Recent publications have addressed specific aspects of the endothelins, such as their roles in disease or the importance of endothelin receptors. However, in this book the entire field of endothelins is covered. This includes the pathways of endothelin production and their regulation, the local and systemic actions of endothelins, receptors for the endothelins and the signalling pathways employed, and the involvement of endothelins in a range of diseases. Attention is also paid to the development through chemistry, pharmacology and toxicology of endothelin antagonists and endothelin-converting enzyme inhibitors, with mention of all the important members of these drug classes. This leads to well-rounded discussions of the potential therapeutic benefit of endothelin inhibitors.

Looking back is a luxury for which scientists normally have little time. This XXV Anniversary Symposium, however, gives the opportunity of reminding us that in Belgium, where the risk of developing multiple sclerosis is among the highest in the world, a great man to whom we all pay tribute, I mean Dr Ludo van Bogaert, in 1957, took the initiative in founding the Belgian Research Group for Multiple Sclerosis. It may sound immodest but since that time members of the Belgian Research Group happen to have an honourable record of important contributions to MS research, quite out of proportion to the financial support they received for it. Indeed, when compared to the situation in English speaking countries, funding of MS research has always been neglected in our country in spite of the fact that in 1958, acting on the advice of the Belgian Research Group, the Belgian National MS Society was founded with the specific object of collecting money for research as well as for social care. At that time, the difficulty in raising funds for research was partly due to the fact that solving the problem of MS appeared almost impossible. Scientists could apparently only too slowly improve their ability to prevent and cure the disease. Media were indifferent to MS which was considered to have no news value, and the public remained uninformed.

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."

Neurologists and non-neurologists alike can no longer ignore diseases of the neuromuscular system. The old dogma that these disorders are both uncommon and untreatable has lost its validity. Recent technological advances have enabled us to study more precisely muscle and nerve anatomy, physiology and biochem istry. Because of this progress, we are now recognizing new neuromuscular di seases as well as diagnosing more subtle cases of myasthenia gravis, myotonia, and metabolic myopathies. Treatment of the neuromuscular diseases has also un dergone dramatic change based on new discoveries in the fields of immunology and pharmacology. No longer are myotonia, periodic paralysis, and malignant hyperthermia untreatable medical curiosities. No longer are cases of steroid-un responsive myositis given up as hopeless. Because of all these advances, non-sur gical physicians and especially neurologists must update their knowledge regard ing the neuromuscular disorders. This book, it is hoped, will help such clinicians in dealing with this task. Emphasis has been placed on the diagnosis and management of these disorders rather than on their pathophysiology. The more uncommon diseases and those of uncertain existence have been omitted purposely and left to the larger and more encyclopedic reference works. Chapter 1 discusses the clinical symptoms and signs of muscle disease and is designed to enable the reader to formulate a differential diagnosis on the basis of the patient's history and physical examination."

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).

The Yearbook compiles the most recent developments in experimental and clinical research and practice in one comprehensive reference book. The chapters are written by well recognized experts in the field of intensive care and emergency medicine. It is addressed to everyone involved in internal medicine, anesthesia, surgery, pediatrics, intensive care and emergency medicine.

The International Skeletal Society is now fifteen years old and as measured in human terms has outgrown its childhood. During this time the ISS has earned worldwide respect and praise for successful work. The International Skeletal Society is an interdisciplinary working group concerned with skeletal diseases, their pathogenesis, diagnosis, and treatment at all ages. At the Annual Closed Meetings of the ISS prominent scientists representing many countries from all over the world gather to exchange ideas in the fields of radiology, pathology, orthopedic surgery, nephrology, and endocrinology. Follow ing these meetings Refresher Courses are offered for students, physicians in train ing, and interested collegues from the various medical specialities. The purpose of these courses is to present the latest developments in clinical practice and research with regard to skeletal diseases. The Society's internationally well-known journal "Skeletal Radiology," which is published by Springer-Verlag, Heidelberg, adds in exchanging updated developments in the field of skeletal disorders. The hereby presented first Book of Members contains a record summarizing the most important milestones and events of the history of the International Skeletal Society up to 1987 in the form of short biographies regarding the members of the Society. The task of gathering all important informations for this book was accom plished by one of the members during his term as President of the ISS. The other one - honorary member - took upon himself the tasks related to publication."

Almost 50 million persons visit another continent each year. It is mainly those 15-18 million travelers from industrialized nations who visit or reside in developing countries that are at increased health risk. To develop effective health protection advice, the health risks of travel and the benefits of prophylaxis (vaccines, new and old drugs, behaviour modification, etc.) should be assessed systematically. The purpose of this book is to improve the protection of the travelers' health by more effective and more uniform recommendations. It contains many data on recent research and represents the first comprehensive account on travel medicine for professionals.

The Second Meeting of the International Society for Trace Element Research in Humans (ISTERH) was held in Tokyo from August 28 through September 1,1989. On August 27, the day preceding the opening of the meeting, a typhoon made a direct attack on Tokyo, welcoming guests from all over the world in a rather violent way. To our great relief, the weather during the week of the meeting turned out to be exceptionally agreeable for that time of year in Tokyo. We were also pleased to see the entire scheduled course of the meeting, including the social activities, carried out smoothly and the contents of the program favorably appraised. The meeting was attended by 518 scientists from 30 countries. Recent unrest following steps toward democratization in the Communist bloc gave rise to some apprehension; therefore, we were particularly pleased to see attendants from China, Eastern Europe, and the Soviet Union. No one could possibly have predicted the drastic change in Eastern Europe that followed, but again, we were relieved to learn (by a subsequent letter) of the safety of an attendant from Rumania, who had been our greatest concern. A total of 384 papers were contributed to the meeting. The abstracts for all have been published in the Journal of Trace Elements in Experimental Medicine, vol 2, No. 2/3 (1989). This proceedings carries 64 subjects introduced in the Special Session.

The aging process involves changes in neurotransmission at different levels. The purpose of this book is to help define the state-of-the-art of the field and to give directives for future research on the aging brain. Following topics are presented: the comparison of normal and pathological aging at the anatomical and neurochemical level; the knowledge of the responses of the aging brain to drug treatment or environmental stress; the neuro/immune and neuro/endocrine setting during aging; and the definition of therapeutical approaches in normal aging. This book will interest physicians and pathologists as well as neurophysiologists.

Genital Papillomavirus Infections provides a state of the art survey on the clinical aspects, diagnosis, treatment, and prevention of genital papillomavirus infections, written by experts in the respective fields. Two introductory sections on epidemiology and molecular biology are followed by chapters on new techniques for the detection of genital papillomaviruses and their presence in genital carcinomas. Contributions on the clinical aspects cover infections of the cervix, male and female external genitalia, urethra, and oral cavity. A discussion of the immunobiology of papillomaviruses ends in an evaluation of the prospects for vaccination, and the application of podophyllotoxin, cryosurgery, laser therapy, and interferon treatment are described in detail. This book is unique in placing a strong emphasis on clinical aspects of genital papillomavirus infections. Mainly addressed to clinicians, it provides practical guidelines on methods for their diagnosis and treatment.

5t The 1 International Moxifloxacin symposium took place in Berlin Germany February 18 - 20,1999. The purpose of this meeting was to introduce the medical and scientific communities to this exciting new fluoroquinolone and to define its role in the management of respiratory tract infections. The fluoroquinolones as a class are an important part of our therapeutic armamentarium and moxi floxacin is a unique addition to this class of compounds. This symposium brought together physician/scientists from around the world to present and discuss the moxifloxacin data. The information from this important meeting are presented in these proceedings and are organized under the following headings: Part I Antimicrobial chemotherapy Part II Pre-clinical microbiology Part III Pharmacology Part IV Clinical needs in the millennium Part V Round table discussion The modifications to the basic quinolone structure resulting in moxifloxacin have produced a drug with unique in vitro, and pharmacokinetic/pharmaco dynamic properties. The drug has a very broad spectrum of antimicrobial activity, is well absorbed and can be taken only once daily. Its profile makes it an excellent therapeutic option for many types of respiratory tract infections. It is hoped that our clinical and laboratory colleagues will be as excited by this data as we are and we look forward to further work with this unique and interesting compound."

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.

International experts examine the role of nitric oxide in various metabolic events such as septic shock, cardiovascular dysfunction, and trauma and hemorrhagic shock. The nitric oxide pathway and nitric oxide synthesis regulation are also discussed.

"De Motu animalium" is sometimes referred to in the medical literature. But who has read it? The book, originally published in Latin, seemingly constitutes the very first treatise on biomechanics. The author, Giovanni Alfonso Borelli (1608 - 1679), was professor of mathematics and physics in Pisa where he worked with Malpighi, who was professor of theoretical medicine and focused Borelli's interest on the movements of living creatures. This was the time of Galileo, Descartes, Newton and many others, when sciences exploded, sometimes leading to conflicts with religious authorities. "De Motu animalium," Borelli's life work, has two parts. In the first part, he analyses the action of the muscles, the movements of the limbs and motions of man and animals, including skating, running, jumping, swimming and flying. The second part deals with what is now called physiology, considered from the point of view of a mechanist: heart beat, blood circulation, breathing, separation of urine from the blood in the kidneys, liver function, reproduction, fatigue, thirst, hunger, fever, and so on. This work shows Borelli to be a genial precursor. He expresses his opinion as a mathematician on problems which afterwards further stimulated the curiosity and endeavours of many generations of researchers. This book will be welcomed by anybody who is interested in the working of living bodies and in the history of human knowledge.

Der ausserordentlich grosse Zuwachs an Wissen seit der ersten Auflage dieses Handbuches vor rund 70 Jahren dokumentiert sich in den hier vorliegenden bei den Banden, die das Gebiet der klinischen Osteologie in reprasentativer Form zur Darstellung bringen. Die Gliederung in einen mehr theoretischen und in einen mehr klinischen Teil erschien aus zwei Grunden notig: Erstens sind fur das Verstandnis der Pathophysiologie der einzelnen Krankheitsbilder heute breite Kenntnisse der physiologischen Grundlagen erforderlich. So schien es ratsam auf den aktuellen Stand der diesbezuglichen endokrinologischen Forschung in Schwerpunktform einzugehen und die modernen Vorstellungen vom Knochenumbau und Kalzium- phosphatstoffwechsel darzustellen. Zweitens gibt es inzwischen eine grosse Zahl osteologischer Untersuchungsmethoden, die - um Wiederholungen bei der Ab- handlung der einzelnen Krankheitsbilder zu vermeiden - ebenfalls der Klinik vorangestellt wurden. Mit diesen Untersuchungen haben eine Reihe neuer quan- titativer Verfahren Eingang in die moderne Osteologie gefunden, die erst in neuerer Zeit eine Objektivierung von Skelettprozessen in diagnostischer und therapeutischer Hinsicht ermoglichen.

In spite of a long history of intense investigation the transmissible spongiform encephalopathies remain a poorly understood family of neurodegenerative diseases. This group of diseases has been described in a wide variety of animal species and includes kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler syndrome in humans, and scrapie, bovine spongiform encephalopathy, and related syndromes in ruminants and rodents. In all cases spongiform degeneration and astrocytosis are seen in specimens of brain and a filterable transmissible agent is present in the brain and some other tissues of affected individuals. However, the precise nature of this agent remains unknown. Agent infectivity, which can so far only be assayed by serial transmission to new individuals, be remarkably resistant to inactivation has been shown to by heat, chemicals, and irradiation. These properties create significant biohazard possibilities during exposure to infected tissues. Transmission between humans was originally reco gnized in the unique epidemiology of kuru in New Guinea tribesmen, and concern about transmission from animals to humans has re-emerged as a result of the current epidemic of bovine spongiform encephalopathy in dairy cattle in Great Britain. Although interspecies transmission has often been achieved experimentally, its efficiency is highly variable. There fore, the possibility of spread of bovine spongiform encephalopathy from cattle to humans or various animal populations cannot be accurately predicted at this time. This volume presents a comprehensive update of know ledge concerning the transmissible spongiform encephalo pathies."

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.

At the beginning of the century the average life span in developed societies was less than 50 years. It is now more than 70 years and will continue to increase in the near future. Aging is a challenge to science and society. There are several theories of aging. The programmed aging hypothesis suggests that aging cannot be altered by any external influence, that aging is programmed from the beginning of life until the end of senescence. Another theory is based on genetic instability, with repair processes correcting errors in the cells that cause aging. Aging processes manifest themselves at the molecular and cellular level, in different organs, and in the whole organism. Most older persons acquire multiple diseases, primarily chronic ones. The multimorbidity of the elderly raises many questions as to nutrition, metabolism, immunity, drug therapy, and rehabilitation. Nutrition may be able to intervene in the aging process. Aging is associated with dec lining immunity and reduced resistance to many diseases, and it is pos sible that nutritional changes in old age contribute to the declining immunity in the elderly. The elderly take 40% of the prescription drugs in Germany and adverse drug reactions are more frequent in geriatric patients. There are not only problems in drug therapy for elderly pa tients, but also in their rehabilitation. The aim of rehabilitation is the restoration of geriatric patients to their former functional and environ mental status."

An up-to-date overview of acute and chronic pancreatitis. The two authors with special interests in this field deal with the aetiology, pathophysiology, and clinical features of these diseases, as well as complications, treatment strategies, and prognostic factors. Two chapters on congenital abnormalities and hereditary pancreatic diseases round off this book. Intelligently-structured for everyday practice, this can also be used as an actual reference book. For gastroenterologists in clinic and practice.

New findings involving the brain in traumatic and septic shock and after brain injury are reported in this book, including pathophysiological and pathohistological results. An experimental and clinical approach to treatment is presented together with specific results obtained from the encephalogram and from histopathological study with regard to the immunohistochemistry of toxic lipid peroxidant products. The latest results of clinical and experimental pathophysiology in inflammatory processes after traumatic brain injury and the therapeutic effects of hypertonic fluid therapy are also discussed.

The clinical biochemistry ofhepatobiliary diseases is very widely studied, and publica tions abound on this topic. However, there is no recent publication that provides a comprehensive collection of the various leading aspects that go to make up this complex theme. Therefore, we thought it useful to gather together a few scientists whose work has focused on the various clinical biochemistry-aspects of these disorders in order that they might discuss their experience and expertise. The aim of the International Satellite Symposium on Clinical Biochemistry in Hepatobiliary Disease, in addition to reviewing the individual aspects, was to describe the state-of-the-art so as to provide useful data for laboratory scientists and also for physicians working in the field of hepatobiliary diseases, and these two aims are clearly reflected in the chapters of this volume. The volume opens with an introductory chapter that gives a general overview of the various aspects of the clinical biochemistry of these disorders, while the closing chapter deals with an important aspect that deserves to be increasingly emphasized in laboratory medicine, i.e., strategies to integrate information coming from the laboratory to make them more useful for clinical diagnosis.

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.

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."

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 . . . . . . . . .