, 1m Kleinsten die wirkliche Wahrheit gibt graBen Gedanken erst Klarheit" KARL THOMAS Each year sees the publication of hundreds of reports of experimental work on the lymphatic tissue, yet morphological studies of the cells involved can be counted on the fingers of one hand. Furthermore, anyone who tries to identify these cells by morphological criteria is accused of sophistry and hair splitting, whereas it is accounted scientifically correct and unbiased to speak of "lymphoid cells," "blast cells" etc. Not so many years ago things were different: there were too many names and too many classifi cations and everyone backed his particular fancy. People thought of cells in terms of rigid classes, nothing then being known about the transformability of mononuclear blood cells. Today we must look for the middle way: cells should be named and defined according to morpho logical criteria but their transformation potential should be borne in mind. Once the cells are analysed and subdivided, it will be simple enough to set up proper classifications afterwards. This book arose out of the conviction that there should be more criteria and more information available on the morphology of human lymphoreticular cells; previously such information had been restricted by the difficulty of the special hematological and cytochemical staining methods."

Over the last decade, high performance Capillary electrophoresis (HPCE) has emerged as a powerful and versatile separation technique that promises to rival high performance liquid chromatography when applied to the separation of both charged and neutral species. The high speed and high separation efficiency which can be attained using any of the various modes of HPCE has resulted in the increased use of the technique in a range of analytical environments. The procedures are, however, still in the early stages of development and several barriers remain to their adoption as the technique of choice for a range of analytical problems. One such barrier is the selection and optimization of the conditions required to achieve reproducible separations of analytes and it is in this area that this new book seeks to give assistance. The book is written by an international team of authors, drawn from both academic and industrial users, and the manufacturers of instruments. At its heart are a number of tables, divided into specific application areas. These give details of published separations of a wide range of archetypal analytes, the successful separation conditions and the matrix in which they were presented. These tables are based on separations reported since 1992 and are fully referenced to the original literature. The tables are supported by discussions of the problems that a particular area presents and the strategies and solutions adopted to overcome them. The general areas covered are biochemistry, pharmaceutical science, bioscience, ion analysis, food analysis and environmental science.

The idea for this treatise on the radiological anatomy of superficial and deep spinal cord vasculature evolved from daily routine neuroradiological work. This was also the reason for subdividing the monograph into a postmortem anatomical and a clinical part. The actual importance of a clear conception of radio anatomic fundamentals was made clear by many clinical conferences with neurologists, neurosurgeons and orthopedists, where a lack of knowledge about medullary syndromes of suspected vascular origin became evident. Also among neuroradiologists there is still widespread uncertainty in the interpretation of myelograms and angiographies in such cases. A study of the spinal cord's angioarchitecture is all the more justified and necessary considering the vast number of descriptions of cerebro vascular anatomy and pathology. The clinical challenge posed by patients suffering from partial or complete transverse spinal lesions has grown due to new diagnostic and therapeutic approaches. Myelography using water-soluble contrast media, X-ray computed tomography, magnetic resonance imaging and spinal angiography today allow and require both earlier and topographically and pathogenetically more exact classification of diseases of the spinal cord and its surrounding structures. Due to progress in microneurosurgery and interventional neuroradiology, even intramedullary lesions have become more and more accessible and treatable. Therefore this monograph mainly addresses those concerned with invasive therapeutic techniques and who are familiar with the interpretation of radio anatomic findings. A comprehensive description of medullary vascular syndromes would be beyond the scope of this treatise."

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.

Analogue to the first edition, the principal characteristic of this work is its casting of pathology as the common nosographic link in the diagnosis, prognosis and treatment of brain tumours. A result of the author's many years of experience in the study of brain tumours and their pathological and clinical characteristics, the book presents different aspects of neurooncology from the perspective of pathology and its biological and clinical correlates. This new, second and enlarged volume preserves all the qualities of the first edition while further amplifying clinical applications and updating biological and pathological problems. The references have been completely revised and new chapters have been added on topics such as neuroimaging, invasion and angiogenesis.
Professor Schiffer is President of the Italian Association of Neurooncology and of the Italian Association of Neuropathology.

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 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.

The International Life Sciences Institute (ILSI), a nonprofit, public foundation, was established in 1978 to advance the sciences of nutrition, toxicology, and food safety. ILSI promotes the resolution of health and safety issues in these areas by sponsoring research, conferences, publications, and educational programs. Through ILSI's programs, scientists from government, academia, and industry unite their efforts to resolve issues of critical importance to the public. As part of its commitment to understanding and resolving health and safety issues, ILSI is pleased to sponsor this series of monographs that consolidates new scientific knowledge, defines research needs, and provides a background for the effective application of scientific advances in toxicology and food safety. Alex Malaspina President International Life Sciences Institute Contents Series Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Part I. Approaches to Assessing the Toxicity of Airborne Toxicants Chapter 1. Standard-Setting as an Integrative Exercise: Alchemy, Juggling, or Science? . . . . . . . . . . . . . . . . . . . . . . . 1 D. v. Bates Chapter 2. Species Differences in Inhalation Toxicology: Variations in Exposure-Dose Relationships and Macrophage Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 J. D. Brain Chapter 3. Cell Populations of the Respiratory System: Interspecies Diversity in Composition, Distribution, and Morphology . . . . . . . . . . . . . . . . . . . . . . . . 25 e. G. Plopper, A. Mir, J. St. George, N. Tyler, A. Mariassy, D. Wilson, S. Nishio, D. Cranz, J. Heidsiek, and D. Hyde Chapter 4. Comparative Metabolic Basis for the Disposition and Toxic Effects of Inhaled Materials . . . . . . . . . . . . . . . . . 41 A. R. Dahl Part II. Methodological Issues in Designing and Conducting Studies with Laboratory Animals Chapter 5. Exposure Facilities and Aerosol Generation and Characterization for Inhalation Experiments. . . . . . . . . .

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.

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."

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.

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."

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.

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.

Polycystic ovarian disease, or polyfollicular ovarian disease, as Dr. Fut terweit prefers to call it, is a disease of uncertain etiology and for which numerous modes of therapy have been advanced. Understanding of its pathophysiology should shed light on factors regulating normal ovarian function; the converse is also true. Recent years have brought about great understanding of the neuro endocrine regulation of gonadal function, as well as of factors in the microenvironment of the ovary which affect its function. It is also ap preciated that cases classified as polycystic ovarian disease actually rep resent a clinical and pathological spectrum which may reflect the effects of diverse etiological factors. In the present volume, Dr. Futterweit presents the fruits of his long interest in and extensive experience with this disease. He thoroughly and thoughtfully reviews the vast amount of basic and clinical information that has been garnered with regard to this condition over the past decade. The numerous theories that have been advanced to explain its etiology are presented in balanced fashion, in addition to a hypothesis, which is well formulated and amenable to clinical testing. His clinical interests and judgment are well represented by his presentation of the diverse manifestations of this condition, the approach to proper diagnosis, and the available therapeutic options. Patients with this disease represent diagnostic and therapeutic prob lems in a situation where manifestations of disease may lead to major emotional stress."

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."

Bone Metastases brings together the many recent developments that are gradually improving the prospects for patients with secondary involvement of the skeleton in a primary cancer elsewhere. The morbidity from bone metastases is extensive, and the palliative and supportive treatment that sufferers require for many months or even years constitutes a major health problem. A multidisciplinary approach is essential since a variety of specialists are involved: radiation and medical oncologists, general and orthopaedic surgeons, general physicians, radiologists and nuclear medicine physicians, symptom control and terminal care specialists. The book's editors, themselves authorities in the fields of oncology and bone disease respectively, have brought together experts from all these disciplines to provide comprehensive coverage of metastatic bone disease. They cover the biology and pathophysiology, hypercalcaemia, imaging, assessment of response to treatment, types of treatment (systemic, radiotherapy, surgery), and symptomatic and supportive care. Particularly new approaches included are magnetic resonance imaging, the assessment of skeletal response and isotope therapy.

Antibodies tagged with fuorescent markers have been used in histochemistry for over 50 years. Although early applications were focused on the detection of microbial antigens in tissues, the use of immunocytochemical methods now has spread to include the det- tion of a wide array of antigens including proteins, carbohydrates, and lipids from virtually any organism. Today, immunohistochemistry is widely used to identify, in situ, various components of cells and tissues in both normal and pathological conditions. The method gains its strength from the extremely sensitive interaction of a specifc antibody with its antigen. For some scientifc areas, books have been published on applications of immu- cytochemical techniques specifc to that area. What distinguished Immunocytochemical Methods and Protocols from earlier books when it was frst published was its broad appeal to investigators across all disciplines, including those in both research and clinical settings. The methods and protocols p- sented in the frst edition were designed to be general in their application; the accompa- ing "Notes" provided the reader with invaluable assistance in adapting or troubleshooting the protocols. These strengths continued to hold true for the second edition and again for the third edition. Since the publication of the frst edition, the application of immuno- tochemical techniques in the clinical laboratory has continued to rise and this third edition provides methods that are applicable to basic research as well as to the clinical laboratory.

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.

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."

The secretion of bioactive products by tumors of the gastroenteropancreatic system results in the development of watery diarrhea that can lead to death in a very short period if not brought under control. Even if the consequences are less dramatic, the patients' ability to lead a normal daily life is seriously impaired, and they may become severely depressed. SandostatinR alleviates the condition by inhibiting peptide release, and its long duration of action makes it an effective and rational adjunct to therapy at all stages. Last year a consensus Round Table Meeting was held in Scottsdale, Arizona, to discuss the optimal use of SandostatinR in this indication. These guidelines offer the results of clinical research and the dosage recommendations arising from them, together with a critical summary of the points of view presented.

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."

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."

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."

Practical Guide to Surgical Pathology with Cytologic Correlation/ A Text andColor Atlas is uniquely designed to examin every organ system, traditional exfoliative cytology, fine needle aspiration cytology, and some significant nonneoplastic diseases of liver, kidney, and skin. The volume juxtaposes concise clinical and pathologic descriptions and the corresponding radiographic, cytologic, and histopathologic illustrations.