This book represents the culmination of the major aspect of Dr. Margot Shiner's professional career. It was she who devised the technique of jejunal biopsy which opened up whole new fields of small intestinal research, including microbiology, immunology, histochemistry and histopathology, thus greatly expanding our knowledge of fundamental aspects of absorptive patho physiology. Later the application of electron microscopy demonstrated the individual cell with its mechanisms both for absorption and for the production of so many chemicals such as mucus, enzymes and hormones. Like the vision from the peak in Darian, it opened up new worlds. The contribution to our understanding of cell structure and function has been greater than the direct elucidation of specific diseases but nevertheless, there are pointers to different mechanisms which could have wide applications. It is a book which serves a double function: On the one hand it is highly technical and a publication for the super expert, recording new landmarks of knowledge and interpretation. On the other hand, it is a book which can indeed fire the imagination of the rising generation of gastroenterologists, paediatricians, pathologists and medical scientists. Having seen the emergence of the art and science of present-day gastro enterology within my professional lifetime and having been able to provide the facilities for her work in the very early days, it is with particular pleasure and pride that I write this foreword."

This volume, the last in this series on cancer growth and Moreover, the current status of plant-derived vinca alka progression, is a companion volume to Volume IX and loids and non-alkaloid natural products is summarized. further explores established and novel approaches for the Advances in hyperthermia and additional approaches for therapy of patients with malignant neoplasms. The stra the therapy of malignancies are also presented. tegies reflected in these volumes are direct extrapolations The volume continues with chapters on bone marrow from the basic science of cancer biology, growth and pro transplantation as well as hematologic and nutritional sup gression described in earlier volumes of this series. Some port for the cancer patient. Blood pressure in the cancer approaches are directed towards the eradication or modifi patient, therapy for nausea and vomiting as well as pain are cation of the properties of heterogeneous malignant tumor discussed. The last chapter is devoted to the problems of the cells at various stages of tumor progression, while other terminally ill, including evaluations of the burden relatives approaches are directed towards modification of the host and friends of the cancer patient have to bear. antitumor defense systems, e. g., enhancement of host anti It is clear that important advances in the basic science of tumor immune reactivity."

Previous volumes in this series have discussed the current progression have identified a variety of targets and strategies state of our knowledge concerning the pathophysiology of to allow these goals to be realized. This volume critically cancer growth and progression. The complexity of the in reviews approaches towards cancer management in man at teraction of malignant neoplasms and the host, the the levels of: detection, diagnosis, surgery, radiology, heterogeneity of malignant cell subpopulations, and the chronobiology and endocrine treatment. existence of metastatic tumor cells resistant to drug thera Several chapters review selected methods of cancer diag pies remain as significant clinical challenges to clinical on nosis. In addition, a variety of on-going and novel ap cologists. Indeed, conventional treatment regimens of che proaches for cancer treatment are also presented in this volume. Progress in the early detection of malignant neo motherapy, surgery and radiology are often ineffective for the therapy of a large variety of established metastatic can plasms, coupled with novel approaches for the therapy of cer in patients. When one considers the insidiousness of such neoplasms, may ultimately yield safe and well-tolerated agents for the selective therapy of solid malignancies. New progressive neoplastic growth and the emergence of con tinuously more aggressive and malignant cellular subpop therapeutic approaches, directed towards the biochemical ulations one is overwhelmed with the challenges inherent in and molecular targets identified in the earlier volumes of this series, may ultimately lead to the generation of new mo attempting to control malignant neoplasms."

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.

on the theories of Planck and Einstein. Rather, until The concept that human disease is a specialized branch of biology is universally accepted today, but in the mid-20th century, the accretion of individual historical perspective, is actually of recent origin. At examples of the biological nature of disease processes provided the framework for an evolutionary change in one time, the heliocentric theories of astronomy and the metallurgic transmutations of alchemy had their thinking. The new psychological and philosophical milieu provided the basis for an unprecedented accel counterparts in magical and vitalistic approaches to eration in the pace of biomedical research. It is clear human disease. Any relation between disease of humans and that of animals was not only unacceptable that the biological revolution of the last 35 years was made possible not only by technological advances and intellectually, but abhorrent theologically. Humans (and their diseases) were unique, and biology was the innovative analytical methods, but also by an intellec domain of those who studied animals and plants. tual emphasis on the unity of biological processes. The unification of biology and the study of human High school students are now aware that there is much disease, though begun some centuries ago, was con to be learned about the human condition by studying spicuously stimulated by the work of Darwin, and bacterial DNA, the chloroplasts of green leaves, or the reached its full flower in this century. For example, kinetics of enzymes in vitro."

Hairy cell Leukaemia (HCL) has always attracted an interest out of all proportion to its frequency and continues to do so. There are two reasons for this. The first is that the disease is unusually responsive to therapy and second is that it has provided a number of important insights into B-cell biology. This monograph is a comprehensive account of hairy cell leukaemia and aims to provide a more detailed account than is available in the existing literature. The work is timely because a consensus has now emerged concerning accurate differential diagnosis a nd curative treatment. These aspects therefore form the focus of the book and are considered in detail. The basic advances in the laboratory that encourage the belief that elucidation of the underlying oncogenic event in the disease may be within reach. The background to this belief is extensively renewed. As a result the monograph will be of interest and practical value to both clinicians and researchers in this and related fields.

Seymour Glagov The last meeting, devoted exclusively to an examination of the atherosclerotic plaque, took place in Chicago 25 years ago under the joint auspices of the Council on Arteriosclerosis of the American Heart Association and the Chicago Heart Association. The proceedings were published subsequently in a volume entitled "Evolution of the Atherosclerotic Plaque", edited by Richard J. Jones (1). Both experimental and human lesions were considered and several provocative new approaches to the disorder were discussed. The electron microscope was being applied systematically to the study of blood vessels at that time, so that details of the infrastructure and cellular composition of the artery wall and of atherosclerotic lesions were presented in some detail. There was, as one result of these explorations, considerable discussion of morphologic evidence suggesting that the principal cell involved in the atherogenic process was neither the fibroblast nor the macrophage, as had been supposed, but the smooth muscle cell. In particular, the findings indicated that this cell could incorporate lipid and become a foam cell.

Human Lymphoma: The Clinical Implications of the REAL Classification is a unique volume. It is based on the recent developments in classification and overall understanding of human lymphoid neoplasms which are relatively common neoplasms and which epidemiological evidence suggests are increasing in frequency. This field has been the cause of confusion in the past as a result of conficting ideas on the classification of lymphoma and related diseases. However a new vision of the field has emerged and the is encapsulated in the pioneering REAL classification and in a forthcoming WHO scheme, both of which are covered in the book. The volume will appeal to hematologists, pathologists and oncologists and will, thanks to a diverse and expert authorship, serve to increase the working knowledge of all three groups.

Spinal Cord Injury or disease can happen to anyone at any time and the effects can be devastating. I found this out personally when I was thrown from the back of a pick up truck at age 15 was left paralyzed from the waist down. It was during my recuperation as a young teenager that I first gained insight into the importance of rehabilitation. My family, doctors, nurses, fellow patients and researchers who were dedicated to helping me over come my personal tragedy helped me pull through. Today, rehabilita tion medicine is taking great strides and empowering the person with the injury to take control of their future, overcome their setbacks and, through collaborative support, reach their personal goals and potential. Since 1987 the Legacy raised by my Man in Motion World Tour (24901 miles wheeled around the world March 1985-May 1987) has pro $13 million dollars to research and rehabilitation in the areas vided over of spinal cord injury. I hope that in some small way this funding has contributed to the development of the vital programmes that supported me and many others. The effects of spinal cord injury are traumatic and life-shattering and require a skilled interdisciplinary approach. I congratulate those who have contributed to this book and challenge each one of you to never give up on your dreams to find the answers to the optimum treatment of spinal cord injury and disease."

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."

It is difficult for a teacher to accept the fact that not all of the information in his or her field is a necessary part of the armamentarium of the student. This holds for histologists, and for that matter, pathologists, biochemists, and ophthalmologists. It may especially hold for those who were trained during exciting periods in the history of their discipline. In the past two decades, information in every basic medical science has increased greatly, perhaps exponentially, and the basic science curriculum has been compressed to the point where the medical student can reasonably be expected to acquire only a superficial knowledge of anyone of these sciences. Hence the information provided must be carefully selected, effectively presented in retainable doses, and useful for understanding material to be presented later in the curriculum and for the solution of clinical problems. In the compact courses of today, the presentation of only enough data to support basic working concepts of structure and function is appropriate. Additional factual information consti tutes trivia, which in our opinion interferes with effective development, reten tion, and use of the concepts. This philosophy has been the basis for the preparation of this book. Consistent with this philosophy, the text is brief, and the content has been carefully examined for its appropriateness to the needs of the medical student."

In any histopathology department, cutaneous biopsies form the major part of the workload. In many instances these may be readily dealt with by experienced pathologists and their documentation represents an essential step in organising therapy. However, in a number of areas dramatic changes have occurred in dermatopathology. The rapidly changing incidence of pigmented lesions of the skin and the availability of diagnostic cell markers in the complex cutaneous lymphomas have meant that for many pathologists a review in these fields will be valu- able. The distribution and pattern of skin pigmentation may allow us to make important assertions and draw importantconclusions about the genetics of skin disease, but also about human variability. Cutane- ous vasculitis is a difficult problem where clinicopathological consulta- tion is vital in diagnosis and the review presented has been written with this verymuch in mind. In the same way, many diagnostic difficul- ties exist in assessing buttous lesions in the skin and for this reason a review was invited. Finally, our understanding of certain skin diseases has been radical- ly altered by knowledge of the dynamics of the changes seen, a field which has also beenstudied with advantage inother systemsin patholo- gy. This volume is intended as an aide to those many pathologists and dermatologists who, often together, are responsible for the pro- vision of clinical care in this demanding field. London C. L. BERRY Contents Melanoma and Other Melanocytic Skin Lesions. With 8 Figures D. WEEDON . Cutaneous Vasculitis.

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."

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."

Diagnosis of tumors is among the most commonly performed tasks in pulmonary pathology, and the chapters on tumors in Dail and Hammar: Pulmonary Pathology have been singled out for special praise for their authoritative discussions and comprehensive lists of references. In reviewing the first edition, "Diagnostic Cytopathology" said: "the chapter on common lung neoplasms is like a book within a book." In revising the chapter on uncommon lung tumors, Dr. Dail "added" nearly 500 new references and 100 new illustrations.
The present proposal is to make the chapters on tumors from the second edition of Pulmonary Pathology available to the broad range of pathology residents and clinicians who will not buy Pulmonary Pathology, 2nd ed. for their personal libraries because of its size and cost.

Many pathologists have little acquaintance with ear, nose concomitant biopsy have become commonplace in the and throat pathology. Some receive few specimens from management of throat disorders. It is hoped that. by ENT tissues; others are deterred from deeper study of the publication of this Atlas, pathologists receiving only material that emanates from regions the normal anatomy occasional specimens will be guided in their provision of of which is so forbidding in its complexity and holds no a report helpful to the clinician and those who are involved familiarity through autopsy investigation, for, apart from with a larger ENT service may be providec with a guide the larynx, there is usually no compelling indication for to the deeper understanding of the subject. examination of the ear, nose or throat at postmortem. Yet. The modern tendency in publication of ristopatholog equally with biopsy specimens from other parts of the ical microphotographs is to omit any statement of their body, the pathologist's report is consequential for the magnification, since it will usually be clear to the reader efficient handling of ear, nose and throat illnesses and what order of enlargement is involved. I n this Atlas, sometimes even for the patient's survival."

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.

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.

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.

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.

Human teratocarcinoma has long held a fascination to the pathologist be- cause of the diversity of the seemingly benign differentiated tissues asso- ciated with the tumor. An understanding of this diversity came with the demonstration of the pluripotent nature of the embryonal carcinoma cell, the stem cell of the tumor, in experimental animals. Single cell clones of murine embryonal carcinomas were derived and the resultant cell lines injected into immunosuppressed hosts, where the embryonal carcinoma stem cell itself gave rise to the wealth of differentiated tissues seen in teratocarcinomas. It was also shown that teratocarcinomas could be pro- duced experimentally by transplantation of staged early mouse embryo to extrauterine sites; subsequent experiments suggested that the embryonal carcinoma stem cell was, in fact, comparable to a normal cell of the em- bryonic ectoderm. Many elegant experiments have since been built on this early work; murine embryonal carcinoma cells are providing the ex- perimental material for a first biochemical evaluation of the earliest dif- ferentiation events in mammalian embryogenesis. In this volume, we relate the beginnings of experimental research on human teratoma. The human embryonal carcinoma cells have been char- acterized and established in vitro, providing an experimental model to study the unique biology of these cells. Monoclonal antibodies, estab- lished from work with these in vitro cultures, provide cell surface probes that define populations of embryonal cells and their derivatives in tumor sections.

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."