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."

This book is the result of several years of enthusiastic planning and effort. Much of this enthusiasm came from the experience of devel{)ping Critical Care Consultant, a large BASIC program for critical care applications (St. Louis, C. V. Mosby, 1985). Working with clinicians showed me that many were interested in learning about clinical applications of computers (and even programming in small doses) but were faced with a paucity of clinical application software. Few had the time or training to develop any such software on their own. After a search through the existing medical literature unearthed relatively little in the way of usable programs, I decided that a series of small clinical applications programs would be of use to the medical community. At the onset a number of strategic decisions were made: (1) the programs would be written in BASIC, in view of its universal popularity, (2) the units used for clinical laboratory tests would be those in common use in the United States, (3) the programs would be simple and easily understood and employ no exotic tricks that were not easily transported across computers, (4) references to the literature would be provided to allow the clinician to critically assess the algorithm or method used himself or to follow up on subsequent criticisms that may have been published, and (5) the programs would demonstrate reasonable standards of software engineering in terms of clarity, trans portability, documentation, and ease of modification."

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.

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 biomedical aspects and a companion volume on psycho social 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, to find better coping techniques and control of environmental stresses, and to attain personal and social goals. Our Goals While preparing for the symposium we knew that the status of the 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."

Why anDther series .on infectiDus disease? The questiDn is a fair .one in view .of the proliferatiDn .of mDnDgraphs, texts, and periDdicals .on the vast subject .of infectiDus disease. The gDal .of this series is tD provide an additiDnal service tD the clinician in the fDrm .of clinical infDrmatiDn nDt usually assembled in .one convenient vDlume. One type .of mDnDgraph presented in this series will CDver a specific infecti.on, detailing microbi.ol.ogic research and clinical aspects. It is h.oped that such a cDmpilati.on will be helpful in bDth its thDroughness and breadth tD the clinician interested in this particular problem. The .other type .of mDnDgraph that this series will pr.ovide will discuss a clinical presentati.on that c.omprises many pDssible specific etiDI.ogies. V.olumes in the series will be multiauthDred, giving us the DppDrtunity tD invite auth.orities in each specific area t.o cDntribute their expertise and experience. Regular revisions are planned SD that each v.olume will remain as current as it is thorDugh. We hDpe that .our gDals are met and that the present series .of mDn.o graphs establishes its .own identifiable and valuable niche in the growing cDmpendium .of resDurce material available tD the clinician. Contents Series Preface ....................................................... VB Contributors .......................................................... Xl Introduction ......................................................... xv 1. Acute Osteomyelitis FRANCIS A. WALDVOGEL ...................................... ."

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.

Our aim in this volume, as in Volume I, HormonaI Correlates of Behavior: A Life Span View, has been to provide a critical assess ment of the state of behavioral endocrinology as weIl as the more usual summary of extant data. Each contributor was asked to probe the strengths and weaknesses of his area as candidly as possible. As aresult, we hope the reader will find this Volume useful as a reference source and as an honest evaluation of our present know ledge of the interaction between hormones and behavior. R. L. Sprott Bar Harbor, 1975 B. E. Eleftheriou v CONTRIBUTORS Robert Ader, Ph.D., Department of Psychiatry, University of Rochester Schoo1 of Medicine and Dentistry, Rochester, New York 14642. F. R. Brush, Ph.D., Experimental Psychology Laboratory, Syracuse University, Syracuse, New York 13210. Robert M. Benson, M.D., Pediatric Endocrine Clinic, Children's Medical and Surgical Center, The Johns Hopkins Hospital and University, Baltimore, Maryland 21205. John J. Christian, Sc.D., Department of Biological Sciences, Univer sity of New York at Binghamton, Binghamton, New York 13901. David A. Edwards, Ph.D., Department of Psychology, Emory University, Atlanta, Georgia 30304. Carl Eisdorfer, Ph.D., M.D., Department of Psychiatry and Behaviora1 Sciences, School of Medicine, University of Washington, Seattle, Washington 98101. Basil E. Eleftheriou, Ph.D., The Jackson Laboratory, Bar Harbor, Maine 04609. Merri11 F. Elias, Ph.D., Department of Psychology and All-University Gerontology Center, Syracuse University, Syracuse, New York 13210.

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."

Clinical research represents an integration of many procedures from the social, biological, and natural sciences. Critical examination of the spectrum of medical inquiries will reveal the full gamut of research activities. Under standing the processes involved in the integration of these investigative and cognitive functions may lead to further advances in creative behavior. The purpose of this book is to formalize this process by identifying, collecting, and organizing the elements and issues involved. During the past thirty years, there have been significant advances in research methodology, many of them stimulated by multi-disciplinary collabo ration. The anticipated barriers to communication were not realized in prac tice. Scientists engaged in mutual problem-solving could accomplish more than their colleagues working in relative isolation. In the, r productive fashion, these multi-disciplinary teams, by pooling their knowledge sets and by devel oping communication mechanisms, created the interfaces between the clini cal, analytical, and communication sciences. These interfaces, while neither complete nor perfect, represent the methodology of interest in accomplishing the capture, evaluation, and utilization of information, or Information Process ing. The list of contributors to this methodology is virtually endless and we acknowledge their enormous and significant efforts."

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.

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.

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.

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.

Alcohol abuse is this culture's most important drug problem. Statistics indicate that it is exacting a great and relentlessly increasing toll of human suffering. It is clear that the problem is not being dealt with in any effective manner. At the invitation of the. Canadian Hepatic Foundation, many of the world's experts gathered in Toronto, May 14-15 1976, to focus attention on one of the most important aspects of the alcohol problem -alcohol induced liver damage. The epidemiology of alcohol induced liver disease was discussed and current views on the pathogenesis of the problem were reviewed. New insight into the pathological alterations of the liver was presented and some of our current therapeutic capabilities were discussed. Dr. Hans Popper summarized the Symposium and presented some of his views on those aspects of the problem which will require early attention by the research community. The Symposium achieved its immediate objective -that of bringing together the committed experts of various disciplines for an updating of our understanding of alcohol and the liver and for a discussion of new approaches to the problem. As a backdrop to the Symposium, however, was large writing on the wall to the effect that we are expending our research talents and efforts on a totally unnecessary problem. Right now we probably know enough and have sufficient resources at our disposal to solve the problem.