Author Mark S. Gold presents the latest medical information on nicotine and tobacco's neurobiological, physiological, and psychological effects. This timely monograph also discusses the latest diagnostic and treatment programs as well as model programs for use by practitioners which were developed by the National Cancer Institute and other eminent organizations. The author also includes a comprehensive history of tobacco use.

In this introductory textbook to epidemiology, students will discover the knowledge and skills required for managing population-based health care under health reform. Fundamental epidemiological techniques are presented teaching students to assess the health status of populations served; determine appropriate interventions based upon knowledge of factors which affect health status; and evaluate the impact of health care systems, programs, technologies, and policies on the health status of populations. Each chapter includes case studies and discussion questions.

Advances in DNA sequencing and phylogenetic inference have created powerful methods to investigate many dangerous human viruses. The Molecular Epidemiology Of Viruses provides a comprehensive introduction to the use of genetic methods in molecular epidemiology and in-depth examples of analyses from many viruses. This book is of interest to researchers in the fields of infectious disease, virology, microbiology, evolutionary biology, epidemiology and molecular biology as well as anyone interested in tracking the spread of disease.

Despite its universality in human female aging, the menopause and its biology are not completely understood. New biologic mechanisms by which sex hormones may be detrimental or confer protection are continually being discovered. We are now starting to understand that the role of the estrogen receptor is not identical in all tissues. Important nongenomic effects for sex hormones have also been described. Hormone replacement therapy (HRT) has produced effects on health risks: some are reduced, some are increased, and the rest remain uncertain. HRT is being used by an increasing number of women to alleviate climacteric symptoms in the perimenopausal period and to prevent osteoporosis and cardiovascular disease later. Positive effects on Alzheimer's disease and dementia on the one hand, and an increase in venous thrombosis on the other, are currently being reported by several groups. Both the preventive benefits and the risk of breast cancer seem to be linked to long-term and current use. HRT requires further testing through specific clinical trials, currently underway in the United States, before confident recommendations may be made about the full range of benefits and risks.

Human reproduction is the most dynamic of processes. The events which lead to the birth of a normal healthy infant have their origin long before actual fertilization. Indeed, the whole process can be looked upon as a continuum. Human fertilization and early development, once sequestered in the protective environment of the fallopian tubes and uterus, have now been exposed in the laboratory. These events have, over time, been extensively observed and catalogued in animal models. The tools of modem morphology and molecular biology have reopened issues long since considered settled as facets of early reproduction are reexplored. This volume, consisting of the proceedings of a workshop on uterine and embryonic factors in early pregnancy, has been designed to enhance that effort. Attention is focused largely on early embryonal development with special attention to the interrelationship between the embryo and the uterus in early pregnancy. Each of the contributing scientists brings with him or her the perspective of one specific discipline or another. The common denominator is the application of emerging techniques in modem molecular biology to problems pertaining to embryonal-uterine interaction. The goal is to consider specific areas of concern in a multidisciplinary way and to reexplore the factors behind early development and implantation. Uterine complement, the function of uterine macrophages immunoregulatory loops in the peri-implantation period, colony stimulating factors and interferon-like factors are reviewed and their interrelationship explored. Uterine angiogenesis factors as well as embryonic growth factors are also considered.

The Frontiers in Cardiovascular Health varies between and within nations, depend ing upon the level at which the battle is fought for better cardiovascular health. According to the 1997 World Health Report, 15 million deaths (i. e. 30% of the total number of deaths) were attributable to cardiovascular diseases and this number is on the rise. The projection for the year 2020 is quite alarming with an expected cardiovascular mortality reaching 50 million. Much of this burden is projected to occur in developing countries, more specifically in the most populous countries of the world, namely China and India. These countries are already burdened with infectious and parasitic diseases and are trying to eradicate such diseases. With increasing life expectancies people all over the world, especially in developing coun tries, are exposed to degenerative atherosclerosis resulting in increased cardiovascu lar mortality and morbidity. In developing countries, resources available for health care are very limited. For example many of the African countries spend less than $10 per person per year on his/her entire health care let alone cardiovascular health. The average health care budget for nearly two thirds of the global population is well below $100 per year, on a per capita basis. Therefore, in developing countries health promotion and primary prevention are the frontiers by necessity. Improving awareness and health education is not only a matter of choice but is an absolute necessity.

Salmonella infections of man and animals continue to be a distressing health problem worldwide. Far from disappearing, the incidence of typhoid fever in developing countries may be far higher than we had imagined. Salmonella food poisoning has increased to one of the major causes of gastroenteritis in the developed world, in itself also an indication that animal salmonellosis is still a major cause for concern. The situation requires a concerted multidisciplinary research effort in order to generate the new information and technology needed to assist in the control of these diseases. This concept was the driving force behind the NATO Advanced Research Workshop on "Biology of Salmonella" held at Portorosa, Messina, Italy, May 11-15, 1992. With additional support from the University of Messina, Medeva Group Research (UK) and the Swiss Serum and Vaccine Research Institute, the meeting brought together epidemiologists, microbiologists, molecular biologists, immunologists and clinicians. All the participants were actively working on different but related aspects of Salmonella and salmonellosis, with most of the leading laboratories worldwide being represented. The workshop provided an excellent opportunity for interdisciplinary consultation; it is not often that the topic of Salmonella and salmonellosis is covered to such breadth and depth in one extended meeting. Keynote addresses by invited speakers were interspersed with offered papers, many by younger members of the scientific community, and this volume presents the collated manuscripts of the lectures and extended summaries of the offered papers.

The papers assembled in this collection comprise a majority of the oral presentations as well as several poster presentations given at the 22nd Annual Symposium arranged by the Bastern Pennsylvania Branch of the American Society for MicrobioloS)'. The symposium would not be possible without the generous support of the many sponsors (see sponsor list) or without the concerted effort of a11 the Committee members. This Symposium series has evolved into an annual Bastern Pennsylvania Branch ASM event that attracts participants from a wide geographie area. It should be noted that one of the hallmarks of these symposia involves interaction between the presenters and those in attendance. Several authors have altered their by the participants. Therefore, the manuscript that manuscripts based on comments fo11ows should be viewed as a group effort of both the participants and presenters. J ames Poupard Lori Walsh Bruee Kleger ix CONTENTS 1 Introduction 1: CURRENT METHODS The Evolution of Antimicrobial Susceptibility Testing Methods . . . . . . . . . . . . . . . 3 James A. Poupard, Stephen F. Rittenhouse, and Lori R. Walsh Antimicrobial Susceptibility Tests: Testing Methods and Interpretive Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Patrick R. Murray Clinician Utilization of Rapid Antibiotic Susceptibility Data: A Prospective Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Franklin P. Koontz SESSION 2: CONTEMPORARY ISSUES IN SUSCEPTIBILITY TESTING When We Should Be Testing, How Often and What to Report . . . . . . . . . . . . . . . 35 Raymond C. Bartlett Areas of Recent Emphasis of the National Committee for Clinical Laboratory Standards Subcommittee on Antimicrobial Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . 61 James H. Jorgensen Non-Traditional Approaches for Quality Control of Antimicrobial Susceptibility Tests . . . . . . . . . . . . . . . . . . . . . . . . .

It is nearly a decade since the first Male Mediated Developmental Toxicity conference was held in Pittsburgh. The continuing public/scientific interest, growing amounts of animal data, introduction of innovative technologies, and increasing quantity of human epidemiological studies all suggest that male-mediated developmental toxicity is of major concern. A number of researchers concluded that a Second International Confer- ence on Male Mediated Developmental Toxicity was necessary. The ensuing volume is particularly timely because it impacts on areas of special emphasis in many countries, with respect to children's and reproductive health, as well as to basic molecular mecha- nisms of environmental insult, and genetic susceptibility and predisposition. The Programme and Local Organizing Committee, composed of Barbara Hales (Chair, McGill University), BernardRobaire (McGill University), Daniel G. Cyr (INRS/ Armand Frappier), Jacquetta M. Trasler (McGill University), Andrew F. Olshan (Uni- versity of North Carolina), Sally Perreault Damey (US EPA), Donald R. Mattison (March of Dimes), and Jan M. Friedman (University of British Columbia), spent over two years identifying individuals who had made key contributions in this field over the past decade and planning various aspects of the meeting. The meeting was held in Montreal in June 2001. A total of 132 persons, coming from five continents and representing some 18countries, took an active role in the proceedings. The conference was considered by all attendees to be a rousing success. Important discussions were held in the four break-out sessions, with a preliminary set of recommendations for action being presented by each panel.

Biometrics in dermatology is an essential tool where data evaluation results in valid interpretations. This book will be the first in this area. One part of the book will describe principal aspects of dermatological research focussing on practical advice. A special part will cover applied biometrics to provide the clinician and researcher with state-of-the-art guidelines to assess the severity of common skin diseases. An additional aspect that will be of interest to pharmacologists addresses pharmacologic assays.

It is remarkable that each month the quantity ofarticles published on AIDS still that address numbers in the thousands. The basic, clinical and sociological aspects this epidemic have been vigorously investigated, and equally as extensively reported in traditional as well as new journals. Therefore, what can the reader ofthis volume expect to find that is different from the information already found in the literature? The authors of this text met in October 1993 to discuss not only AIDS and its effects on the nervous system but also to address the problem from the point of view of the diverse technologies that are used in understanding the disease. Just as the recog nition ofoncogenic viruses gave us insights into cellular genes that govern growth, the study ofHIV-I in the nervous system has opened new areas ofinvestigation in the nervous system. Use of human fetal and glioma-derived cell cultures, discovery of toxins in the nervous system, release and damage of cytokines in the brain, the neuropathic effects of HIV proteins, the investigation of new treatment for neuro AIDS, and virus detection strategies to identify latent HIVI infection are described in this volume. Basic and clinical investigators from more than thirty laboratories around the world contributed to the ideas discussed at the meeting, "Technical Advances in AIDS Research in the Human Nervous System."

This IMA Volume in Mathematics and its Applications MATHEMATICAL APPROACHES FOR EMERGING AND REEMERGING INFECTIOUS DISEASES: MODELS, AND THEORY METHODS is based on the proceedings of a successful one week workshop. The pro ceedings of the two-day tutorial which preceded the workshop "Introduction to Epidemiology and Immunology" appears as IMA Volume 125: Math ematical Approaches for Emerging and Reemerging Infectious Diseases: An Introduction. The tutorial and the workshop are integral parts of the September 1998 to June 1999 IMA program on "MATHEMATICS IN BI OLOGY. " I would like to thank Carlos Castillo-Chavez (Director of the Math ematical and Theoretical Biology Institute and a member of the Depart ments of Biometrics, Statistics and Theoretical and Applied Mechanics, Cornell University), Sally M. Blower (Biomathematics, UCLA School of Medicine), Pauline van den Driessche (Mathematics and Statistics, Uni versity of Victoria), and Denise Kirschner (Microbiology and Immunology, University of Michigan Medical School) for their superb roles as organizers of the meetings and editors of the proceedings. Carlos Castillo-Chavez, es pecially, made a major contribution by spearheading the editing process. I am also grateful to Kenneth L. Cooke (Mathematics, Pomona College), for being one of the workshop organizers and to Abdul-Aziz Yakubu (Mathe matics, Howard University) for serving as co-editor of the proceedings. I thank Simon A. Levin (Ecology and Evolutionary Biology, Princeton Uni versity) for providing an introduction.

This volume is based on the program of the Second International Conference on Drugs of Abuse, Immunity and AIDS, held in Clearwater Beach, FL in June 1992. The Conference was supported in part by the University of South Florida College of MediCine with financial assistance from the National Institute on Drug Abuse. The focus of this conference was the effects of drugs of abuse on immunity. It is now widely recognized that psychoactive drugs of abuse, including marijuana, cocaine, and opiates, as well as alcohol, have marked effects in an individual, including effects on their nervous system and behavior. In the past two decades, the scope of studies concerning the effects of some drugs of abuse have also involved investigations of alterations of various physiologic parameters including effects on the immune system. and the influence of such immune alterations on normal physiological responses. In this regard, participants in this Second International Conference provided newer information concerning both basic and clinical aspects of drugs of abuse and immunity, especially immunodeficiencies. In this regard, advances have been made in recent years concerning the nature and mechanisms whereby the immune system is regulated and the possible mechanisms by which drugs of abuse influence such immune systems. In particular, the emergence of psychoneuroimmunology as a new discipline the last decade has heightened interest in the immune responses influenced by psychoactive drugs. This has resulted in interdisciplinary investigations involving both clinical and basic scientists, including microbiologists, immunologists, physiologists, psychiatrists, oncologists, psychologists, etc.

Pharmacokinetic variability of contraceptive steroids is a relatively under-explored area of contraceptive research, and hardly a common point of discussion among those who plan and deliver family planning services. Nevertheless, numerous independent studies over the last 15 years have indicated that women in different regions of the world vary in their pharmacokinetic response to contraceptive steroids. The causes of such variability are not known, but it has important consequences for contraceptive effectiveness. It may also offer insight to the basis of contraceptive side-effects. The impetus for this volume was to collect documentation of pharmacokinetic variability of contraceptive steroids, and to explore both the possible causes and implications of these data. Factors known to affect steroid pharmacokinetics, such as concurrent use of specific medications, are reviewed by Back and Orme. Other factors known to affect endogenous steroid dynamics are presented in chapters by Bradlow, Longcope, Goldin and Snow, because of their possible role in contraceptive steroid pharmacokinetics.

Generation of oxidants or reactive oxygen species is a natural process of human biology. Mitochondrial respiration, phagocytic activity and cyclooxygenase activation are all essential processes of life, which also generate oxidative species. In humans, chronic oxidative stress often coupled with deficiency of antioxidant defenses is associated with the aging process and can lead to the development of disorders such as cancer and arterial disease. Major cardiovascular conditions in which oxidative damage has been strongly implicated include atherosclerosis, myocardial ischemia and reperfusion, coronary restenosis and congestive heart failure. Compelling evidence points to oxidative stress as an important trigger in the complex chain of events leading to atherosclerosis. The expression of chemotactic factors and adhesion molecules is modified by oxidative stress. Exposure to superoxide ions activates the NF-kappa B regulatory complex and triggers the transcription of several atherosclerosis related genes. These events lead to the accumulation of macrophages in the arterial wall. Macrophages avidly incorporate oxidized low-density lipoproteins (LDL) to form foam cells. The activity of matrix metalloproteinases is also regulated by oxidative stress. This activity appears to be closely coupled with smooth muscle cell activation and migration. Matrix metalloproteinases have also been implicated in the pathophysiology of plaque rupture. Antioxidant supplementation including vitamin E decreases susceptibility ofLDL to oxidation and retards the progression of atherosclerosis in animal models.

Recent Developments in Graves' Ophthalmopathy offers an overview of the pathogenesis, assessment and management of patients with thyroid-associated eye disease. Each chapter is written by an expert and truly represents the current state of the art on the particular topic. This book can therefore almost be considered a textbook on this enigmatic disorder. Recent Developments in Graves' Ophthalmopathy is designed for all those interested in this disease, including basic scientists, clinical endocrinologists, ophthalmologists, radiotherapists, and orbital surgeons. The book gives a comprehensive overview of all aspects of Graves' ophthalmopathy. Subjects covered include the pathology of Graves' eye disease and the controversial views on its autoimmune pathogenesis; assessment of the eye changes using reliable measurements; medical management of Graves' eye disease with an overview of the many treatment options available to the clinician, including orbital radiotherapy and other immunosuppressive treatments; management of the thyroid disease; and finally, the techniques for performing various surgical procedures, which are explained and illustrated.

Distinguished contributors analyze the problem of homelessness from a clinical perspective, focusing on the major health problems found among the homeless, special populations within the homeless, and strategies for improvement and change.

Based on findings from a sample of nearly 1,100 Puerto Ricans living in the New York area, this book posits that adhering to traditional cultural values (for example, the family) has the socially desirable consequence of discouraging such deviant behaviors as substance abuse. The authors conclude that promoting specific values will not prevent certain individual and social ills; rather, promoting a 'sense of tradition' itself is needed.

When an accident involves many people and when its consequences are many and serious, we speak of a disaster. Disasters have the same causal fac tors as accidents: they differ from accidents by the gravity of consequences, not by causes. The action of a single individual may result in thousands of deaths and huge financial losses. The metal fatigue of a screw may, by a chain of events, cause an explosion killing hundreds or lead to a break in a dam and a devastating flood. The fact that minor and unpredictable acts can lead to disasters is im portant because it allows us to predict that the years to come will bring with them more disasters with ever more severe consequences. The density ofhu man populations is growing. By the year 2025 some four fifths of the world's population will be living in urban settings. An explosion or a gas leak in a densely populated area will cause incomparably more damage than a simi lar event in a rural area. Modern technology is immensely powerful (and its power is continuing to grow) and can be used in a disastrous manner. Ag gression is just as possible now as it was in the past, but the tools of aggression are vastly more dangerous than ever before. This book, edited by Johan M. Havenaar, Julie G. Cwikel, and Evelyn J. Bromet, is therefore very timely.

The papers contained in this volume were presented ati the Golden Jubilee Cancer Prevention Conference, "The Biology and Prevention of Aerodigestive Tract Cancers," sponsored by The University of Texas M. D. Anderson Cancer Center in Houston, Texas, February 21-23, 1991. The purpose of the conference was to further the understanding of the biology, epidemiology, and prevention of aerodigestive tract cancers. Advances in under standing the biology of aerodigestive tract cancers have led to successful early chemoprevention trials. Chemopreventive agents in current use are capable 9f reversing premalignant lesions, as well as reducing the number of second primary cancers of the head and neck. These trials hold the promise that effective prevention methods for these cancers will be forthcoming in the foreseeable future. Carcinogenic exposures appear to affect the entiry epithelial lining of the upper aerodigestive tract, a phenomena described as "field cancerization. " This process contributes to the development of both synchronous and metachronous aerodigestive tract cancers. It also provides a sound rationale for the chemoprevention of these cancers. Animal models are important for identifying the critical components of field cancerization and for testing potentially new chemopreventive agents and regimens. The hamster lung carcinogen esis model and the hamster cheek model are discussed. Aerodigestive tract cancers account for about 20% of newly diagnosed invasive cancers. Cigarette smoking and alcohol consumption are the most important risk factors for these cancers."

Until recently, studies of women's health received scant research attention in the context of the overall magnitude of research conducted on health. Even for health issues that affect both men and women, most research has been limited to male subjects, leaving a large gap in our knowledge base concerning women's health. Finally, the decade of the 1990s is ushering in a shift in this inequity. In 1990 the U.S. National Institutes of Health issued a compelling report citing the lack of sufficient research on women's health as a major gap in our knowledge, and a mandate has been issued to add women as study subjects in research or to document why they have not been included. Such directives will undoubtedly lead to a much-needed burgeoning of research activities in the area of women's health as we approach the twenty-first century. Despite limited research resources, however, there have been steady, scientifically rigorous voices in the wilderness for the last several years, and many of the best investigators are represented in this volume. These workers have led the vanguard in exploring psychosocial factors that are likely to differentially affect women's and men's health. For example, women and men engage in social roles that often differ, if not in quantity, then certainly in quality. Sex differences in role expectations, environmen tal qualities, role burdens related to the domains of work and family, and abilities to adapt to and cope with stressful situations may have a distinctive impact on health."

Seer, forecaster, prophet, geomancer, or tout - all predict future events as physicians must. The medical activity is prognosis from the Greek pro (forward) and gnosis (special knowledgeL thus foreknowledge, and the practitioner is the prognosticator, a sobriquet which falls unhappily upon the ear. Like it or not, there is nothing more critical in the management of chronic rheumatic conditions than a reasonably clear picture of what time and disease will bring. The knowledge is so much a part of ordinary medical thinking that we rarely grace it with the label prognosis. But, like so much of "ordinary medical thinking" (an oxymoron, perhaps), quantitative data are very thin and the chestnuts of personal observation and authority figure assertion loom large. Unlike several books I have seen or written, this one on prognosis needs no justification. The entirety of a person's life contributes to and confounds what the future holds. The ingredients include education levet income, support structures such as family, housing, occupation, availability of medical services, diagnosis, treatment, rate of disease progression, age, gender, race, marital status, and others too numerous to mention or too arcane to be recognized. One would think the task of estimating prognosis impossible. And yet there is light on the horizon -we do know a few things such as the effect of high rheumatoid factor titers on the prognosis of RA or the likely outcome of certain kidney lesions in SLE.

Few topics in women's medicine today are as fraught with confusion and controversy as the question of appropriate treatment for menopausal symptoms and the prevention of negative long term health outcomes common to post-menopausal women. Cardiovascular disease (CVD), osteoporosis, and cancer -- the most common causes of death, disability and impaired quality of life for women -- can potentially be prevented or forestalled by dietary, behavioral, and drug interventions. A better understanding of the natural history of the menopause is critical to providing better care. If women and their physicians have a better understanding of predictors of risk, they could make more informed decisions about interventions related to menopausal symptoms, CVD, osteoporosis and gynecologic and breast cancer. Few other recently introduced medical interventions have as great a potential of affecting morbidity and mortality as does hormone replacement therapy (HRT). HRT has produced effect on health risk: some are reduced, some are raised, and some uncertain, and these data are interpreted differently by various scientific, medical and consumer groups.

Statistical methods are becoming more important in all biological fields of study. Biometry deals with the application of mathematical techniques to the quantitative study of varying characteristics of organisms, populations, species, etc. This book uses examples based on genuine data carefully chosen by the author for their special biological significance. The chapters cover a broad spectrum of topics and bridge the gap between introductory biological statistics and advanced approaches such as multivariate techniques and nonlinear models. A set of statistical tables most frequently used in biometry completes the book.

'Each topic is covered in sufficient depth, currency, and clarity to be of value to the neophyte and the seasoned researcher/clinician.' --- American Journal of Psychiatry, from a review of a previous volume The current volume addresses a range of issues across this diverse field, including the effects on society, physiology and biochemistry, clinical pathology, and trends in treatment.