This volume represents the formal presentations and discussions which took place during a three-day meeting in March 1988 at The University of Texas M. D. Anderson Cancer Center in Houston. It is" dedicated to my friend of more than thirty years, Prof. Dr. Klaus Joachim Ziilch, who died in Berlin on December 2. 1988 while this volume was still in preparation. Klaus Zulch had devoted a significant portion of his professional life to a better understanding of central nervous tumors. Over the past two decades he served as the Director of the Collaborating Center for CNS Tumors, under the auspices of the World Health Organization (WHO), and it was largely through his efforts that the work of the CelJ. ter in developing criteria for a histologic classification of these neoplasms was kept alive. Without his stimulus this Houston meeting would probably not have taken place. In early 1987 he approached me with the idea of convening, at an early date, a meeting in Houston in collaboration with the Department of Neuro-Oncology of the Cancer Center, of which I was then Chairman. The purpose of this proposed meeting was to discuss recent research developments that might have a profound influence on the classification of brain tumors and ultimately necessitate revision of the "Blue Book" of the WHO on Histological Typing 0/ Tumours 0/ the Central Nervous System.

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 last volume dealing with lung cancer in this series in Cancer Treatment and Research was published in 1986 and entitled Lung Cancer: Basic and Clinical Aspects. The present book continues the outline of the previous volume by presenting up-to-date information on lung cancer in critical reviews of new important basic and clinical concepts of lung cancer. The present volume has broadened the scope by also including chapters dealing with issues such as epidemiology, prophylaxis, and histopathology of lung cancer. The content of the book thus reflects the increasing awareness of a global disease that is more and more in focus, not only scientifically but also politically. The latter fact results increasingly in changes in health legisla tion, with prevention measures influencing everyday life. The great interest in the disease is natural, considering that more than one patient dies from lung cancer every minute globally. The first chapter is from the Cancer Unit, WHO, Geneva, and describes in detail the epidemiologic features of lung cancer, which is the second most frequent cancer in the world with 660,500 new cases annually; it will soon surpass stomach cancer as the leader. Thirty-one percent of the cases occur in developing countries, where the increase is especially dramatic."

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series which focuses on an emerging area of cancer research. In 1968, R. H. Williams first reported that elevated prostaglandin levels are present in human medullary carcinoma. Since that time, the concept that arachidonic acid metabolites may be involved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family ofbioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respectively. Cyclooxygenase products consist of diverse products such as prostaglandin E2 (PGE2), prostacyclin (PGI2) and thromboxane A2 (TXA2), whereas lipoxygenase products consist ofhydroperoxy fatty acids and mono-, di-and tri-hydroxy acids including leukotrienes, lipoxins, and epoxides. The precursor fatty acids for the cyclooxygenase and lipoxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis --the release of substrate. This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengt Samuelsson's extensive study ofthe metabolism of prostaglandins indicate that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in the vicinity oftarget tissues leading to the concept that prostaglandins are local rrormones or autocoids. Altered production, qualitative and/or quantitative, of prostaglandins and leukotrienes has been implicated in the development of a number of disease states (e. g.

This timely work reflects the growing importance of research into the nature of sleep and its medical aspects. One of the first of its kind, this work on the neuroimmunology of sleep provides an introduction to the interplay between these two key and interlinked areas. Written both from a basic and a clinical perspective, the volume is an invaluable information resource for biomedical professionals and students of the human biology.

Highly practical guide written from both a basic and clinical perspective.

In Cellular Cancer Markers leading pathologists and physicians review today's most promising cellular cancer markers, an important emerging class of prognostic markers that can be used in the clinical evaluation of cancer patients. The markers reviewed have been chosen because they are biologically relevant to the growth of cells and possess an accurate and reproducible assay for detection. They also are predictors of tumor behavior, are useful in making clinical decisions, and are cost effective.
Cellular Cancer Markers provides a status report for markers of tumor cell activation, proliferation, and longevity that makes possible an informed judgment regarding the value of many newly proposed tumor markers. It also offers insight into the latest approaches to diagnosing cancer and an appreciation of how these marker-based tests can clarify the prognosis of cancer.

The advances in science and medicine we are now experiencing are unprec edented and exciting. Life expectancy is prolonged, and quality of life is much improved. We learn of fabulous new discoveries made at the bench or the bedside every week. Many diseases have been totally eliminated, others can be significantly improved by new therapeutic formulations. Much of the success can be attributed to a better understanding of disease processes and the specific targeting of new and more effective medications. As is the case in many areas of successful human endeavour, there can be a downside. In the case of drugs and chemicals it is their adverse effects which are of concern. Of course, every effort is made to devise medications that are safe, and the need to elucidate and understand mechanisms are crucial, yet adverse effects remain a problem. They can be unpredictable and diverse. Drugs have been shown to induce virtually the whole gamut of human liver pathology from acute fulminant hepatitis to chronic active hepatitis to cirrho sis and even malignancy. Hence the possibility of adverse drug effects must be considered in the differential diagnosis of many patients with liver disease. This is well recognized and is very important; indeed, removal of the offending agent can often lead to reversal of the adverse effect. This is an area of hepatology where we can really make a difference."

During the past three decades, histology has seen enormous progress, thanks to new techniques and new investigation instruments. Numerous discoveries of important structures and morphofunctional phenomena have been described in a wealth of papers of ever increasing size and complexity. These publi cations have become difficult to follow, not only because of their number, but also because of a disparity of terminology and the multitude of synonyms employed by different authors. All of this makes reading and comprehension of the progress that has been achieved laborious, even for histologists, but especially for students, researchers in other basic branches of medicine, or clinicians who have to consult histological texts during their studies or investigations. In order to facilitate the orientation of all those interested in histology, a concise and practical volume in encyclopedic style, defining and, at the same time, illustrating fundamental histolog ical terms, enumerating synonyms, and describing morpho functional phenomena has become necessary, both because a work of this genre does not exist and because the list of Latin terms elaborated by the International Anatomical Nomenclature Committee in 1977 does not give illustrations or definitions of histological terms. The present work attempts to redress this deficiency."

Essentials of Autopsy Practice is dedicated to updating the modern pathologist on the issues related to the autopsy. This first volume contains 12 topical chapters which are not covered in any other text. It comprises the most recent developments in current autopsy and relevant subjects that have not yet been covered in current autopsy textbooks. This is what makes this book exceptional in its field. The book will be of interest to both trainees and consultants in all sub-branches of pathology including forensic pathology. The subject matter will also appeal to other areas of clinical medicine and will make a good reference book.

This volume is the work product of an international group of authors who are experienced in the field of musculoskeletal allografts. The chapters are written by experts in many differing areas of allografting and represents the current knowledge in this rapidly changing dynamic field. The reconstructive community and their patients owe a significant debt of gratitude to Doctors Czitrom and Winkler for this volume. William F. Enneking, M. D. Preface What follows is the result of a timely project bringing together the newest ideas of top experts worldwide in a rapidly growing technology: Orthopaedic Allograft Surgery. The title of the book reflects a method rather than a speciality. It transgresses well established subspecialities of orthopaedic surgery such as joint replacement, oncology, spine, trauma and sports medicine. The technology encompasses knowledge of tissue banking, biology and biomechanics, both in a research and clinical sense. The common denominator for those interested is the need and ability to provide or use allogeneic tissues in orthopaedic applications. Inherent to a multiauthored text based on chapters written by authors from many parts of the world is a variety in format and style. While we tried to some extent reducing large discrepancies, there was no attempt made to eliminate dissimilar ities. We did not aim for a homogeneous textbook. Rather, we asked for originality, novelty, individuality in the presentation of data and concepts. Consequently, chapters vary in format from that seen in a scientific article to that of a descriptive essay."

General pathologists see many biopsies from transplanted organs but few are in large enough centres so that this forms the bulk of their work. The book describes the changes which can be observed in transplantation in all of the major organ systems that are routinely transplanted and there are accounts of the pathology of infections and of the immunological difficulties that are faced by these patients. The volume will be a valuable guide for those who wish to braoden their knowledge in this field.

More than ten years have elapsed since the publication of the first edition of Tumors and Tumorlike Lesions of Bone and Joints in 1981. During this period significant progress has been made in diagnosis, and particularly in staging and treatment of bone tumors. In most centers, limb-sparing surgery has replaced the more radical ablative surgery, with or without preoperative chemotherapy. This became possible due to the introduction and increased application of newer high-quality imaging techniques (CT and MRI) and in particular the use of new cytomorphologic methods of diagnosis, especially immunohisto chemistry. These advances in diagnosis and treatment have been reflected by the publication of new editions of several important text books, since their authors - pathologists, orthopedic surgeons, and radiologists - felt the necessity of updating their works in recent years. However, in these publications different criteria of classification were adopted. The number of cases compiled at the Latin American Registry of Bone Pathology increased from 4913 primary bone tumors and more than 1100 tumorlike lesions at the time of publication of the first edition of this book, to 5274 bone tumors and 1665 tumorlike lesions by the end of December 1985, when I finished my work as head of the Registry and occupied the positions of Professor of Orthopedic Pathology at St. Louis University Medical Center and Distinguished Visiting Professor at Rush-Presbyterian-St. Luke's Medical Center in Chicago.

One would rarely have the opportunity to augment his medical library with a more exhaustive examination of the subject matter than is contained herein. Would only that all areas of one's professional responsibilities be available in such a complete, didactic, written form. Having a decided interest in the subject of head and neck paragangliomas for the past decade, I have had the opportunity to explore the subject through published medical literature and personal investi gation, and feel qualified to commend Doctors Zak and Lawson on their dedica tion, accuracy, and thoroughness in this presentation. One seeking any particular aspect of knowledge from historical to an up-to-date concept on the subject of paragangliomas will find his answer here. Vincent J. Hyams CAPT MC USN Chairman, Otolaryngic Pathology Department Armed Forces Institute of Pathology Washington, D.C. Preface One of us (F.G.Z.) initially became interested in the paraganglionic system when as a resident in pathology at The Mount Sinai Hospital, he performed an autopsy on an elderly woman with an intracranial tumor of the posterior fossa, which extended through the jugular foramen into the neck in a dumbbell fashion."

Developmental cancer products (oncodevelopmental markers, ODM) not only serve as diagnostic and prognostic indicators but also may be used to study the nature of the carcinogenic process and the biology of tumors. For many years oncologists have searched for markers of cancer cells that would permit unequivocal recognition of cancer in contrast to noncancerous tissue. The earliest and still most widely used method of identification of cancer tissue or cells is the structural resemblance of cancer tissue to fetal or immature tissue. Pathologists not only recognize cancer by its morphologic similarity to fetal tissues, but also in many instances can relate the behavior of a given tumor to the degree of tissue differentiation. Thus, poorly differentiated tumors that resemble fetal tissue generally grow more rapidly and metastasize earlier than do well-differentiated tumors that more closely resemble adult tissue. In recent years the commonality of fetal and cancer tissue has been extended to products of tumor cells that, can be analyzed by biochemical, immunological, or physiological techniques. Increas ingly, products of cancer cells similar to fetal products are being identified and studied. These products range from cell-surface markers (fetal or differentiation antigens), placental proteins, hormones, and isoenzymes to a multitude of products, such as carcinoembryonic antigen (CEA), alphafetoprotein (AFP), lymphocyte markers, and nucleic acids, such as tRNA, that are produced in small amounts by v vi PREFACE continually differentiating cells in the adult but in much greater amounts by tumors."

Information analysis centers were developed to help the scientist and practitioner cope with the ever increasing mass of published and unpublished information in a specific field. Their establishment resulted from a further extension of those pressures that had brought about the formation of the specialized primary journal and the abstracting services at the turn of the century. The information analysis center concept was greatly advanced by the 1963 report of the President's Science Advisory Committee Panel on Science Information. This report stated: " . . . scientific interpreters who can collect relevant data, review a field, and distill information in a manner that goes to the heart of a technical situation are more help to the overburdened specialist than is a mere pile of relevant docu ments. " Such specialized information centers are operated in closest possible contact with working scientists in the field. These centers not only furnish information about ongoing research and dis seminate and retrieve information but also create new information and develop new methods of infor mation analysis, synthesis, and dissemination. The continually expanding biomedical literature produced by scientists from the world's laboratories, research centers, and medical centers led the National Institute of Neurological Diseases and Stroke in 1964 to initiate a National Neurological Information Network of specialized centers for neurological information. The Centers are designed to bring under control and to promote ready access to important segments of the literature."

This represents the third volume in a series on cancer markers pub- lished by the Humana Press. The first volume, published in 1980, stressed the relationship of development and cancer as reflected in the production of markers by cancer that are also produced by normal cells during fetal development. The concept that cancer represents a problem of differentiation was introduced by Barry Pierce in describing differenti- ation of teratocarcinomas. Highlighted were lymphocyte markers, alphafetoprotein, carcinoembryonic antigen, ectopic hormones, enzymes and isozymes, pregnancy proteins, and fibronectin. The second volume, published in 1982 and coedited with Britta Wahren, focused on the diagnostic use of oncological markers in human cancers, which were systematically treated on an organ by organ basis. At that time, the application of monoclonal antibodies to the identification of cancer markers was still in a very preliminary stage. A general introduc- tion to monoclonal antibodies to human tumor antigens was given there by William Raschke, and other authors included coverage of those mark- ers then detectable by monoclonal antibodies in their chapters.

A critical phase in coronary heart disease, unstable angina, is thoroughly discussed in contributions by well-known experts. Since myocardial infarction still belongs to the main causes of death, this topic is highly relevant for the present research and possible future treatment of coronary heart disease. The major recent advances made in the pathophysiology, diagnosis and therapy of unstable angina are reported in depth.

The impetus for compiling this book was the recent development of culture strains of neuroblastoma and glial cells and the immediate and enthusiastic way they have been taken up as model systems. After the first sudden rush of activity, it seems appropriate to pause, to assess progress, and to contemplate the future contributions that may be possible using these culture techniques. Long before the advent of established strains, cultures of nervous tissue had already contributed to neurobiology. Ross Harrison, in 1906, in a single experimental series, established tissue culture as a promising new technique in cell biology and settled the Golgi-Cajal controversy as to whether axonic processes originated as outgrowths from the cell body or were formed first in the intercellular spaces and were later connected to the cell body. Harrison observed process growth from nerve cells in cultures, thus settling the matter in favor of Cajal. Of great importance to neurobiology is the discovery by Rita Levi-Montalcini of nerve growth factor. Cultures of spinal ganglia played a major role in the discovery, isolation, and characterization of the factor (Levi-Montalcini et ai., 1954). In my opinion, this discovery, although very well known, has not yet been adequately recognized for its germinal influence on neurobiology and embryology. Progress since the advent of clonal cultures has been more modest. I would like to cite two pieces of work which emphasize the technical ad vantages of these cultures."

The field of cellular, molecular, and developmental neuroscience repre sents the interface between the three large, well established fields of neu roscience, cell biology, and molecular biology. In the last 10 to 15 years, this new field has emerged as one of the most rapidly growing and exciting subdisciplines of neuroscience. It is now becoming possible to understand many aspects of nervous system function at the molecular level, and there already are dramatic applications of this information to the treatment of nervous system injury, disease, and genetic disorders. Moreover, there is great optimism that new strategies will emerge soon as a result of the explosion of information. This book was written to introduce students to the major issues, ex perimental strategies, and current knowledge base in cellular, molecular, and developmental neuroscience. The concept for the book arose from a section of an introductory neuroscience course given to first-year medical students at the University of Virginia School of Medicine. The text pre sumes a basic, but not detailed, understanding of nervous system orga nization and function, and a background in biology. It is intended as an appropriate introductory text for first-year medical students or graduate students in neuroscience, neurobiology, psychobiology, or related pro grams;..and for advanced undergraduate students with appropriate back ground in biology and neuroscience. While some of the specific information presented undoubtedly will be outdated rapidly, the "gestalt" of this emerging field of inquiry as presented here should help the beginning stu dent organize new information."

Essentials of Autopsy Practice updates the modern pathologist on issues related to the autopsy. This volume contains topical chapters on the pathology of shock, religious attitudes to death, incised wounds, radiological investigations, metabolic disorders in childhood, maternal deaths, body alterations and piercings which are comprehensive, unique and educational. It brings the literature together into a modern, up-to-date review of the subject, each authored by experts in their field. It comprises the most recent developments in current autopsy practice making the book unique and exceptional - a valuable aid for the bench top, autopsy suite, laboratory or library. A hands-on reference book, Essentials of Autopsy Practice is of interest to both trainees and consultants in all sub-branches of pathology including forensic pathology. It can also be used by non-medical staff involved in the dead, such as nurses, police, lawyers and bereavement officers.

This atlas deals with conditions commonly encountered in the male genital tract. Whilst the majority of illustra tions are photomicrographs, photographs of macro scopic specimens are also used to illustrate important features in distinguishing different pathological con ditions. Special emphasis is placed on the small biopsy specimens obtained from prostate and testis in modern urological practice and the importance of clinico pathological co-operation in pathological practice is stressed. Recent advances in our knowledge of testicu lar tumours are discussed and illustrated. The text is not entirely descriptive and attempts to give an intellectual framework around which histopathological diagnosis in this field can be practised. A modest number of references are included; they have not been singled out as representing milestones in the development of our knowledge of these conditions - the choice has rather more centred upon recent reports from which a litera ture search can be mounted if required. The atlas in no way pretends to be an encyclopaedic reference of con ditions of the male genital tract but attempts to provide an up-to-date comprehensive discussion of the histo pathology of this system. Acknowledgements I am most grateful to Mr Keith Gordon for developing all the photomicrographs and to Mr Geoff Gilbert and his staff in the Audio-Visual Department of the City Hospital who took the majority of the macroscopic illustrations. I must particularly thank my secretary, Mrs Dorothy Clay ton, for typing and retyping my draft chapters and for deciphering my hieroglyphics."

Decoding the significance of proteinuria as an indicator of severity or prognosis in kidney disease is a stimulating challenge to students and practitioners of nephrology. Sir Richard Bright in 1827 associated pro with the disease that bears his name. In the subsequent more teinuria than a century and a half, however, the meaning of the linkage between proteinuria and renal disease remains elusive. Proteinuria is discovered on routine urinalysis in about 10 million Americans, most of whom express no symptoms of kidney disease, each year. From the studies of Robinson (updated in these pages), we know that proteinuria, per se, can be present for 20 years without change in re nal function, as described in orthostatic proteinuria. By contrast, pro teinuria may be the harbinger of swift kidney destruction, rarely cul minating in clinical collapse, a syndrome typifying "malignant proteinuria" as detailed herein by Avram. Although proteinuria is ubiquitous, an orderly management strategy for rational handling of proteinuria of less than nephrotic range is lack ing. Separation of tubular proteinuria and transient proteinuria of fever is now possible routinely. This book provides a record of the contribu tions of investigators and clinicians whose work forms the substrate for production of understanding and, ultimately, marching orders for prac titioners seeking optimized management for their proteinuric patients."

This is a book about renal cysts and cystic kidneys. Its contributors have created a resource of current information in a field that once aroused only curiosity, but that now stands at the leading edge of molecular nephrology. Its authorship includes 'oldtimers', who bring the wisdom of experience, and 'newcomers', whose presence attests to the contributions made by the investigative and technological advances of the past decade. Its text is organized to carry the reader from renal cyst to cystic renal disease. Each of its chapters defines or explores a challenge or an advance. Cells that line renal cysts are diverse in structure, type, and perhaps function. The cysts themselves lie within an interstitium that is not normal and may influence cyst development and growth. Experimental analogs of human disease offer increasing opportunities to basic researchers to examine, in sequence and under controlled circumstances, those events that favor nephron dilation, cyst growth and ultimate renal failure.

Despite the amazing progress made by the stereotactic technique, particularly regarding the localization of the target, despite the extreme caution, which stereotactic neurosurgeons apply at every step of the procedures, despite the routine roentgenologic and physiologic controls (depth EEG, electric stimulation) preceding the production of a lesion, there remains a certain degree of uncertainty regarding the position, shape and extent of the lesion as well as of the electrode track and also regarding unintended lesions in the vicinity. The final answer to these questions depends on the anatomical control. Thus we must be grateful to the authors, who performed 3700 subcortical stereotactic interventions, that they present a careful comparison of the clinical and of the pathologic anatomic findings, in the cases whose brains could be studied. They demonstrate what degree of exactness can be expected from the stereotactic technique. They also present a careful outline of the morphology, physiology, biochemistry and pathology of the structures that are affected in Parkinson patients. In addition this monograph permits one to familiarize oneself with the methods of stimulation and destruction practiced by the authors. The relevant literature is conscientiously quoted. A study of this mono graph will benefit not only the stereotactic neurosurgeon, but also neurophysiologists, pathologists and practicing neurologists.

With the advent of enzyme histochemistry, which this field and simplistic theories will be expanded or revealed hitherto unseen pathological differences discarded. between muscle disorders, muscle biopsy assumed Diseased muscle cells, as any other cell type, show an important diagnostic role. The investigation is easily only limited morphological changes. However bizarre, performed and is being undertaken with increasing very few of these changes, if any, are pathognomonic of frequency. Nevertheless there is still a tendency to a single disease. The exact significance of microscopic regard its interpretation as highly specialized and out findings is to a large extent determined by their clinical side the province of the general histopathologist. In this context. Thus, although this is an atlas, it is definitely atlas I have tried to lift the veil of neuropathological not designed to promote 'spot' histological diagnoses. I mystique and to describe and illustrate the basic have aimed to provide a guide to pathological reactions reactions of muscle cells. of muscle which will be useful to the practising histo Interpretation of the biopsy depends not only upon pathologist and all students of neuro-muscular disease. recognition of morphological abnormalities, but upon I hope that recognition of the lack of specificity of understanding why they occur. Throughout the atlas I individual morphological features will encourage the have attempted to correlate morphological changes . close clinico-pathological correlation which is essential with pathogenetic mechanisms."