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.

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 seventeenth annual symposium sponsored by the Texas Research Institute of Mental Sciences was held October 23-26, 1983, in Houston, Texas. The theme was Aging 2000: Our Health Care Destiny. This volume on social, psychological, economic, and ethical aspects and a companion volume (Volume I) on biomedical aspects include edited versions of the presentations by about 80 speakers. Their papers were directed at practitioners, researchers, and medical educators who will be active and productive in the year 2000, and we focused on those who would influence the evolution of care of elderly persons during the next 17 years. We chose topics that would be of particular interest to teachers and current planners in the disciplines concerned with delivery of health and social services. We believe that having a core of more qualified and better trained practitioners will help the population of aged persons achieve a higher level of physical and mental health, life satisfaction and happiness, find better coping techniques and control of environmental stresses, and attain personal and social goals. Our Goals While preparing for the symposium we knew that the status ofthe art in 1983 obviously would be the base from which we would work, but we asked our speakers to give priority to future planning and directions.

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

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

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

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

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

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