A comprehensive reference guide to the successful performance of pediatric autopsies and to the optimal recognition and interpretation of their pathologic findings. The authors cover such major developmental disorders as hydrops, chromosomal defects, and congenital abnormalities, metabolic disorders, and review the major organ systems. Additional chapters address sudden infant death, cytogenetics, the medical and forensic autopsy, special procedures, cultures and infection control, and biological hazards at the autopsy. Numerous standard reference tables, copious illustrations and drawings, and an appendix at the end of each chapter provide a wealth of practical information and bibliographic citations.

In 1971, J. Folkman published in the New England Journal of Medicine a hypothesis that tumor growth is angiogenesis-dependent. Folkman introduced the concept that tumors probably secrete diffusible molecules that could stimulate the growth of new blood vessels toward the tumor and that the resulting tumor neovascularization could conceivably be prevented or interrupted by angiogenesis inhibitors. Solid and haematological tumors consist of an avascular and a subsequent vascular phase. Assuming that this depends on the release of angiogenic factors, acquisition of angiogenic capability can be seen as an expression of progression from neoplastic transformation to tumor growth and metastasis.

Beginning in the 1980 s, the biopharmaceutical industry began exploiting the field of antiangiogenesis for creating new therapeutic compounds for modulating new blood vessels in tumor growth. In 2004, Avastin (Bevacizumab), a humanized anti-VEGF monoclonal antibody, was the first angiogenesis inhibitor approved by the Food and Drug Administration for the treatment of colorectal cancer. At present, it has been estimated that over 20,000 cancer patients worldwide have received experimental form of antiangiogenic therapy.

This book offers a historical account of the relevant literature. It also emphasizes the crucial and paradigmatic role of angiogenesis as a biological process and the significance of antiangiogenic approach for the treatment of tumors."

The classification of tumors is important for understanding tumor histogenesis, for predicting prognosis, for differential diagnosis, and for recommending appropriate therapy. Since 1836, when pancreatic cancer was first described, progress has been made in pancreatic cancer morphology, and a number of classifications have been proposed. All of these classifications are mainly based on morphological characteristics. Some are too detailed to be of practical use while others are more pragmatic. Some of the inherent problems in the previous classifications included difficulties in obtaining an adequate number of pan creatic tumors for examination and insufficient clinical data and follow-up. With the increasing incidence of pancreatic cancer in many parts of the world during the past six decades, and with the availability of more tumors to patho logists, advances have been made in pancreatic tumor studies. Classifications by Cubilla and Fitzgerald and by Kloppel, which are generally similar, mostly considered prominent morphological features and their histogenesis. These pathology-oriented classifications, although complete, were not practical from the standpoint of clinicians concerned with the prognosis of individual tumors."

Single Best Answer (SBA) and Extended Matching Question (EMQ) examinations are increasingly popular means of testing medical students and those undertaking postgraduate qualifications in a number of subject areas. Written by a final year medical student, junior doctors and an experienced clinician, Single Best Answers and EMQs in Clinical Pathology provides invaluable guidance from authors who understand from personal experience that detailed and accurate explanations are the key to successful revision. This book presents 200 SBA-style and 50 EMQ-style questions arranged by sub-specialty area as well as a practice exam of random questions. A clear discussion of how the correct answer was reached and other options ruled out for every question is given at the end of each section, making this book an excellent learning aid during all stages of undergraduate clinical studies and beyond into postgraduate training, and particularly while preparing for medical finals.

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.

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.

1 2 3 O. D. Wiestler , U. Schlege1 , andJ. Schramm lInstitut flir Neuropathologie, Universitatskliniken Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany 2Neurologische Universitatsklinik, Sigmund-Freud-Str. 25, 53127 Bonn, Germany 3Neurochirurgische Universitatsklinik, Sigmund-Freud-Str. 25,53127 Bonn, Germany In contrast to various other neoplastic disorders, there has still been no dramatic progress in the treatment of gliomas. Modem microsurgical and imaging techniques have made more tumors surgically accessible and have allowed a more extensive surgical resection. However, these new developments have not improved the clinical outcome. Recently, molecular biological studies on genes and genetic loci affected in tumors of the nervous system have yielded significant new insights into pathoge- netic machanisms. Many neuro-oncologists are therefore looking forward to transla- ting molecular genetic findings into novel diagnostic and therapeutic strategies for the management of these devastating neoplasms. We have produced this volume with the intention of highlighting major developments in both molecular and clinical neuro-oncology and of stimulating the communication and cooperation between these two fields. Two major families of growth-controlling genes have emerged from the past decade of intense research on the molecular genetics of tumors: oncogenes and tumor suppressor genes. Oncogenes are characterized by their potential to stimulate the growth of susceptible cells whereas tumor suppressor genes share a growth-inhibi- ting property. A stringently controlled interplay between these two regulatory me- chanisms is required to maintain a stable composition of tissues.

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."

Contents: Intracranial Pressure and Mass Displacements of the Intracranial Contents. - Special Neuropathology - Morphology and Biology of the Space-Occupying and Atrophic Processes with Their Related Neuroradiological Changes of Diagnostic Significance. - Cerebral Angiography. - Pneumoencephalography. - Myelography. - Spinal Angiography. - Discography. - Ossovenography and Epidural Venography. - References. - Subject Index.

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."

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.

When it comes to bacterial disease, we are living in a state of false security. Antibiotics have indeed brought unprecedented health benefits, protection from and cure of bacterial diseases during the past 50 years. But there are ominous signs that the fortress and the defenses built on antibiotics are crumbling. They are crum bling because we wittingly or unwittingly created selective con ditions for the emergence of superior pathogens that can no longer be controlled by antibiotics. There are numerous warnings. After a long period of eclipse tuberculosis has now emerged as a serious threat unchecked by antibiotic treatment. Recent years have seen reports of cholera epidemics, of anthrax infections, of serious problems with Salmonella and even with E. coli, just to name a few. Mankind is in a race with microbial invaders. The challenge is to anticipate and respond to developments that affect the precarious balance between man and microbe. This will re quire new knowledge and it will take time for an effective appli cation of that knowledge."

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."

This second edition, completely revised and expanded with a new chapter on lower extremity trauma, presents chapters written by widely recognized authorities in the field of human traumatic injury. The topics covered range from automobile restraint systems to cell and tissue biomechanics, and will interest a variety of scholars and professionals including physicians; biomechanical researchers; mechanical, biomedical and automotive engineers; as well as attorneys and jurists involved in accidental injury cases.

Significant progress has doubtlessly been made in the field of cere bral protection compared to earlier centuries, as recently reviewed by Elisabeth Frost (6). She cites the recommendations for treat ment of brain trauma by Areteus, a Greek physician of the second century A. D. He expressed quite modem views with regard to the need for prompt action considering complications that follow even minor symptoms. He advised burr holes for evacuation of hema toma in seizures, the use of diuretics and, most interestingly, also hypothermia. German surgeons of the 17th century had little more to offer than prescriptions of which the most effective constituent was alcohol (10). Thus, Sir Astley Cooper was probably the next surgeon to make noteworthy contributions when advising the use of leeches to the temporal artery and other means of bleeding in stead of surgical intervention in cases of raised intracranial pressure (loc. cit. 6). Although our knowledge has greatly expanded during the last two decades, extensive discussions have led to only few conclusions. Promising results from animal studies were translated to clinical sit uations only to yield controversial and sometimes confusing results. Since the observations of Brierly (5) on ischemic cell damage, im proved information on structural aspects, probably even related to concomitant biochemical studies, should allow the validity of thera peutic concepts to be verified. Investigations on cerebral ischemia have led to the differentiation of synaptic transmission failure and membrane failure."

This volume is based on a workshop "Modulation of Synaptic Transmission and Plasticity in Nervous Systems" held in n Ciocco, Castelvecchio, Pascoli, Italy, from September 8th to 13th, 1987. The purpose of the meeting was to bring together scientists working on plasticity in nervous systems on different levels. The contributions can be subgrouped into six fields of research: 1) Presynaptic Modulation of Chemical Neurotransmission 2) Postsynaptic Signal Transduction 3) Modulation of Synaptic Transmission and Plasticity in the Hippocampus 4) Modulation of Neuromuscular Transmission 5) Molecular and Cellular Analysis of Conditioning in Marine Snails 6) Analysis of Learning and Memory in Insects Understanding how nervous systems and in particular our brain processes and stores information has been a major challenge in science for centuries and will remain for some time to come. Not until recently neurobiologists agreed to seek plasticity of behavior primarily in the modulation of the properties of synapses between nerve cells. This is to be understood within the context provided by a neural circuitry. An important stimulus came from the work on the marine snail Aplysia, where learning processes can be described as a modulation of transmitter release, traced back to a complete chain of molecular events in an identified neuron. Learning became a topic of molecular biology. Three systems appear particularly promising for this approach: insects, in particular Drosophila, marine snails and the mammalian hippocampal tissue. Our views on neurotransmission have rapidly changed.

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.

This volume is a compilation of papers presented at the Tenth International Symposium on Brain Edema held on October 20-23, 1996, in San Diego, California. This follows the sequence of meetings that was initiated 31 years ago in the First International Symposium held in Vienna. Subsequent symposiums were held in Mainz, Montreal, Berlin, Groningen, Tokyo, Baltimore, Bern, and Tokyo CY okohama). A considerable number of papers was chosen from over 100 papers that were received. The organizers wish to thank the Advisory Committee for the excellent work done in selection of the papers. We also wish to thank all the persons who contributed to the success of the Tenth International Symposium, especially the staff who worked behind the scenes. These papers were reviewed, edited, approved or disapproved by the Editorial Board. Those manuscripts that were felt not pertinent to this publication were not accepted by the Editorial Board. Therefore, the excellent quality of those that are in the book are a reflection of the authors' dedication and work and that of those of the Editorial Board in their review process. For the reader's convenience, the papers are structured according to the various disease processes which are associated with the primary topic: hypertension, hydrocephalus, infection, ischemia, tumor, etc. We do hope that the reader will enjoy the articles and that they will provide an impetus and insight for future work.

The first International Symposium on Brain Edema was organized by Dr. Klatzo and Dr. Seitelberger and held in Vienna in 1965. The second Symposium was held in Mainz in 1972 and organized by Dr. H. J. Reulen and Dr. K. Schiirmann, the third in Montreal in 1976 by Dr. H. M. Pap- pius, the fourth in Berlin in 1979 by Dr. J. Cervos-Navarro, and the fifth in Groningen in 1982 by Dr. K. G. Go. This volume contains the papers presented at the 6th International Sym- posium on Brain Edema, held in Tokyo, Japan, November 7-10, 1984. The invited lectures by Dr. I. Klatzo, Dr. A. Hirano, Dr. S. I. Rapoport, Dr. B. K. Siesj6, Dr. H. M. Pappi us, Dr. K. A. Hossmann, and Dr. D. M. Long are included as special chapters. On behalf of the organizing committee, I wish to express my deep ap- preciation to all the participants for their contribution toward making this meeting so fruitful and significant. Moreover, the great success of this Sym- posium depended on the high quality of the invited lectures and presen- tations by experts in various fields, as well as on the free and enthusiastic discussion. I was deeply impressed with the papers presented by all the authors, who endeavored to elucidate their subjects. The editors have made only minor corrections and rearrangements, since prompt publi- cation was considered to be important.

Vor die Therapie setzten die Gotter die Diagnose. Otto NiigeJi Renal biopsy has decisively enriched renal diagnostics. Kidney diseases may be monitored during their entire course, and new techniques - such as immunofluorescence and electron microscopy - may be systematically applied, resulting in novel insights into the morphogenesis, pathogenesis, and etiology of kidney lesions. These insights, in turn, have served as new starting points, in the spirit of the quotation above, for the institution of causal therapy by the clinician. This work presents our findings based on 20 years of experience in evaluating renal biopsies. As of the end of 1974, our computer-supported, systematic clinical, morphologic, and follow-up evaluation of case material consisted of over 2000 biopsies, including 679 examined by electron microscopy and 400 by immunofluorescence microscopy. The subsequent 500 biopsies (400 studied by electron microscopy and 300 by immunofluorescence) were con sidered qualitatively only. In order to enhance qualitative findings with quantitative data, it was necessary to devise new methods for quantifying electron-microscopic findings. Additionally, we attempted to correlate cyto logic and immunofluorescent observations to integrate the isolated findings of electron microscopy into a vital cytologic pattern of reactions. We also attempted to evaluate the almost overwhelming flood of publications, especially those appearing within the last 10 years. The idea for this book was conceived a decade ago. At that time, however, our own experience in renal biopsy diagnostics seemed insufficient to sup port such a major undertaking."

1. Concepts on the Causal Genesis of Human Intestinal Tumors The action of chemical substances has a significant role in the genesis of human tumors. It is assumed that most human tumors are induced by exogenous chemical noxae (Schmahl, 1970;Heidelberger, 1975; and others). In the course of intensive efforts to discover the principles of tumor etiology, important insights have resulted in recent years. These are that chemical carcinogens do not only arise as products of our tech nological civilization, but that they also occur in nature as potent solitary carcinogens and cocarcinogens (e. g., as plant products). For review, see Hecker (1972) and Preuss mann (1975). Not only "complete" carcinogens are significant for the genesis of tu mors, but also substances which are first transformed to the actual carcinogenic com pound in the organism (Schmahl, 1975). The causal significance of exogenous noxae in carcinogenesis is indicated by the fact emphasized by Bauer (1963) that malignant tumors occur predilectively at those sites in the body which are in direct or indirect contact with the environment. This applies especially to the intestinal tract."

During the past few years, a considerable number of monographs on bone tumors have been published. They are mainly restricted to bone tumors as clinical-pathological entities, since their diagnosis, more than that of other tumors, requires the interdisciplinary cooperation between orthopedic specialist, radiologist, and pathologist. However, investiga tions concerning the histogenesis of bone tumors are rather limited, although they might be helpful in explaining the unique morphological heterogeneity of tumors of the skeletal system. Furthermore, the histo genetic approach in the study of bone tumors may facilitate the inter pretation of the advanced cytobiological methods available for improv ing classification and diagnosis. Therefore, this volume presents recent pathological advances in the biological characterization of bone tumors. A major chapter deals with the differential diagnosis of Ewing's sarcoma as regards its demarcation from the so-called neuroectodermal tumor of bone. The analysis of the ground substances in bone-forming tumors may be helpful for their classification. Therefore the volume includes a chapter on the biochemical and histochemical analysis of different osteosarcoma types. Recently it has become clear that in addition to different collagen types which are not specific for bone tissue, several bone-specific proteins occur, one of which is osteonectin. Its distribu tion is obviously important for the classification and diagnosis of osteo blastic tumors. Proliferative behavior is of major importance for the diagnosis of malignant tumors.

This volume contains all the invited papers, symposium contributions and workshop reports of the 7th International Congress of Human Genetics, held in West Berlin from September 22 to 26, 1986. The organizers of this congress made sure to gain the cooperation of the leading scientists in the field from all over the world. These contributions therefore document the enormous progress made in human genetics research in recent years. The volume covers a wide range of topics, from analysis of the human genome to basic mechanisms, diagnosis and therapy of hereditary diseases, and to distribution of normal and pathological genes and DNA variation in human populations. Ethical issues raised by modern developments are discussed thoroughly. The volume is a must for all scientists and medical doctors working in human genetics research, its teaching and practical applications.

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."

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.