Alcohol abuse is this culture's most important drug problem. Statistics indicate that it is exacting a great and relentlessly increasing toll of human suffering. It is clear that the problem is not being dealt with in any effective manner. At the invitation of the. Canadian Hepatic Foundation, many of the world's experts gathered in Toronto, May 14-15 1976, to focus attention on one of the most important aspects of the alcohol problem -alcohol induced liver damage. The epidemiology of alcohol induced liver disease was discussed and current views on the pathogenesis of the problem were reviewed. New insight into the pathological alterations of the liver was presented and some of our current therapeutic capabilities were discussed. Dr. Hans Popper summarized the Symposium and presented some of his views on those aspects of the problem which will require early attention by the research community. The Symposium achieved its immediate objective -that of bringing together the committed experts of various disciplines for an updating of our understanding of alcohol and the liver and for a discussion of new approaches to the problem. As a backdrop to the Symposium, however, was large writing on the wall to the effect that we are expending our research talents and efforts on a totally unnecessary problem. Right now we probably know enough and have sufficient resources at our disposal to solve the problem.

Human Health: The Contribution of Microorganisms is the first major work to concentrate on probiotics in humans. It presents both new and established data on the origins and importance of commensal floras, the history and characteristics of probiotics, the use of probiotics in clinical situations, and preclinical and volunteer studies. It also covers commercial issues such as the difficulties involved in the large scale production and formulation of live microorganisms, and the marketing techniques used to sell products containing bacteria. It contains contributions from internationally recognised experts in both science and industry. Written with both professional and lay audiences in mind, Human Health: The Contribution of Microorganisms will be an indispensable text and reference source for scientists, clinicians, and pharmaceutical/food technologists.

This book assumes that it is no longer tenable to work in healthcare without considering the person as a whole being constituted by a rich weaving of mind, body, culture, family, spirit and ecology. The MindBody approach embraces this "whole." But how does it transform clinical practice and training for the clinician and treatment for the patient/client? The book collects together the experiences from a diverse range of clinical practitioners (including psychotherapy, specialist medicine, general practice, physiotherapy, occupational therapy, dietetics, nursing, and complementary and alternative medicine practitioners) who have deliberately chosen to integrate a MindBody philosophy and skill set in their clinical practices. All reflect deeply on their unique journeys in transforming their clinical encounters. Most have been trained in the dominant Western framework and have inherited the classical dualistic approach which typically keeps mind and body apart. This dualistic clinical ethos values clinician expertise, labeling, diagnosis, measurement, and grouped phenomena. The MindBody approach retains the best of the classical model as well as valuing personal experience, patient/client story, the unique patterning of the individual s illness and disease, and the healing elements of the relationship between the clinician and the patient/client. The MindBody transformation of the clinician is a challenging journey, and each clinician experiences this uniquely. From these stories the reader can see vividly the ways in which conventional healthcare can break out of its current restrictive paradigm creating new satisfaction for the clinicians and much wider treatment outcomes for patients and clients."

This volume contains the proceedings of a symposium held in Marseille on April 6, 1992, on the topic "Heterogeneity of Alzheimer's disease. " This was the eighth of a continuing and very successful series of meetings related to Alzheimer's disease organized by the Fondation Ipsen pour la Recherche Therapeutique. These symposia, known as "Colloques medecine et recherche," started in 1987 and have dealt with widely different aspects of the disease such as immunology, genetics, neuronal grafting, biological markers, imaging, growth factors, and last year's less conventional topic of Neurophilo- sophy and Alzheimer's disease. The next IPSEN symposium dedicatet to Alz- heimer's disease will take place in Lyon on June 21, 1993, and will deal with "Amyloid protein precursors in development, aging, and alzheimer's disease. " It is being organized by Konrad Beyreuther, Colin Masters, Marc Trillet, and Yves Christen. Until a few years ago, several names were used to refer to the most common cause of dementia in the elderly. They included such terms as "senile psycho- sis," "organic brain syndrome," and "senile dementia. " Following Kraepelin, the term "Alzheimer's disease" was often restricted to an uncommon condition starting at a younger age (before 60 or 65 years of age).

This book brings together a range of academic, industry and practitioner perspectives on translational medicine (TM). It enhances conceptual and practical understanding of the emergence and progress of the field and its potential impact on basic research, therapeutic development, and institutional infrastructure. In recognition of the various implications TM has for public health policy and commercial innovation, the book addresses the major systemic aspects of the field. The contributors explore the dynamic interactions and key challenges in translating new science into viable therapies for the clinic, which includes recognizing the importance of social, commercial, and regulatory environments in addition to good science.

LEADERSHIP IN VETERINARY MEDICINE Leadership in Veterinary Medicine provides both theoretical and practical information for veterinary professionals who are contemplating leadership or currently facing day-to-day leadership challenges. This much-needed book introduces and explores key leadership concepts in the veterinary context whilst encouraging self-reflection through real-world scenarios. Each chapter outlines a particular leadership concept or issue and includes a topic summary, discussion questions, full references and further reading suggestions. This thought-provoking text: Explores the principal areas of leadership for both veterinary professionals and for those leading veterinary professionals Discusses various leadership styles, competencies, behaviours and perspectives Addresses topics such as leadership assessment, organisational dynamics, interpersonal communication, remote and virtual leadership, and collaboration skills Assists readers in developing strategy, leading change, creating effective teams and improving staff engagement Includes practical cases and examples highlighting challenges in veterinary leadership Leadership in Veterinary Medicine is a must-read for all veterinary professionals in leadership posts, for those aspiring to be leaders and for instructors in veterinary schools and veterinary nursing training organisations.

It has been over 30 years since the first clinically important member of the quinolone class, nalidixic acid, was introduced into medical practice. The modification produced in the quinolone nucleus by introducing a fluorine at the 6-position led to the discovery of the newer fluoroquinolones with enhanced antibacterial activities as compared to nalidixic acid. By now a great deal of preclinical and clinical experience has been obtained with these agents. The intense interest in this class of antibacterial agents by chemists, micro biologists, toxicologists, pharmacologists, clinical pharmacologists, and clini cians in various disciplines encouraged us to summarize the information on the history, chemistry, mode of action and in vitro properties, kinetics and efficacy in animals, mechanisms of resistance, toxicity, clinical pharmacology, clinical experience, and future prospects in one volume of the Handbook of Experimental Pharmacology. As this series deals predominantly with "experimental" characteristics of drugs, our volume is dedicated specifically to quinolones and emphasizes principally their preclinical and clinical phar macological characteristics, despite the existence of several summaries on quinolones. The chemistry of the quinolones is described in detail. The chapter on the mode of action of quinolones reports the conclusive evidence that gyrase is the intracellular target of the quinolones; however, another enzyme, topoisomerase IV, may also be a target for quinolones, and the exact mechanisms by which quinolones act bactericidally are far from being understood."

As little as 30 years ago, cardiovascular research at Bayer was just a small sideline with in an environment dominated by chemotherapy research, and only 15 years ago, Bayer's pharmaceutical business was confined to European and Latin Ameri can countries, with sales in cardiovascular pharmaceuticals close to zero. It goes without saying that Adalat has changed the company as a whole in its research, development, and marketing, both in Germany and, most importantly, world wide. In research and development, Adalat has led the way in to new areas such as hypertension, acute neurology, dementia, atherosclerosis, and heart failure. In pharmacology, Adalat was present at the dawning of the second phar macological revolution, which started out from whole animal models and progres sed, via in vitro screening and pharmacological research on the DHP receptor, down to the molecular level with the cloning of calcium-channel proteins. Having followed the Adalat story closely in its early years as a bench scientist, let me take this opportunity to thank the inventors, the scientists, and the investigators who have helped to tap the broad potential of calcium-channel blockade with dihyd ropyridines in general and Adalat in particular. But, success should not obscure our vision. There is no reason for us to rest on our laurels: it will take true innovations in cardiovascular research to top the gold standard set by Adalat. Let us take up the challenge.

On the occasion of a symposium in Salzburg, an international team of clinicians and pharmacologists presented recent results in profile efficacy, safety and therapeutic use of the antibiotic substance Ciprofloxacin. Of special interest for clinicians will be the clinical outcome in patients with nosocomial pneumonia and other infections of the lower respiratory tract.

Free radicals appear to play a mojor role in many neurological (and non neurological) dieseases. Both acute and degenerative disorders are thought to involve free radicals reactions in tissue injury (for a list see this book page 18). This issue is very important for basic science and for therapeuthic approach as well. In order to review and discuss the place of free radicals in psychiatry and neurology, a joint meeting was initiated by the World Health Organization and the Fondation Ipsen in Paris on June 17-18,1991. This book contains the papers presented during this meeting. Although the papers included in this volume have been produced in the framework of WHO/Fondation Ipsen review of knowledge about free radicals and brain disorders, they express the views of the individual authors rather than a consensus of the participants at the meeting. They do not necessarily represent the decision or stated policy of the World Health Organiszation or the Fondation Ipsen. The editors wish to express their appreciation to Mrs Mervaillie for the organization of the meeting and Mrs M.-L. Gage for her editorial assis tance. L. Packer, L. Prilipko, Y Christen Contents Free Radical Scavengers and Antioxidants in Prophylaxy and Treatment of Brain Diseases L. Packer ........................................... 1 Reactive Oxygen Species and the Central Nervous System B. Halliwell .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 . . . . . . . . .

This book presents a unique collection of clinical cases to help combat the difficulty of diagnosis and treatment of Syncope. Medical professionals using this book are provided with a reference to a large array of succinctly described and illustrated clinical scenarios. Each case is presented with the results of appropriate tests and critical comments about the evaluation, diagnosis and treatment according to guidelines. Syncope is considered a difficult diagnostic and treatment problem for all who work in the field. Regardless of your prior knowledge, you will find the case studies easy to digest, enlightening, and immediately pertinent to improving the care patients - giving you confidence in your diagnosis and your advice. The editors have developed a lively and easy-to-read book with a focused expert editorial commentary, offering the reader a broader and easily understood context for each case, as well as key citations from the literature. Syncope Cases is a valuable contribution to your collection; edited by seven prominent authorities on the management of syncope from four countries, with more than 130 contributors, this book provides a unique additional step in the fostering of a better understanding of the many factors that can cause syncope, with the ultimate goal of facilitating the delivery of more precise and cost-effective care for syncope patients. It is a contribution that should be widely read, and one that offers the possibility of distinctly enhancing medical care of the syncope patient.

On the occasion of a research visit to Thailand in my capacity as a member of the governing board of the South Asia Institute of the University of Heidelberg, I saw for the first time the severe clinical picture of dengue with haemorrhagic symptoms among Thai children. This visit had been made possible by Profes sor Dr. med. Dr. rer. nat. Ouay Ketusinh of Bangkok, to whom I wish to express my sincere thanks in this place. In 1972 the German medical literature - the periodical Medizinische Klinik, vol. 87, pp. 152-56, to be precise - had drawn attention to this new phenomenon in the disease panorama of South East Asia, indicating a change in dengue fever from being a relatively benign tropical dis ease to a form having serious clinical and epidemiological ramifications. During the ten years following my first publication the new clinical picture, described as "dengue haemorrhagic fever," has become a standard component in the Thailand's system of notifiable diseases. So too, the World Health Orga nization publishes regular reports in its Weekly Records. On March 30/31, 1981, its Regional Office for South East Asia convened a special conference in New Delhi, thus emphasizing the significance of the diffusion of this new clini cal picture in the states of South East Asia."

Bronchoscopy means pictures: but to comprehend an image we have to learn to see. These excellent photographs, all taken by the author himself, not only instruct us in the art of seeing just about all there is to see in the bronchial system but also illustrate many relationships between visual appearances and the clinical situation. They go even further in correlating bronchoscopic find ings with the function of the lung. Treated in this way, the image comes alive. Anyone who has come to know DE KOCK as a brilliant clini cian, or who has worked with him in the lung function labo ratory - he has made important contributions in this field also would have expected him to produce a monograph of this calibre. Now we have such a book. It contains the selected results of many years' solid work. Due attention is, of course, also accorded the merits of the various bronchoscopic techniques which provide the essential background to satisfactory results. In writing this book DE KOCK has succeeded in projecting a vivid image of the bronchi and the functional lung into our mind's eye. This work undoubtedly opens new prospects in improved care of our patients.

Experimental gerontological research is necessary to obtain optimal information and thus ensure proper drug therapy for the elderly. Most older persons acquire multiple diseases, first of all chronic diseases. They involve complex problems of a physical, social, and psychological nature. The multimorbidity of the elderly raises many questions in drug therapy. By contrast with our extensive knowledge of pharmacokinetics and pharmacodynamics in younger age groups, few facts are available in respect of the elderly. A variety of factors may influence drug therapy. Physiological and pathological age-related changes of molecules, cells, organs, and the total organism may interact to enhance or inhibit drug therapy in higher age groups. It is well known that elderly patients are overmedicated and therefore the incidence of adverse drug reactions increases with age. Elderly patients with multimorbidity often have a diminished body clearance of drugs; age-related changes of the kidney seems to be one of the most important factors in this regard. Far less important than the elimination of drugs through the kidney is their excretion in the bile. So far results have disclosed that oxidative steps in drug clearance are more likely to be disturbed than phase II reactions. Furthermore; changes in distribution volume and age-related alterations in receptor sensitivity also influence the clearance of drugs in the elderly.

When I was about fifteen, my Biological Seiences teacher, Prof. N. Benacchio, lent me a book by Paul de Kruif "The Microbe Hunters" and I remained fascinated by infectious diseases. I was intrigued by the potency of virulent bacteria which are constantly trying to invade our bodies and often overcome what today we call innate and adoptive immunity. Indeed, shortly after that, I was struck by his tragic death due to peritonitis. Later, while studying medicine (although medical knowledge in the 1950s was almost primordial compared with today), I soon realised how the various biological systems were wonderfully organised but at the same time frail and how our life could end in a few minutes. Slowly it became obvious that our "wellness" was the result of a dynamic and very unstable equilibrium between health and disease. This unstable equilibrium could be broken forever if the body's response could not reverse the pathological state. I stuck a sort ofposter on the wall ofmy room with these three words and connecting arrows: HEALTH -? DISEASE -? DEATH As I don't believe in another world after death, it became obvious to me that we should make every possible effort not only to delay death, but to try always to shift the equilibrium to the left. In this book, I will try to show that this can be achieved, as a last resort, even with ozonetherapy.

Our aim in this volume, as in Volume I, HormonaI Correlates of Behavior: A Life Span View, has been to provide a critical assess ment of the state of behavioral endocrinology as weIl as the more usual summary of extant data. Each contributor was asked to probe the strengths and weaknesses of his area as candidly as possible. As aresult, we hope the reader will find this Volume useful as a reference source and as an honest evaluation of our present know ledge of the interaction between hormones and behavior. R. L. Sprott Bar Harbor, 1975 B. E. Eleftheriou v CONTRIBUTORS Robert Ader, Ph.D., Department of Psychiatry, University of Rochester Schoo1 of Medicine and Dentistry, Rochester, New York 14642. F. R. Brush, Ph.D., Experimental Psychology Laboratory, Syracuse University, Syracuse, New York 13210. Robert M. Benson, M.D., Pediatric Endocrine Clinic, Children's Medical and Surgical Center, The Johns Hopkins Hospital and University, Baltimore, Maryland 21205. John J. Christian, Sc.D., Department of Biological Sciences, Univer sity of New York at Binghamton, Binghamton, New York 13901. David A. Edwards, Ph.D., Department of Psychology, Emory University, Atlanta, Georgia 30304. Carl Eisdorfer, Ph.D., M.D., Department of Psychiatry and Behaviora1 Sciences, School of Medicine, University of Washington, Seattle, Washington 98101. Basil E. Eleftheriou, Ph.D., The Jackson Laboratory, Bar Harbor, Maine 04609. Merri11 F. Elias, Ph.D., Department of Psychology and All-University Gerontology Center, Syracuse University, Syracuse, New York 13210.

Clinical research represents an integration of many procedures from the social, biological, and natural sciences. Critical examination of the spectrum of medical inquiries will reveal the full gamut of research activities. Under standing the processes involved in the integration of these investigative and cognitive functions may lead to further advances in creative behavior. The purpose of this book is to formalize this process by identifying, collecting, and organizing the elements and issues involved. During the past thirty years, there have been significant advances in research methodology, many of them stimulated by multi-disciplinary collabo ration. The anticipated barriers to communication were not realized in prac tice. Scientists engaged in mutual problem-solving could accomplish more than their colleagues working in relative isolation. In the, r productive fashion, these multi-disciplinary teams, by pooling their knowledge sets and by devel oping communication mechanisms, created the interfaces between the clini cal, analytical, and communication sciences. These interfaces, while neither complete nor perfect, represent the methodology of interest in accomplishing the capture, evaluation, and utilization of information, or Information Process ing. The list of contributors to this methodology is virtually endless and we acknowledge their enormous and significant efforts."

PATIENT FLOW: Reducing Delay in Healthcare Delivery is dedicated to improving healthcare through reducing the delays experienced by patients. One aspect of this goal is to improve the flow of patients, so that they do not experience unnecessary waits as they flow through a healthcare system. Another aspect is ensuring that services are closely synchronized with patterns of patient demand. Still another aspect is ensuring that ancillary services, such as housekeeping and transportation, are fully coordinate with direct patient care. Past experience shows that effective management of healthcare delays can produce dramatic improvements in medical outcomes, patient satisfaction, and access to service, while also reducing the cost of healthcare. The 15 chapters of this book exposes the healthcare community of researchers, practitioners and administrators to a set of techniques and strategies that can be used by clinicians and administrators to substantially reduce delays in healthcare delivery. It is the first book treatment to have reduction in patient delay as its sole focus, and therefore, provides the foundation by which hospitals can implement change. Reflecting the highly interdisciplinary and practitioner nature of this book, the chapters have been written by doctors, nurses, industrial engineers, system engineers and geographers, and thus, these perspectives provide the comprehensive view needed to address the problem of patient delay.

The book provides a "hands-on" discussion and methods for solving a variety of problems that inhibit prompt and swift health care delivery. Some examples are:

• presents a set of breakthrough strategies that use "real-time" monitoring systems for continuous improvement;
• offers techniques for scheduling staff needs to match patterns in patient demand, and thus reduce predictable delays;
• utilizes simulation modeling techniques for both healthcare design and process improvement;
• provides methods for forecasting the demand for healthcare on a region-wide basis;
• presents queueing theory as a general method for modeling patient waits in healthcare;
• outlines rapid delivery of medication in the event of a catastrophic event, such as a pandemic or terrorist attack;
• demonstrates the importance of optimizing care as patients transition from one care setting to the next care setting with an emphasis on clinical outcomes and the business case;
• provides project management tools to guide the implementation of patient flow projects.

This book is the result of several years of enthusiastic planning and effort. Much of this enthusiasm came from the experience of devel{)ping Critical Care Consultant, a large BASIC program for critical care applications (St. Louis, C. V. Mosby, 1985). Working with clinicians showed me that many were interested in learning about clinical applications of computers (and even programming in small doses) but were faced with a paucity of clinical application software. Few had the time or training to develop any such software on their own. After a search through the existing medical literature unearthed relatively little in the way of usable programs, I decided that a series of small clinical applications programs would be of use to the medical community. At the onset a number of strategic decisions were made: (1) the programs would be written in BASIC, in view of its universal popularity, (2) the units used for clinical laboratory tests would be those in common use in the United States, (3) the programs would be simple and easily understood and employ no exotic tricks that were not easily transported across computers, (4) references to the literature would be provided to allow the clinician to critically assess the algorithm or method used himself or to follow up on subsequent criticisms that may have been published, and (5) the programs would demonstrate reasonable standards of software engineering in terms of clarity, trans portability, documentation, and ease of modification."

Prevention of disease and injury, including early identification of risks and disease and optimal control of potentially debilitating or fatal complications of chronic conditions, is the area of clinical medicine that holds the greatest promise for improving human health. Each year a long list of major, but potentially preventable health problems exacts a terrible human and financial toll. These problems urgently need our attention, especially as major advances in curative medicine become more complex and costly. Prevention of disease and injury may well be the central health issue of our time, an issue of vital concern to every quarter of our society. Now is a very good time to promote prevention. Citizens and some social groups are increasingly aware of and interested in health and fitness issues. There is great enthusiasm about-even obsession with-health, and we are seeing an astonishing proliferation of health publications and media presentations for laymen, fitness and weight control cen ters, exercise programs, health food stores, disease support groups, health education programs, and do-it-yourself diagnostic kits. All of this betokens an increased health consciousness on the part of public and perhaps signals greater individual accountability for health."

The primary purpose of this book is to bridge the gap be tween the practice of clinical medicine and diagnostic radi ology. It is intended primarily for utilization by medical students in training and by nonradiologist physicians. In this world of rapidly expanding knowledge in the many specialties of medicine, it is becoming increasingly difficult for many physicians to stay abreast of the newer and constantly changing modalities of diagnosis as well as the therapeutic regimens of the common as well as the less common disease processes within their realm of practice. This book will enable the busy clinician to utilize the consultative services offered by his or her colleagues in diagnostic radiology with maximum effectiveness. The most common clinical applications of the more recent imag ing modalities (i. e. , nuclear medicine, ultrasound, comput erized tomography, and magnetic resonance imaging) have been categorized and condensed into a format that will be both comprehensible and useful on a daily basis for those physicians routinely requesting these diagnostic examina tions for their patients. For simplicity, the book is divided, whenever feasible, into organ systems and subdivided into the multiple classifications of pathologic states (i. e. , con genital, trauma or iatrogenic, inflammatory, and neo plasm). In addition, there are brief comments related to the vii specific advantages and disadvantages as well as the cost effectiveness of each modality.

The Fifth World Congress of the International Society for Diseases of the Esophagus was held in the historic city of Kyoto, Japan, from August 5 through 8, 1992. Approximately 40 countries throughout the world participated and roughly 500 presentations were made. Excellent authors were selected and they were requested to send in their manuscripts for publication of this book. It is our ardent hope that this book will prove to be beneficial to the doctor interested in the esophagus and that it will provide the reader with first-hand information from leading scientists and clinicians in this field. The incidence of esophageal diseases vary greatly from country to country and in recent years, worldwide interest in these diseases has resulted in various international studies. The International Society for Diseases of the Esophagus was inaugurated by Professor Komei Nakayama in 1979 and since that time it has actively contributed to the exchange of information regarding these diseases and has made endeavors in bringing about advancement in the struggle against diseases of the esophagus in every way possible.

The seventeenth annual symposium sponsored by the Texas Research Institute of Mental Sciences was held October 23-26, 1983, in Houston, Texas. The theme was Aging 2000: Our Health Care Destiny. This volume on biomedical aspects and a companion volume on psycho social aspects include edited versions of the presentations by about 80 speakers. Their papers were directed at practitioners, researchers, and medical educators who will be active and productive in the year 2000, and we focused on those who would influence the evolution of care of elderly persons during the next 17 years. We chose topics that would be of particular interest to teachers and current planners in the disciplines concerned with delivery of health and social services. We believe that having a core of more qualified and better trained practitioners will help the population of aged persons achieve a higher level of physical and mental health, life satisfaction and happiness, to find better coping techniques and control of environmental stresses, and to attain personal and social goals. Our Goals While preparing for the symposium we knew that the status of the art in 1983 obviously would be the base from which we would work, but we asked our speakers to give priority to future planning and directions."

Why anDther series .on infectiDus disease? The questiDn is a fair .one in view .of the proliferatiDn .of mDnDgraphs, texts, and periDdicals .on the vast subject .of infectiDus disease. The gDal .of this series is tD provide an additiDnal service tD the clinician in the fDrm .of clinical infDrmatiDn nDt usually assembled in .one convenient vDlume. One type .of mDnDgraph presented in this series will CDver a specific infecti.on, detailing microbi.ol.ogic research and clinical aspects. It is h.oped that such a cDmpilati.on will be helpful in bDth its thDroughness and breadth tD the clinician interested in this particular problem. The .other type .of mDnDgraph that this series will pr.ovide will discuss a clinical presentati.on that c.omprises many pDssible specific etiDI.ogies. V.olumes in the series will be multiauthDred, giving us the DppDrtunity tD invite auth.orities in each specific area t.o cDntribute their expertise and experience. Regular revisions are planned SD that each v.olume will remain as current as it is thorDugh. We hDpe that .our gDals are met and that the present series .of mDn.o graphs establishes its .own identifiable and valuable niche in the growing cDmpendium .of resDurce material available tD the clinician. Contents Series Preface ....................................................... VB Contributors .......................................................... Xl Introduction ......................................................... xv 1. Acute Osteomyelitis FRANCIS A. WALDVOGEL ...................................... ."