A HISTORY OF MALIGNANT HYPERTHERMIA Malignant hyperthermia (MH) is a hereditary disorder of muscle. Undoubtedly, individuals have possessed this trait since time immemorial. However, because the trait is usually only unmasked in the presence of potent inhalational anaesthetic agents or non-depolarizing skeletal muscle relaxants, the existence of malignant hyperthermia was not suspected until we" after the dawn of the modern anaesthetic era. In the early years of ether and chloroform anaesthesia, monitoring was minimal. Body temperature was never measured. A finger on the pulse, and observation of respirations and skin colour were the most that could be expected. Death was not infrequent and usually unexplained (1). By the beginning of the twentieth century, reports of fulminant fever and tachycardia (rapid heart rate) during or immediately after anaesthesia often ending in death, were being described with increasing frequency in the medical literature (2-6). As a number of cases from New York had occurred during summer months, they were initially thought to be a form of heat stroke due to overly hot operating theatres (2-6). However, one enterprising anaesthetist (5: ' checked the weather reports for the days on which some of these so called "heat strokes" had occurred. He found that on the days i'n question the ambient 0 temperature had never been in excess of 72 F. Environmental heat, therefore, could not have been a cause of at least some of these reactions.

The revised fourth edition of Evidence-Based Gastroenterology and Hepatology continues to provide the most current, evidence-based information for determining the appropriate medical and surgical options for screening for, diagnosing, and treating gastrointestinal conditions. With contributions from an international team of leading experts in the field, the 4th edition includes practical recommendations for the care of individual patients based on the latest scientific evidence.

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 social, psychological, economic, and ethical aspects and a companion volume (Volume I) on biomedical 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, find better coping techniques and control of environmental stresses, and attain personal and social goals. Our Goals While preparing for the symposium we knew that the status ofthe 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.

With the advent of enzyme histochemistry, which this field and simplistic theories will be expanded or revealed hitherto unseen pathological differences discarded. between muscle disorders, muscle biopsy assumed Diseased muscle cells, as any other cell type, show an important diagnostic role. The investigation is easily only limited morphological changes. However bizarre, performed and is being undertaken with increasing very few of these changes, if any, are pathognomonic of frequency. Nevertheless there is still a tendency to a single disease. The exact significance of microscopic regard its interpretation as highly specialized and out findings is to a large extent determined by their clinical side the province of the general histopathologist. In this context. Thus, although this is an atlas, it is definitely atlas I have tried to lift the veil of neuropathological not designed to promote 'spot' histological diagnoses. I mystique and to describe and illustrate the basic have aimed to provide a guide to pathological reactions reactions of muscle cells. of muscle which will be useful to the practising histo Interpretation of the biopsy depends not only upon pathologist and all students of neuro-muscular disease. recognition of morphological abnormalities, but upon I hope that recognition of the lack of specificity of understanding why they occur. Throughout the atlas I individual morphological features will encourage the have attempted to correlate morphological changes . close clinico-pathological correlation which is essential with pathogenetic mechanisms."

An ever greater number of our contemporaries will reach a very much greater age than their ancestors. Longevity is one of the most fertile fields for paradoxes: it is clear that the same causes do not produce the same effects at the age of ten and at the age of one hundred! On the subject of longevity, the "recipe book" is far from having been written. Nevertheless, the Fondation IPSEN has chosen a few of these paradoxes to discuss and try and explain them.

Intensive Care Medicine has been continuously growing and expanding, culturally, technically and geographically. Monitoring and instrumentation are continuously improving and more and more hospitals are getting Intensive Care facilities. The costs have proportionally increased over the years, so that ICUs represent today a major cost for health structures. Since the available resources are limited, a real need is emerging to set the limits and indications of Intensive Care. It is understood that the problem not only involves medical considerations, but also ethical and economical aspects of the utmost importance. For the first time in Europe, this book edited by Reis Miranda and his colleagues tackles systematically the many structural aspects of the European Intensive Care. The organisation and financing of health care in the Old Continent is deeply different from the American one, and the results and consequent proposals obtained in the USA cannot simply be transferred to this side of the Atlantic Ocean. Weare extremely pleased to welcome this first European attempt to discuss the Intensive Care problem. It lays no claims to giving definite replies in a continuously developing field, but it will surely become the basis for future discussions and proposals. I am particularly happy that this work has mainly developed within the European Society of Intensive Care, whose final target is to ensure a common standard of therapy in our old Europe, beyond national differences. We warmly congratulate the authors, and I am sure that their work will find wide diffusion and consent.

The Sapporo International Symposium on "Recent Advances in Nitric Oxide Research" was held in Sapporo, Japan, in 1997, following the Fifth International Meeting on the Biology of Nitric Oxide in Kyoto, Japan, organized by Dr. Salvador Moncada, Dr. Noboru Toda, and Dr. Hiroshi Maeda. The field of nitric oxide research continues to expand rapidly, and our understanding of the physiological and pathophysiological roles of NO has increased greatly. The Kyoto Meeting was stimulating and informative, providing impetus for the Sapporo Symposium, which I had the great honor to organize. To communicate the information from these events, Dr. Ichiro Sakuma and I decided to publish this book. The contents of its chapters were contributed by the participants who were active at the Sapporo symposium and cover the majority of the presentations made during that symposium. Dr. Csaba Szabo of Children's Hospital Medical Center in Cincinnati (U. S. A. ) reviews the roles of peroxynitrite and poly(ADP-ribose)synthetase in shock, inflammation, and reperfusion injury, and Dr. David A. Geller and his colleagues of the University of Pittsburgh (U. S. A. ) review the regulation and function of NO in the liver. As contributions from the Hokkaido University School of Medicine (Sapporo), Dr. Hiroko Togashi and colleagues present their data on transient cerebral ischemia and NO production, Dr.

The best conferences are often those where the participants are from a mixture of different disciplines. There is a cross fertilization of ideas and a wider perspective of common problems. The 6th International Meeting on Clinical Laboratory Organization and Management, held in Noordwijkerhout, The Netherlands, on 24th-28th June 1987 lived up to its promise of a stimu lating program and differing views from a wide range of international par ticipants. The theme of the conference was "Laboratory Data and Patient Care" and this provided a forum for discussion of many aspects of laboratory input into the diagnosis and monitoring of disease. The titles of the papers in this book of the proceedings will give some indication of the breadth of topics discussed, ranging from problems of laboratory management and pro fessional leadership to educating the clinician in the most cost effective testing strategies; and computer aided diagnosis to the best presentation of data and graphical displays. The backgrounds of the participants were equally wide, ranging from medical statisticians and computer experts to practising clinicians and heads of clinical laboratories. There was also a significant number of delegates from commercial companies who were able to inject a different perspective on many problems. This blend of backgrounds and disciplines promoted much discussion and new avenues for research and development."

Parasitic Disease, second edition remains unique in its emphasis on depictions of complete life cycles and its skillful knitting of basic and clinical information. Superbly illustrated with black and white and color photomicrographs and halftone drawings, it is an ideal text for medical, graduate, and advanced undergraduate students of parasitology and an excellent reference for physicians and researchers.

This is the second of a number of international symposia which will, I hope, continue to be held until atherosclerosis is no longer a major problem. The first symposium was held three years ago in Athens, Greece, under the chairmanship 1 of Dr. Constantinos]. Miras , who, although he could not attend this symposium, participated actively in the deliberations of this Program Committee. Atherosclerosis together with its sequelae constitute the most important source of morbidity and mortality in civilized countries. While a major attack is being made on the consequences, the sequelae of this disease, not enough attention is being paid to the basic cause, atherosclerosis. Yet, if the basic disease were eradicated, the major concern of this symposium, the sequelae would constitute only a minor and rare disease group. The approach of the Program Committee was to bring together experts in the multiple disciplines which have a bearing on atherosclerosis. There is a great need for an exchange of ideas from various groups studying the basic process in many divergent ways. The hope we have is that those present (or those later studying the Proceedings) may be stimulated to attack the problem in new ways. Perhaps a breakthrough will be made or, at least, a brick or two added to build the structure, a rampart needed to defend against atherosclerosis. Better still, their contributions may help to confine it to a small area.

At the Sixth Wiggers Bernard Conference, a group of scientists from various disciplines discussed new findings relating to nitric oxide synthase inhibitor in shock, sepsis, and organ failure. Dedicated to the presentation and discussion of both positive and negative findings related to the use of NOS inhibitors, the meeting served as a forum for issues relating to specific and non-specific inhibitors, as well as the role of nitric oxide-oxygen radical interactions. Both experimental and clinical data were presented in the trauma and sepsis field.

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 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 provides a detailed overview of the function of the nervous system in fever and its role in antipyresis. The volume opens with an introductory account of fever, its physiology and adaptive role, and explains the mechanisms of thermoregulation. Sufficient information about bacterial pyrogens, 'endogenous' pyrogenic cytokines, body temperature regulation and survival value of fever and its ubiquity is given to enable readers to follow the central nervous system's involvement. The book should enable graduate students and researchers in neuroscience and other disciplines to understand the impact of their studies in the overall processes of fever. It will also be of benefit to pharmacologists studying anti-pyretics and the central nervous system function of these drugs. Academic clinicians will find this a more comprehensive overview of fever than other available texts. Finally, the author challenges some well-established dogmas in this area and sets an agenda for future research.

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."

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."

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.

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 . . . . . . . . .

Are you new to clinical teaching and looking for practical advice? Would you like to challenge and improve your current teaching style? Do you want to direct change in teaching practice within a department or institution? If your answer to any of the above is yes, then Making Sense of Clinical Teaching is the resource for you. It offers the novice and more experienced teacher concise advice in how to pinpoint and build upon existing strengths, address areas where confidence is lacking, develop mentoring skills, challenge existing practice, and influence strategic developments. Making Sense of Clinical Teaching will enable you to: Add new skills to your teaching repertoire Stimulate your creative thinking Challenge current practice and facilitate the development of new strategies Improve your coaching and mentoring skills and ultimately meet the needs of your students and improve their learning experience

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.