Dr Taylor's book analyses the disease concept as it developed in medical history and seeks to clarify it with the help of concepts largely derived from logical class theories. A solution is proposed to the problem of how to distinguish between the class of 'patients' and the class of 'healthy persons' which corresponds to the actual diagnostic practices of doctors. The earliest theories of disease postulated concrete entities which exist independently of the body. The notion of disease entity has lost its original ontological connotations and instead its important feature has become the possession of a unitary and self-contained character. Dr Taylor describes the modern theories as essentially 'reactive' in character, that is the symptoms of a disease are the bodily reactions to the 'noxae'. After seeing the subject in its historical content, Dr Taylor goes on to discuss in detail the notion of the classification of diseases, making extensive use of modern views on the logic of classes.

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."

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."

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."

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.

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 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."

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.

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 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.

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."

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."

Mohs surgery is a highly effective treatment for certain cutaneous and oral pharyngeal cancers. The procedure allows for the precise and complete removal of cancers while preserving significant amounts of normal tissue. Through the presentation and orientation of the specimens' complete surgical margin on pathology slides, the location of tumor foci and other relevant findings can be correlated with their locations on the surgical wound. The ability to create perfect slides for histological examination lies at the core of effective Mohs surgery. These procedures have a 99 per cent cure rate for certain cancers when implemented correctly. This book describes the methods the dermatologist, pathologist, or technician can use to optimize the Mohs technique and produce the highest-quality slides and highest cure rates possible.

First published in 1992, this volume provides a systematic survey of the dibenzanthracenes and of their chemical, physiochemical and biological properties. The carcinogenic potential of the dibenzanthracenes - an important subclass of polycyclic aromatic hydrocarbons - has been extensively studied and documented since their identification as animal skin carcinogens was first demonstrated in the 1930s. the volume treats the nomenclature, the chemical and physical properties and the synthesis and preparation of the five principal isomers of the dibenzanthracenes series: dibenz (a, h), - dibenz (a, c), -dibenz (aj) anthracene, benzo(a)naphthacene and pentacene. Other chapters are devoted to their occurrence and analysis in the environment, in industrial processes and effluents, and in foodstuffs. The second part addresses their biological activity and reviews the metabolism, cellular interactions, toxicology mutagenicity and carcinogenicity of the dibenzanthracenes. The final chapter is devoted to structure-activity relationships in this class of aromatic compounds. This is the first comprehensive account of this important group of environmental pollutants and carcinogens. It will be of interest to all scientists studying carcinogenesis, and the mutagenicity and toxicology of environmental pollutants.

First published in 1988, this volume surveys the chemical synthesis and biological activity of the benz a]anthracenes. These compounds occur in smoke and mineral oils and a few have been shown to be potent carcinogens. This volume was the first to review, systematically and in depth, the organic synthesis of these compounds as well as their metablolism, interactions with nucleic acids and protein, mutagenicity and carcinogenicity. Such studies have important implications in determining mechanism and specificity of chemically induced carcinogenesis.

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.

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.

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.

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."