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.

Close cooperation between those involved in clinical treatment and pathology is imperative in head and neck surgery, as in all surgical fields. The degree of cooperation depends, on the one hand, on the knowledge that the head and neck surgeon has about the possibilities and limits that confront the pathologist, and on the other hand, on the knowledge that the pathologist has about the special problems of head and neck pathology and their management by the surgeon. Within the last 15 years, the knowledge of larynx growths and their treatment has changed rapidly. Parallel to this increase in knowledge, the technical possibilities in histopathology have also increased. For this reason, the authors of this volume present an up-to-date view of the whole scope of the pathology and clinical treatment of larynx tumours.

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.

Cancer has become the most critical health problem in the United States. It is expected that 25% of the people will develop this dread disease, and many of these will die from the malady. The causes of cancer are varied, but the best estimate available is that 70--90% arise from environmental factors. These statistics have triggered widespread governmental action along two lines: (l) An effort to identify those chemicals and conditions that give rise to malignant processes has been mounted by the Carcino genesis Testing Program, the National Cancer Program, and subse quently, the National Toxicology Program. (2) Regulatory laws have been enacted that are administered by agencies such as TSCA, FIFRA, EPA, FDA, OSHA, and so on, whose mission is to minimize public ex posure to carcinogens. Since direct verification that specific chemicals induce cancer in hu of unanticipated expo mans is necessarily limited to known incidences sure and is therefore rare, most chemicals are identified as carcinogens only by laboratory experiments. At present, the only accepted procedure is long-term animal bioassay, and not only are these studies expensive and time-consuming, but current worldwide resources permit the evalua tion of only 300-400 chemicals per year, a miniscule amount compared to what is available in the commercial world: 30,000 existing chemicals, with approximately 700 new such materials being introduced every year."

W. TH. DAEMS This volume contains the papers presented at a Boerhaave Course for Post graduate Education on The cell-biological aspects of disease: the plasma membrane and lysosomes. One of the purposes of this introduction is to explain the reasons for this choice of subject. The first question which might be asked - why a postgraduate course on the cell biological aspects of disease was considered neccessary - is not difficult to answer: the impact of the basic sciences on medicine is im measurably strong, and among these sciences cell biology has contributed immensely to the advances made in medicine during recent decades. It has provided clues leading to general insights into etiology and pathogenesis as well as to the development of diagnostic tools and a basis for therapeutic methods. These insights derived mainly from the still-increasing body of knowledge about the architecture of cells. Initially, this knowledge arose from the notion that cells are either simply bags full of enzymes or complex sponge like structures in which all organelles are permanently interconnected (Fig. 1). Later, this notion was replaced by a highly schematized picture of the cell as an essentially two-compartment structure (Fig. 2) in which cell organelles are discrete units separated from each other by membranes, enabling each organelle to maintain an internal microenvironment with optimal conditions for its specific metabolic pro cesses."

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.

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."

This book represents the culmination of the major aspect of Dr. Margot Shiner's professional career. It was she who devised the technique of jejunal biopsy which opened up whole new fields of small intestinal research, including microbiology, immunology, histochemistry and histopathology, thus greatly expanding our knowledge of fundamental aspects of absorptive patho physiology. Later the application of electron microscopy demonstrated the individual cell with its mechanisms both for absorption and for the production of so many chemicals such as mucus, enzymes and hormones. Like the vision from the peak in Darian, it opened up new worlds. The contribution to our understanding of cell structure and function has been greater than the direct elucidation of specific diseases but nevertheless, there are pointers to different mechanisms which could have wide applications. It is a book which serves a double function: On the one hand it is highly technical and a publication for the super expert, recording new landmarks of knowledge and interpretation. On the other hand, it is a book which can indeed fire the imagination of the rising generation of gastroenterologists, paediatricians, pathologists and medical scientists. Having seen the emergence of the art and science of present-day gastro enterology within my professional lifetime and having been able to provide the facilities for her work in the very early days, it is with particular pleasure and pride that I write this foreword."

The secretion of bioactive products by tumors of the gastroenteropancreatic system results in the development of watery diarrhea that can lead to death in a very short period if not brought under control. Even if the consequences are less dramatic, the patients' ability to lead a normal daily life is seriously impaired, and they may become severely depressed. SandostatinR alleviates the condition by inhibiting peptide release, and its long duration of action makes it an effective and rational adjunct to therapy at all stages. Last year a consensus Round Table Meeting was held in Scottsdale, Arizona, to discuss the optimal use of SandostatinR in this indication. These guidelines offer the results of clinical research and the dosage recommendations arising from them, together with a critical summary of the points of view presented.

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.

Organ transplantation has almost disappeared from headlines in the daily press, possibly because it failed to fulfill exaggerated expectations. Transplanta tion pathology has become more and more important, not only with relation to therapeutic transplantations but even more in its fundamental theories. There is some analogy here to the development in space science where spectacular achievements were followed by sobering frustrations and where, for the time being, the effect on technology is more fruitful than the outcome of the original far-reaching projects. That transplant rejection was defined, in most of its stages, as an immunologic process, has given many new impulses to immunology in general. Transplantation assays have become a pet experiment in immunobiology and an abundant source of general information and knowledge. The implications of such a development could not be predicted when the present volume was outlined and planned. In accordance with the concept of WILLI MASSHOFF, general transplantion pathology was given a central position as a fundamental science, while the chapters on the transplantation of various tissues are of a more paradigmatic character. It was MASSHOFF who invited competent authors and who managed to balance their articles, despite some overlapping, so as to draw a comprehensive picture of contemporary transplanta tion pathology. WILLI MASSHOFF died while he was editing the first manuscripts. As co-editors we have undertaken to complete the publication that we began together."

Practical Guide to Surgical Pathology with Cytologic Correlation/ A Text andColor Atlas is uniquely designed to examin every organ system, traditional exfoliative cytology, fine needle aspiration cytology, and some significant nonneoplastic diseases of liver, kidney, and skin. The volume juxtaposes concise clinical and pathologic descriptions and the corresponding radiographic, cytologic, and histopathologic illustrations.

Hairy cell Leukaemia (HCL) has always attracted an interest out of all proportion to its frequency and continues to do so. There are two reasons for this. The first is that the disease is unusually responsive to therapy and second is that it has provided a number of important insights into B-cell biology. This monograph is a comprehensive account of hairy cell leukaemia and aims to provide a more detailed account than is available in the existing literature. The work is timely because a consensus has now emerged concerning accurate differential diagnosis a nd curative treatment. These aspects therefore form the focus of the book and are considered in detail. The basic advances in the laboratory that encourage the belief that elucidation of the underlying oncogenic event in the disease may be within reach. The background to this belief is extensively renewed. As a result the monograph will be of interest and practical value to both clinicians and researchers in this and related fields.

Human Lymphoma: The Clinical Implications of the REAL Classification is a unique volume. It is based on the recent developments in classification and overall understanding of human lymphoid neoplasms which are relatively common neoplasms and which epidemiological evidence suggests are increasing in frequency. This field has been the cause of confusion in the past as a result of conficting ideas on the classification of lymphoma and related diseases. However a new vision of the field has emerged and the is encapsulated in the pioneering REAL classification and in a forthcoming WHO scheme, both of which are covered in the book. The volume will appeal to hematologists, pathologists and oncologists and will, thanks to a diverse and expert authorship, serve to increase the working knowledge of all three groups.

It is difficult for a teacher to accept the fact that not all of the information in his or her field is a necessary part of the armamentarium of the student. This holds for histologists, and for that matter, pathologists, biochemists, and ophthalmologists. It may especially hold for those who were trained during exciting periods in the history of their discipline. In the past two decades, information in every basic medical science has increased greatly, perhaps exponentially, and the basic science curriculum has been compressed to the point where the medical student can reasonably be expected to acquire only a superficial knowledge of anyone of these sciences. Hence the information provided must be carefully selected, effectively presented in retainable doses, and useful for understanding material to be presented later in the curriculum and for the solution of clinical problems. In the compact courses of today, the presentation of only enough data to support basic working concepts of structure and function is appropriate. Additional factual information consti tutes trivia, which in our opinion interferes with effective development, reten tion, and use of the concepts. This philosophy has been the basis for the preparation of this book. Consistent with this philosophy, the text is brief, and the content has been carefully examined for its appropriateness to the needs of the medical student."

In any histopathology department, cutaneous biopsies form the major part of the workload. In many instances these may be readily dealt with by experienced pathologists and their documentation represents an essential step in organising therapy. However, in a number of areas dramatic changes have occurred in dermatopathology. The rapidly changing incidence of pigmented lesions of the skin and the availability of diagnostic cell markers in the complex cutaneous lymphomas have meant that for many pathologists a review in these fields will be valu- able. The distribution and pattern of skin pigmentation may allow us to make important assertions and draw importantconclusions about the genetics of skin disease, but also about human variability. Cutane- ous vasculitis is a difficult problem where clinicopathological consulta- tion is vital in diagnosis and the review presented has been written with this verymuch in mind. In the same way, many diagnostic difficul- ties exist in assessing buttous lesions in the skin and for this reason a review was invited. Finally, our understanding of certain skin diseases has been radical- ly altered by knowledge of the dynamics of the changes seen, a field which has also beenstudied with advantage inother systemsin patholo- gy. This volume is intended as an aide to those many pathologists and dermatologists who, often together, are responsible for the pro- vision of clinical care in this demanding field. London C. L. BERRY Contents Melanoma and Other Melanocytic Skin Lesions. With 8 Figures D. WEEDON . Cutaneous Vasculitis.

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."

, 1m Kleinsten die wirkliche Wahrheit gibt graBen Gedanken erst Klarheit" KARL THOMAS Each year sees the publication of hundreds of reports of experimental work on the lymphatic tissue, yet morphological studies of the cells involved can be counted on the fingers of one hand. Furthermore, anyone who tries to identify these cells by morphological criteria is accused of sophistry and hair splitting, whereas it is accounted scientifically correct and unbiased to speak of "lymphoid cells," "blast cells" etc. Not so many years ago things were different: there were too many names and too many classifi cations and everyone backed his particular fancy. People thought of cells in terms of rigid classes, nothing then being known about the transformability of mononuclear blood cells. Today we must look for the middle way: cells should be named and defined according to morpho logical criteria but their transformation potential should be borne in mind. Once the cells are analysed and subdivided, it will be simple enough to set up proper classifications afterwards. This book arose out of the conviction that there should be more criteria and more information available on the morphology of human lymphoreticular cells; previously such information had been restricted by the difficulty of the special hematological and cytochemical staining methods."

This volume, the last in this series on cancer growth and Moreover, the current status of plant-derived vinca alka progression, is a companion volume to Volume IX and loids and non-alkaloid natural products is summarized. further explores established and novel approaches for the Advances in hyperthermia and additional approaches for therapy of patients with malignant neoplasms. The stra the therapy of malignancies are also presented. tegies reflected in these volumes are direct extrapolations The volume continues with chapters on bone marrow from the basic science of cancer biology, growth and pro transplantation as well as hematologic and nutritional sup gression described in earlier volumes of this series. Some port for the cancer patient. Blood pressure in the cancer approaches are directed towards the eradication or modifi patient, therapy for nausea and vomiting as well as pain are cation of the properties of heterogeneous malignant tumor discussed. The last chapter is devoted to the problems of the cells at various stages of tumor progression, while other terminally ill, including evaluations of the burden relatives approaches are directed towards modification of the host and friends of the cancer patient have to bear. antitumor defense systems, e. g., enhancement of host anti It is clear that important advances in the basic science of tumor immune reactivity."

Previous volumes in this series have discussed the current progression have identified a variety of targets and strategies state of our knowledge concerning the pathophysiology of to allow these goals to be realized. This volume critically cancer growth and progression. The complexity of the in reviews approaches towards cancer management in man at teraction of malignant neoplasms and the host, the the levels of: detection, diagnosis, surgery, radiology, heterogeneity of malignant cell subpopulations, and the chronobiology and endocrine treatment. existence of metastatic tumor cells resistant to drug thera Several chapters review selected methods of cancer diag pies remain as significant clinical challenges to clinical on nosis. In addition, a variety of on-going and novel ap cologists. Indeed, conventional treatment regimens of che proaches for cancer treatment are also presented in this volume. Progress in the early detection of malignant neo motherapy, surgery and radiology are often ineffective for the therapy of a large variety of established metastatic can plasms, coupled with novel approaches for the therapy of cer in patients. When one considers the insidiousness of such neoplasms, may ultimately yield safe and well-tolerated agents for the selective therapy of solid malignancies. New progressive neoplastic growth and the emergence of con tinuously more aggressive and malignant cellular subpop therapeutic approaches, directed towards the biochemical ulations one is overwhelmed with the challenges inherent in and molecular targets identified in the earlier volumes of this series, may ultimately lead to the generation of new mo attempting to control malignant neoplasms."

Polycystic ovarian disease, or polyfollicular ovarian disease, as Dr. Fut terweit prefers to call it, is a disease of uncertain etiology and for which numerous modes of therapy have been advanced. Understanding of its pathophysiology should shed light on factors regulating normal ovarian function; the converse is also true. Recent years have brought about great understanding of the neuro endocrine regulation of gonadal function, as well as of factors in the microenvironment of the ovary which affect its function. It is also ap preciated that cases classified as polycystic ovarian disease actually rep resent a clinical and pathological spectrum which may reflect the effects of diverse etiological factors. In the present volume, Dr. Futterweit presents the fruits of his long interest in and extensive experience with this disease. He thoroughly and thoughtfully reviews the vast amount of basic and clinical information that has been garnered with regard to this condition over the past decade. The numerous theories that have been advanced to explain its etiology are presented in balanced fashion, in addition to a hypothesis, which is well formulated and amenable to clinical testing. His clinical interests and judgment are well represented by his presentation of the diverse manifestations of this condition, the approach to proper diagnosis, and the available therapeutic options. Patients with this disease represent diagnostic and therapeutic prob lems in a situation where manifestations of disease may lead to major emotional stress."

Fresh research has opened up new vistas in forensic pathology that are allowing for closer national and international cooperation between pathologists and scientists in a range of medical and scientific disciplines. At the same time, autopsy and laboratory techniques are undergoing rapid evolution, with new procedures coming on stream while existing processes yield additional -- and more accurate -- results. This sixth volume of reviews in forensic pathology provides professionals working in the field with cutting-edge material on the latest key advances in the fields of traumatic death, sudden natural death and death time estimation. Now with numerous color illustrations, the book gives forensic experts across the world a fully up-to-date guide to contemporary procedures and theory in forensic science and medicine. The chapters cover an exhaustive range of aspects in the discipline, from the analysis of sudden natural deaths in infancy and childhood to the cardiac proteomics approach in the study of cases involving sudden cardiac death. Other specialist chapters deal with the forensic investigation of deaths in aviation and as a result of accidents involving all- terrain vehicles. The volume covers fresh research in the use of protein markers for the estimation of post-mortem intervals, and features a chapter telling the story of the medico-legal investigation into the deaths resulting from the 9-11 terrorist attacks on the World Trade Center.Comprehensive and current, this fresh volume of reviews is an essential resource for professionals who need to stay ahead of the game in a fast-moving and exciting field of scientific endeavor.

Over the last decade, high performance Capillary electrophoresis (HPCE) has emerged as a powerful and versatile separation technique that promises to rival high performance liquid chromatography when applied to the separation of both charged and neutral species. The high speed and high separation efficiency which can be attained using any of the various modes of HPCE has resulted in the increased use of the technique in a range of analytical environments. The procedures are, however, still in the early stages of development and several barriers remain to their adoption as the technique of choice for a range of analytical problems. One such barrier is the selection and optimization of the conditions required to achieve reproducible separations of analytes and it is in this area that this new book seeks to give assistance. The book is written by an international team of authors, drawn from both academic and industrial users, and the manufacturers of instruments. At its heart are a number of tables, divided into specific application areas. These give details of published separations of a wide range of archetypal analytes, the successful separation conditions and the matrix in which they were presented. These tables are based on separations reported since 1992 and are fully referenced to the original literature. The tables are supported by discussions of the problems that a particular area presents and the strategies and solutions adopted to overcome them. The general areas covered are biochemistry, pharmaceutical science, bioscience, ion analysis, food analysis and environmental science.

Analogue to the first edition, the principal characteristic of this work is its casting of pathology as the common nosographic link in the diagnosis, prognosis and treatment of brain tumours. A result of the author's many years of experience in the study of brain tumours and their pathological and clinical characteristics, the book presents different aspects of neurooncology from the perspective of pathology and its biological and clinical correlates. This new, second and enlarged volume preserves all the qualities of the first edition while further amplifying clinical applications and updating biological and pathological problems. The references have been completely revised and new chapters have been added on topics such as neuroimaging, invasion and angiogenesis.
Professor Schiffer is President of the Italian Association of Neurooncology and of the Italian Association of Neuropathology.