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.

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."

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.

This second International Symposium on Mucus in Health and Disease once again brings together basic scientists such as Biochemists, Anatomists, Biologists and Clinicians who are dealing with aspects of mucus in the various tracts of the body where it is of such great functional importance. It is fitting that the meeting should take place at Manchester University where there is so much activity in this field and our grateful thanks are due to Or Eric Chantler for his untiring efforts in organising this meeting. At the first Mucus meeting, Sir Francis Avery Jones stated "this is a subject which will justify further Symposia, both local and international." As he predicted, this meeting succeeds the first and adds further to our progress in understanding the complex and unique structure and function of the mucus secretion in its various sites of the body. Much was learned from the first meeting and it is hoped that the second will be an appropriate successor to it. The emphasis in this meeting has been to encourage discussion and the presentation of research material. In this respect, review articles have been kept to a minimum. The structure of the Conference has been organised around eight keynote addresses: one on the biosyn thesis of the general mucus glycoproteins and another on its physical properties. Other keynote papers are on the biochemical and clinical aspects of mucus in the respiratory, gastrointestinal and urogenital tracts by recognised authorities in these subjects."

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.

The revised fourth edition of Evidence-Based Gastroenterology and Hepatology continues to provide the most current, evidence-based information for determining the appropriate medical and surgical options for screening for, diagnosing, and treating gastrointestinal conditions. With contributions from an international team of leading experts in the field, the 4th edition includes practical recommendations for the care of individual patients based on the latest scientific evidence.

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.

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 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."

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."

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.

Human Health: The Contribution of Microorganisms is the first major work to concentrate on probiotics in humans. It presents both new and established data on the origins and importance of commensal floras, the history and characteristics of probiotics, the use of probiotics in clinical situations, and preclinical and volunteer studies. It also covers commercial issues such as the difficulties involved in the large scale production and formulation of live microorganisms, and the marketing techniques used to sell products containing bacteria. It contains contributions from internationally recognised experts in both science and industry. Written with both professional and lay audiences in mind, Human Health: The Contribution of Microorganisms will be an indispensable text and reference source for scientists, clinicians, and pharmaceutical/food technologists.

The danger of infection remains the most serious drawback to internal fixation. Prevention, using all available prophylactic measures should be the central feature in every surgical department. Though the infection rate may remain below the acceptable level of 2 %, the infected patient derives little comfort from the large number of excellent results in other people. We must discover the best way to offer these patients a favourable prognosis. This should not be based on intuition but on clear proven guiding principles. Planning the treatment for a patient whose internal fixation has become septic must decide between steps which may have advantages or disadvan tages. The disadvantage of the presence of a foreign body must be weighed against the advantage of rigidity. The authors have taken up this challenge by planned animal experiments to study the healing of internally fixed fractures which have been infected with staphylococci. They have shown that under stable conditions, even massive infection did not destroy the healing process in cortical bone. Even under these circumstances fracture union, in the form of primary bone healing, can occur even if with less regularity than in unin fected internal fixation.

This volume contains the proceedings of a symposium held in Marseille on April 6, 1992, on the topic "Heterogeneity of Alzheimer's disease. " This was the eighth of a continuing and very successful series of meetings related to Alzheimer's disease organized by the Fondation Ipsen pour la Recherche Therapeutique. These symposia, known as "Colloques medecine et recherche," started in 1987 and have dealt with widely different aspects of the disease such as immunology, genetics, neuronal grafting, biological markers, imaging, growth factors, and last year's less conventional topic of Neurophilo- sophy and Alzheimer's disease. The next IPSEN symposium dedicatet to Alz- heimer's disease will take place in Lyon on June 21, 1993, and will deal with "Amyloid protein precursors in development, aging, and alzheimer's disease. " It is being organized by Konrad Beyreuther, Colin Masters, Marc Trillet, and Yves Christen. Until a few years ago, several names were used to refer to the most common cause of dementia in the elderly. They included such terms as "senile psycho- sis," "organic brain syndrome," and "senile dementia. " Following Kraepelin, the term "Alzheimer's disease" was often restricted to an uncommon condition starting at a younger age (before 60 or 65 years of age).