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."

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."

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.

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 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 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.

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."

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.

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.

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."

Blood Supply of Bone: Scientific Aspects provides a comprehensive description of the development and physiology of blood supply to the skeleton. Investigative techniques for different types of bone in the body are discussed and the effects of disturbed circulation and the vascular control of osteogenesis is described. This highly illustrated and authoritative volume contains much revised material and many new illustrations reflecting 25 years of advances in this research field since the publication of its well-known precursor in 1971. The wealth of information will not only be invaluable to orthopaedic surgeons, rheumatologists, and radiologists but also pathologists, sports medicine specialists and bone metabolism research workers.

This volume covers, in a logical sequence, the brain neuroscience which underpins current management of malignant brain tumours. Cellular and molecular studies are considered, as well as current concepts of histopathological classification and grading. The clinical manifestations and natural history of these tumours is set in context by a discussion of the pathophysiology of intracranial mass lesions. Special attention is given to low-grade and childhood tumours. The more common cerebral gliomas and cerebral metastases are also examined. Diagnostic imaging methods are described and the differential diagnosis of benign and malignant tumours is explored. The final chapters are devoted to conventional and innovative methods, along with the results, of treatment by surgery, radiation, chemotherapy and immunotherapy.

Over recent years, much renal research has focused on the pathology of the glomerulus, where many primary renal insults occur. However, nearly thirty years have passed since Risdon's study made the apparently anomalous observation that the extent of damage to the tubulointerstitial compartment is the major determinant of renal outcome in a variety of human glomerular diseases. This volume covers various aspects of tubulointerstitial disease, and starts with an update on cystic disease of the kidney, by Drs. WILSON and FALKENSTEIN, which includes recent experimental data on the altered properties of cystic epithelium. My own chapter gives an overview of the mechanisms of tubulo interstitial damage in progressive renal disease and includes a dis cussion of the possible role of cytokines, vasoactive peptides and peptide growth factors found over the last few years to be secreted by renal tubular cells. These comments are expanded in the contribution by Dr. WOLF and Professor NEILSON, who provide a detailed account of the cellular biology of tubulointerstitial growth. The earliest studies from the 19608 attempted to correlate histo morphometry of the tubulointerstitium with renal outcome. Dr. KHAN and Professor SINNIAH provide us with an update on mor phometric methods as applied to the kidney using new techniques. Similar techniques are employed by Dr. IVANYI and Professor OLSEN who give a detailed stereomorphological account of tubulitis both in acute allograft rejection, where its- recognition is central to the diagnosis, and in other forms of tubulointerstitial disease."

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 early development of the mammalian embryo belongs to a period which, for the student, provides the particularly deep fascination connected with the processes of germination of the fIrst tender buds of life. Moreover, developmental biology encompasses a very large part of biology; if broadly dermed - almost all of it. The same is true for the fIeld of pathology if the manifold possibilities of disorders of the orderly arranged pathways of developmental processes are considered. Normal development in its earliest steps - and it would be diffI cult to see it otherwise - means the functioning of very intricate systems of complex inter dependent cycles controlled by structural, genetic, physiological and biochemical determi nants. However, disturbances interfering with them in their very different ways, can lead to fetal death, disorders of growth and differentiation, malformation and disease, sometimes as late as in the next generation or later. This is, indeed, the concern of the pathologist to whom and to whose interest in developmental pathology, this book is dedicated. The outlines of the present volume were conceived at a symposium on "Control of early em bryogenesis and factors responsible for failure of embryonic development" held May 1-4, 1974 in Travemtinde and sponsored by the Deutsche Forschungsgemeinschaft. Almost fIfty active participants attended this conference. At the time and in keeping with the purpose of the conference, publication of the proceedings was not envisaged."

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.

Although most textbooks of neurology contain a certain amount of pathological informa tion, neuropathology has often been treated in isolation. However, neuropathology has a close relationship to clinical neurology, neurosurgery and neuroradiology. Thus, advances in the rapidity and accuracy of pathological diagnosis have often led to changes in clinical management and, recently, improvements in clinical diagnosis, particularly CT scanning, have brought about a change in emphasis in the practice of neuropathology. In this textbook we have sought to present a widely based account of neuropathology in combination with information from clinical experience. We chose this approach in order to emphasize the close interrelation between clinician and pathologist. The book grew out of a course organised jointly by two neurologists and two neuropathologists from the Depart ments of Neuropathology and Neurology of The London Hospital and The University of Southampton. It is hoped that the book will be useful not only to pathologists, neurologists, neurosurgeons, and neuroradiologists, but also to general physicians. In a period of rapid advance in knowledge it is important to recognise how changes in the clinical and laboratory disciplines overlap. In order to make the most of consultations with pathologist colleagues the clinician must know what skills and techniques are available in the laboratory, and similarly, the pathologist must keep abreast of changes in clinical practice. In the past the clinician and pathologist have often been slow to appreciate advances in each other's fields."

With the introduction of antibiotics acute inflammatory disease has ceased to be the dominant problem in general medical practice and its place is now increasingly occupied by chronic inflamma tory disease of which the rheumatic diseases constitute the most important group. lwo aspects of these diseases need to be consid ered, their aetiology and their pathogenesis. In some respects the latter is more important since even when the aetiology is known, as for example the haemolytic streptococcus in rheumatic fever, the mechanism by which the infecting agent accomplishes the development of the lesions that characterise the disease are still largely unknown. Still more so is this the case in rheuma toid arthritis and other chronic inflammations where the aetio logical agents are unknown. In an attempt to clarify the pathogenic mechanisms involved, sev eral attempts have been made to induce comparable lesions in ex perimental animals, partly to test underlying hypotheses, and partly to provide test situations for the trial of new therapeu tic agents. In view of the deficiencies in the current drug treat ment of chronic inflammatory disease there are many who feel that this is largely due to the inadequacy of the models avail able for test purposes."

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."

The aim of this book is to expand the clinical information given by computed tomograms (CTs) of cerebral infarcts. Anatomical sections are displayed parallel to the CT correlate in the hope that the interpretation of pathogenesis will provide valuable clinical data at a time when the number of angiographies performed in cerebrovascular cases has diminished rapidly. For better understanding of pathogenesis our concepts concerning the process of infarction have been summarized on the basis of schematic draw ings. K.-J. ZULCH KOln Acknowledgments I am most grateful to Professor Hoeffk: en for permission to use computed tomograms from his institution, to Herr GOldner and Frau Miihlhover for their technical assistance, and to Frau Goldner for help during the editorial work. My particular thanks go to my friend Professor W.S. Fields, Houston, who undertook the great burden of styling the English text. My gratitude is expressed to Dr. Dr. h.c. multo Heinz Gotze and Springer Verlag for the excellent layout and quality of this book."

Immunology, in all its facets of immunochemistry, humoral immunity, cellular immunity, immunodiagnosis, and immunotherapy, is currently the most rapidly advancing discipline of clinical and experimental oncology. But as in most developing subjects, it is continually beset with problems of methodology and nomenclature, both of which are often intertwined. Indicative of this problem are our circular definitions of antigen and antibody. Another fre quent problem is the use of the words "specific" and "associated" when characterizing re actions to tumors or the antigenic properties of neoplasms. When applied to cancer, these terms are obviously very dependent upon the methods used to demonstrate these qualities. Indeed, the very diverse nature and multitude of types of cancer preclude our making gen eralizations or categorical statements regarding tumor "specificity. " Similar problems arise when one considers that many antigens found in malignant tumors share certain properties with embryonic or fetal tissues. First, these observations emphasize a lack of true tumor specificity, for which reason the category of oncofetal antigens has been established. Second, whether or not such antigens are truly oncofetal depends upon the method of detection used, and it has been found that here too specificity decreases as the antigen assay increases in sen sitivity. Thus, whether substances can be truly oncofetal in nature still remains a matter of debate, and such terms must therefore be used in an operational sense.

La pathologie vasculaire a ete tres marquee par les progres biologiques de ces vingt demieres annees. Le systeme arteriel est main tenant considere comme un organe a part entiere. Modelee au cours de l'organogenese par les facteurs hemodynamiques, Ie paroi arterielle maintient une structure hautement organisee et des proprietes mecaniques qui dependent directement des conditions de pression et de debit. La monocouche endotheliale developpe 2 une surface de plusieurs centaines de m a l'interface sang-tissu; elle est a la fois un organe endocrine complexe synthetisant de nombreuses proteines qui participent a l'hemostase, une surface thromboresistante et hemocompatible, une barriere de permeabilite contr6lant les echanges sang-tissus. Les cellules musculaires lisses constituent un tissu multifonctionnel, contractile, assurant la synthese des composants structuraux responsables des proprietes mecaniques de la paroi arterielle, la transmission de la force contractile, et une etonnante activite reparatrice en reponse aux agressions. Tout ceci est soumis a un ensemble complexe de communications cellulaires qui font de l'endothelium un veritable systeme recepteur pour la paroi vasculaire. Parallelement, ou a la suite de ces progres, l'angeiologie s'est progressivement affirmee comme une specialite clinique. Debordant Ie cadre de la chirurgie vasculaire, elle integre les concepts physiopathologiques au diagnostic et au traitement des maladies arterielles. De cet effort d'integration est ne cet ouvrage, cherchant a concilier les connaissances fondamentales es plus recentes et la demarche clinique.