Significant progress has doubtlessly been made in the field of cere bral protection compared to earlier centuries, as recently reviewed by Elisabeth Frost (6). She cites the recommendations for treat ment of brain trauma by Areteus, a Greek physician of the second century A. D. He expressed quite modem views with regard to the need for prompt action considering complications that follow even minor symptoms. He advised burr holes for evacuation of hema toma in seizures, the use of diuretics and, most interestingly, also hypothermia. German surgeons of the 17th century had little more to offer than prescriptions of which the most effective constituent was alcohol (10). Thus, Sir Astley Cooper was probably the next surgeon to make noteworthy contributions when advising the use of leeches to the temporal artery and other means of bleeding in stead of surgical intervention in cases of raised intracranial pressure (loc. cit. 6). Although our knowledge has greatly expanded during the last two decades, extensive discussions have led to only few conclusions. Promising results from animal studies were translated to clinical sit uations only to yield controversial and sometimes confusing results. Since the observations of Brierly (5) on ischemic cell damage, im proved information on structural aspects, probably even related to concomitant biochemical studies, should allow the validity of thera peutic concepts to be verified. Investigations on cerebral ischemia have led to the differentiation of synaptic transmission failure and membrane failure."

This volume is based on a workshop "Modulation of Synaptic Transmission and Plasticity in Nervous Systems" held in n Ciocco, Castelvecchio, Pascoli, Italy, from September 8th to 13th, 1987. The purpose of the meeting was to bring together scientists working on plasticity in nervous systems on different levels. The contributions can be subgrouped into six fields of research: 1) Presynaptic Modulation of Chemical Neurotransmission 2) Postsynaptic Signal Transduction 3) Modulation of Synaptic Transmission and Plasticity in the Hippocampus 4) Modulation of Neuromuscular Transmission 5) Molecular and Cellular Analysis of Conditioning in Marine Snails 6) Analysis of Learning and Memory in Insects Understanding how nervous systems and in particular our brain processes and stores information has been a major challenge in science for centuries and will remain for some time to come. Not until recently neurobiologists agreed to seek plasticity of behavior primarily in the modulation of the properties of synapses between nerve cells. This is to be understood within the context provided by a neural circuitry. An important stimulus came from the work on the marine snail Aplysia, where learning processes can be described as a modulation of transmitter release, traced back to a complete chain of molecular events in an identified neuron. Learning became a topic of molecular biology. Three systems appear particularly promising for this approach: insects, in particular Drosophila, marine snails and the mammalian hippocampal tissue. Our views on neurotransmission have rapidly changed.

Soft tissue tumors are a very heterogeneous group of tumors in terms of histogenesis, morphology, cytogenetics, molecular biology, clinical manifestation, and prognosis. Their spectrum is fascinating for morphologists and basic scientists alike. Yet precisely this variability in the morphologic manifestation of soft tissue tumors, specifically their histologic and cytologic patterns, presents great difficulties to any effort to categorize them. Although many soft tissue tumors are today defined not only by histology but also by immunohistochemical, cytogenetic, and molecular biological findings, the histogenesis of many soft tissue tumors, in particular malignant ones, continues to be unknown. This is associated with the fact that the actual precursor cells that lead to these tumors have frequently not yet been identified. For this reason, the customary classification of malignant soft tissue tumors is primarily not histogenetic, but actually according to the dominant phenotype, however characteristic it is. Of course, an exact morphologic examination of soft tissue tumors con tinues to be an essential prerequisite for making a diagnosis and determining a therapy. The use of a wide range of additional modern examination techniques, however, can make a substantial contribution toward more precisely defining the biological behavior of a tumor, which without doubt can have therapeutic implications.

This volume is a compilation of papers presented at the Tenth International Symposium on Brain Edema held on October 20-23, 1996, in San Diego, California. This follows the sequence of meetings that was initiated 31 years ago in the First International Symposium held in Vienna. Subsequent symposiums were held in Mainz, Montreal, Berlin, Groningen, Tokyo, Baltimore, Bern, and Tokyo CY okohama). A considerable number of papers was chosen from over 100 papers that were received. The organizers wish to thank the Advisory Committee for the excellent work done in selection of the papers. We also wish to thank all the persons who contributed to the success of the Tenth International Symposium, especially the staff who worked behind the scenes. These papers were reviewed, edited, approved or disapproved by the Editorial Board. Those manuscripts that were felt not pertinent to this publication were not accepted by the Editorial Board. Therefore, the excellent quality of those that are in the book are a reflection of the authors' dedication and work and that of those of the Editorial Board in their review process. For the reader's convenience, the papers are structured according to the various disease processes which are associated with the primary topic: hypertension, hydrocephalus, infection, ischemia, tumor, etc. We do hope that the reader will enjoy the articles and that they will provide an impetus and insight for future work.

The first International Symposium on Brain Edema was organized by Dr. Klatzo and Dr. Seitelberger and held in Vienna in 1965. The second Symposium was held in Mainz in 1972 and organized by Dr. H. J. Reulen and Dr. K. Schiirmann, the third in Montreal in 1976 by Dr. H. M. Pap- pius, the fourth in Berlin in 1979 by Dr. J. Cervos-Navarro, and the fifth in Groningen in 1982 by Dr. K. G. Go. This volume contains the papers presented at the 6th International Sym- posium on Brain Edema, held in Tokyo, Japan, November 7-10, 1984. The invited lectures by Dr. I. Klatzo, Dr. A. Hirano, Dr. S. I. Rapoport, Dr. B. K. Siesj6, Dr. H. M. Pappi us, Dr. K. A. Hossmann, and Dr. D. M. Long are included as special chapters. On behalf of the organizing committee, I wish to express my deep ap- preciation to all the participants for their contribution toward making this meeting so fruitful and significant. Moreover, the great success of this Sym- posium depended on the high quality of the invited lectures and presen- tations by experts in various fields, as well as on the free and enthusiastic discussion. I was deeply impressed with the papers presented by all the authors, who endeavored to elucidate their subjects. The editors have made only minor corrections and rearrangements, since prompt publi- cation was considered to be important.

Vor die Therapie setzten die Gotter die Diagnose. Otto NiigeJi Renal biopsy has decisively enriched renal diagnostics. Kidney diseases may be monitored during their entire course, and new techniques - such as immunofluorescence and electron microscopy - may be systematically applied, resulting in novel insights into the morphogenesis, pathogenesis, and etiology of kidney lesions. These insights, in turn, have served as new starting points, in the spirit of the quotation above, for the institution of causal therapy by the clinician. This work presents our findings based on 20 years of experience in evaluating renal biopsies. As of the end of 1974, our computer-supported, systematic clinical, morphologic, and follow-up evaluation of case material consisted of over 2000 biopsies, including 679 examined by electron microscopy and 400 by immunofluorescence microscopy. The subsequent 500 biopsies (400 studied by electron microscopy and 300 by immunofluorescence) were con sidered qualitatively only. In order to enhance qualitative findings with quantitative data, it was necessary to devise new methods for quantifying electron-microscopic findings. Additionally, we attempted to correlate cyto logic and immunofluorescent observations to integrate the isolated findings of electron microscopy into a vital cytologic pattern of reactions. We also attempted to evaluate the almost overwhelming flood of publications, especially those appearing within the last 10 years. The idea for this book was conceived a decade ago. At that time, however, our own experience in renal biopsy diagnostics seemed insufficient to sup port such a major undertaking."

1. Concepts on the Causal Genesis of Human Intestinal Tumors The action of chemical substances has a significant role in the genesis of human tumors. It is assumed that most human tumors are induced by exogenous chemical noxae (Schmahl, 1970;Heidelberger, 1975; and others). In the course of intensive efforts to discover the principles of tumor etiology, important insights have resulted in recent years. These are that chemical carcinogens do not only arise as products of our tech nological civilization, but that they also occur in nature as potent solitary carcinogens and cocarcinogens (e. g., as plant products). For review, see Hecker (1972) and Preuss mann (1975). Not only "complete" carcinogens are significant for the genesis of tu mors, but also substances which are first transformed to the actual carcinogenic com pound in the organism (Schmahl, 1975). The causal significance of exogenous noxae in carcinogenesis is indicated by the fact emphasized by Bauer (1963) that malignant tumors occur predilectively at those sites in the body which are in direct or indirect contact with the environment. This applies especially to the intestinal tract."

During the past few years, a considerable number of monographs on bone tumors have been published. They are mainly restricted to bone tumors as clinical-pathological entities, since their diagnosis, more than that of other tumors, requires the interdisciplinary cooperation between orthopedic specialist, radiologist, and pathologist. However, investiga tions concerning the histogenesis of bone tumors are rather limited, although they might be helpful in explaining the unique morphological heterogeneity of tumors of the skeletal system. Furthermore, the histo genetic approach in the study of bone tumors may facilitate the inter pretation of the advanced cytobiological methods available for improv ing classification and diagnosis. Therefore, this volume presents recent pathological advances in the biological characterization of bone tumors. A major chapter deals with the differential diagnosis of Ewing's sarcoma as regards its demarcation from the so-called neuroectodermal tumor of bone. The analysis of the ground substances in bone-forming tumors may be helpful for their classification. Therefore the volume includes a chapter on the biochemical and histochemical analysis of different osteosarcoma types. Recently it has become clear that in addition to different collagen types which are not specific for bone tissue, several bone-specific proteins occur, one of which is osteonectin. Its distribu tion is obviously important for the classification and diagnosis of osteo blastic tumors. Proliferative behavior is of major importance for the diagnosis of malignant tumors.

This volume contains all the invited papers, symposium contributions and workshop reports of the 7th International Congress of Human Genetics, held in West Berlin from September 22 to 26, 1986. The organizers of this congress made sure to gain the cooperation of the leading scientists in the field from all over the world. These contributions therefore document the enormous progress made in human genetics research in recent years. The volume covers a wide range of topics, from analysis of the human genome to basic mechanisms, diagnosis and therapy of hereditary diseases, and to distribution of normal and pathological genes and DNA variation in human populations. Ethical issues raised by modern developments are discussed thoroughly. The volume is a must for all scientists and medical doctors working in human genetics research, its teaching and practical applications.

When 1 first developed an interest in the pathology of bone 1 found that there were relatively few books on the subject available. Much of my information had either to be obtained from searching the journals or from senior colleagues in the field, who, 1 should add, were always more than willing to teach me. With this memory in mind, 1 have endeavoured to produce a book which 1 hope is of a convenient size and yet will hold sufficient information to be of use mainly to the pathologist faced with a bone problem. This is not intended to be an all-embracing source of knowledge on the subject; indeed, such a task could not be undertaken by a single author in these days of the rapid increase in information even in small subspecialist areas within bone pathology. Although this book is written mainly for the pathologist, it is hoped that it may also be of interest and value to orthopaedic surgeons, rheumatolog ists and radiologists. Most of the illustrations are original and many of the drawings are my own. There has been a long tradition of interest in bone pathology at The London Hospital, which has resulted in a wealth of material being available to me from the archives of the Department of Morbid Anatomy. A few of the photo graphs are those of Prof. H. Turnbull; the observant reader will detect these, since the scales used are not metric."

Marburg and Ebola virus, the two species within the family Filoviridae, are among the most pathogenic agents causing fulminant hemorrhagic fever in humans and nonhuman primates. The chronology of filovirus epidemics and epizootics proves that these viruses are prototypes of emerging/re-emerging pathogens. Since the discovery of Marburg virus in 1967 until the recent Ebola virus outbreaks in Central and West Africa filoviruses have not only raised the interest of scientists, but have also been a matter of high public concern. With the advent of recombinant DNA technology our knowledge on the genome structure and the replication strategies of these agents has significantly increased. This volumes gives an overview on many aspects of filovirus research and summarizes recent advances in the field. The topics addressed include the molecular biology of filoviruses, pathogenesis, epidemiology, immune response, as well as clinical aspects and diagnostic measures.

General pathologists see many biopsies from transplanted organs but few are in large enough centres so that this forms the bulk of their work. The book describes the changes which can be observed in transplantation in all of the major organ systems that are routinely transplanted and there are accounts of the pathology of infections and of the immunological difficulties that are faced by these patients. The volume will be a valuable guide for those who wish to braoden their knowledge in this field.

The processes of distention and recoil have an essential role in the functions of arteries and lungs. In both organ systems, these processes involve to a great extent the connective tissues, in particular the manner in which the extracellular materials are arranged to afford such movements. This book concerns the microenvironment of the connective tissues in the walls of arteries and the stroma of lungs. Proteoglycans, collagen, and elastic fibers and their interrelationships are discussed by eight scientists who are established researchers in this area. Their reports include important findings on how this microenvironment is altered in diseases such as atherosclerosis, emphysema, and pulmonary fibrosis. The concepts developed result from studies at the biochemical, macromolecular, ultrastructural, and light microscopic levels. Taken col lectively, the reports focus attention upon the role of the connective tissues in arterial and lung distensibility and how alterations in the connective tissues result in the loss of this function. Medical researchers and physicians interested in arterial or lung functions or diseases will find the scientific approaches and findings of the authors innovative and provocative. Students of stereologic morphometry will be particularly interested in the quantitative studies of cells and fibers in arterial walls; histologists and pathologists will find the chapter on histochemical staining interesting from both a scientific and historic viewpoint.

This atlas deals with conditions commonly encountered in the male genital tract. Whilst the majority of illustra tions are photomicrographs, photographs of macro scopic specimens are also used to illustrate important features in distinguishing different pathological con ditions. Special emphasis is placed on the small biopsy specimens obtained from prostate and testis in modern urological practice and the importance of clinico pathological co-operation in pathological practice is stressed. Recent advances in our knowledge of testicu lar tumours are discussed and illustrated. The text is not entirely descriptive and attempts to give an intellectual framework around which histopathological diagnosis in this field can be practised. A modest number of references are included; they have not been singled out as representing milestones in the development of our knowledge of these conditions - the choice has rather more centred upon recent reports from which a litera ture search can be mounted if required. The atlas in no way pretends to be an encyclopaedic reference of con ditions of the male genital tract but attempts to provide an up-to-date comprehensive discussion of the histo pathology of this system. Acknowledgements I am most grateful to Mr Keith Gordon for developing all the photomicrographs and to Mr Geoff Gilbert and his staff in the Audio-Visual Department of the City Hospital who took the majority of the macroscopic illustrations. I must particularly thank my secretary, Mrs Dorothy Clay ton, for typing and retyping my draft chapters and for deciphering my hieroglyphics."

Intracranial germ cell tumors are a group of uncommon neoplasms of the central nervous system. The clinical features and natural history of these lesions are quite unique and variable. While intracranial germ cell tumors have been a fascination to neurooncologists for decades, the relatively small number of patients seen in any single institution has hampered the important clinical investigation that is so needed. This text is complete with detailed information concerning the epidemiology, pathology, oncological biology, clinical findings, radiology, and treatment options including surgical strategy, radiotherapy, and chemotherapy for this heterogeneous group of neoplasms. The ongoing clinical trials concerning the optimization of therapy are efficiently summarized. An important final segment addresses the late sequelae of therapy which is of great significance since the majority suffering from these tumors are young patients. This first and only book on intracranial germ cell tumors includes excellent and comprehensive data sheets, illustrations, and radiograms. It provides a detailed and outstanding reference source for physicians taking care of patients with intracranial germ cell tumors, and will be a very welcome edition to their reference libraries.

Scientists from both academia and industry in many countries have closely cooperated to arrive at a consensus on the descriptions of all the types of tumour and preneoplastic lesions encountered in laboratory mice. The series of fascicles should provide information and guidelines especially adapted for international use in practical toxicologic pathology. Images showing the typical appearance of the discussed lesions and references to the most recently published papers complete the information presented here.

Cyclosporin has had a remarkable effect on clinical organ transplantation. Prior to its introduction, considerable advances had been made in the grafting of vital organs, particularly the kidney, heart and liver. In many developed countries, however, transplantation was not considered wo-rthwhile in terms of gain for the investment of resources. The improved results of kidney grafts following the use of cyclosporin has changed this attitude. For all types of organ transplantation, cyclosporin has resulted in an improvement of functional graft survival and has allowed a reduction in steroid dose and, in some cases, no steroids at all. It has permitted the first successful experimental transplantation of the heart and lungs in primate species by Reitz and colleagues and their results were applied directly to the clinic. It was largely due to the introduction of cyclosporin that the Washington Consensus Meeting on Liver Transplantation came to a favourable recommendation and the result has been the proliferation of units performing liver transplantation, approximately fifty in North America and another fifty in Europe, where previously there had been a handful. Having been involved in cyclosporin for organ grafting from the beginning, I have been able to witness these developments which have far exceeded my expectations once the nephrotoxicity of cyclosporin was demonstrated in man. It is fitting that Dr.

A practical hands-on bench book covering difficult areas of autopsy for the modern pathologist. Rutty's book is unique - chapters deal with issues never previously discussed and have been specifically selected to fill a gap in the market, not just re-hash old ideas.

Designed for consultants and trainees alike, not only pathologists of all types but also non-medics involved with the dead in any way - lawyers, police, bereavement officers, undertakers. The first volume has become a reference aid to autopsy issues for all grades of lawyers. Thus the audience that the book reaches is greater than a pure autopsy or forensic pathology textbook.

Intermediate Filaments focuses on desmin and other intermediate filaments in disease and health. This new volume will serve as a resource for graduate students and researchers in the field.

Glomerulonephritis is one of the commonest causes of end-stage renal failure worldwide. Although there have been considerable advances in the management of renal failure by dialysis and transplantation, there has been relatively little progress in its prevention. This volume sets out to review current practice in the treatment of glomerulonephritis, which is aimed both at controlling the clinical manifestations, e.g. nephrotic syndrome, and at preventing the progression to renal failure. The term glomerulonephritis covers a wide range of conditions with different immunological, histological and clinical features. This volume therefore starts with reviews of the immunology and pathology of different types of glomerulonephritis. This is followed by detailed consideration of the treatment of the commoner primary and secondary forms of the disease. There are separate chapters on special circumstances, such as glomerulonephritis in pregnancy or following renal transplantation. In each chapter, attempts are made to review the evidence for the effectiveness of treatment, based on controlled trials, immunopathological principles and the authors' considerable experience. Although some aspects of the treatment of glomerulonephritis can be found in the standard texts on renal disease, this volume provides an up-to-date, thoroughly referenced, and practical guide to management. As such, it should be of value to nephrologists and general physicians, including those in training, and to postgraduate students of nephrology.

Pathology and Pathobiology of Rheumatic Diseases glows with the uncommon precision of the pathologist, the clarity of the tea cher, and the unswerving commitment of the investigator. Fass bender has produced a major contribution to the literature of rheumatic diseases. The practical experience and wisdom brought together in this book, substantiated by excellent exam ples of histopathology, produce a landmark for all who have made the study of rheumatic diseases their profession. The enor mous achievements made in molecular biology, genetics, struc tural biochemistry, and clinical science have been assembled in this book to interact in a meaningful way with the anatomical histology of the rheumatic diseases. It is not easy for any single investigator to paint the picture of a disease process, from its clinical description to its mechanisms, and then to a defined hypothesis, and finally an understanding. Nonetheless, Fassbender has done this in a clear and convincing way that integrates our current knowledge of this group of dis eases. Scientific discovery in medicine moves from the bedside to the bench, back to the bedside, and then back to the bench, etc. It is this iterative process of new observation and new discovery that has given us the achievements in medicine over the past century."

The ability of an epithelial cell to adhere to its neighbor and to the extracellular environment is an essential process that defines in part a normal multicellular organism. In the post-genomic era of cancer biology, it is known that epithelial tumors are multi-clonal and are genetically unstable. In contrast, during the process of tumor metastasis, which is the major cause of death from cancer, a restricted set of adhesion molecules are displayed on the tumor cell surface. The adhesion molecules provide a selective advantage for migration of the tumor cell to a distant site. In this volume, the expression of specific adhesion molecules within human cancer tissues are highlighted. The expression signatures from published DNA microarray and immunohistochemistry studies are detailed. The concept that the alteration of specific adhesion molecules influence the cancer migration ability and cancer damage responses is detailed in this volume; both features are essential for the survival of an invading tumor cell. Defining the minimal adhesion receptors preserved on cancer cells during tumor progression will define the metastatic adhesion signature. Understanding the metastatic adhesion signature will reveal vulnerabilities that could be exploited for the prevention and/or eradication of the invading cancer cell.

In recent years a growing number of proteases have been identified that catalyse peptide bond hydrolysis in the plane of the cellular membrane. These so-called intramembrane-cleaving proteases (I-CLiPs) are involved in a diverse range of cellular processes, including cell regulation, signalling, quorum sensing, protein processing, lipid metabolism and the unfolded protein response. Some I-CLiPs play critical roles in diseases such as Alzheimer s and viral infection. The authors, who are all world leaders in this exciting field of cell biology, provide an overview of the various proteases including recent data derived from the structural determination of some of the I-CliPs, and discuss the various roles that these proteases play in biology and disease. The aim of this book is to provide an update on this emerging group of unusual but important proteases for both the specialist and those with a broader interest in proteases. Amongst the target audience will be protease researchers, enzymologists, those working in academia and the pharmaceutical industry on biological processes and diseases involving I-CLiPs."

Internationally recognized investigators review the latest developments in, and novel approaches to, understanding the prion protein and prion diseases at the molecular level. Utilizing a variety of cutting-edge techniques, these distinguished scientists seek to define the normal function of a prion protein, to detect and measure the early immune response to prion disease, and to discover possible therapeutic targets. They also use transgenic mice and new electrophysiological investigations to elucidate the pathogenetic mechanisms involved in prion diseases. State-of-the-art and richly insightful, Molecular Pathology of the Prions captures for basic and clinical neuropathologists the latest developments and approaches to understanding the pathogenesis of prion diseases, and by analogy suggests possible research techniques for the more common proteinopthies, such as Alzheimer's and Parkinson's diseases.

Having been originally introduced as a term to facilitate discussion of a specific group of patients regarded as entering a state of unawareness following coma, the Persistent Vegetative State (PVS) has established itself as an apparently discrete medical condition with clear-cut implications for ethicists and lawyers that exceed any scientifically based understanding. As a consequence of this upgrading, conclusions drawn about the status and hence the management of this uncommon condition have been increasingly extended to other patients with much more common forms of disability.

This book traces the origins of prevailing perceptions about PVS and submits these to critical examination. In doing this it comes to the conclusion that inadequate attention has been paid to acknowledging what is not known about affected individuals and that assumptions have consistently come to be traded as facts. Re-examination of the basis of the PVS and the adoption of a more scientific approach is long overdue and is owed to the community at large which has generally been provided by many medical practitioners with a dumbed-down account of the condition.

The book will be of interest to philosophers, medical graduates and neuroscientists but is also intended to remain accessible to the general reader with an interest in the wider implications of trends in medical thinking for attitudes towards many classes of patient. It has an extensive bibliography and will be of specific interest to bioethicists and lawyers with professional interests in PVS. "