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.

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 I also thank those col leagues who allowed me to include their published and unpublished material; their names, and also those of the publishers who kindly granted copyright permission, are given in the individual figure captions."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."

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.

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."

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."

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.

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.

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.

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.

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.

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.

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 very first international working discussion on slow infections of the nervous system was entitled "Slow, Latent, and Temperate Virus Infec tions" and was held at the National Institutes of Health (NIH) in December 1964. The primary impetus was the discovery and investigation of kuru in New Guinea by D. Carleton Gajdusek, M. D. This working discussion brought together investigators in human and veterinary medicine, virolo gists, microbiologists, and neuropathologists actively engaged in laboratory work with viruses that illustrated properties of latency, masking, slowness, or temperateness, with emphasis on subacute and chronic neurologic dis eases of unknown etiology. In the Preface to the monograph of published papers presented at the working discussion, Gajdusek and Gibbs wrote the following: After microbiology had given solution to the etiology of most acute infections of the central nervous system and after fungi and bacteria had been incriminated in impor tant chronic disorders of the nervous system such as torula and tuberculosis men ingitis, we have been left, in neurology, with a wide range of subacute and chronic affections of the central nervous systems of unknown etiology. Some of these diseases, still listed as idiopathic, are among the most prevalent afflictions of the central nervous system. Many others with familial patterns of occurrence do not yet have their basic pathogenesis or underlying metabolic defect elucidated, although we tend to think of them as genetically mediated."

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."