The decisive factor in trauma is that many processes first occur at the cellular level before they can be determined in laboratory tests, and recognition of them has only recently found its way into intensive care practice. Yet knowledge of the pathophysiology of these processes is essential for an early diagnosis of multiple organ failure and the implementation of adequate therapy, which ultimately make the patient's survival possible. Professor Schlag, an internationally renowned scientist and clinician, has been concerned with the basic pathophysiological principles of shock for many years. In this book he has brought together for the first time an international team of authors primarily from the USA and Europe, who present their collective findings of trauma, shock, development of the organ in shock and early failure and of sepsis-like syndrome, and development of septic multiple organ failure. Patienten mit Multiorganversagen haben immer noch eine schlechte Prognose in der intensivmedizinischen Behandlung, insbesondere wenn sie noch zusatzlich in einen septischen Schock geraten. Hier hilft auch oft eine breite Abdeckung mit modernsten Antibiotika nicht weiter. Neue Ansatze fur eine Therapie dieser problempatienten haben sich in den letzten Jahren durch Erkenntnisse der pathophysiologischeen Vorgange die zum Schock fuhren ergeben. Herr Professor Schlag hat als anerkannte Kapazitat auf dem Gebiet der Traumatologie und Schockforschung fur dieses erste umfassende Werk zu den Grundlagen des Multiorganversagens eine beeindruckende Liste von mehr als 50 international renommierten Autoren zusammenbekommen. Das Buch ist nicht nur eine Aufarbeitung aller Grundlagen des Schocks und Multiorganversagens sondern zudem ein ausgezeichnetes Nachschlagewerk fur jeden intensivmedizinisch tatigen Klinikarzt, egal ob er aus der Anasthesie, der Inneren Medizin oder der Unfallchirurgie kommt."

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.

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."

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."

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.

Six members of the Herpesviridae family are human pathogens, including herpes and 2 (HSV-I and 2), Epstein-Barr virus (EBV), varicella zoster simplex virus I virus (VZV), human cytomegalovirus (HCMV), and human herpesvirus 6 (HHV 6). Each of these viruses is capable of causing distinct diseases of varying severity in children, young adults, and the aged. The diseases range from infection of epithelial tissue to the infection of internal organs and white blood cells. A common feature of the six pathogenic human herpesviruses is their ability to latently infect different cell types in which the viral DNA is not integrated and is unable to express its pathogenicity. Reactivation of the herpesviruses is a result of cellular processes which reactivate viral genes, leading to virus progeny and to signs of infection. Due to their ability to become latent after initial infection, once the pathogenic herpesviruses infect children they are maintained throughout life, having the potential of cause various diseases upon reactivation.

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.

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.

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."

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."

for the design of control programs; in extreme cases (as dis cussed below, by Fine et al., this volume, and elsewhere) it can happen that immunization programs, although they protect vaccinated individuals, actually increase the overall incidence of a particular disease. The possibility that many nonhuman animal populations may be regulated by parasitic infections is another topic where it may be argued that conventional disciplinary boundaries have retarded investigation. While much ecological research has been devoted to exploring the extent to which competition or predator-prey interactions may regulate natural populations or set their patterns of geographical distribution, few substan tial studies have considered the possibility that infectious diseases may serve as regulatory agents (1,8). On the other hand, the many careful epidemiological studies of the trans mission and maintenance of parasitic infections in human and other animal populations usually assume the host population density to be set by other considerations, and not dynamically engaged with the disease (see, for example, (1,2)). With all these considerations in mind, the Dahlem Workshop from which this book derives aimed to weave strands together -- testing theoretical analysis against empirical facts and patterns, and identifying outstanding problems -- in pursuit of a better un derstanding of the overall population biology of parasitic in fections. For the purpose of the workshop, the term "parasite" was de fined widely to include viruses, bacteria, protozoans, fungi, and helminths."

An insight into new advances of current interest in metal toxicology, such as mechanisms important in risk-assessment for human health. The book also has chapters on emerging conceptual problems including resistance to metal toxicity effects on gene expression, alongside principles regarding drug-chelation of metals, the potential use of prophyrins as indicators of metal exposure and toxicity. The toxicology of specific metals of major public health concern are discussed in depth, such as mercury, aluminum, arsenic, chromium, and cadmium. Of interest to basic scientists as well as public health administrators.

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.

In recent years, the progress made in the prevention of mortality and morbidity caused by communicable diseases and malnutrition has changed the disease spectrum in both developed and, particularly developing countries. As a result, noncommunicable diseases, includ ing genetic disorders, have achieved considerable importance in public health. Furthermore, it is now evident that inherited predisposition is important in a number of common diseases that occur in later life, such as atherosclerosis, coronary heart disease, hypertension, diabetes mellitus, and in some rheumatic, oncological, and mental illnesses that appear at an early stage and develop into severe handicaps in predisposed people. Rapid advances in gene mapping concerned with international human genome research make it almost certain that the use of new genetic knowledge will dramatically increase the requirement for genetic approaches in the control of a wide spectrum of diseases, and will provide possibilities for their prevention and treatment in the form of changes in lifestyle, diet modification, periodic check-ups, or the administration of gene therapy. It appears that one of the main problems in delivering genetics services is the difficulty involved in informing the health profession and the community of the real sig nificance of genetic problems. There is, therefore, a need for international collaboration in improving genetic health education at all levels and in improving health through genetic approaches."

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."

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.

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."

For some time now, the study of cognitive development has been far and away the most active discipline within developmental psychology. Although there would be much disagreement as to the exact proportion of papers published in developmental journals that could be considered cognitive, 50% seems like a conservative estimate. Hence, a series of scholarly books devoted to work in cognitive development is especially appropriate at this time. The Springer Series in Cognitive Developmemt contains two basic types of books, namely, edited collections of original chapters by several authors, and original volumes written by one author or a small group of authors. The flagship for the Springer Series is a serial publication of the "advances" type, carrying the subtitle Progress in Cognitive Development Research. Each volume in the Progress sequence is strongly thematic, in that it is limited to some well defined domain of cognitive-developmental research (e. g., logical and math ematical development, development of learning). All Progress volumes will be edited collections. Editors of such collections, upon consultation with the Series Editor, may elect to have their books published either as contributions to the Progress sequence or as separate volumes. All books written by one author or a small group of authors are being published as separate volumes within the series. A fairly broad definition of cognitive development is being used in the selection of books for this series."

Volume 10 of Advances in Disease Vector Research consists of seven chapters on vectors that affect human or animal health and six chapters on plant pathogens and their vectors. In Chapter 1, Yasuo Chinzei and DeMar Taylor discuss hormonal regulation of vitellogenesis in ticks. Many blood sucking insects and ticks transmit pathogens by engorgement, which induces vitellogenesis and oviposition in adult animals. To investigate the pathogen transmission mechanism in vector animals, information on the host physiological and endocrinological conditions after engorgement is useful and important because pathogen development or proliferation occurs in the vector hosts at the same time as the host reproduction. Chinzei and Taylor have shown that in ticks, juvenile hormone (JH) is not involved in the endocrinological processes inducing vitellogenin biosynthesis. Synganglion (tick brain) factor(s) (vitellogenesis inducing factor, VIF) is more important to initiate vitellogenesis after engorgement, and ecdysteroids are also related to induction of vitellogenin synthesis. In their chapter, based mainly on their own experimental data, the authors discuss the characterization of main yolk protein, vitellogenin (Vg) , biosynthesis and processing in the fat body, and hormonal regulation of Vg synthesis in tick systems, including ixodid and argasid ticks.

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.

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.

Now, in one volume, the latest research from the areas of molcular biology, neurochemistry and behavior analysis of drug abuse and dependence, with, wherever possible, an integration of the data from these various levels of analysis. The ensuing reports point to the complexity of the phenomenon of abuse and dependence and clearly demonstrate that it is determined by a variety of variables from molecular biology and genetics through behavioral history. This complexity is shown, however, to be responsive to rigorous scientific analysis and our success to date gives rise to hope that this distressing public health problem can ultimately be brought under control. Each of the chapters is written by a leading researcher in the field.