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 differentiation between the muscarinic and the nicotinic ef- fects of acetylcholine led to the subdivision of the cholinergic ner- vous system into two categories. Further studies showed that stimu- lating and inhibiting muscarinic effects could be demonstrated in different organs. For instance, gastric secretion and gastrointestinal motility are stimulated, while heart rate and the vascular muscula- ture are inhibited. For decades, it could not be determined whether the various ef- fects were mediated by different subgroups of muscarinic receptors, but eventually, with the availability of agonists and antagonists to muscarinic receptors, and using various techniques, the existence of at least two such subgroups could be ascertained . . Mt receptors are defined by their high affinity for the antagonist pirenzipine in comparison to M2 receptors. This subdivision of muscarinic receptors has since been proved beyond doubt by experi- ments in vivo and in vitro, by receptor binding studies, by histoauto- radiography, and by electrophysiological studies. However, these different classes of muscarinic receptors have not been found to relate to different types of effects; instead both excit- atory and inhibitory effects appear to be linked to each class. For ex- ample, excitation of gut motility and inhibition of cardiac contrac- tile activities both appear to be mediated by M2 receptors, while ex- citation of some nerves in sympathetic ganglia and inhibition of some myenteric nerves may be mediated by M receptors.

H. Hafner, G. Moschel, N. Sartorius The size of the world's population aged over 65 was estimated at about 250 million in 1980; by the year 2025 it is expected to grow to about 760 million (see Hauser, this volume). This sharp increase in life expectancy at birth, in some countries amounting to almost 100% in only a hundred years, has resulted from better nutrition and improved living conditions, hygiene and medical care. Not only life expectancy at birth, but also further life expectancy in advanced age has shown a clear, though more moderate increase. This increased life expectancy, together with a simultaneous fall in birth rates, has caused the mean age of the world population and, especially, the average age of the population of industrial nations to climb substantially in recent times, a development which will reach its peak only some decades from now. For these demographic reasons alone, health care authorities will have to devote more attention to the health problems of the elderly. The main task of medical research is to develop improved methods of disease prevention and treatment. Yet, because the full benefits of such research are only realized after many years of work, researchers have already begun to respond to demographic pressures by focussing part of their efforts on the study of illnesses characteristic of old age.

Immunology, in all its facets of immunochemistry, humoral immunity, cellular immunity, immunodiagnosis, and immunotherapy, is currently the most rapidly advancing discipline of clinical and experimental oncology. But as in most developing subjects, it is continually beset with problems of methodology and nomenclature, both of which are often intertwined. Indicative of this problem are our circular definitions of antigen and antibody. Another fre quent problem is the use of the words "specific" and "associated" when characterizing re actions to tumors or the antigenic properties of neoplasms. When applied to cancer, these terms are obviously very dependent upon the methods used to demonstrate these qualities. Indeed, the very diverse nature and multitude of types of cancer preclude our making gen eralizations or categorical statements regarding tumor "specificity. " Similar problems arise when one considers that many antigens found in malignant tumors share certain properties with embryonic or fetal tissues. First, these observations emphasize a lack of true tumor specificity, for which reason the category of oncofetal antigens has been established. Second, whether or not such antigens are truly oncofetal depends upon the method of detection used, and it has been found that here too specificity decreases as the antigen assay increases in sen sitivity. Thus, whether substances can be truly oncofetal in nature still remains a matter of debate, and such terms must therefore be used in an operational sense.

The acute abdomen is one of the most frequent, most dangerous and most difficult problems that the diagnostic radiologist has to deal with. This comprehensive manual presents a clinico-radiologic approach to the use of diagnostic imaging techniques for acute abdominal conditions. Imaging techniques, radiologic symptoms and clinical conditions are treated separately. This lucid format, together with a detailed subject index, offer the reader a quick and reliable reference aid in daily practice. The text is clearly structured and concise in style, and provides helpful practical hints, including discussion of diagnostic pitfalls. It is supported by a wealth of illustrations covering native diagnosis, ultrasonography, computer tomography and angiography.

"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.

Surgery as a medical discipline has from its beginnings appealed to the imagination of many. It is therefore not surprising to find that its colourful past has induced quite a few authors to take up their pens. The truth of this in the Netherlands is witnessed by a number of dissertations and monographs and especially by the numerous articles related to the history of surgery which have appeared in the medical weekly Nederlands Tijdschrift voor Geneeskunde, particularly during the two decades preceding the Second World War. The memorial volume, published in 1977 by the 'Nederlandse Vereniging voor Heelkunde' (Association of Surgeons of the Netherlands) has thoroughly covered the history of Dutch surgery since the tum of the century, but a chronological survey of the earlier events which led to these modem achievements is still wanting. This book has been written with a view to meeting this need. In it, Dutch surgery has by no means been taken as an isolated phenomenon, but considered in its context with European surgery as a whole. Foreign influences on the on surgery abroad are discussed Netherlands and, conversely, Dutch influences whilst contemporary medical thinking is set against a cultural and political back ground. It is hoped that this approach will allow the book to exceed the narrow boundaries of'campanilismo' and make it of interest to non-Dutch readers as well."

The application of immobilized enzymes in medicine is the main objective of this book. The author reviews natural and synthetic carriers for enzyme immobilization, chemistry of enzyme binding, and in-vitro and in-vivo properties of immobilized enzymes. Four chapters are dedicated to clinical use of immobilized enzymes.

This book is designed to be a physician's guide for those interested in diving and hyperbaric environments. It is not a detailed document for the erudite researcher; rather, it is a source of information for the scuba-diving physician who is searching for answers put to him by his fellow nonmedical divers. Following the publication of The Underwater Handbook: A Guide to Physiology and Performance for the Engineer there were frequent requests for a companion volume for the physician. This book is designed to fill the void. Production of the book has been supported by the Office of Naval Research and by the Bureau of Medicine and Surgery, Research and Development Command, under Navy Contract No. NOOOOI4-78-C-0604. Our heartfelt thanks go to the many authors without whose contributions the book could not have been produced. These articles are signed by the responsible authors, and the names a e also listed alphabetically in these preliminary pages. Every chapter was officially reviewed by at least one expert in the field covered and these reviewers are also listed on these pages. Our thanks go to them for their valuable assistance. We are grateful to Marthe Beckett Kent for editing Chapter III. Our thanks also go to Mrs. Carolyn Paddon for typing and retyping the manuscripts, and to Mrs. Catherine Coppola, who so expertly handled the many fiscal affairs.

This volume is intended to cover research in the field of muscle morphology since publication of the previous edition by Haggquist in 1956. The development of new techniques, coupled with an intensified interest in muscle, has resulted in a vast literature which no single person could review, especially within the limitations of one volume. When I accepted the flattering offer to write a new edition, I quickly abandoned any hope of a comprehensive review. Instead, I tried to consider, within my limits, those lines of research which I believe to be important for the understanding of mammalian and ultimately human muscles under normal, experimental, and pathological conditions. It would be naive to suggest that muscle can be adequately described in purely morphologi cal aspects; I would characterize the results of my effort as "muscle as seen with the eyes of a morphologist." It gives me pleasure to acknowledge the help of several colleagues who read and commented on drafts of individual chapters: Dr. Brenda Eisenberg, Chicago; Dr. Else Nygaard, Copenhagen; Dr. Stefano Schiaffino, Padova; Dr. Michael Sjostrom, Umea; Dr. Lars Erik Thornell, Umea. None of these individ uals can be held responsible for any error or obscurity that persists. Indeed, without their assistance there would have been more. I also thank those col leagues who allowed me to include their published and unpublished material; their names, and also those of the publishers who kindly granted copyright permission, are given in the individual figure captions."

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."

Man has always been curious about himself, a curiosity that began centuries ago with an examination of the soul, and that extended in the period of the Renaissance to his anatomy and certain functions such as the circulation of the blood. Chemical science entered the scene in the 18th century, and burst into prominence in the 19th century. As the various chemical elements were discovered, many were found to be present in body fluids and tissues. Organic compounds were recognized; it became known that body heat was produced by the combustion of food; chemical transformations such as the production of fat from carbohydrate were recognized; and in the 1850s it was determined that young animals differed from adults in certain aspects of body composition. As methods for chemical analysis evolved, they were applied to samples of body fluids and tissues, and it became apparent that life depended on chemical normality; and most importantly it was realized that given the necessary amount of food and water the body had the ability to maintain a degree of constancy of what Claude Bernard called the milieu interieur, in other words its interior chemical en vironment."

Advances in molecular biology describing important enzyme systems involved in drug conjugation and deconjugation reactions and recent work indicating the importance of drug and xenobiotic conjugates as transport forms of biologically active compounds are reviewed comprehensively. Part One describes molecular events associated with the expression and regulation of transferases and hydrolases involved in Phase II drug conjugation and deconjugation. Part Two deals with the regulation of Phase II conjugation, and Part Three reviews critically the importance of drug conjugates in pharmacology and toxicology. This volume is an up-to-date source of information on this topic and will be of broad interest to pharmacologists and toxicologists.

During the last decade it has become evident that the brain is an important target for hormones. Although it has been discovered only recently that the brain contains numerous peptide hormones, the role of pituitary and hypo thalamic hormones in brain activity has been the subject of basic studies for quite some time. Peptide hormones are involved in mental performance. pain perception, food and water metabolism. sleep. sexual behaviour and nursing behaviour, and disturbances in the hormonal climate of the brain may be associated with psychopathology. cognitive disturbances and. possibly. addic tion. The clinical influence of neurohypophysial hormones and their frag ments is studied today on learning and memory. on inadequate behaviour and addiction, in Parkinson's disease. Lesch-Nyhan syndrome. depression and schizophrenia. Fragments of adrenocorticotrophin have been shown to affect motivation, concentration and attention. and neuropeptides derived from -lipotrophin are probably involved in psychopathology. Thyrotrophin releasing hormone has been implicated in depression. and lutein-releasing hormone in sexual disturbances. In spite of the impressive experimental data; clinical results to date have been controversial and. to some extent. anecdotal. In some cases they have been exciting. and in others disappointing. It was against this background that the International Health Foundation decided to organize and sponsor their workshop on 'The brain as an endo crine target organ in health and disease' at which the papers appearing in this book were presented."

The objective of this book is to provide information that will be useful to people in a variety of disciplines who wish to learn more about normal aging processes in the human body. Although gerontologists in the biological sciences are making great strides in research on human aging and documenting this work in mono graphs, texts, and review chapters, this information is generally not easily acces sible nor is it comprehensible to nonprofessionals in these fields. This book is intended to provide a summary of this work, along with its implications for psy chological functioning of the aging individual. The majority of the book is devoted to describing the results of research on the physiological changes in the human body with aging and to seeking explana tions for these age effects. This description has been approached in such a way as to make it readable for the nonspecialist, but also to focus on research issues that will be useful reading for those who are currently working in these parti cular areas. In addition, throughout the book, I have tried to develop some themes regarding physiological and psychological adaptation during adulthood."

Infections of Leisure provides a thorough yet concise examination of the infectious risks and diseases of leisure time activity. Encompassing a wide range of medical and social interests, chapters provide practical, clinical guidelines for the diagnosis and management of various infectious risks in the garden, at the shore, on fresh water, on camping trips, traveling abroad, and on the farm. Additional chapters include up-to-date information on foodborne illnesses, and on animal-associated infections, with particular attention given to housepets. The rising prevalence of Lyme Disease, hepatitis and food poisoning make this volume vitally important. Family practitioners, internists, infectious disease specialists, pediatricians, and emergency room physicians will all benefit from the indispensable and practical information presented in this unique, groundbreaking volume.

Volume 9 in this series consists of four chapters on vectors that affect human or animal health and six chapters on plant pathogens and their vectors. In Chapter 1, Alex S. Raikhel discusses vitellogenesis in mosquitoes: the cornerstone of the reproductive cycle involving massive production of yolk precursors by the fat body and their accumulation in developing oocytes. In anautogeneous mosquitoes, vitellogenesis is dependent on the availability of a blood meal and, as a consequence, is linked to transmission of pathogens. Therefore, elucidation of mechanisms governing the mosquito vitellogenesis is critical for the successful development of novel strategies in vector and disease management. Previous reviews on mosquito vitellogenesis have dealt predominantly with hormonal control. The goal of this review, however, is to summarize significant progress which has been achieved in understanding mosquito vitellogenesis at the cellular, biochemical and molecular levels. It is with these disciplines that we expect to fully understand the mechanisms governing this key process in mosquito reproduction.

Primary care medicine is the new frontier in medicine. Every nation in the world has recognized the necessity to deliver personal and primary care to its people. This includes first-contact care, care based in a posi tive and caring personal relationship, care by a single healthcare pro vider for the majority of the patient's problems, coordination of all care by the patient's personal provider, advocacy for the patient by the pro vider, the provision of preventive care and psychosocial care, as well as care for episodes of acute and chronic illness. These facets of care work most effectively when they are embedded in a coherent integrated approach. The support for primary care derives from several significant trends. First, technologically based care costs have rocketed beyond reason or availability, occurring in the face of exploding populations and diminish ing real resources in many parts of the world, even in the wealthier nations. Simultaneously, the primary care disciplines-general internal medicine and pediatrics and family medicine-have matured significantly."

Over the years a number of excellent books have classified and detailed drug drug interactions into their respective categories, e.g. interactions at plasma protein binding sites; those altering intestinal absorption or bioavailability; those involving hepatic metabolising enzymes; those involving competition or antagonism for receptor sites, and drug interactions modifying excretory mechanisms. Such books have presented extensive tables of interactions and their management. Although of considerable value to clinicians, such publica tions have not, however, been so expressive about the individual mechanisms that underlie these interactions. It is within this sphere of "mechanisms" that this present volume specialises. It deals with mechanisms of in vitro and in vivo, drug-drug, drug food and drug-herbals interactions and those that cause drugs to interfere with diagnostic laboratory tests. We believe that an explanation of the mechanisms of such interactions will enable practitioners to understand more fully the nature of the interactions and thus enable them to manage better their clinical outcome. If mechanisms of interactions are better understood, then it may be pos sible for the researcher to develop meaningful animal/biochemical/tissue cul ture or physicochemical models to which new molecules could be exposed during their development stages. The present position, which largely relies on patients experiencing adverse interactions before they can be established or documented, can hardly be regarded as satisfactory. This present volume is classified into two major parts; firstly, pharmacoki netic drug interactions and, secondly, pharmacodynamic drug interactions."

Multiple sclerosis is an unique disease with a tremendous impact on social life in countries with moderate climates. Its cause is unknown. In recent years however hopes have been raised that the disease might be fought, and possibly cured. With the disappearance of poliomyelitis as the main paralyzing disease multiple sclerosis has taken its place as the single disease that is responsible for paralyzing the young with an incurable affliction of long duration, for social disruption and for an 1 economic impact that is estimated to be higher than heart disease * A multi-national, mUlti-disciplinary approach to this extremely disabling disease is urgently needed in this phase of hopeful scientific developments. The Commission of the European Communities therefore sponsored a Con ference on Multiple Sclerosis Research in Europe on 29,30 and 31 January 1985 in Nijmegen, The Netherlands, with the aim of formulating practical proposals for such cooperation in the Communities. This volume contains the papers read at that conference.

After a long period of neglect, the gastrointestinal tract is increasingly being recog nized as an important target of anesthetics and anesthesia-related processes, as well as of conditions and treatments related to peri- and postoperative period and inten sive care. Drugs used in anesthesia and intensive care and physiological or pathologi cal changes in the perioperative period affect the digestive system in its function from the pharynx to the colon. Prolonged postoperative ileus or stasis of propulsive peri stalsis in the critically ill or multiply injured patient may impair enteral nutrition and give rise to complications such as sepsis or multiple organ failure. In view of this new understanding of the clinical relevance of gut function, we felt that a book on problems of the gastrointestinal tract in anesthesia, the perioperative period, and intensive care was badly needed. The present volume is the product of an international symposium which brought together physiologists, pharmacologists, experimental and clinical anesthetists, gastroenterologists, surgeons, and intensive care physicians to discuss all major contemporary aspects of bowel function in health and under the influence of anesthesia, surgery, and intensive care."

A concise yet complete overview of the treatment of cardiovascular instability in the critically ill patient. The authors consider all aspects, ranging from basic physiology and pathophysiology to diagnostic tools and established and novel forms of therapy. The whole is rounded off with an integration of these principles into a series of clinically relevant scenarios.

The Tenth International Conference on Intracellular Protein Catabolism was held in Tokyo Japan, October 30-November 3, 1994. under the auspices of the International Committee on Proteolysis (lCOP). ICOP meetings have been held biennially in the USA, Europe, and Japan in turn. The previous three ICOP meetings (7th to 9th) were held in Shimoda, Japan, in 1988. in WildbadKreuth, Germany, in 1990, and in Williamsburg. Virginia, in 1992. Previous meetings were held in resort areas, this was the first meeting held in a large city. Attendance has grown every year so that nearly 400 participants from 19 different countries attended the Tokyo meeting. At the meeting, novel and updated results on the structure-function. physiology, biology, and pathology of proteases and inhibitors were discussed, together with cellular aspects of proteolysis and protein turnover. Thirty-nine invited papers and eight selected posters were presented orally and 171 poster presentations were discussed. This book documents almost all of the lectures and some selected posters. Since the world of proteolysis and protein turnover is expanding very rapidly. far beyond our expectations, it is impossible to cover all the new aspects of this field. However, this book will give an idea of the current status, trends. and directions of the field, and information necessary to understand what is and will be important in this field. Further. the editors hope that the novel ideas, approaches. methodologies, and important findings described in this book will stimulate further study on proteolysis and protein turnover.