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.

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.

Advances in biochemistry, cell biology, genome-wide mutagenesis - coupled with molecular technology, including gene microarray and transgenic and knock-out animals - have been instrumental in understanding the cellular processes and molecular pathways of self-tolerance and autoimmune diseases. The molecular definition of these pathways and processes has led to novel treatments for certain auto-immune diseases that are based on the pathogenesis of diseases rather than on broad-spectrum immunosuppression. This book reviews many of these current developments and proposes future novel approaches for understanding the pathogenesis of auto-immune diseases and designing novel therapy. This book covers three major areas of auto-immunity: the basic mechanisms of immunological tolerance, pathogenesis of auto-immune diseases, and some novel therapies. This book should be useful for immunologists, molecular biologists, rheumatologists, and clinical scientists.

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.

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."

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.

There have been many advances in the field of gastrointestinal pa thology which are of considerable clinical significance during the 13 years since the last publication of a volume of Current Topics in Pathology devoted to this subject. Many have arisen from the app lication of new techniques of histochemistry, immunocytochemi stry, quantitative morphometry and molecular and cell biology to gastrointestinal diseases, but some, notably the recognition of the association of Campylobaeter pylori with the commonest type of chronic gastritis, have been achieved using such long established 'routine' histological procedures that one wonders how their signifi cance had escaped recognition for so long. The topics covered in this volume have been selected because they present advances of relevance to the diagnostic clinical pathologist. However, they re present the personal selection of the editor, and are in no way exhaustive. Many other examples of progress in our understanding of the pathophysiology of gastrointestinal diseases have been omit ted, either because of the confines of space or because they have been well reviewed recently in other publications. Most of the workload of the practising gastrointestinal patholo gist involves the diagnosis and assessment either of inflammation or of neoplasia in the alimentary tract, and this is reflected in the topics presented in this book."

In Videofluorscopic Studies of Speech in Patients with Cleft Palate, Drs. M.L. Skolnick and E.R. Cohn present multiview videofluoroscopy as a technique for the radiological evaluation of speech defects in patients with cleft palate. Dr. Skolnick's invaluable contributions as both the originator and leading authority on the subject are discussed in a concise, clinical fashion. Topics examined include the anatomy and imaging of the velopharyngeal portal; the equipment and techniques of multiview videofluoroscopy; the interpretation of results and various patterns of velopharyngeal closure; Passavant's Ridge and patterns of velopharyngeal closure; normal and abnormal speech production; and the evaluation of test results. This book is the only source which concisely and completely describes the technique and its interpretations for those who need a description of the clinical procedure.

In commissioning this volume of Current Topics in Pathology, the editor of the series, Prof. Sir Colin Berry, asked me to produce something "which is aimed at the general pathologist but from the point of view of the neuropathologist who knows what is not being done well." This was easier said than done. Many aspects of neuropathology are encountered only infrequently in general pathology and are best dealt with by re ferral of material to a specialist unit. Others need more extensive investigation than is practicable in a general pathology setting. Yet neurological disorders in general are common and are encountered by general histopathologists, paediatric and forensic pathologists on a daily basis, particularly in autopsy practice. In inviting contributions to this volume of Current Topics in Pathology, I therefore biased the con tents towards disorders in which the conduct of the autopsy and the initial approach to neuropathological investigation are of critical importance in making the diagnosis. The authors all have a wealth of experience and expertise and I believe that this is reflected in their approach, which is both personal and practical. Indeed, the emphasis in this book is very much on the provision of practical advice. All of the chapters contain guidelines on the conduct of autopsies as well as infor mation on the macroscopic and basic histological assessment of the nervous system in the relevant disorders."

The last few years have witnessed major developments in molecular biology which have had a significant impact on biomedical knowledge. As a result new concepts in cell biology have emerged, new etiologic agents have been discovered, and new drugs have become available. Furthermore, the world of mediators, cytokines, and humoral factors has enlarged considerably in a relatively short period and this has modified our views of diverse physio pathologic processes as well as opened up new therapeutic prospects. In addition, recent technologic advances have revolutionized our diagnostic methodology and have greatly enhanced the power of our therapeutic resources. All these factors have contributed to a substantial remodeling of both liver science and clinical hepatology, and these changes have generated the motivation for the production of the present book, which attempts to give an account of well-known clinical facts in the light of current thinking. It is the fruit of the coordinated work of experts from different countries in three continents. In a sense, it is a manifestation of the fact that inter national cooperation is becoming increasingly important not only in the expansion of science but also in its exposition. We hope that Hepatobiliary Diseases will be useful to both students and clinicians and that internists, gastroenterologists, and general practitioners will find in its contents a satifactory coverage of their field of interest."

This book has been written from two points of view: firstly, from the viewpoint of those who are involved in the diagnosis and treatment of lymphoid malignancies, who must meet the challenge of integrating the new biological insights into their knowledge of these diseases; and secondly, from the viewpoint of those who are involved in basic biological approaches to malignancy and immunology, who wish to know more about the function of the lymphoid tissues and their malignant diseases. Neoplasia of lymphocytes is a focus for considering many of the most important biological advances impinging on cancer in the past two or three decades, because malignant lymphoproliferative diseases offer unequalled opportunities for studying many aspects of cancer. We probably know more about lymphocytes than other normal cells because of the ease with which they can be obtained. For the same reason we probably know more about malignant lymphocytes. One or other aspect of most of the momentous advances in biology of the past two or three decades has implications for lymphoid malignancies: hybridoma technology and the use of monoclonal antibodies, gene technology, the understanding of oncogenes and growth factors in the control of growth and differentiation, insights into causation of cancer by potent tumour promoters such as the phorbol esters and by viruses, and knowledge of the control of growth function of lymphocytes themselves. Conversely, many of the advances in understanding lym phocytic leukaemias and lymphomas have implications for other cancers."

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

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

The preceding decade has seen the production of many cancer at lases. As with other techniques of descriptive epidemiology, these atlases have proved valuable in identifying areas for further re sear~h employing the methods of analytical epidemiology. How ever, the various cancer atlases produceq to date have failed to pro vide a common format of presentation, which has limited their comparability and frustrated in a large measure any attempt to compare risks across national boundaries, boundaries which in terms of environmental exposures may have little meaning. In this volume, many features of cancer atlases are presented and there are discussions on the areas where moves towards standardization could greatly increase the utility of the finished product. In contrast to topographic maps, i. e., representations of natural and man-made features on the surface of the earth, thematic maps concentrate on displaying the geographical occurrence and varia tion of a single phenomenon - the "theme" of the map. The link between thematic and base mapping is rather strong as the themat ic information to be depicted is of greater value if displayed on an accurate base map. Further, the thematic map generally uses statis tical data which are frequently related to internal administrative boundaries for enumeration. The major reason for constructing a thematic map is to discover the spatial structure of the theme of the map and to then relate the structure to some aspects of the under lying environment.

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.

This is an invaluable collection of information designed to help residents, fellows, and students - as well as any already qualified medical professional interested in revising the essentials of skin conditions - to master the basics of skin pathology. Using the principle of pattern recognition, it simplifies the multitude of dermatopathologic signs by using easy-to-memorize images of what the key features look like - photomnemonics. There are also helpful sections on the technical aspects of dermatopathology and on the key findings at each level of the skin. Organized simply and abundantly illustrated, this text will be an indispensable guide to revision for all its readers.

The ability to diagnose cancer by simple measurement of a serum or tissue' 'marker" has been a goal of medical science for many years. There is ample evidence that tumor cells are different from normal cells and pro duce substances that can be detected by currently available immuno chemical or biochemical methods. These "cancer markers" may be se creted proteins, enzymes, hormones, fetal serum components, monoclonal immunoglobulins, cell surface components, or cytoplasmic constituents. The purpose of this book is to present the current status of our knowledge of such cancer markers. The first tumor marker identified by laboratory means was Bence Jones protein. In a series of lectures delivered to the Royal College of Phy sicians in London in 1846, Dr. H. Bence Jones described studies on a urine sample sent to him with the following note: "Dear Dr. Jones-The tube contains urine of very high specific gravity. When boiled it becomes slightly opaque . . . . etc. " Dr. Jones found that heating of the urine after addition of nitric acid resulted in formation of a heavy precipitate; acid ad dition may have been required to bring the urine to pH 4-6 at which Bence Jones proteins are more likely to precipitate when heated. This urinary pre cipitate was associated with a bone disease termed "mollities ossium. " H. Bence Jones, Papers on Chemical Pathology, Lecture III. Lancet 2, 269-274 (1847)]."

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.