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."

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."

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.

In this book, precursors of gastric cancer are described histopathologically, especially about the precancerous conditons and precancerous lesions of the stomach. In addition to those precancerous changes stated in previous monographs and textbooks, some newly recognized gastric dysplasias are proposed. In order to be able to ovjectively evaluate the atypism of dysplasic changes, achievements of morphometric studies were presented.

The methods of molecular biology, biochemistry, immunocytochem istry, and in-situ hybridization introduce new opportunities for the classification and functional characterization of cell receptors under normal conditions and for a better understanding of pathogenetic mechanisms in human diseases. The cellular localization and trans location of receptor proteins can be identified using morphological methods, and it is apparent that receptors and receptor defects play an important role in pathology, notably in genetic diseases, endocrine disorders, atherosclerosis, infections, and cancer. In this volume in ternational experts give a current review of the morphology and pathological aspects of cell receptors. The complex communication of multicellular organisms is coordi nated by two regulatory systems: neural and humoral. Both systems function via signaling substances (ligands) and signal-recognizing and -transmitting molecules, called receptors. The historical develop ment of the receptor concept is based upon Paul Ehrlich's theory of "receptors in the immune system," Langley's "receptive substances in postssynaptic membranes," and Earl Sutherland's discovery of "sec ond messengers" (cAMP and Ca2])."

The origins of this book go back to the first electron microscopic studies of the central nervous system. The cerebellar cortex was from the first an object of close study in the electron microscope, repeating in modern cytology and neuroanatomy the role it had in the hands of RAMON y CAJAL at the end of the nineteenth century. The senior author vividly remembers a day early in 1953 when GEORGE PALADE, with whom he was then working, showed him an electron micrograph of a cerebellar glomerulus, saying "That is what the synapse should look like. " It is true that the tissue was swollen and the mitochondria were exploded, but all of the essentials of synaptic structure were visible. At that time small fragments of tissue, fixed by immersion in osmium tetroxide and embedded in methacrylate, were laboriously sectioned with glass knives without any predetermined orientation and then examined in the electron microscope. After much searching, favorably preserved areas' were studied at the cytological level in order to recognize the parts of neurons and characterize them. Such procedures, dependent upon random sections and uncontrollable selection by a highly erratic technique of preservation, precluded any systematic investigation of the organization of a particular nucleus or region of the central nervous system. It was difficult enough to distinguish neurons from the neuroglia.

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."

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."

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.

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.

Advances in breast cancer research, achieved through the progress of knowledge and development of new therapies, have been translated into improved quality of care for breast cancer patients. Clinical investigations and clinical trials have made the largest contribution to the body of knowledge that finds its way to the patient. Never before during the past decades of management of breast cancer has there been such a fruitful intellectual cross-fertilization of ideas among individuals involved in the generation of hypotheses, basic research, development of drugs and treatments, conduct of clinical trials, and statistical evaluation - the results of all of which are now translated into progress in clinical care. Even issues such as the quality of life of breast cancer patients, once the domain for few, are now being openly addressed by trials and discussed in a much broader forum. The IVth International Conference on the Adjuvant Therapy of Primary Breast Cancer, also known as the st. Gallen Conference, was again attended by more than 800 scientists and clinicians interested in this broad spectrum of breast cancer research and the interactions between such diverse fields of interest and specialties as cancer pathology, molecular biology, and psychosocial oncology. This volume collects findings and conclusions presented at the conference.

During the past years a considerable number of books have been published on atherosclerosis research. Much attention has been focused on the biochemical properties of lipoproteins and the involvement of lipoprotein metabolism in the atherogenic process. The monograph presented here focuses on morphologic studies of atherosclerotic plaque. One chapter deals with the pathobiochemical changes in the arterial wall at the inception of atherosclerosis. Recently the specific role of macro phages in atherogenesis has been the object of much interest. A morphological study of their role and differentiation is the topic of another chapter. This is complemented by a study of lipoprotein receptors on macrophages and smooth muscle cells both in cell culture and in situ, based on electron microscopic investiga- tions. An immunohistological study on the in situ localization promotes our understanding oflipoprotein metabolism in the arterial wall. The morphologic aspects of more advanced lesions are present- ed in studies of collagens and angiogenic processes in the athero- sclerotic vessel wall. Experimental investigations have also been useful for understanding the pathogenetic aspects of atherosclerosis; one crrapter concentrates on the metabolism of fibromuscular and atheromatous plaques in an experimental model. A final chapter deals with transplant arteriopathy and its possible parallels with conventional atherosclerosis. The widespread discussion of athero- genesis is focused on the arterial wall and its morphological alter- ations, emphasizing once again the importance of morphological research for understanding the pathological basis of disease. Borstel and Magdeburg E. VOLLMER and A.

The decisive factor in trauma is that many processes first occur at the cellular level before they can be determined in laboratory tests, and recognition of them has only recently found its way into intensive care practice. Yet knowledge of the pathophysiology of these processes is essential for an early diagnosis of multiple organ failure and the implementation of adequate therapy, which ultimately make the patient's survival possible. Professor Schlag, an internationally renowned scientist and clinician, has been concerned with the basic pathophysiological principles of shock for many years. In this book he has brought together for the first time an international team of authors primarily from the USA and Europe, who present their collective findings of trauma, shock, development of the organ in shock and early failure and of sepsis-like syndrome, and development of septic multiple organ failure. Patienten mit Multiorganversagen haben immer noch eine schlechte Prognose in der intensivmedizinischen Behandlung, insbesondere wenn sie noch zusatzlich in einen septischen Schock geraten. Hier hilft auch oft eine breite Abdeckung mit modernsten Antibiotika nicht weiter. Neue Ansatze fur eine Therapie dieser problempatienten haben sich in den letzten Jahren durch Erkenntnisse der pathophysiologischeen Vorgange die zum Schock fuhren ergeben. Herr Professor Schlag hat als anerkannte Kapazitat auf dem Gebiet der Traumatologie und Schockforschung fur dieses erste umfassende Werk zu den Grundlagen des Multiorganversagens eine beeindruckende Liste von mehr als 50 international renommierten Autoren zusammenbekommen. Das Buch ist nicht nur eine Aufarbeitung aller Grundlagen des Schocks und Multiorganversagens sondern zudem ein ausgezeichnetes Nachschlagewerk fur jeden intensivmedizinisch tatigen Klinikarzt, egal ob er aus der Anasthesie, der Inneren Medizin oder der Unfallchirurgie kommt."

Medical imaging is an important topic and plays a key role in robust diagnosis and patient care. It has experienced an explosive growth over the last few years due to imaging modalities such as X-rays, computed tomography (CT), magnetic resonance (MR) imaging, and ultrasound. This book focuses primarily on model-based segmentation techniques, which are applied to cardiac, brain, breast and microscopic cancer cell imaging. It includes contributions from authors working in industry and academia, and presents new material.

Laboratory Animal Medicine has made enor We deeply appreciate the efforts of each of the mous strides in the 47 years since R. Jaffe published authors and co-authors of the 23 chapters in this his "Anatomy and Pathology of Spontaneous Dis two volume work. In some instances the reader will eases of Small Laboratory Animals" in 1931. So note what appears to be repetition in certain chap ters. This repetition was allowed to stand in some much new information had accumulated that in a cases because different approaches seemed useful, new edition in 1958, Jaffe, aided by Cohrs and Meessen, needed the assistance of 46 colleagues to although efforts were made to delete most of the do the subject justice. Like its predecessor, this two redundancy which inevitably arises in a venture of volume comprehensive treatise on "Pathologie der this kind. We will be grateful if our colleagues point out errors and send us specific and general Laboratoriumstiere" was written in German and criticism of this work to allow corrections in the thus not readily available to the widening circle of event of reprinting or a next edition. veterinarians and pathologists who now are inter One objective has been to assemble current in ested in laboratory animals. Aside from the need to have a comprehensive formation in the pathologic aspects of diseases of review of laboratory animal pathology in English, laboratory animals."

Due to the topology and structure of the lymph nodes, their role in the pathogenesis and development of diseases is a very special one. Each organ and even each organ-related region of the body has its own group of lymph nodes, specific topological reactions, such as in circumscribed inflammation or in the metastatic spread of malignant tumors. On the other hand, all the lymph nodes of an organism join in a uniform function effected by highly differentiated structures. Volume 84 of Current Topics in Pathology presents our current knowledge about the structure and reaction patterns of this "sec ondary" lymphoid organ. Despite our original intention to publish all the contributions in one book, it became necessary to divide them: Part 1 focuses on the involved nodal compartments, cell types, and functions, while Part 2 describes their reactions in inflammatory, neo plastic, and immune-deficient diseases. Even with the cooperation of more than 30 authors, the coverage cannot be exhaustive. The scope of both parts is limited to those reactions that can be described by direct and indirect morphological methods, including modern tech niques such as immune electron microscopy."

New techniques make it possible for investigators to examine and sometimes quantify various aspects of nuclear morphology and function; now they can derive clinically and biologically useful information about the nucleus. This book draws together a series of techniques which have been successfully applied to the study of the nucleus of tumour cells. These are of fundamental importance to researchers in tumour histopathology and medical oncology. Detailed reviews are given of various aspects of the morphology, ploidy and karyotypic status and function of the nuclei in the cells of tumours and preneoplastic lesions. Topics covered include nuclear morphology in tumour diagnosis, the ultrastructure of the nucleus, karyotypic analyses of solid tumours, flow cytometric assessment of nuclear ploidy and other parameters, histomorphometry of the nucleus, and in situ hybridisation.

Sarcomas represent a group of rare tumors which arise from the largest tissue compartment of the body, but account only for about 1 % of all malignancies. Among this group of tumors, soft tissue sarcomas in adults are, in addition to osteosarcomas, the most important. In the diagnostic workup of soft tissue sarcomas modern radiological investigation methods such as CT and MRI techniques are being critically evaluated. While it is widely accepted that the conventional, stained microscopic specimen is still the cornerstone for properly planned treatment stra tegies, immunohistochemistry has come to play an indis pensable role in accurate classification. Reviewing the surgical techniques, the treatment of musculo-skeletal malignancies, especially of soft tissue sarcomas, has changed considerably over the past decades. While amputation used to be the surgical treatment of choice limb-saving procedures have now become an im portant therapeutic modality in treating such lesions, particularly in combination with percutaneous or interstitial radiotherapy. Despite adequate local treatment, many patients with soft tissue sarcomas will ultimately develop metastatic disease, usually in the lungs. For this reason, effective ad juvant systemic treatment should be given simultaneously with or soon after treatment of local disease. The results of several randomized trials evaluating adjuvant chemotherapy have been reported in the meanwhile, indicating im proved, disease-free survival with a trend towards improved overall survival. In disseminated disease, drug combi- VI Preface nations or single agents are used as palliative treatment and might help to improve survival in selected subgroups."

I was gratified by the most favorable reception and wide usage received by the first edition of this book. A decade seems to be a short period for a book on pathology, and yet it witnessed many important changes of concepts, along with a formidable growth of knowledge. The second edition required extensive reorganization. There are new chapters on mitochondriopathies, on peroxisomal diseases and on spongy myelino pathies. Major revisions and new additions were necessary in many chapters, for instance those on the dysplasias of the cerebral and of the cerebellar hemispheres, which were largely reorganized. The chapters on perinatal pathology were reordered and reorganized to give a more logical sequence of prenatal, perinatal and postnatal lesions. The entire text was worked over for brevity. A wealth of new references was added with the. aim of staying abreast with the literature up to summer 1988. All refer ences were double checked for errors. My gratitude goes to Mrs. Gisela Ropte and Mrs. Cynthia Bunker for their untiring, diligent help. As a result, this second edition is an essentially rewritten text. Advance in the prevention of human suffering is based on a thorough understand ing of the nature of disease. I hope that this text will continue to be of service in this behalf. Perhaps it may also reflect and foster the intellectual curiosity which makes the "reading of brains" so interesting an occupation. Gottingen, 1989 Reinhard L.

This two-volume treatise, the collected effort of more than 50 authors, represents the first comprehensive survey of the chemistry and biology of the set of molecules known as peptide growth factors. Although there have been many symposia on this topic, and numerous publications of reviews dealing with selected subsets of growth factors, the entired field has never been covered in a single treatise. It is essential to do this at the present time, as the number of journal articles on peptide growth factors now makes it almost im anyone person to stay informed on this subject by reading the possible for At the same time it is becoming increasingly apparent that primary literature. these substances are of universal importance in biology and medicine and that the original classification of these molecules, based on the laboratory setting of their discovery, as "growth factors," "lymphokines," "cytokines," or "colony-stimulating factors," was quite artifactual; they are in fact the basis of a common language for intercellular communication. As a set they affect es sentially every cell in the body, and in this regard they provide the basis to develop a unified science of cell biology, germane to all of biomedical research."

Rarely have the many mechanisms that might underlie neural plasticity been examined as explicitly as they are in this broad, lavishly illustrated treatment of plasticity in the somatosensory system. The reader is provided with state-of-the-art knowledge of connections at all levels of the somatosensory system. The authors examine the propensity for changes of connectivity in both the mature and developing mammal and make clear proposals regarding the mechanisms underlying these changes. Their functional significance to relevant psychophysical and neurological observations is also discussed.

Pathology in general is closely linked with clinical medi- cardiographic changes may be desired and therefore a cine and in cardiovascular pathology this interdepend- short section has been included on cutting the heart ence is, perhaps, greater than in most other specialities. according to conventionally used echocardiographic In recent years great advances in investigatory proce- planes. dures have taken place, including the examination of The heart can only react to physiological changes or fresh endomyocardial tissue obtained by bioptome, per- damage in a limited way and therefore a separate chapter mitting not only clinico-pathological correlation but also on hypertrophy and dilatation and another chapter deal- examination at histochemical and ultrastructural levels. ing with changes in the endocardium, which reflect hae- Angiography has gained wider usage and two-dimen- modynamic alteration and may additionally show sional echocardiography is no longer the preserve of diagnostic features, are also included. Degeneration to- specialized units. Percutaneous coronary transluminal gether with changes in connective tissue and ischaemic angioplasty is a relatively new approach to relieving heart disease are separately presented. Atherogenesis, obstructive coronary artery disease. Cardiac pathology recognition of myocardial infarction and the earliest mor- has therefore moved apace, providing not only a back- phological changes discernible at histochemical and ground to clinical manifestations but also visual proof for ultrastructural levels of investigation, which are within other investigations such as immunology and virology. the scope of modern routine laboratories, are empha- Such investigations have played an essential role in sized.