This second volume reports on the reaction patterns of lymph nodes in neoplastic and immunodeficient diseases. Based on the contents of volume 1, it presents a detailed survey of lymph node structures and their cellular components under these conditions. The patterns of nodal reactions to the development and spread of cancer have recently been investigated and discussed by several authors. Here, the immediate interactions between tumor tissue and the regional nodes have been assessed in experimental models and in human material. Using modern morphological methods such as im munohistochemistry on the light and electron microscopic level, new insights have been gained into the stepwise process of lymphogenous metastasis. Macrophages/reticulum cells were found to playa signifi cant role in this process, which is duly emphasized. Based on appro priate animal models, one chapter focuses on various subtypes of these cellular elements and their role in the two separate phases of tumor spread and the development of true metastases. The induction of fibronectin in lymph nodes is effected by tumor cells forming a special part of the extracellular matrix. The multifunctional fibronec tin molecule serves as a mediator between tumor cells and fibroblasts, furthering the formation of tumor stroma. This volume also contains a comprehensive survey of primary im munodeficiency syndromes and their nodal manifestations, reference being made to the most recent immunological knowledge."

Few subjects in gynecology, let alone in medicine in general, have provoked such inter est or study as cervical cancer. Although the wealth of monographs and books publish ed on the subject would seem to obviate the need for more, the great advances made in the medical sciences and in gynecological experience and techniques in recent years call for, if not require, a new book on cervical cancer to bring together the latest ideas and trends in its methods of study, diagnosis, and treatment. Although precancerous lesions have become more common, the number of women developing invasive cervical carcinomas has not increased, owing in part to programs of patient education, in part to screening examinations sponsored by the government. The gynecologist is now able to detect with well-tried and proved techniques precan cerous states of the cervix, and to treat these effectively before they become invasive cancer. Accordingly, recent interests in cervical cancer have shifted from the classic descrip tion of invasive carcinoma to newer studies of cause, diagnosis, therapy, and terminol ogy of its precursors. As the reader will learn, epidemiological studies as guides for the future account for, and justifiably so, an important part of this book. New knowledge about changes in the morphology of cervical carcinoma confirms its dependency on hormonal stimulation. Furthermore, modem experiences serve to explain which therapy is best. Overlapping of concepts and opinions between some chapters could not be avoided."

Malignant melanoma is the focus of investigations which range from basic re search to clinical trials with conventional therapy and with biological response modifiers. The involvement of investigators with different backgrounds in combi nation with recent progress in biotechnology has facilitated the characterization of the antigenic profile of melanoma cells, the analysis of the structural and function al properties of melanoma-associated antigens, and the application of immuno diagnostic and immunotherapeutic approaches to melanoma. As a result, a large body of information about various aspects of melanoma has been rapidly accumu lated during the past few years. In organizing this book I aimed at providing a readily available source of infor mation on the current research in melanoma. To this end I invited investigators with active research programs to contribute chapters describing and discussing the significance of their most recent results. To facilitate the preparation of the manu scripts and to avoid duplicating other recently published books on melanoma, I discouraged the contributors from providing extensive reviews of the literature on the various topics. Although I made every effort to be as complete as possible in the selection of the contributors, while writing this preface I realized that I had overlooked at least three investigators whose work should have been included.

The clinical biochemistry ofhepatobiliary diseases is very widely studied, and publica tions abound on this topic. However, there is no recent publication that provides a comprehensive collection of the various leading aspects that go to make up this complex theme. Therefore, we thought it useful to gather together a few scientists whose work has focused on the various clinical biochemistry-aspects of these disorders in order that they might discuss their experience and expertise. The aim of the International Satellite Symposium on Clinical Biochemistry in Hepatobiliary Disease, in addition to reviewing the individual aspects, was to describe the state-of-the-art so as to provide useful data for laboratory scientists and also for physicians working in the field of hepatobiliary diseases, and these two aims are clearly reflected in the chapters of this volume. The volume opens with an introductory chapter that gives a general overview of the various aspects of the clinical biochemistry of these disorders, while the closing chapter deals with an important aspect that deserves to be increasingly emphasized in laboratory medicine, i.e., strategies to integrate information coming from the laboratory to make them more useful for clinical diagnosis.

This book was conceived with the object of presenting to doctors and medical students with a potential interest in the disciplines of orthopaedic surgery, diagnostic radiology and orthopaedic pathology, a volume which would contain basic and essential information concerning those disorders of the skeleton in which a common interest exists. Diagnosis in such conditions is dependent on close collaboration between specialists in these subjects. As medical knowledge has advanced, so the necessity for detailed specialisation has increased. As a result co-operation in a combined approach has become of great importance. The method of presentation, in the form of Exercises, is designed to permit readers to test their own diagnostic ability. The book consists of ninety-four problems of diagnosis which might be encountered in any orthopaedic unit. The case material has been chosen to emphasise those conditions in which appreciation and integration of the clinical, radiological and pathological features are required in order to establish the diagnosis.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons }Vhy such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.

The examination of excavated human bone finds is mainly the domain of anthropologists and forensic pathologists, the former working with ancient and historical specimens, the latter with modern finds. The methodological and diagnostic approaches to these skeletal finds are the same, regardless of the time of burial. For physical an thropology, bodily human relics are dealt with as historical resources which give clues to ancient population structure, population develop ment, life-style and subsistence. They are thus able to help scientists understand the present state of human populations. The identification of the finds, whether species diagnosis or the evaluation of individual parameters such as sex, age at death, body size and shape, kinship and pathology follows the same procedure used by forensic patholo gists, whose task is the identification of bodily relics in cases of crime, mass disaster and the like. However, there are other disciplines which benefit from excavated bone finds. Anatomy gains insights into the morphological variability of the skeleton in time and place. The implications for modern physi cians and pathologists are at least two-fold: pathological specimens are suitable to unravel the distribution of many diseases and the susceptibility of individuals to pathogens in pre-antibiotic populations. In addition to this epidemiological aspect, exhumed specimens often exhibit advanced states of bone disease which are no longer or only very rarely present in today's industrialized populations because of efficient surgical intervention and pharmacological treatment."

The region of the skull base was long considered a surgical barrier because of its complex anatomy. With few exceptions, the region immediately beyond the dura or bony skull base constituted a "no man's land" for the surgeon working from the other direction. A major reason for this was the high morbidity associated with operative procedures in that area using traditional dissection techniques. This situation changed with the advent of the operating microscope. Used initially by ear, nose and throat specialists for resective and reconstructive surgery of the petrous bone and parana sal sinuses, the operating microscope was later introduced in other areas, and neurosurgeons began using it in the mid-1960s. With technical equality thus established, the groundwork was laid for taking a new, systematic, and interdisciplinary approach to surgical problems of the skull base. Intensive and systematic cooperation between ear, nose and throat surgeons and neurologic surgeons had its origins in the departments of the University of Mainz bindly supported by our chairmen Prof. Dr. Dr. hc Kurt Schiirmann (Department of Neurosurgery) and Prof. Dr. W. Kley (Depart ment of Ear, Nose and Throat Diseases, Head and Neck Surgery). The experience gained from this cooperation was taught in workshops held in Hannover from 1979 to 1986, acquiring a broader interdisciplinary base through the participation of specialists from the fields of anatomy, patholo gy, neuroradiology, ophthalmology, and maxillofacial surgery.

Continuing progress has been made since the first edition of Artificial Liver Support was published. Liver transplantation has however become an estab lished therapy for a relatively small number of patients who remain patients for life. There therefore continues to be a great need for the development of other forms of artificial liver support. Improved intensive care utilizing improved plasma exchange, dialysis, sclerotherapy, and intracranial pressure monitoring have improved survival in fulminant hepatic failure. Progress has also been made in lipid membrane detoxification, in cell cultures, and in cell transplantation, and the isolation of various liver cell growth factors has led to deep insight into the mechanisms of liver regeneration. This book gives the clinician and the researcher detailed information about established new methods of clinic work and laboratory research, and describes new experimental approaches indicating the direction of future research. G. BRUNNER M. Mno Preface to the First Edition The regenerative capacity of the liver cell is almost unlimited. Therefore after acute liver damage, be it viral, toxic, hypoxic, or surgical in origin, restitutio ad integrum is the usual outcome. In two forms of liver disease, however, this is not the case: in fulminant hepatic failure, liver regeneration often is not fast enough to keep the organism alive; in end-stage cirrhosis, regeneration is disturbed by a hypertrophic architecture of fibrotic tissue. For these extreme forms of liver disease and for critical situations before and after liver surgery, artificial liver support is needed.

I am honored to have been invited to write a foreword for this book, because tumors of the yolk sac have been a preoccupation of mine since the days of my residency, now more than 3 decades ago. At that time, a 3-year-old boy died of a testicular cancer of unknown histo genesis. It was bad enough that the child died, but it bothered me even more that medical science did not know the histogenesis of the tumor that destroyed him, and I decided to study testicular cancer. For re search training I sought out F. J. Dixon, who had written the Armed Forces Fascicle on testicular tumors. Dr. Dixon and I showed that embryonal carcinoma was a multipoten tial malignant stem cell that differentiated into the three embryonic germ layers of murine teratocarcinoma. This led to the idea that the normal counterpart of embryonal carcinoma must also be multi potent, and we focused on the preimplantation embryo for the histo genesis of the tumor. This idea was strengthened by the discovery that embryonal carcinoma cells made embryoid bodies in the ascites and it was possible to observe the development of these bodies in vitro. These observations led to the idea that embryonal carcinoma was a caricature (gross misrepresentation) of early development, and car cinomas in general were a caricature of the process of renewal of their normal counterpart."

Society is showing increasing concern for disorders related to aging that lead to a loss of brain function. In view of the enormous proportion of elderly people in our society today, brain aging is more than ever subject to challenge to us all, not only politicians and health authorities, but every individual who is confronted with the difficult situation of watching the mental powers of apparently healthy elderly friends, neighbours, or relatives fail, often with alarming rapidity. This challenge is directed especially toward us scientists. As one of our colleagues succinctly put it 2 years ago at the close of our First International Symposium on Brain Aging: "Do something. We are not dealing here with just another disease; we are concerned with human dignity. " More than any statistics, these words convinced me that Tropon's decision to leave the field of classic CNS pharmacology and move into the field of gerontopsychopharmacology was the right one, even though we knew that success would be uncertain and that, even if it finally comes it will be many years hence. At this point, let me add a personal comment: each one of us is judged by his or her own success. We live in a competitive society where success counts. This applies not only to the businessman, but also to the scientist, in particular, to those in industry.

The blood basophils lead a shadowy existence in the field of hematology, even now, 100 years after their discovery by PAUL EHRLICH. In clinical medicine they were hardly noticed for many decades, since they occur in such small numbers in the blood that small and moderate variations in the basophil count were not detectable with common count ing methods. This situation has changed since the in troduction of direct counting methods. It was noticed, for example, that the blood basophil count is increased in hy perlipemia. In the field of pathology the blood basophil was prac tically overlooked until recently. This was due to the fact that with common fixations in aqueous solutions the granules dissolve, so that the cells can no longer be stained specifically and therefore escape observation. This problem was solved through special fixing solu tions. However, interest in the blood basophils remain ed confined to only a few research groups.

Competitive binding techniques such as radioimmunoassay (RIA) are widely used to measure an enormous variety of compounds in biological fluids. Current methods have 1 2 arisen from the pioneering work ofYalow and Berson in the U. S. A. and Ekins in the u. K. Much of the early development was concerned with the analysis of protein hormones, and nearly a decade passed before attention focussed also on small molecules such as steroids and drugs. The potential of immunoassay methods for drug monitoring in clinical and forensic laboratories and in addict treatment programmes resulted in the commercial production of immunoassays for various therapeutic and abused drugs, making the technique available to laboratories lacking the facilities to raise their own antisera and synthesise labelled compounds. However, commercial assays are not only expensive but are restricted in range, and so it is advantageous for a forensic laboratory to have the capability to devise "in-house" immunoassays suited to its particular requirements. This chapter describes the theory and practice of RIA in forensic drug analysis. Much of the theory and some of the practice are applicable to immunoassays in which non isotopic labels are used, but such assays are not described in detail since, to date, the versatility and sensitivity of RIA have made it the immunoassay technique of choice in forensic toxicology. The particular advantages of RIA are its sensitivity and the fact that samples such as haemolysed blood can be assayed with little or no prior preparation."

Oral Pathology as part of the Head and Neck Pathology is an interdisciplinary field of science. The oral mucosa and the saliva are reflectors of many systemic diseases of the organism and therefore valuable parameters of the diagnosis and prognosis of pathological processes. In the last years many new methods have been integrated in the diagnostic repertoire. Proliferation markers are of predicitive value and characterize the biological behavior of a tumor. Markers are such as oncogenes, growth factor receptors or genetic aberrations. The importance of these new markers shall be discussed concerning the different types of oral cancers and salivary gland tumours.

Alcohol abuse ranks among the most common and also the most severe environmental hazards to human health. Its significance is heightened by the possibility of prevention by elimination of the habit, however, rarely exerted. The incidence of deleterious effects on human health has relentlessly risen in the past years for a variety of factors. They include migration of populations and, particularly, increased urbanization. Thus, in some parts of the world, population groups previously spared have become involved, which is also re flected in the increasing number of breweries and distilleries in the developing countries. Social, religious, and gender-related barriers to alcohol consumption are loosening, and the financial improvement of some segments of populations now enable them to buy alcoholic beverages. Thus the greatest percentage rise in the United States has recently been in black women. Adolescents and young people drink more alcoholic beverages than ever, and growing alcohol abuse by pregnant women has let to an increase of the incidence of the fetal alcohol syndrome. While the social and behavioral, including psychiatric, consequences of alcoholism are staggering, the gastrointestinal and, particularly, hepatic manifestations are the most widespread somatic effects, and chronic hepatic disease in alcoholics appears to cause the greatest cost to society. Indeed, mortality from liver cirrhosis is considered a reliable index of alcohol consumption in a country."

Various nouns have been used in the past to describe the Black races of South Africa and these terms will be used interchangeably in the text. They include "Bantu, African, Negro and Black". Although the currently recommended term is that of "Blacks of South Africa", many articles have been published in the Medical literature referring to Bantu, e. g. , "Bantu Siderosis", and other articles have appeared referring to African, e. g. , "African Cardiomyopathy". The material for this study was derived from the pathology laboratory at Barag wanath Hospital (2,500 beds) which serves the town of Soweto, a Black town of ap prOximately 1 million inhabitants ten miles southwest of Johannesburg. There may, of course be differing incidence rates for various diseases in different parts of South Africa, although the overall trend is fairly uniform. No figures are available as to how long the inhabitants of Soweto have lived in the town or whether a significant percent age originated in rural areas. No comparisons were therefore attempted between dis ease in rural and urban areas. The material in this book deals essentially with pathol ogy in the urban Black. This book is not a comprehensive study of pathology in the black Community. Only certain aspects are dealt with, particularly those topics of in terest to the author.

The tumors of the brain similar to other pathological changes of that particular organ claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in basic neurosciences and medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale and is permanently being critically modified or changed due to fundamental new insights which come up in always shorter intervals. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper disposability for rational management and therapeutic strategies.

Our understanding of inflammation has increased rapidly in recent years, due in large part to the impact of molecular biology and gene identification and cloning. This book brings together ideas from a number of different biochemical disciplines which are frequently not integrated. The first chapter gives a visual overview of the subject; the remaining chapters are organized into three themes: the affector molecules, the regulatory components and the processes of inflammation itself. This book is essential reading for the busy physician or pathologist who wants to be up-to-date with the latest developments in immunology as they affect the diagnosis and treatment of many conditions.

Neurosurgery o/the Future: Computers and Robots in Clinical Neurosurgical Practice and in Training - a Philosophical Journey into the Future Many present day neurosurgeons believe that they already obtain good results in operative surgery with the benefit of the operating microscope and other aids which have become available in the last three decades and that the introduction of computers and robots to the operating theatre is superfluous. However, it is clear from analogy with the function of the airline pilot, another profession where there are great demands on manual skill and on spatial awareness, that these devices do have much to offer neurosurgery. Classical neurosurgery, in the time of Cushing, Dandy and Scarff, was based on a three dimensional picture of the patient's brain formed in the surgeon's mind and often illustrated in elegant drawings. Such pictures were based on neuroradiological studies by pneumoencephalography, ventriculography or by angiography. Generally these stud ies showed the presence and position of a lesion by displacement of normal brain structures and the picture was built up by interference. This was then converted by the experienced neurosurgeon into a plan for the craniotomy site and the trajectory of the surgical approach. Once the brain was exposed further pre-operative information was obtained by visual inspection and by palpation with the brain needle. These classical forms ofneuroradiology have largely been superseded by computerised tomography and by magnetic resonance imaging."

Alcohol and other drugs of abuse are major contributing factors to liver disease and its pathology. Alcoholic cirrhosis causes thousands of deaths each year in the United States, and encourages liver replacement. A better understanding of the mechanisms of liver pathology will significantly aid basic researchers and physicians in treating and preventing liver damage. This book is designed especially for those researchers wishing to understand alcoholic liver disease. Therefore the role of alcohol in changing nutrition and its nutritional effects on liver disease are reviewed. The generation of free radicals during alcohol use has been found to be an important cause of membrane changes, of cancer development, and of lipid alterations-and thus of liver pathology. In addition to alcohol, other drugs of abuse, including morphine, cocaine, marijuana, and caffeine have also been shown to be significant contributors to liver pathology. The prevalence of drug and alcohol use and abuse today means that liver disease will continue as a major social and medical problem. The explanation of its biological origins cannot fail to help us better understand and treat the disease in the years to come.

It is a great honor and pleasure for cerebral infarction have been carried me to have Springer-Verlag publish out. Dr. Yoshimoto hoped that the this volume entitled "Treatment of results of research done in our depart Cerebral Infarction." I am much in ment over the last sixteen years con debted to my colleagues for my success cerning cerebral infarction could be in publishing this book. published. Moved by his enthusiasm, I have engaged in clinical work in my colleagues took their share in writ the field of neurosurgery for these few ing each article. I suggested to them decades and I have performed more that this volume should cover primarily than 5,000 major operations of intra the results of our own research, but that cranial surgery. Throughout this time, at the same time it should also include it has been my privilege to conduct a 2- the results of related work done by neurosurgical experts throughout the hour-morning research seminar in our department every Wednesday and to world. Therefore, I hope that this book supervise a great deal of research. At will interest many investigators who these seminars my fellow research have devoted themselves to research in workers and I have exchanged many the field of neuroscience. ideas about the study of neurosurgery My colleagues acknowledge that and we have designed many animal our research has been stimulated and experiments."

Increasing specialisation in pathology reflects the progressive changes in medical practise. The advent of a specialist with a new interest in a hospital or clinic may present the pathologist with a need to extend his or her knowledge to be able to work closely with the clinical practi tioner in order to provide adequate clinical care. Some sub-specialisations are long established, such a one is neu ropathology. However, an exclusive specialist practise is generally con fined to neurosurgical centres and much neuropathology is of necessity, executed by geneni.l pathologists. The areas covered by this volume are those which are commonly managed by the generalist. Professor Adams' account of how the skull and brain should be examined here will give confidence to many by defining a good technique and the careful description of various kinds of vascular injury lesions resulting from raised intracranial pressure will help to clarify repeated difficulty. More subtle forms of damage are also considered in detail. Professor Weller provides a detailed account of how the central nervous system may be examined in a way which permits all of us to prepare material which will allow adequate investigation of central nervous system disease and the proper examination of peripheral nerves. This chapter will become a "handbook" and will be of interest to those in training and established practitioners. Muscle biopsy is also dealt with; this is an area of investigative concern for many gener alists. The role of that singular neuropathological technique is very clearly emphasized.

If you want practical information on how to use this book please refer to "Note to the Readers" p. VII. Histochemistry and cytochemistry are essential tools in biomedical research and routine service laboratories. Most texts on histochemistry fall into one of two categories: 1. Encyclopaedic texts covering all or nearly all information available on the whole or selected parts of histochemistry. 2. Reviews or surveys of methods found to be useful by the author(s). While the former category often appeals to the more philosophically inclined reader, direct guidance on the selection of technique may be difficult to find. In contrast, the latter category are often excellent sources for details on how to perform a particular method with a reasonable chance of success. Consideration of the exact mechanism of staining, of possible reasons for failure, and of alternative techniques are, however, frequently lacking. This book is an introduction to the scientific basis of histochemistry and is intended to provide a background for the selection and development of appro priate methods. It is not a "cook book" and readers expecting exhaustive methodological descriptions will be disappointed. Although most ofthe contributors to this book would not describe themselves as histochemists, they have all at some time found it essential to develop a basic understanding of histochemistry. This book contains the information they would have greatly appreciated ready access to at that time."

More than a quarter century has passed since the initial descriptions of tardive dyskinesia (Schonecker, 1957; Sigwald et aI., 1959). The earliest epidemiologic study of this disorder was carried out in Roskilde, Denmark, by Uhrbrand and Faurbye (1960); the term tardive dyskinesia was first used a few years later in a subsequent paper (Faurbye et aI., 1964). Despite 25 years of intensive investiga- tive scrutiny, the syndrome persists, and approaches to its prevention and treat- ment continue to have limited efficacy. It is thus fitting to evaluate what has already been learned and consider future directions for research. . Tardive dyskinesia is generally dermed as an involuntary movement disorder, mainly involving the mouth, which attends long-term neuroleptic exposure. Beyond these simple facts, however, there has been relatively little consensus about this disorder. A desire to address the controversies associated with tardive dyskinesia prompted the organization of an international symposium at Kolle- kolle, just outside Copenhagen. This publication comprises all 26 presentations.

The enormous importance of the diseases of the locomotor system in all populations and the large component of general clinical practice which they represent have not, in the past, been matched by an appropriate pathological effort. Increasing expectation of an active and long life has resulted in a great increase in specialisation in Rheumatology and rehabilitation of those with crippling diseases. This volume presents many of the pathological advances that have followed this clini cal interest, beginning with reviews of changes in biological materials obtained by in vasive investigation of joints, continuing with an account of therapy Goint replace ment) and also describing a "new" hazard - hyperbaric injury. Experimental models of joint disease are also described as are other entities such as crystal deposition dis ease. A detailed consideration of the electron microscopy of bone tumours is included since this data is not widely available in current texts. Finally, the role of the HLA system in rheumatic disease is included, indicating the value of close co-operation between clinician and pathologist in defining and link ing the various rheumatic syndromes. London Contents Examination of Synovial Fluid. With 9 Figures P.A. Revell ........................................... . The Synovial Biopsy. With 20 Figures F. Eulderink. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 25 Tissue Reactions to Joint Prostheses and the Products of Wear and Corrosion. With 20 Figures P.A. Revell. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73 Bone and Joint Diseases in Workers Exposed to Hyperbaric Conditions."