essential to identify T cell epitopes, especially immunodominant CD8 + T cell epitopes. Vaccinia is a large virus and we hypothesize that we can develop a rapid approach to localize gene fragments encoding human T cell epitopes and to identify them precisely using peptides using PCR-generated DNA fragments containing virus genes transfected into antigen presenting cells. Complementary strategies will employ peptide libraries and studies in transgenic mice expressing common human MHC class I molecules. The immunodominance of human T cell epitopes on vaccinia virus will be analyzed. The results of this research project will provide valuable information relative to basic studies of human T cell memory and data useful for the design and analyses of experimental smallpox vaccines. The methods we will establish in this project may be applicable to other large viruses as well as bacteria for the definition of human T cell epitopes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PUBLIC HEALTH RESPONSE Principal Investigator & Institution: Burke, Donald S.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008 Summary: This "Public Health Response Research" project is submitted as one of six research projects in the application for a multi-institutional Middle Atlantic Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Diseases Research. The objective of this project is to immediately accelerate the clinical evaluation and deployment of new biomedical technologies that may be crucial for an effective public health 0response to a bioterrorism or emerging infectious disease event. The project encompasses three sub-projects, all of which involve immediate evaluation of novel biotechnologies in human subjects. Sub-project 1 is designed to rapidly transition novel
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needle-free technologies for vaccine administration into routine use. The specific aims of this sub-project are to evaluate cutaneously administered immunostimulatory patches to boost responses to anthrax vaccines and botulinum toxoid, to evaluate intranasal administration of recombinant anthrax protective antigen, and to evaluate jet injector administration of recombinant anthrax protective antigen. Sub-project 2 is designed to use measurements of peripheral blood lymphocyte gene expression profiles from vaccinated persons to improve the diagnosis, prognosis, and prevention of smallpox vaccine adverse events. The specific aims of this sub-project are to define the natural history of vaccinia-induced immune dysregulation, to correlate favorable and unfavorable outcomes with specific gene transcript profiles, and to use the technology to identify individuals at increased risk of vaccine adverse reactions. Sub-project 3 is designed to evaluate rapid innovative genomics- and proteomics-based diagnostic technologies in real emergency room settings. The specific aims of this project are to evaluate novel universal bacterial and viral diagnostics, to evaluate blood lymphocyte gene expression profiles in common febrile illnesses, like influenza, that could be mistaken for bioterror threats, and to use mass spectrometry-based proteomics on respired air from patients to diagnose acute pulmonary infections. As additional new genomics- and proteomics-based technologies are generated from the Middle Atlantic RCE and elsewhere, they will be rapidly evaluated for their utility in the public heath biodefense response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMALLPOX VACCINE CLINICAL RESEARCH CENTER Principal Investigator & Institution: Belshe, Robert B.; Professor of Medicine & Microbiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: With the imminent institution of smallpox vaccination for healthcare workers and first responders, there is an urgent need to better understand the biology of vaccinia infection in humans. In response, we are creating a new Core Facility, the Smallpox Vaccine Clinical Research Center, to coordinate and facilitate clinical/translational research on smallpox for the MRCE. The Smallpox Vaccine Clinical Research Center will serve two allied missions. First, it will be the clinical/translational research arm of the MRCE, facilitating the research designed to answer critical questions about viral shedding, protective immunity, and susceptibility to poxvirus infections (see the Strategic Projects of Storch, Kazura, and Belshe, section C). In this mode it will directly support and execute translational research protocols on projects of special interest to the MRCE mission. The initial protocols will test the efficacy and mechanism of action of vaccinia immune globulin; an additional project is to fully characterize the immunologic responses of a non-responder to vaccinia immunization. Standard research protocols for characterizing individuals with severe adverse effects to smallpox vaccination will also be supported. The Smallpox Vaccine Clinical Research Center will serve its second mission by becoming the regional center for the diagnosis and care of individuals with serious adverse effects after smallpox vaccination. In addition to providing state of the art diagnostics and care, for these individuals, when appropriate, the Smallpox Vaccine Clinical Research Center will offer to enroll them into clinical/translational protocols on the adverse effects of smallpox vaccination. If possible, these individuals will undergo many of the detailed virologic, immunologic, and genetic studies outlined in the projects of Drs. Storch, Kazura, and Belshe. Some of these individuals may have immunodeficiencies (e.g. those with generalized vaccinia or progressive vaccinia) and these will be fully characterized. In this capacity the Smallpox Vaccine Clinical
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Research Center will also become a database for adverse effects to smallpox vaccine in this area, and facilitate any national efforts in this area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPEUTICS FOR POX, FILO AND OTHER VIRAL PATHOGENS Principal Investigator & Institution: Schneller, Stewart W.; Professor; Chemistry; Auburn University at Auburn Auburn University, Al 36849 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The possibility for biological terrorism has moved from the realm of speculation into reality. As a consequence, the National Institute of Allergy and Infectious Diseases has identified a number of agents that pose the greatest threat and has recommended that therapeutic agents be developed against them. Among that group of pathogens are smallpox and the viral hemorrhagic fevers (including the filoviruses Ebola and Marburg). In preparation for possible release of smallpox, plans are well underway to avail sufficient quantities of smallpox vaccine for a large number of people. However, within this population, there are individuals who will not be able to tolerate the vaccine or, for pre-existing health and/or age reasons, will not be suitable to receive vaccine protection. Thus, for these and other reasons, therapeutic agent development has been recommended by the NIAID. This proposal deals with two therapeutic goals in this direction: (i) agents for treating smallpox infection for instances where the vaccine was ineffective, not available or not administered for reasons just outlined, and (ii) drugs to counteract the effects of vaccination when administered. For the filoviruses Ebola and Marburg, which manifest themselves differently than smallpox but still produce horrendous effects, there are currently no pre-infection vaccines nor post-infection therapeutics available. To address these situations, plans are put forth for designing and developing drugs that would act by inhibiting viral replicative steps following infection by these viruses. Focus will be on nucleosides and nucleotides that affect, primarily, nucleic acid metabolism. A consortium of 3 chemists and 10 virologists has been assembled for this purpose. Because of the extensive collaborations that have been ongoing for some time by this group of chemists and virologists, it can be expected that promising anti-orthopoxvirus and anti-filovirus agents will be uncovered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VACCINIA VIRUS-SPECIFIC T-CELL PHENOTYPES Principal Investigator & Institution: Rock, Michael T.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Vaccinia virus, despite its high level of reactogenicity, remains the only available option for protection against smallpox infection. Due to concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination currently is being reintroduced. However, the immune defense mechanisms protecting a person from smallpox after vaccination are not completely understood. The smallpox vaccine provides a unique opportunity to evaluate T cell responses in truly separate cohorts (naive and experienced) to begin delineating the phenotypes and functional characteristics of these cells in protection from disease. Using state-of-the-art polychromatic flow cytometry, we can now examine a multitude of lymphocyte subsets in the peripheral blood that previously were inaccessible, each with a unique functional and phenotypic profile. By studying patients with adverse events,
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we may be able to assign clinical relevance to some of these subsets. The goal of this research program is 1) to identify the functional and phenotypic profile of vaccinia virus-specific T cells elicited following smallpox immunization and 2) to examine the persistence of vaccinia-specific T cells in vaccinia-experienced vaccinees and the breadth of the immune response in immune and non-immune subjects by determining the Vbeta repertoire usage by those T lymphocytes. Distinct T cell subsets respond differently to viral infections and characterization of these subsets may lead to a better understanding of the immune response and the role of these cells in shaping long-term memory responses. Thus, we will learn not only about immunity to vaccinia, but also learn about the basic biology of virus-specific T cell responses. This work will provide a foundation for comparison of the cellular immunogenicity induced by other candidate vaccines, such as further attenuated viruses like MVA, or cell culture derived vaccinia. Given that a true efficacy trial cannot be conducted with these vaccines, likely correlates of immunity are needed for comparative purposes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIROLOGY AND SMALLPOX VACCINATIONS Principal Investigator & Institution: Storch, Gregory; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The broad objective of this project is to use conventional and molecular techniques to define the virologic events following smallpox vaccination in vaccinianaive and vaccinia-experienced individuals. The specific alms are to: 1) Define the virologic events associated with smallpox vaccination. 2) Determine whether multiple viral variants are present within the Dryvax vaccine, and if so, to investigate their role in the virology of smallpox vaccination and in adverse reactions. 3) Define the virologic events associated with adverse reactions to smallpox vaccination. 4) Examine the virologic response to treatment with vaccinia immune globulin (VIG) and/or cidofovir in vaccinees who require these therapies to control adverse reactions. A quantitative real-time PCR assay will be developed and used to measure the level of vaccinia DNA at regular intervals after vaccination. Specimens will also be cultured for vaccinia virus. These studies will be useful for defining the possible contagiousness of individuals having smallpox vacciniation and for helping determine the need for donor deferral for voluntary blood donations. The data will also provide a basis for studies of the immunology and immunogentics of vaccinia. Studies will be performed of Dryvax vaccine to define variants within the vaccine virus. In collaboration with the Genome Sequencing Center, the complete nucleotide sequence of 5 variant strains will be determined. Specific assays will be developed and used to define the contribution of variants to immunogenicity and reactogenicity of the vaccine. Smallpox adverse reaction clinics will be established at each participating medical center to evaluate individuals with possible adverse reactions. Individuals seen in these clinics will be recruited to participate in detailed studies of the virology, immunology, and immunogenetics of smallpox vaccination. These studies will investigate the virology of adverse reactions, the relationship between viral and immunologic events, and the genetic basis for both. For individuals having severe adverse reactions, virologic studies will be used to help evaluate and guide therapy with VIG and cidofovir. The studies described will form a basis for evaluating Dryvax as well as future smallpox vaccines. The assays to be developed and the clinics to be established will provide an infrastructure that will be available to respond to a bioterrorist attack on the United States. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VULNERABILITY TO SMALLPOX DUE TO DECLINING CTL IMMUNITY Principal Investigator & Institution: Mbawuike, Innocent N.; Molecular Virology & Microbiol; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Discontinuation of smallpox vaccination since 1971 has led to waning of acquired immunity in the U.S. general population, thus, raising the risk of major epidemics from intentional release of smallpox by terrorists or unfriendly governments. The CDC has shown that vaccinia immunization, which led to the eradication of smallpox worldwide, caused excess rates of severe complications and death among older persons. Since higher morbidity and mortality rates from many other viral infections in older persons have been attributed to a deficiency in virus-specific HLA-restricted CTL response, the elderly will be expected to possess reduced vacciniaspecific CTL activity and therefore be more susceptible to smallpox disease as well as complications from vaccinia immunization. The goals of this study are to: 1) profile the sero-prevalence and memory CD8+ CTL activity status against vaccinia in representative young adult and elderly U.S. populations, 2) identify easily detectable and quantifiable surrogates of CTL competence against smallpox infection and 3) explore immunological basis for complications from vaccinia vaccination. Levels of vaccinia-specific memory CD8 CTL activity will be determined in peripheral blood lymphocytes of U.S. born healthy adults (35-49 and 50-64 years old) and elderly adults (~65 years old) who have previously been vaccinated with vaccinia and compared with young adults (18-32 years old) who are recent (<1 year) vaccinia recipients or vaccinia naive. Virus serum neutralization antibody and virus specific IgG antibody titers will be determined and correlated with CTL activity. The frequency of CD8+ T cells expressing interferon (IFN)-gamma (a CTL surrogate) and interleukin (IL)-4 (a CTL antagonist) will be measured using ELISPOT and flow cytometry. The functions of IFN-gamma and IL-4 will be assessed using antisense oligonucleotides and/or antibodies. Selected proinflammatory cytokines and chemokines (IL-1a, TNF-a, IL-6, IL-8 and lL-13) will be analyzed. It is postulated that among previously vaccinated persons: a) the elderly will have significantly reduced CD8+ CTL memory in comparison to younger persons, b) levels of vaccinia-specific antibody and memory CD8+ CTL activity will decline with time, c) IFN-gamma production will be a good surrogate of CTL activity and d) increases in specific pro-inflammatory cytokines or chemokines will be associated with the intensity of vaccinia vaccination lesions. The results should provide guidance in decisions to revaccinate the public, particularly the elderly and other immunodeficient persons, in the event of a biological attack with smallpox and offer needed insight into the mechanism of vaccinia complications in the elderly. Data from recent vaccinees might also serve as reference values for new smallpox vaccines that might be developed since specific correlates of immunity against smallpox (other than a vaccine "take") are currently not available. By correlating these responses with vaccinia lesion sizes in new vaccinees, markers of severe complications from vaccinia vaccination may be identified. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 “smallpox vaccine” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for smallpox vaccine in the PubMed Central database: •
Canada stocks up on smallpox vaccine, pushes bioterrorism training. by Kondro W.; 2001 Nov 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81639
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Clinical and immunological study of percutaneous revaccination in children who originally received smallpox vaccine subcutaneously. by Cherry JD, Rolfe UT, Dudley JP, Garakian AJ, Murphy M.; 1978 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=274885
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Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines. by Drexler I, Staib C, Kastenmuller W, Stevanovic S, Schmidt B, Lemonnier FA, Rammensee HG, Busch DH, Bernhard H, Erfle V, Sutter G.; 2003 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140931
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New Generation of Cell Culture Assay for Smallpox Vaccine Potency. by LeparcGoffart I, Poirier B, El Zaouk A, Tissier MH, Fuchs F.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179801
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Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. by Belyakov IM, Earl P, Dzutsev A, Kuznetsov VA, Lemon M, Wyatt LS, Snyder JT, Ahlers JD, Franchini G, Moss B, Berzofsky JA.; 2003 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=170940
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 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. 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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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 smallpox vaccine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “smallpox vaccine” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for smallpox vaccine (hyperlinks lead to article summaries): •
A study of the effect of simultaneous vaccination with BCG and smallpox vaccine in newborn infants. Author(s): Lin HT. Source: Bulletin of the World Health Organization. 1965; 33(3): 321-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5294917
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ACIP issues guidelines on the use of smallpox vaccine in a pre-event vaccination program. Author(s): Schroeder BM; Advisory Committee on Immunization Practices; National Vaccine Advisory Committee; Healthcare Infection Control Practices Advisory Committee. Source: American Family Physician. 2003 August 1; 68(3): 554, 557-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12924838
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Administering smallpox vaccine: a two-pronged risk. Author(s): Perry J, Jagger J. Source: Nursing. 2004 January; 34(1): 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738067
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Adverse reactions to smallpox vaccine: the Israel Defense Force experience, 1991 to 1996. A comparison with previous surveys. Author(s): Haim M, Gdalevich M, Mimouni D, Ashkenazi I, Shemer J. Source: Military Medicine. 2000 April; 165(4): 287-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10803002
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An emergent poxvirus from humans and cattle in Rio de Janeiro State: Cantagalo virus may derive from Brazilian smallpox vaccine. Author(s): Damaso CR, Esposito JJ, Condit RC, Moussatche N. Source: Virology. 2000 November 25; 277(2): 439-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11080491
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Appropriate technology in the development of freeze-dried smallpox vaccine. Author(s): Collier LH. Source: Who Chron. 1980 May; 34(5): 178-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7376637
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Attenuated smallpox vaccine. Author(s): Krugman S, Katz SL. Source: The New England Journal of Medicine. 1970 February 5; 282(6): 344. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5410834
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Attenuated smallpox vaccine. Author(s): Neff JM. Source: The New England Journal of Medicine. 1970 February 5; 282(6): 343-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5410833
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By the way doctor. I was relieved to read that the United States will soon have enough smallpox vaccine for everyone. Should my family and I be vaccinated? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2002 July; 9(11): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12138026
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Caution in the administration of smallpox vaccine. Author(s): Prozesky OW, Smith LS. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1978 July 1; 54(1): 4-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=694695
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Claim that smallpox vaccine protects against HIV is premature, say critics. Author(s): Lenzer J. Source: Bmj (Clinical Research Ed.). 2003 September 27; 327(7417): 699. Erratum In: Bmj. 2003 October 25; 327(7421): 987. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512458
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Clinical and immunological study of percutaneous revaccination in children who originally received smallpox vaccine subcutaneously. Author(s): Cherry JD, Rolfe UT, Dudley JP, Garakian AJ, Murphy M. Source: Journal of Clinical Microbiology. 1978 February; 7(2): 158-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=632346
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Clinical laboratory experiences with a more attenuated Enders' measles virus vaccine (Moraten) combined with smallpox vaccine. Author(s): Weibel RE, Stokes J Jr, Buynak EB, Leagus MB, Hilleman MR. Source: Pediatrics. 1969 April; 43(4): 567-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4304934
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Clinical responses to undiluted and diluted smallpox vaccine. Author(s): Frey SE, Couch RB, Tacket CO, Treanor JJ, Wolff M, Newman FK, Atmar RL, Edelman R, Nolan CM, Belshe RB; National Institute of Allergy and Infectious Diseases Smallpox Vaccine Study Group. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1265-74. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923490
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Clonal vaccinia virus grown in cell culture as a new smallpox vaccine. Author(s): Weltzin R, Liu J, Pugachev KV, Myers GA, Coughlin B, Blum PS, Nichols R, Johnson C, Cruz J, Kennedy JS, Ennis FA, Monath TP. Source: Nature Medicine. 2003 September; 9(9): 1125-30. Epub 2003 August 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925845
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Complement requirement of the neutralizing antibody appearing after immunization with smallpox vaccine. Author(s): Nishimura C, Nomura M, Kitaoka M, Takeuchi Y, Kimura M. Source: Jpn J Microbiol. 1968 June; 12(2): 256-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5303512
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Consent and compensation: a social compact for smallpox vaccine policy in the event of an attack. Author(s): Faden RR, Taylor HA, Seiler NK. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1547-51. Epub 2003 Jun 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12802754
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Current status of smallpox vaccine. Author(s): LeDuc JW, Becher J. Source: Emerging Infectious Diseases. 1999 July-August; 5(4): 593-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458973
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Dose-related effects of smallpox vaccine. Author(s): Frey SE, Newman FK, Cruz J, Shelton WB, Tennant JM, Polach T, Rothman AL, Kennedy JS, Wolff M, Belshe RB, Ennis FA. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1275-80. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923489
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Efficacy of UK smallpox vaccine questioned. Author(s): Hodgson J. Source: Nature Biotechnology. 2002 September; 20(9): 859-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12205491
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Ethical considerations in the formation of smallpox vaccine policy. Author(s): Taylor HA, Faden RR. Source: Biosecur Bioterror. 2003; 1(1): 47-52. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040215
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Evaluation of two kinds of smallpox vaccine: CVI-78 and calf lymph vaccine. I. Clinical and serologic response to primary vaccination. Author(s): Wesley RB, Speers WC, Neff JM, Ruben FL, Lourie B. Source: Pediatric Research. 1975 August; 9(8): 624-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1098000
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Evaluation of two kinds of smallpox vaccine: CVI-78 and calf lymph vaccine. II. Clinical and serologic observations of response to revaccination with calf lymph vaccine. Author(s): Speers WC, Wesley RB, Neff JM, Goldstein J, Lourie B. Source: Pediatric Research. 1975 August; 9(8): 628-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1171424
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Freeze-dried smallpox vaccine; report of a trial in Kuala Lumpur. Author(s): Maitland HB. Source: Med J Malaya. 1965 September; 20(1): 8-10. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4221441
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From the Centers for Disease Control and Prevention. Supplemental recommendations on adverse events following smallpox vaccine in the pre-event vaccination program: recommendations of the Advisory Committee on Immunization Practices. Author(s): Advisory Committee on Immunization Practices. Source: Jama : the Journal of the American Medical Association. 2003 April 23-30; 289(16): 2064. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709453
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History and recent developments of smallpox vaccine. Author(s): Singh LM. Source: J Indian Med Assoc. 1977 March 1; 68(5): 105-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=903636
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Immunity conferred by smallpox vaccine. How long does immunity last? Author(s): Jacobs A. Source: Bmj (Clinical Research Ed.). 2002 May 11; 324(7346): 1157; Author Reply 1157. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003901
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Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox. Author(s): Earl PL, Americo JL, Wyatt LS, Eller LA, Whitbeck JC, Cohen GH, Eisenberg RJ, Hartmann CJ, Jackson DL, Kulesh DA, Martinez MJ, Miller DM, Mucker EM, Shamblin JD, Zwiers SH, Huggins JW, Jahrling PB, Moss B. Source: Nature. 2004 March 11; 428(6979): 182-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15014500
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Incidental subcutaneous administration of high dosage smallpox vaccine in vaccinated adults. Author(s): Toma E, Mihancea N, Paun L, Mihailescu R, Popescu E. Source: Arch Roum Pathol Exp Microbiol. 1981 April-June; 40(2): 137-42. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7305648
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Key information regarding smallpox vaccine. Author(s): Mair M, Borio L. Source: Biosecur Bioterror. 2003; 1(1): 53-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040216
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Large-scale use of freeze-dried smallpox vaccine prepared in primary cultures of rabbit kidney cells. Author(s): Hekker AC, Bos JM, Rai NK, Keja J, Cuboni G, Emmet B, Djalins J. Source: Bulletin of the World Health Organization. 1976; 54(3): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1088108
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Letter: Smallpox vaccine for herpes zoster. Author(s): Chang SL. Source: Jama : the Journal of the American Medical Association. 1974 April 1; 228(1): 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4406140
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Myocarditis: the unexpected return of smallpox vaccine adverse events. Author(s): Chen RT, Lane JM. Source: Lancet. 2003 October 25; 362(9393): 1345-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585633
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Mysteries of the smallpox vaccine. Author(s): Bhattacharya S. Source: Journal of Biosciences. 2003 March; 28(2): 141-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12711804
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Outcry greets US plan to test smallpox vaccine on children. Author(s): Check E. Source: Nature. 2002 November 14; 420(6912): 110. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12432349
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Positive response to US smallpox vaccine policy. Author(s): Nierengarten MB. Source: The Lancet Infectious Diseases. 2003 February; 3(2): 60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560175
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Potency and stability of freeze-dried smallpox vaccine. Author(s): Huang CT, Tsai CF. Source: Taiwan Yi Xue Hui Za Zhi. 1970 July; 69(7): 362-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5290113
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Questions and answers about autoimmunity and the smallpox vaccine. Author(s): Halsey N, Rose N. Source: Isr Med Assoc J. 2003 January; 5(1): 40-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592957
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Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Author(s): Wharton M, Strikas RA, Harpaz R, Rotz LD, Schwartz B, Casey CG, Pearson ML, Anderson LJ; Advisory Committee on Immunization Practices; Healthcare Infection Control Practices Advisory Committee. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 April 4; 52(Rr-7): 1-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12710832
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Recruitment begins for US smallpox vaccine trial. Author(s): McLellan F. Source: Lancet. 2001 November 17; 358(9294): 1708. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728564
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Response to smallpox vaccine in persons immunized in the distant past. Author(s): Frey SE, Newman FK, Yan L, Lottenbach KR, Belshe RB. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3295-9. Erratum In: Jama. 2003 July 16; 290(3): 334. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824212
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Responses to smallpox vaccine. Author(s): Frelinger JA, Garba ML. Source: The New England Journal of Medicine. 2002 August 29; 347(9): 689-90; Author Reply 689-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201305
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Responses to smallpox vaccine. Author(s): Sauri MA. Source: The New England Journal of Medicine. 2002 August 29; 347(9): 689-90; Author Reply 689-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200560
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Risk of cutaneous vaccinia from health care workers who receive smallpox vaccine. Author(s): Mermel LA. Source: Jama : the Journal of the American Medical Association. 2003 February 19; 289(7): 844-5 Author Reply 845. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588263
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Safety of the smallpox vaccine among military recipients. Author(s): Nass M. Source: Jama : the Journal of the American Medical Association. 2003 October 22; 290(16): 2123-4; Author Reply 2124. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570942
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Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. Author(s): Belyakov IM, Earl P, Dzutsev A, Kuznetsov VA, Lemon M, Wyatt LS, Snyder JT, Ahlers JD, Franchini G, Moss B, Berzofsky JA. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 5; 100(16): 9458-63. Epub 2003 July 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869693
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Should smallpox vaccine be made available to the general public? Author(s): May T, Silverman RD. Source: Kennedy Institute of Ethics Journal. 2003 June; 13(2): 67-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14569990
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Should smallpox vaccine be tested in children? Author(s): Baltimore RS, Jenson HB. Source: Current Opinion in Infectious Diseases. 2003 June; 16(3): 237-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821814
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Should you volunteer for the smallpox vaccine? Author(s): Lorenzo P. Source: Rn. 2003 April; 66(4): 69-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12715459
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Simultaneous administration of live measles virus vaccine and smallpox vaccine. Author(s): Sherman PM, Hendrickse RG, Montefiore D, Peradze T, Coker G. Source: British Medical Journal. 1967 June 10; 2(553): 672-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6024526
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Skin reaction following immunization with smallpox vaccine: a personal perspective. Author(s): Urkin J. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 July; 72(1): 43-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889714
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Smallpox and smallpox vaccine: ocular and systemic risks and ethical uncertainties. Author(s): Chous AP, Hom GG. Source: Optometry. 2003 September; 74(9): 583-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515981
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Smallpox and smallpox vaccine--just the facts. Author(s): Sawyer PP. Source: Home Healthcare Nurse. 2003 February; 21(2): 130. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574685
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Smallpox and the smallpox vaccine controversy. Author(s): Baltimore RS, McMillan JA. Source: The Pediatric Infectious Disease Journal. 2002 August; 21(8): 789-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12192171
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Smallpox vaccine and pregnancy. Author(s): Amstey MS, Gall SA. Source: Obstetrics and Gynecology. 2002 December; 100(6): 1356; Author Reply 1356. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12468187
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Smallpox vaccine development quickened. Author(s): Birmingham K, Kenyon G. Source: Nature Medicine. 2001 November; 7(11): 1167. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689864
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Smallpox vaccine encephalomyelitis. (Case report). Author(s): Vega LA. Source: W V Med J. 1969 September; 65(9): 300-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4389849
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Smallpox vaccine for the treatment of recurrent herpes infection. Author(s): Schoub BD. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1982 August 7; 62(7): 189. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7101068
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Smallpox Vaccine Injury Compensation Program: administrative implementation. Interim final rule. Author(s): Health Resources and Services Administration, HHS. Source: Federal Register. 2003 December 16; 68(241): 70079-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677536
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Smallpox Vaccine Injury Compensation Program: Smallpox (Vaccinia) Vaccine Injury Table. Interim final rule. Author(s): Health Resources and Services Administration, HHS. Source: Federal Register. 2003 August 27; 68(166): 51492-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952013
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Smallpox vaccine policy: the national debate. Author(s): Benjamin GC. Source: Physician Executive. 2002 September-October; 28(5): 64-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12416388
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Smallpox vaccine program lagging. Author(s): Piotrowski J. Source: Modern Healthcare. 2003 May 19; 33(20): 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12800582
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Smallpox vaccine program launched amid concerns raised by expert panel, unions. Author(s): Stephenson J. Source: Jama : the Journal of the American Medical Association. 2003 February 12; 289(6): 685-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12585929
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Smallpox vaccine revisited. Author(s): Capriotti T. Source: Dermatology Nursing / Dermatology Nurses' Association. 2002 December; 14(6): 387-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592794
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Smallpox vaccine revisited. Author(s): Capriotti T. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 2002 August; 11(4): 193-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12219432
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Smallpox vaccine, past and present. Author(s): Peterson B. Source: J Am Osteopath Assoc. 1975 February; 74(6): 565-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1089705
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Smallpox vaccine. Author(s): Committee on Infectious Diseases. American Academy of Pediatrics. Source: Pediatrics. 2002 October; 110(4): 841-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359807
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Smallpox vaccine. Author(s): Joseph PR. Source: Pediatric Annals. 2000 May; 29(5): 263. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10826318
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Smallpox vaccine. Author(s): Katz J. Source: Science. 1999 September 24; 285(5436): 2067. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10523198
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Smallpox vaccine: contraindications, administration, and adverse reactions. Author(s): Maurer DM, Harrington B, Lane JM. Source: American Family Physician. 2003 September 1; 68(5): 889-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678138
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Smallpox vaccine: don't do it. Author(s): Cohen HW, Eolis SL. Source: The American Journal of Nursing. 2003 March; 103(3): 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626934
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Smallpox vaccine: not worth the risk. Author(s): Annas GJ. Source: The Hastings Center Report. 2003 March-April; 33(2): 6-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760109
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Smallpox vaccine: problems and prospects. Author(s): Poland GA, Neff JM. Source: Immunology and Allergy Clinics of North America. 2003 November; 23(4): 73143. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753389
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Smallpox vaccine: the reality, the risk. Author(s): Taccetta-Chapnick M. Source: Rn. 2003 July; 66(7): 52-8; Quiz 60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900999
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Smallpox vaccine--do school nurses know how to respond? Author(s): Bobo N. Source: Nasnewsletter. 2002 September; 17(5): 14-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12298227
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Status of nation's smallpox vaccine reserve improves. Author(s): Traynor K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 May 1; 59(9): 822, 827. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004457
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Take rates by double versus single insertions of smallpox vaccine in revaccinees. Author(s): Lane JM, Mack TM, Millar JD. Source: Public Health Reports (Washington, D.C. : 1974). 1970 October; 85(10): 928-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4990250
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The age-dependent risk of postvaccination complications in vaccinees with smallpox vaccine. Author(s): Gurvich EB. Source: Vaccine. 1992; 10(2): 96-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1347190
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The big deal about smallpox. Smallpox vaccine program leaves many unanswered questions. Author(s): Jacobs L. Source: Revolution. 2003 January-February; 4(1): 22-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685326
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The Jenner bicentenary: the introduction and early distribution of smallpox vaccine. Author(s): Baxby D. Source: Fems Immunology and Medical Microbiology. 1996 November; 16(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8954347
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The Jenner bicentenary; still uses for smallpox vaccine. Author(s): Baxby D. Source: Epidemiology and Infection. 1996 June; 116(3): 231-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8666065
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The new cell culture smallpox vaccine should be offered to the general population. Author(s): Bicknell W, James K. Source: Reviews in Medical Virology. 2003 January-February; 13(1): 5-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516058
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The smallpox vaccine and postvaccinal encephalitis. Author(s): Roos KL, Eckerman NL. Source: Seminars in Neurology. 2002 March; 22(1): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170398
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The smallpox vaccine debate. Author(s): Veenema TG. Source: The American Journal of Nursing. 2002 September; 102(9): 33-8; Quiz 38-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394016
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Thrombocytopenic purpura after smallpox vaccine. Author(s): Burke PJ, Shah NR. Source: Pa Med. 1981 September; 84(9): 49-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7312385
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Treatment of verrucae with smallpox vaccine. Author(s): Lawrence KR. Source: J Am Podiatry Assoc. 1971 January; 61(1): 12-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5163447
Studies
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Treatment of verrucae with smallpox vaccine. Author(s): Hemphill WJ. Source: Jama : the Journal of the American Medical Association. 1969 January 13; 207(2): 368. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5818168
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Treatment of verrucae with smallpox vaccine. Author(s): Thompson KW. Source: Jama : the Journal of the American Medical Association. 1969 January 13; 207(2): 368. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5818167
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Treatment of warts with smallpox vaccine. Author(s): Belisario JC. Source: The Medical Journal of Australia. 1971 December 18; 2(25): 1277-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5134725
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UK awards contract for smallpox vaccine. Author(s): Habeck M. Source: The Lancet Infectious Diseases. 2002 June; 2(6): 321. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12144887
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UK smallpox vaccine comes under fire from US. Author(s): Dyer O. Source: Bmj (Clinical Research Ed.). 2002 August 10; 325(7359): 298. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169498
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Under scrutiny: smallpox vaccine recommendations. Author(s): Kemper AR, Davis MM. Source: Expert Opinion on Pharmacotherapy. 2003 August; 4(8): 1207-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877631
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US dilutes smallpox vaccine supplies. Author(s): Cimons M. Source: Nature Medicine. 2001 December; 7(12): 1265. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726949
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US smallpox vaccine programme stalls as volunteers balk. Author(s): Ault A. Source: Lancet. 2003 May 10; 361(9369): 1626. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747889
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USA firms up smallpox vaccine plans. Author(s): Senior K. Source: The Lancet Infectious Diseases. 2002 November; 2(11): 649. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409031
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USA to increase smallpox vaccine stockpile. Author(s): Bradbury J. Source: The Lancet Infectious Diseases. 2001 December; 1(5): 290. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11871793
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Wart treatment by vaccination with smallpox vaccine: a preliminary report. Author(s): McGee AR. Source: Can Med Assoc J. 1968 July 20; 99(3): 119-21. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5676076
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What you need to know about the smallpox vaccine. Author(s): Karber S, Fasano N. Source: Nursing. 2003 June; 33(6): 36-42; Quiz 43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799585
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CHAPTER 2. CLINICAL TRIALS AND SMALLPOX VACCINE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning smallpox vaccine.
Recent Trials on Smallpox Vaccine The following is a list of recent trials dedicated to smallpox vaccine.7 Further information on a trial is available at the Web site indicated. •
Dose Safety, Tolerability, and Immunogenicity of a New Smallpox Vaccine in Adults without Previous Smallpox Vaccination Condition(s): Smallpox Study Status: This study is currently recruiting patients. Sponsor(s): Acambis Purpose - Excerpt: The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053508
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Phase I Trial of Smallpox Vaccine Condition(s): Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will test the safety of an experimental vaccine called Modified Vaccinia Virus Ankara (MVA) for use against the smallpox virus. It will also
7
These are listed at www.ClinicalTrials.gov.
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investigate how many injections of MVA are needed to produce immunity against vaccinia virus, which is closely related to the smallpox virus. An effective smallpox vaccine exists, but it can cause side effects that, on rare occasions, can be lifethreatening. The FDA gave new license approval for Dryvax on 10/25/02, but has not been used in the general population since smallpox was eradicated worldwide. Both the MVA and Dryvax(r) (Registered Trademark) vaccines are made using the vaccinia virus, however the MVA vaccine contains a more attenuated, or weakened, form of the virus. [http://www.fda.gov/cber/products/smalwye102502.htm] Healthy normal volunteers between 18 and 30 years of age, who have never been vaccinated with a smallpox vaccine, may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests, including an HIV test and a pregnancy test for women of childbearing potential. MVA, placebo and Dryvax(r) (Registered Trademark) will be administered by different methods. The MVA vaccine and placebo are injected into an arm muscle with a needle and syringe. The Dryvax(r) (Registered Trademark) vaccine is administered, as it was for many years, with a special forked needle that is poked lightly into the skin of the upper arm, usually 15 times, in a process called scarification. When the vaccine works, a small pus-filled blister forms, followed by a scab and then scarring at the site of the vaccination. The formation of the blister and scab is called a take, indicating that the vaccine is effective and is evidence of the development of immunity. The development of a take suggests that an individual will be protected against smallpox for at least a few years. If scarification does not take, it can either mean that the person already has immunity or that the vaccine did not work. Participants will be assigned to groups, as well as, product randomly. For instance, the first study participant could be enrolled into group 3. The Dryvax(r) (Registered Trademark) dose is given as a challenge to see if the person has a take. A reduced take response or no take, could suggest that MVA is able to produce an immune response. The dosing schedules vary from 12 to 24 weeks and volunteers are in the study a total of 24 to 36 weeks, depending on the number of injections. Participants will be observed for at least 1 hour after each injection. They will come to the clinic a week after MVA or placebo injections and at least twice a week after Dryvax(r) (Registered Trademark) for about 21 days to have the injection site evaluated and photographed. At each visit, participants will be asked about how they are feeling and if they are taking any medications. Blood and urine tests will be done on injection days and at follow up visits scheduled 1 and 4 weeks after each immunization as well as 12 weeks after the Dryvax(r) (Registered Trademark) challenge dose. Additional tests may be done between visits if medically necessary. Phase(s): Phase I; MedlinePlus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046397 •
Dose On Safety, Tolerability, and Immunogenicity of ACAM2000 Smallpox Vaccine in Adults With Previous Smallpox Vaccination Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): Acambis Purpose - Excerpt: The objective of this study is to determine the minimum dose of ACAM2000 needed to produce a cutaneous reaction in at least 90% of a population of healthy adults at least 28 years of age and previously vaccinated against smallpox.
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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053482 •
Effect of Dose, Safety, Tolerability of a New Smallpox Vaccine in Adults Without Previous Smallpox Vaccination Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): Acambis Purpose - Excerpt: The purpose of this study is to examine the safety and the effectiveness of a new vaccine for the prevention of the disease, smallpox. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053495
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Human Immune Response to Smallpox Vaccine Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to attempt to identify the immune response of healthy adults to an investigational dilution of the Dryvax smallpox vaccine. In addition, we will try to determine whether certain genetic characteristics influence the size of the sore around the vaccination site, and use blood samples from subjects in the study to make a new form of antibody that could be given to people with vaccine side effects. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068198
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Study of Reactogenicity, Safety, Immunogenicity, and Pock Lesion Formation of a Cell-Cultured Smallpox Vaccine Compared to Dryvax(r) Condition(s): Smallpox Study Status: This study is no longer recruiting patients. Sponsor(s): DynPort Vaccine Company Purpose - Excerpt: This study will evaluate the safety and efficacy of both Dryvax(r) and the new cell-cultured vaccine (CCSV) in a comparative fashion. Across 3 cohorts, 150 vaccinia-naive volunteers will be randomly assigned to receive either CCSV (100 volunteers) or Dryvax(r) (50 volunteers) in a blinded fashion. Subjects will be followed closely for up to 6 months and a subgroup of volunteers will be followed up to 3 years in order to evaluate the duration of immunity following vaccination. Another cohort
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will enroll 100 vaccinia-experienced volunteers and randomly assign them to receive either CCSV (50 volunteers) or Dryvax(r) (50 volunteers) and a sub group will be followed up to 3 years. A fifth cohort will enroll 100 vaccinia-naive volunteers and randomly assign them to receive different dilutions of CCSV (1:1, 1:5, 1:25, and 1:50). Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042094 •
Safety, Tolerability, and Immune Response of ACAM3000 Modified Vaccinia Ankara (MVA) Smallpox Vaccine in Adults Condition(s): Smallpox Study Status: This study is not yet open for patient recruitment. Sponsor(s): Acambis; National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to gather information on the safety and the effectiveness of an investigational vaccine for the prevention of smallpox disease. Smallpox was one of the major causes of death and sickness through the first half of the 20th century, but a global program of smallpox eradication resulted in the elimination of the natural disease. The last cases of smallpox in the United States occurred in 1949 in Texas. Today, only laboratory workers who work with smallpox-related viruses, military personnel, and health care workers are vaccinated. Historically, individuals in the US were vaccinated with a product such as Dryvax(r), which contains the virus vaccinia in the same family as smallpox. This virus could promote immunity to smallpox, but not produce the disease itself. Although effective, these vaccines are not safe to use in people with atopic dermatitis (eczema, allergic immune response to allergens), children less than 1 year of age, and people with a compromised immune system, occurring in certain diseases (HIV positive individuals and AIDS), and following treatment with certain types of drugs. It is important to find a safe vaccine that can be used to protect people who cannot receive routine vaccinia-based smallpox vaccine. The vaccine in this study is known as Modified Vaccinia Ankara or MVA vaccine. It is the objective of this study to find out if MVA vaccine is safe and effective in providing immunity to smallpox. The effectiveness of this vaccine will be measured in two ways. The first way is to find out if there are specific antibodies in your blood following MVA vaccination. Antibodies are chemicals your body produces to fight smallpox virus. The second way is to see whether or not there is a typical skin reaction following vaccination with a traditional smallpox vaccine, given about three months after vaccination with the MVA vaccine. The typical reaction in an unvaccinated person to smallpox vaccine is formation of a blister or "pox" which occurs at the site of vaccination. In a person with immunity to smallpox the skin reaction is much less, and typically consists of a little swelling at the site of vaccination. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00079820
Clinical Trials 47
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 “smallpox vaccine” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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•
For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 3. BOOKS ON SMALLPOX VACCINE Overview This chapter provides bibliographic book references relating to smallpox vaccine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on smallpox vaccine 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: 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 “smallpox vaccine” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “smallpox vaccine” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “smallpox vaccine” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Dr. Jenner and the Speckled Monster: The Search for the Smallpox Vaccine by Albert Marrin; ISBN: 0525469222; http://www.amazon.com/exec/obidos/ASIN/0525469222/icongroupinterna
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Jenner's Smallpox Vaccine: The Riddle of Vaccina Virus and Its Origin by Derrick Baxby; ISBN: 0435540572; http://www.amazon.com/exec/obidos/ASIN/0435540572/icongroupinterna
Chapters on Smallpox Vaccine In order to find chapters that specifically relate to smallpox vaccine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search
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to book chapters and smallpox vaccine 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 “smallpox vaccine” (or synonyms) into the “For these words:” box.
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CHAPTER 4. PERIODICALS AND NEWS ON SMALLPOX VACCINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover smallpox vaccine.
News Services and Press Releases One of the simplest ways of tracking press releases on smallpox vaccine 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 “smallpox vaccine” (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 smallpox vaccine. 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 “smallpox vaccine” (or synonyms). The following was recently listed in this archive for smallpox vaccine: •
Siga soars after smallpox vaccine works in mice Source: Reuters Industry Breifing Date: March 22, 2004
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•
New smallpox vaccine looks safer than old - study Source: Reuters Health eLine Date: March 10, 2004
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Bavarian Nordic in the black on smallpox vaccine Source: Reuters Industry Breifing Date: March 04, 2004
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Breastfed baby exposed to smallpox vaccine virus Source: Reuters Health eLine Date: February 10, 2004
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Heart problems not tied to smallpox vaccine Source: Reuters Health eLine Date: October 02, 2003
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Concerns about sequelae of smallpox vaccine, anthrax cleared up Source: Reuters Medical News Date: October 02, 2003
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US gives more cash to Danish smallpox vaccine firm Source: Reuters Industry Breifing Date: September 25, 2003
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Study suggests smallpox vaccine may fight AIDS Source: Reuters Health eLine Date: September 12, 2003
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Most people given smallpox vaccine in past probably still immune Source: Reuters Industry Breifing Date: August 18, 2003
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UK goes abroad to boost smallpox vaccine supplies Source: Reuters Industry Breifing Date: July 30, 2003
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Bavarian to test its smallpox vaccine against rival Source: Reuters Industry Breifing Date: July 15, 2003
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Weakened smallpox vaccine is safer, research shows Source: Reuters Industry Breifing Date: July 14, 2003
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New smallpox vaccine looks safe in tests Source: Reuters Health eLine Date: July 14, 2003
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Diluted smallpox vaccine safe and effective after previous immunization Source: Reuters Industry Breifing Date: June 24, 2003
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U.S. urges smallpox vaccine for monkeypox exposure Source: Reuters Health eLine Date: June 11, 2003
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U.S. bans rodent transport and advises smallpox vaccine to limit monkeypox Source: Reuters Medical News Date: June 11, 2003
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•
Advisers reiterate need to wait before giving smallpox vaccine to first responders Source: Reuters Medical News Date: May 27, 2003
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US to buy new smallpox vaccine once available Source: Reuters Industry Breifing Date: May 23, 2003
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US plans to buy new smallpox vaccine once available Source: Reuters Health eLine Date: May 23, 2003
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Smallpox vaccine-related myopericarditis and encephalomyelitis cases under investigation Source: Reuters Industry Breifing Date: May 22, 2003
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Smallpox vaccine candidates often fail to recall skin disorders Source: Reuters Industry Breifing Date: May 05, 2003
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Smallpox vaccine refusers cite compensation concerns, low threat of attack Source: Reuters Industry Breifing Date: May 01, 2003
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CDC reports 103 pregnancies in smallpox vaccinees Source: Reuters Health eLine Date: May 01, 2003
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CDC reports 103 pregnancies among smallpox vaccinees Source: Reuters Industry Breifing Date: May 01, 2003
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US smallpox vaccine campaign linked with 45 serious adverse events Source: Reuters Medical News Date: April 24, 2003
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DynPort smallpox vaccine shows fewer side effects than Dryvax in phase I study Source: Reuters Medical News Date: April 17, 2003
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DynPort smallpox vaccine induces fewer side effects than Dryvax in phase I study Source: Reuters Industry Breifing Date: April 17, 2003
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Heart patients barred from smallpox vaccine Source: Reuters Health eLine Date: March 27, 2003
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US investigating death of nurse who received smallpox vaccine Source: Reuters Industry Breifing Date: March 26, 2003
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Smallpox vaccinee's death prompts deferral for people with heart disease Source: Reuters Medical News Date: March 26, 2003
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US contracts for safer smallpox vaccine Source: Reuters Health eLine Date: February 25, 2003
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No serious smallpox vaccine sequelae documented in US civilians Source: Reuters Medical News Date: February 20, 2003
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NY healthcare workers prepare for smallpox vaccine Source: Reuters Health eLine Date: February 14, 2003
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Hong Kong stocks up on smallpox vaccines Source: Reuters Industry Breifing Date: February 14, 2003
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Hong Kong stocking up on smallpox vaccines Source: Reuters Health eLine Date: February 14, 2003
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Few serious side effects seen among 100,000 military smallpox vaccinees Source: Reuters Medical News Date: February 13, 2003
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CDC system monitors smallpox vaccine side effects Source: Reuters Health eLine Date: February 06, 2003
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US delivers first civilian smallpox vaccines Source: Reuters Health eLine Date: January 23, 2003 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. 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 “smallpox vaccine” (or synonyms) into the search box, and click on “Search News.” As this service is
Periodicals and News 55
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 “smallpox vaccine” (or synonyms). If you know the name of a company that is relevant to smallpox vaccine, 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 “smallpox vaccine” (or synonyms).
Academic Periodicals covering Smallpox Vaccine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to smallpox vaccine. In addition to these sources, you can search for articles covering smallpox vaccine 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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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute8: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
8
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
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.9 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:10 •
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
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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
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
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
9
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). 10 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 Gateway11 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.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “smallpox vaccine” (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 2925 148 774 6 2 3855
HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 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.15 Simply search by “smallpox vaccine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
11
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
12
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). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14 15
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 Biologists16 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.17 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.18 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/.
16 Adapted 17
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. 18 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 smallpox vaccine 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 smallpox vaccine. 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 smallpox vaccine. 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 “smallpox vaccine”:
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Childhood Immunization http://www.nlm.nih.gov/medlineplus/childhoodimmunization.html Influenza http://www.nlm.nih.gov/medlineplus/influenza.html Monkeypox Virus Infections http://www.nlm.nih.gov/medlineplus/monkeypoxvirusinfections.html Smallpox http://www.nlm.nih.gov/medlineplus/smallpox.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on smallpox vaccine. 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: •
Smallpox and HIV: Questions and Answers Contact: Education Training and Research Associates, PO Box 1830, Santa Cruz, CA, 95061-1830, (800) 321-4407, http://www.etr.org. Summary: This pamphlet answers questions about getting a smallpox vaccine if one is infected with the human immunodeficiency virus (HIV). The vaccine can protect people from smallpox. Although the risk of getting sick following vaccination is small for most people, it is much higher for people with HIV. The pamphlet explains what smallpox is, what happens if someone gets smallpox, and why someone with HIV is at greater risk for illness following a smallpox vaccination. It also identifies other people at risk of illness from the vaccine and provides alternative methods of protecting oneself from the disease. 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 “smallpox vaccine” (or synonyms). The following was recently posted: •
Recommendations for using smallpox vaccine in a pre-event smallpox vaccination program. Supplemental recommendations of the Advisory Committee on
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Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 February 26; 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3623&nbr=2849&a mp;string=smallpox+AND+vaccine •
Smallpox vaccine Source: American Academy of Pediatrics - Medical Specialty Society; 2002 September; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3451&nbr=2677&a mp;string=smallpox+AND+vaccine
•
Supplemental recommendations on adverse events following smallpox vaccine in the pre-event vaccination program: recommendations of the Advisory Committee on Immunization Practices Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 April 4; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3727&nbr=2953&a mp;string=smallpox+AND+vaccine
•
Updated interim CDC guidance for use of smallpox vaccine, cidofovir, and vaccinia immune globulin (VIG) for prevention and treatment in the setting of an outbreak of monkeypox infections Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 June 12 (revised 2003 Jun 25); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3851&nbr=3066&a mp;string=smallpox+AND+vaccine 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: •
Smallpox Summary: This smallpox page from CDC has the latest smallpox vaccine recommendations, public health response plan, factsheets, and clinical information about smallpox. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6323
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Smallpox Vaccine
Smallpox Basics Summary: This is a brief factsheet about smallpox and the smallpox vaccine. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6971
•
Smallpox Information from the U.S. Department of Health and Human Services Summary: This smallpox page presents basic information about smallpox and the smallpox vaccine and features information for specific audiences: kids, teens, parents, primary health care providers, public Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7076 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 smallpox vaccine. 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/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to smallpox vaccine. By consulting all of associations
Patient Resources 69
listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with smallpox vaccine. 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 smallpox vaccine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “smallpox vaccine” (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 “smallpox vaccine”. 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 “smallpox vaccine” (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 “smallpox vaccine” (or a synonym) into the search box, and click “Submit Query.”
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71
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.19
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
19
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)20: •
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
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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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/
•
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/
•
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/
20
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 73
•
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
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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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/
•
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
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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/
Finding Medical Libraries 75
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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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
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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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).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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SMALLPOX VACCINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agammaglobulinemia: An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood. [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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergens: Antigen-type substances (hypersensitivity, immediate). [NIH]
that
produce
immediate
hypersensitivity
Allogeneic: Taken from different individuals of the same species. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form
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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] 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] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [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] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Anthrax Vaccines: Vaccines or candidate vaccines used to prevent anthrax. [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] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU]
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Arteries: The vessels carrying blood away from the heart. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] 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] 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] 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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Bispecific antibodies: Antibodies developed in the laboratory to recognize more than one protein on the surface of different cells. Examples include bispecific antibodies 2B1, 520C9xH22, mDX-H210, and MDX447. [NIH] Bladder: The organ that stores urine. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH]
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Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [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] 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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [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] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Cardiac: Having to do with the heart. [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 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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The
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concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [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] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] 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] 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]
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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] 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] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [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] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] 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] Dermal: Pertaining to or coming from the skin. [NIH]
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Dermatitis: Any inflammation of the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [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 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] 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] Ectromelia: Gross hypo- or aplasia of one or more long bones of one or more limbs. The concept includes amelia, hemimelia, and phocomelia. [NIH] Ectromelia Virus: A species of orthopoxvirus infecting mice and causing a disease that involves internal organs and produces characteristic skin lesions. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH]
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Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] 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] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [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] Epidemics: A period of increased prevalence of a particular disease in a population. [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] Epithelial: Refers to the cells that line the internal and external 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.
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[NIH]
ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [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] Exhaustion: The feeling of weariness of mind and body. [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] Extracellular: Outside a cell or cells. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Filovirus: A genus of the family Filoviridae containing two species: Ebola virus and Marburg virus. Both were originally associated with African monkeys but are capable of causing severe hemorrhagic disease in humans. The natural host of either virus is unknown. Transmission is by close personal contact. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] 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,
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the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [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] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Freeze-dried: A method used to dry substances, such as food, to make them last longer. The substance is frozen and then dried in a vacuum. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] 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] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [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] 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] 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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [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]
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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] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [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] 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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic Fever with Renal Syndrome: An acute febrile disease occurring predominately in Asia. It is characterized by fever, prostration, vomiting, hemorrhagic phenonema, shock, and renal failure. It is caused by any one of several closely related species of the genus Hantavirus. The most severe form is caused by Hantaan virus whose natural host is the rodent Apodemus agrarius. A milder form is caused by Seoul virus and related species and transmitted by the rodents Rattus rattus and R. norvegicus. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU]
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Herpes Zoster: Acute vesicular inflammation. [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]
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] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] 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] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] 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]
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Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Memory: The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]
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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU]
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Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [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] 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] Intestinal: Having to do with the intestines. [NIH] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [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]
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] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Local Government: Smallest political subdivisions within a country at which general governmental functions are carried-out. [NIH] Localized: Cancer which has not metastasized yet. [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).
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[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 that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH]
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Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] 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] 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] 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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]
Myalgia: Pain in a muscle or muscles. [EU]
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Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] 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] 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] Neutralization: An act or process of neutralizing. [EU] 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] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [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] Orthopoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirninae, comprising many species infecting mammals. Viruses of this genus cause generalized infections and a rash in some hosts. The type species is Vaccinia virus. [NIH]
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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]
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] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] 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]
Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] 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] Phocomelia: Congenital deformity that leaves the child without legs. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized
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regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polychromatic: Erythrocyte that, on staining, shows various shades of blue combined with tinges of pink. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary vaccination: First or principal vaccination ( = introduction of a vaccine into the body for the purpose of inducing immunity). [EU] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] 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] 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
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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] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] 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] 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] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH]
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Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [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] 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] 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] Rinderpest: A viral disease of cloven-hoofed animals caused by Morbillivirus. It may be acute, subacute, or chronic with the major lesions characterized by inflammation and ulceration of the entire digestive tract. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH]
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Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] 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] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] 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] 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] 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]
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Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Technology Transfer: Spread and adoption of inventions and techniques from one geographic area to another, from one discipline to another, or from one sector of the economy to another. For example, improvements in medical equipment may be transferred from industrial countries to developing countries, advances arising from aerospace engineering may be applied to equipment for persons with disabilities, and innovations in science arising from government research are made available to private enterprise. [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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] 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] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific
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biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [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] 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] 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] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [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] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Variola Virus: A species of Orthopoxvirus causing infections in humans. No infections have been reported since 1977 and the virus is now believed to be virtually extinct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]
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Veins: The vessels carrying blood toward the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] 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] 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] 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 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] 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] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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]
Xenograft: The cells of one species transplanted to another species. [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]
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INDEX A Acceptor, 14, 79, 96 Adjuvant, 6, 79 Adverse Effect, 17, 21, 24, 79, 100 Aerosol, 13, 22, 79 Affinity, 14, 79 Agammaglobulinemia, 23, 79 Algorithms, 15, 79, 81 Alimentary, 79, 96 Alleles, 15, 17, 79 Allergens, 46, 79 Allogeneic, 79, 89 Alternative medicine, 54, 79 Amino Acid Sequence, 79, 80, 88 Amino Acids, 79, 80, 83, 88, 96, 98, 99, 102 Anaesthesia, 80, 91 Anal, 80, 87 Anaphylatoxins, 80, 83 Anemia, 80, 93 Animal model, 7, 9, 21, 80 Anthrax, 4, 7, 9, 18, 24, 52, 80 Anthrax Vaccines, 24, 80 Antibodies, 4, 7, 10, 14, 15, 16, 17, 18, 20, 27, 46, 80, 81, 89, 90, 91, 93, 94, 97 Antibody, 5, 7, 10, 14, 16, 17, 20, 23, 27, 31, 45, 79, 80, 83, 86, 89, 90, 91, 94, 98, 100 Antigen, 13, 23, 24, 79, 80, 83, 84, 90, 91 Antigen-Antibody Complex, 80, 83 Antigen-presenting cell, 80, 84 Aplasia, 80, 85 Arteries, 81, 82, 84, 94 Assay, 4, 8, 14, 26, 28, 81 Atopic, 4, 9, 46, 81 Attenuated, 7, 10, 11, 16, 26, 28, 30, 33, 35, 44, 81, 85 Attenuation, 4, 11, 81 Autoimmune disease, 81 Autoimmunity, 34, 81 Autologous, 81, 89 Autologous bone marrow transplantation, 81, 89 B Bacillus, 7, 9, 18, 80, 81 Bacteria, 23, 80, 81, 94, 97, 99, 100, 102 Base, 81, 84, 88, 92, 101 Biochemical, 79, 81, 87 Biological response modifier, 9, 81, 92 Biomarkers, 8, 81
Biopsy, 81, 96 Biotechnology, 28, 31, 54, 61, 81 Bioterrorism, 4, 16, 17, 19, 22, 23, 28, 81 Bispecific antibodies, 14, 81 Bladder, 81, 97, 102 Blister, 44, 46, 81 Blood pressure, 82, 94 Blood vessel, 82, 83, 93, 100, 101, 102 Body Fluids, 81, 82, 102 Bone Marrow, 81, 82, 89, 90, 93, 100 Bowel, 80, 82, 85 Bowel Movement, 82, 85 Branch, 75, 82, 91, 93, 98, 100, 101 C Calcium, 82, 83 Carbohydrates, 82 Carbon Dioxide, 82, 87, 99 Cardiac, 21, 82, 95 Cell Division, 81, 82, 97 Cell membrane, 12, 82 Cell Size, 82, 88 Cell Transplantation, 82 Chemokines, 9, 27, 82 Chemotactic Factors, 82, 83 Chin, 83, 94 Chromosomal, 83, 97 Chronic, 83, 85, 91, 99, 101 Cidofovir, 26, 67, 83 Clinical trial, 3, 6, 20, 43, 47, 61, 83, 99 Cloning, 81, 83 Codon, 12, 83, 88 Complement, 14, 17, 20, 21, 31, 80, 83, 93 Computational Biology, 61, 83 Conjunctiva, 84, 91 Connective Tissue, 82, 84, 85, 92 Contraindications, ii, 38, 84 Corneum, 84, 86 Coronary, 84, 94 Coronary Thrombosis, 84, 94 Cowpox, 11, 15, 20, 21, 84, 102 Cowpox Virus, 11, 20, 21, 84, 102 Curative, 84, 101 Cutaneous, 9, 35, 36, 44, 80, 84, 102 Cysteine, 82, 84 Cytokine, 5, 21, 84 Cytoplasm, 82, 84, 86, 99 Cytotoxic, 4, 15, 84 Cytotoxicity, 8, 16, 84
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D Databases, Bibliographic, 61, 84 Defense Mechanisms, 25, 84 Dendrites, 84 Dendritic, 9, 12, 84 Dendritic cell, 9, 84 Density, 84, 88 Dermal, 9, 84 Dermatitis, 4, 9, 46, 85 Dermis, 9, 85, 101 Developing Countries, 85, 101 Diagnostic procedure, 55, 85 Diffusion, 85 Digestive system, 47, 85 Digestive tract, 85, 99 Dilution, 7, 19, 45, 85 Direct, iii, 21, 85, 99 Disease Progression, 85, 103 Disease Transmission, 85, 103 Disease Transmission, Vertical, 85, 103 Dissociation, 79, 85 E Ectromelia, 7, 10, 23, 85 Ectromelia Virus, 7, 10, 23, 85 Eczema, 10, 46, 85 Effector, 9, 16, 83, 86 Efficacy, 4, 6, 8, 9, 12, 14, 17, 18, 20, 22, 24, 26, 31, 45, 86 Embryo, 86, 91 Emulsion, 86, 87 Encephalitis, 10, 18, 19, 40, 86 Encephalitis, Viral, 86 Encephalomyelitis, 37, 53, 86 Endemic, 86, 93 Endotoxins, 83, 86 Environmental Health, 60, 62, 86 Enzymatic, 82, 83, 86 Enzyme, 86, 98, 103 Epidemics, 27, 86 Epidermal, 9, 86, 103 Epidermis, 9, 81, 84, 85, 86, 90, 98 Epithelial, 12, 86 Epitope, 5, 8, 17, 28, 86 ERV, 62, 87 Erythrocytes, 14, 80, 82, 87 Esophagus, 85, 87, 96, 100 Excitation, 87 Exhaustion, 87, 93 Exogenous, 85, 87 Expiratory, 87 Expiratory Reserve Volume, 87 Extracellular, 14, 84, 87
F Family Planning, 61, 87 Febrile, 24, 87, 89, 93 Filovirus, 25, 87 Filtration, 15, 87 Fixation, 17, 87 Flow Cytometry, 5, 8, 25, 27, 87 Fluorescence, 87, 88 Fluorescent Dyes, 87, 88 Fovea, 87, 88 Fractionation, 14, 88 Freeze-dried, 29, 32, 33, 34, 88 G Gallbladder, 85, 88 Gas, 82, 85, 87, 88, 90, 95, 101 Gene, 4, 12, 21, 23, 24, 79, 81, 88 Gene Expression, 21, 24, 88 Generator, 12, 88 Genetic Code, 88, 95 Genetics, 88, 91 Genital, 88, 103 Genomics, 24, 88 Genotype, 88, 96 Gland, 88, 92, 96, 97, 99, 100, 101 Governing Board, 88, 97 Government Agencies, 18, 88, 97 Graft, 88, 89, 90, 91 Graft Rejection, 89, 91 Growth, 85, 89, 92, 95, 96 H Hair follicles, 85, 89 Half-Life, 16, 89 Haplotypes, 18, 89 Haptens, 79, 89 Headache, 89, 91, 102 Hematologic malignancies, 4, 89 Hematopoietic Stem Cell Transplantation, 4, 89 Hemoglobin, 80, 87, 89 Hemorrhage, 89, 98, 100 Hemorrhagic Fever with Renal Syndrome, 8, 89 Heredity, 88, 89 Herpes, 33, 37, 89, 90 Herpes Zoster, 33, 89, 90 Heterogeneity, 79, 90 Homologous, 13, 79, 90 Horny layer, 86, 90 Host, 5, 8, 11, 18, 19, 87, 89, 90, 91, 102, 103 Humoral, 9, 10, 20, 22, 23, 89, 90 Humour, 90 Hydrogen, 79, 81, 82, 90, 94, 96
107
Hypersensitivity, 79, 90 Hypersensitivity, Immediate, 79, 90 I Id, 67, 68, 74, 76, 90 Immune Sera, 90 Immune system, 20, 22, 46, 80, 81, 90, 91, 93, 95, 102, 103 Immunity, 4, 5, 6, 7, 15, 19, 20, 22, 23, 24, 26, 27, 32, 44, 45, 46, 90, 91, 97, 102 Immunization, 4, 7, 10, 15, 17, 20, 22, 23, 24, 26, 27, 44, 52, 66, 67 Immunocompromised, 14, 19, 22, 90 Immunocompromised Host, 22, 90 Immunodeficiency, 4, 14, 20, 22, 66, 90 Immunogenetics, 7, 10, 26, 91 Immunogenic, 16, 91 Immunoglobulin, 14, 80, 91, 94 Immunologic, 4, 5, 9, 18, 20, 24, 26, 79, 83, 90, 91 Immunologic Memory, 9, 91 Immunology, 8, 15, 17, 20, 26, 39, 40, 79, 88, 91 Immunosuppressive, 20, 90, 91 Immunosuppressive therapy, 91 Immunotherapy, 6, 91 Impairment, 91, 94 In vitro, 20, 91, 101 In vivo, 19, 91 Indicative, 49, 91, 102 Induction, 21, 91 Infarction, 84, 91, 94 Inflammation, 85, 86, 90, 91, 95, 99 Influenza, 24, 66, 91 Ingestion, 80, 91 Inhalation, 79, 91 Inoculum, 11, 92 Insight, 27, 92 Interferon, 4, 20, 27, 92 Interferon-alpha, 92 Intestinal, 92, 103 Intracellular, 14, 91, 92 Intramuscular, 92, 96 Intravenous, 92, 96 Intrinsic, 79, 92 Invasive, 90, 92 K Kb, 60, 92 L Labile, 83, 92 Large Intestine, 85, 92, 99 Lesion, 27, 45, 92, 100 Lethal, 6, 12, 16, 22, 92
Leukemia, 89, 92 Leukocytes, 82, 83, 92 Library Services, 74, 92 Liver, 85, 86, 88, 92 Local Government, 18, 92 Localized, 87, 91, 92, 96 Lymph, 9, 17, 32, 90, 92, 93 Lymph node, 9, 92, 93 Lymphadenopathy, 17, 93 Lymphatic, 91, 92, 93, 101 Lymphatic system, 92, 93, 101 Lymphocyte, 8, 15, 24, 25, 80, 93 Lymphocyte Subsets, 25, 93 Lymphoid, 9, 80, 93 Lymphoma, 89, 93 Lymphoproliferative, 4, 93 Lytic, 16, 93, 99 M Major Histocompatibility Complex, 89, 93 Malaria, 6, 13, 93 Malaria, Falciparum, 93 Malaria, Vivax, 93 Manifest, 25, 93 Measles Virus, 30, 36, 93 Mediate, 16, 93 MEDLINE, 61, 93 Membrane, 82, 83, 84, 94, 95, 102 Memory, 5, 8, 9, 15, 20, 23, 26, 27, 94 Mental, iv, 3, 48, 60, 62, 83, 85, 94, 98 Mental Disorders, 48, 94, 98 Mental Health, iv, 3, 48, 60, 62, 94, 98 Mercury, 87, 94 MI, 77, 94 Microbe, 94, 101 Microorganism, 94, 96, 103 Migration, 9, 94 Molecular, 3, 4, 11, 15, 17, 21, 26, 27, 61, 63, 81, 83, 94 Molecule, 80, 81, 83, 85, 86, 87, 94, 96, 97, 99, 102 Monitor, 6, 94 Monoclonal, 7, 10, 14, 16, 18, 20, 94, 98 Monoclonal antibodies, 7, 10, 16, 20, 94 Mononuclear, 16, 94 Morbillivirus, 93, 94, 99 Myalgia, 91, 94 Myocarditis, 21, 33, 95 Myocardium, 94, 95 N Naive, 7, 9, 15, 17, 25, 26, 27, 45, 95 Nasal Mucosa, 91, 95 NCI, 1, 47, 59, 95
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Necrosis, 91, 94, 95 Need, 4, 16, 20, 22, 24, 26, 42, 49, 53, 69, 95 Neoplasms, 89, 95 Nerve, 83, 84, 95, 100 Networks, 15, 18, 95 Neural, 15, 90, 95 Neutralization, 5, 14, 27, 95 Nitrogen, 87, 95 Nucleic acid, 25, 88, 95 Nucleus, 84, 94, 95 O Ocular, 36, 95 Ophthalmology, 87, 95 Organ Culture, 95, 101 Orthopoxvirus, 20, 21, 25, 84, 85, 95, 102 Oxidation, 79, 96 P Palliative, 96, 101 Pancreas, 81, 85, 96, 102 Papilla, 96 Papillary, 9, 96 Parenteral, 7, 9, 96 Particle, 20, 96 Pathogen, 5, 11, 18, 92, 96 Pathogenesis, 7, 10, 18, 19, 20, 23, 96 Patient Education, 66, 72, 74, 77, 96 Peptide, 5, 15, 23, 96, 98 Percutaneous, 28, 30, 96 Peripheral blood, 16, 24, 25, 27, 89, 92, 96 Phallic, 87, 96 Pharmacologic, 89, 96, 101 Pharynx, 91, 96 Phenotype, 15, 96 Phocomelia, 85, 96 Physical Examination, 44, 96 Physiologic, 89, 96, 99 Plague, 96, 102 Plants, 81, 82, 96, 100, 102 Plasma, 14, 80, 82, 89, 97, 103 Plasma cells, 80, 97 Plasmid, 12, 19, 97, 102 Policy Making, 88, 97 Polychromatic, 25, 97 Polymorphism, 15, 97 Polysaccharide, 80, 97 Practice Guidelines, 62, 66, 97 Precursor, 86, 97 Prevalence, 27, 86, 97 Primary vaccination, 6, 15, 32, 97 Progression, 80, 97 Progressive, 23, 24, 89, 95, 97, 99 Projection, 84, 97
Prophylaxis, 16, 18, 97, 102 Prospective study, 17, 97 Prostate, 81, 97, 102 Protein C, 79, 83, 97 Protein S, 81, 88, 98, 99 Proteins, 5, 16, 17, 19, 22, 79, 80, 82, 83, 94, 95, 96, 97, 98, 99, 100, 101 Proteolytic, 83, 98 Pruritic, 85, 98 Psychiatry, 87, 98 Psychic, 94, 98 Public Health, 7, 10, 23, 39, 62, 67, 98 Public Policy, 61, 98 Publishing, 28, 98 Pulmonary, 6, 24, 82, 98, 103 Pulse, 12, 94, 98 Purpura, 40, 98 R Race, 94, 98 Radiation, 88, 90, 98 Radiation therapy, 88, 98 Radioactive, 89, 90, 94, 98 Radiological, 96, 98 Radiopharmaceutical, 88, 98 Randomized, 86, 99 Receptor, 14, 80, 99 Recombinant, 4, 5, 6, 11, 16, 21, 24, 99, 102 Recombinant Proteins, 5, 99 Rectum, 82, 85, 88, 92, 97, 99 Refer, 1, 83, 87, 89, 95, 99 Reference Values, 27, 99 Regimen, 86, 99 Renal failure, 89, 99 Replicon, 20, 99 Research Design, 14, 24, 99 Respiration, 82, 94, 99 Ribosome, 99, 102 Rinderpest, 4, 99 Risk factor, 14, 97, 99 Risk patient, 5, 99 Rod, 81, 99 S Salivary, 85, 99 Salivary glands, 85, 99 Screening, 12, 14, 83, 99 Sebaceous, 85, 99 Sebaceous gland, 85, 99 Sepsis, 7, 10, 99 Serologic, 32, 99 Serum, 27, 80, 83, 90, 99, 100 Shedding, 8, 17, 24, 100, 103 Shock, 89, 100
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Side effect, 13, 14, 23, 44, 45, 53, 54, 79, 100, 101 Skull, 100, 101 Smallpox, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 43, 44, 45, 46, 49, 51, 52, 53, 54, 66, 67, 68 Sneezing, 100 Solvent, 15, 100 Somatic, 90, 100 Specialist, 69, 100 Species, 79, 81, 82, 84, 85, 87, 89, 93, 94, 95, 98, 100, 101, 102, 103 Specificity, 4, 16, 17, 79, 100 Spinal cord, 86, 100 Spinous, 86, 100 Spores, 92, 100 Stem cell transplantation, 4, 89, 100 Stem Cells, 89, 100 Stimulus, 87, 91, 100 Stomach, 85, 87, 96, 100 Stroke, 48, 60, 100 Subacute, 91, 99, 101 Subclinical, 91, 101 Subcutaneous, 33, 96, 101 Subspecies, 100, 101, 102 Suction, 87, 101 Sweat, 85, 101 Sweat Glands, 85, 101 Synergistic, 8, 101 Systemic, 6, 36, 82, 91, 98, 101, 102 T Technology Transfer, 18, 101 Temporal, 21, 101 Terminator, 83, 101 Therapeutics, 6, 7, 10, 13, 18, 25, 101 Thrombosis, 98, 100, 101 Thymus, 90, 93, 101 Tissue, 9, 17, 19, 80, 81, 82, 83, 84, 86, 88, 89, 90, 92, 93, 94, 95, 96, 99, 100, 101, 102 Tissue Culture, 17, 19, 101 Toxic, iv, 84, 86, 90, 101, 102 Toxicity, 6, 94, 101 Toxicology, 6, 62, 101 Toxins, 18, 80, 81, 86, 91, 94, 101
Toxoid, 24, 102 Transfection, 81, 102 Transfer Factor, 90, 102 Translation, 8, 102 Translational, 8, 18, 24, 102 Transplantation, 90, 93, 102 Tularemia, 7, 10, 102 Tumor marker, 81, 102 U Ulceration, 99, 102 Unconscious, 84, 90, 102 Urethra, 97, 102 Urine, 44, 81, 102 V Vaccine, ii, iv, 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 49, 51, 52, 53, 54, 55, 62, 65, 66, 67, 68, 69, 79, 97, 102 Vaccinia Virus, 4, 6, 7, 8, 10, 13, 16, 17, 20, 21, 22, 23, 26, 28, 31, 43, 102 Variola, 4, 5, 7, 9, 10, 12, 13, 20, 22, 102 Variola Virus, 4, 10, 13, 20, 22, 102 Vascular, 85, 90, 91, 102 Vector, 7, 9, 102 Veins, 82, 103 Venous, 14, 98, 103 Ventricle, 98, 103 Vesicular, 90, 100, 102, 103 Veterinary Medicine, 61, 103 Viral, 4, 5, 6, 8, 11, 15, 17, 18, 19, 21, 24, 25, 26, 27, 86, 91, 99, 103 Viral Load, 5, 15, 103 Virulence, 4, 19, 81, 101, 103 Virus Shedding, 8, 103 Vitro, 20, 103 Vivo, 19, 103 W Warts, 41, 103 White blood cell, 80, 92, 93, 97, 103 X Xenograft, 80, 103 Y Yeasts, 96, 103
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Smallpox vaccine
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Smallpox vaccine
