I am very happy and honoured to have so many famous contrib utors from around the world presenting their knowledge and experience in this book, including Dr. Rufer who, as early as 1967, attempted to improve the pressure-volume curve of a child dying from RDS using dried surfactant from dogs; Drs. Enhorn ing and Robertson who were the first to treat rabbit fetuses with surfactant replacement and impressively demonstrated that sur factant improved lung mechanics; and Dr. Fujiwara who at the end of the 1970's had already successfully treated the first babies with surfactant replacement and published this work al ready in 1980. Thus, the idea of surfactant replacement therapy is now more or less 20 years old and almost 10 years have passed since the first publication by Dr. Fujiwara of his impressive clinical results. Up to now (September, 1988) about 2,200 babies have been treated worldwide with tracheal instillation of surfactant, with most promising results. The type of surfactant used varies from pure natural extracts from bovine or pig lungs, to surfactant extracted from human amniotic fluid, to pure phospholipids. To date, however, there is still no surfactant commercially available (except in Japan), in spite of the fact that it is urgently awaited by neonatologists and intensive care doctors throughout the world. This volume is based on the contributions presented at the international congress on Surfactant Replacement Therapy which was held in Rotterdam, The Netherlands, in November 1987."

The gratifYing response to the first edition of Tuberculosis has prompted this revision. There are many important changes incorporated into this edition, including the dramatic effect of AIDS on the incidence and clinical mani festations of mycobacterial infection, new developments in epidemiology and bacteriology, and thoroughly updated therapeutic recommendations and principles of prophylaxis. The chapters that deal with clinical manifestations of tuberculosis have also been updated and include important and clinically applicable information on manifestations of tuberculosis in both the normal and immunocomprom ised host. As with the first edition, it is hoped that this text will continue to represent a definitive resource for both the basic scientist and the clinician who deal with the prevention and treatment of mycobacterial infection. II Preface to the First Edition We have just witnessed the lOOth anniversary of Koch's discovery of the tubercle bacillus. This event did not end the centuries-long saga of tuber culosis, however; it was but one major step in the ongoing struggle to un derstand and combat this disease. Tuberculosis is very much with us today, and its clinical manifestations and principles of treatment must be understood by both the primary care physician and the specialist. This monograph covers all aspects of tuberculosis in a single volume. It is divided into three parts, covering, respectively, general considerations, clin ical manifestations, and atypical mycobacterial infection."

This volume forms part of a prestigious series and covers the latest advances in our understanding of the pathophysiology and treatment of asthma. Our understanding of asthma has changed dramatically in recent years, and much of this new information is brought together in this volume written by inter nationally recognised authorities. The aim of the book is to review in depth the changing concepts of inflammatory processes in asthma and to discuss the implications for research of this common chronic disease. Many of the advances in and future therapy our understanding of asthma have originated from a pharmacological approach, and this volume highlights the promising new options for pharma cological intervention. It is hoped this book will be invaluable for research scientists and clinic ians involved in asthma research and will be a major reference resource for chest physicians and those involved in the development of novel pharmaceu tical entities. Each chapter is extensively referenced, generously illustrated with clear diagrams and photographs, and represents a state-of-the-art review of this growing area. c.P. PAGE P.l. BARNES Contents CHAPTER 1 The Pathology of Asthma: An Overview L.A. LAmNEN and A. LAmNEN. With 10 Figures ...................... 1 A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 1 . . . . . . . . . . . . . . . B. Methods to Investigate the Pathology of Human Asthma ............ 1 C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks ........................... 2 I. Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 4 . . . . . . . . . . . . . . II. Eosinophils ............................................... 7 III. Neutrophils.............................................. 10 D. Bronchial Epithelial Inflammation During an Asthma Attack. . . . . .. . 10 E. Epithelial Regeneration .... . . . . . . . . . . . . . . . . . . . . . . .. . . 12 . . . . . . . . ."

The purpose of this series of volumes is to present a comprehensive view of the complications that result from the use of acceptable diagnostic and therapeutic proce dures. Individual volumes will deal with iatrogenic complications involving (I) the alimentary system, (2) the urinary system, (3) the respiratory and cardiac systems, (4) the skeletal system and (5) the pediatric patient. The term iatrogenic, derived from two Greek words, means physician-induced. Originally, it applied only to psychiatric disorders generated in the patient by autosug gestion, based on misinterpretation of the doctor's attitude and comments. As clinically used, it now pertains to the inadvertent side-effects and complications created in the course of diagnosis and treatment. The classic categories of disease have included: (1) congenital and developmental, (2) traumatic, (3) infectious and inflammatory, (4) metabolic, (5) neoplastic, and (6) degenerative. To these must be added, however, iatrogenic disorders-a major, although generally unacknowledged, source of illness. While great advances in medical care in both diagnosis and therapy have been accom few decades, many are at times associated with certain side-effects plished in the past and risks which may result in distress equal to or greater than the basic condition. Iatrogenic complications, which may be referred to as "diseases of medical progress," have become a new dimension in the causation of human disease."

In this state-of-the-art exploration of a hugely dynamic and fast-evolving field of research, leading researchers share their collective wisdom on the role that stem cells could play in the context of physiological stress and lung injury. The text focuses on reviewing the most relevant-and recent-ideas on using local, endogenous, and exogenous progenitor/stem cells in preventing and treating injury to the lung. The lungs are one of the most complex organs in the human body, with a mature adult lung boasting at least 40 morphologically differentiated cell lineages. Our entire blood supply passes through the lung's alveolar units during oxygenation. This interaction with the outside world, along with the intricacies of its structure, makes the lung a highly susceptible organ that is vulnerable to numerous types of injury and infection. This means that the mechanisms of lung repair are in themselves correspondingly complex. Because of their multipotentiality, as well as the fact of the lung's relatively rapid cell turnover, stem cells are thought to be an important alternative cell-base therapy in lung injury. Despite the controversial nature of stem cell research, there has been growing interest in both local and endogenous stem cells in the lung. This highly topical book with chapters on everything from using mesenchymal stem cells in lung repair to the effect of physical activity on the mobilization of stem and progenitor cells, represents an exciting body of work by outstanding investigators and will be required reading for those with an interest in the subject.

Among malignant tumors, adenocarcinomas of the esophagogastric junction show the highest increase in incidence over the past three decades in Western industrialized countries. This special volume, with contributions from experts in the field, covers all aspects of the disease. Etiology, pathogenesis, classification, and clinical staging are discussed, and there is special emphasis on state of the art treatment techniques. The latter range from endoscopic mucosal resections or limited surgical resections for early cancers to multimodality treatment options for locally advanced tumors. Emerging quality issues in surgical management are addressed. Detailed attention is also paid to other important recent developments, including molecular response prediction, early metabolic response evaluation by PET and PET-CT, the diagnosis of micrometastases, and the use of sentinel node technology. This volume will be of interest to all clinicians concerned with the diagnosis and management of this malignancy.

th This volume contains selected lectures presented at the 12 International Conference on Advances in Prostaglandin, Leukotriene and Other Bioactive Lipid Research: Basic Science and Clinical Applications which was held in Istanbul, Turkey, on August 25-29, 2002. This meeting brought together basic and clinical scientists for the purpose of discussing advances in bioactive lipid research with.special attention to cancer, cardiovascular diseases, gastrointestinal diseases and respiratory diseases. Topics covered included: the role of leukotrienes and lipoxins in of inflammation, the cytochrome P450 pathway, the genetics and genomics bioactive lipids, lipid peroxidation, apoptosis, angiogenesis, isoprostanes, receptors and inhibitors, cyclooxygenase and lipoxygenase pathways and inhibitors, prostaglandin synthases and receptor signaling, phospholipases and inhibitors. Sessions included plenary lectures with expertise in particular areas, oral presentation on selected topics and general poster sessions. J.M. Drazen (Boston, USA) discussed anti-leukotriene treatment in asthma patients while C. Brink (paris, France) presented the recent advances in leukotriene receptors. The recent advances in cytochrome p450 pathway described in the session organized by J.C. McGiff (Valhalla, NY, USA). T. Shimizu (Tokyo, Japan) and M. Balazy (Valhalla, NY, USA) gave an update on phospholipases and arachidonic acid peroxydation. The editors are greatful to the Organizing, Programme and Advisory Committees for their valuable contributions. We greatfully acknowledge the generous financial support provided by PharmaciaIPfizer, Fako Pharmaceuticals Inc. and Novartis Pharmaceuticals Inc. ofthe contributors to this volume, in particular We are also greatful to all to those who delivered their manuscripts by or before the requested deadline.

The chest X-ray (CXR) or chest radiograph remains the most commonly ordered imaging study in medicine, yet paradoxically is often the most complex to learn, recall, and master effective and accurate interpretation. The chest radiograph includes all thoracic anatomy and provides a high yield, given the low cost and single source. This guide presents a structured lexicon for use by readers to reproducibly describe radiographic abnormalities of the chest detected on plain film CXRs. The lexicon is designed to provide readers with clinically significant differentiation of abnormalities detected. The content is structured to relate specific combinations of distinct radiographic findings to classes/groupings of pathological etiologies of those findings. Recognizing the individual findings and identifying their combination or lack of combination with other individual findings allows readers to create effective differential diagnoses that can then be further evaluated using other imaging procedures and/or non-radiographic clinical information. The book includes hundreds of images, including radiographs, CTs, graphics, and analogous models to help teach otherwise complex processes and radiographic principles.

It is a pleasure to contribute a brief foreword to this new, comprehensive 1980s saw an explosion of knowledge in pul text on the pneumonias. The is every reason to expect it to continue through monary science, and there the end of the century. As a result, it is becoming increasingly difficult to keep up with all the important advances, even in a restricted area of interest. For this reason, books such as the present one that collate the latest findings on an important clinical topic in a convenient, readable form provide a valuable service. This book is a salutary reminder that there is life beyond molecular and cell biology. Important though these disciplines are, some of us regret the lemming-like rush into these fashionable fields at the expense of more traditional pulmonary science. One result of this rush has been an increas ingly large number of residents and fellows who are unable to interpret the results of blood gas assays or who are completely at sea when presented with a patient who requires mechanical ventilation. The present perception that research funding is available only in molecular and cell biology has produced some unfortunate distortion of training programs. I pity the poor medical student in some of our most prestigious medical schools who is taught by a molecular biologist or neurophysiologist how the lung works. I wish the book well."

Pulmonary Immunotoxicology is a comprehensive exploration of the effects of various inhaled materials upon the immune system of the respiratory tract. It will be useful to investigators in the field of pulmonary toxicology and immunotoxicology, and to those involved in administration and regulation of matters related to inhaled materials. It can also serve as a textbook for a course in pulmonary immunotoxicology at graduate or advanced undergraduate level. Pulmonary Immunotoxicology comprises four sections. The first provides basic background concepts essential for understanding pulmonary immunotoxicology, including discussions of the normal structure and function of the respiratory system, its basic immunology, and the manner by which inhaled particles and gases are removed from the air and deposited upon respiratory tract surfaces. The second section provides an overview of the major types of pathological consequences which can arise from immunomodulation within the respiratory tract, including hypersensitivity and asthma, inflammation and fibrosis, as well as immunosuppression and autoimmunity. The third section, which comprises the largest portion of the book, deals specifically with major classes of airborne agents that are known to alter the immune function of the respiratory tract. These are arranged into major classes: organic agents, metals, gases, particles, biologics, and complex mixtures. The fourth and final section of the book explores the area of risk assessment, including discussions of the basic concepts of risk assessment as they apply specifically to immunotoxicologic effects upon the lungs, and the use of biomarkers as indices of potential pulmonary immunotoxic responses to inhaled materials.

The publication of Bronchoalveolar Mast Cells and Asthma marks the emergence of The Bloomsbury Series in Clinical Science, an important and novel series that will highlight, review and record major areas of research, development and practice in the field of clinical science. A number of other monographs are now in an advanced state of preparation and their release will establish not only their individual significance but that of the series as a whole. My thanks are due to the Editorial Board who have provided the ideas and selected the authors and whose continuing enthu siasm is so vital to the success of the series. Michael Jackson of Springer-Verlag merits special thanks for initially realising the potential of such a series and then guiding us all through to the time of its launch. Marianne Williams has supported us all and has provided the important link between Editorial Board and pub lisher. The author of this first publication, Kevin Flint, was tragically killed during its preparation, and we hope that the book will serve as a tribute to the memory of Kevin for all who were lucky enough to know him. Barry Hudspith has been of enormous help in finalising the work and in shaping the form of the book."

The Fourth International Workshop on "In Vitro Effects of Mineral Dusts on Cells" was held on September 20 - 23, 1988 in Auberge Estrimont, Orford, Quebec, Canada. The emphasis of the N. A. T. O. Advanced Research Workshop was the use of cell and organ culture and lavage cell populations obtained from man and laboratory animals to elucidate cellular and molecular events occur ring after their interaction with fibrous and nonfibrous particulates, including metal compounds. In seven sessions, an international representation of scientists from 17 countries (Austria, Belgium, Canada, France, Federal Republic of Germany, India, Japan, Netherlands, Norway, Poland, Portugal, Union of South Africa, Sweden, Switzerland, United Kingdom, United States of America, and Yugoslavia) presented recent research findings in the following areas: Epithelial cell injury and proliferation by minerals. Physico-chemical properties of minerals in relation to their biologic effects. Mechanisms of dust-induced pneumoconioses. Clinical and experimental studies. Mechanisms of cytotoxicity, mutagenicity and carcinogenicity. Oxidants, cytotoxicity and disease. Mechanisms of mineral-induced inflammation. Mechanisms of carcinogenesis. A session on "Questions, risk and public policy" provided a lively discussion on the relevance of in vitro experiments to carcinogenicity studies in man and their implications in the formation of regulatory policies. VI The organizing committee for this workshop was: Co-Chairs: B. T. Mossman (USA) and R. Begin (Canada) E. G. Beck (FRG) A. Lange (Poland) A. Brody (USA) P. Nettesheim (USA) R. C. Brown (UK) Q. Rahman (India) J. Bignon (France) K. Robock (FRG) Fisher G.

The interrelated syndromes of shock and the adult respiratory distress to attract the attention of both clinical and syndrome (ARDS) continue laboratory scientists. This reflects both the size of the problem and its unresponsiveness to current lines of treatment. Doubtless, a greater appreciation of the underlying pathophysiological disturbances during the past two decades has led to appropriate action and increased survival in the early stages but once established these syndromes have remained remarkably immune to a wide spectrum of therapeutic modalities. This observation stresses the importance of prevention but also indicates the need for continued research into the nature of the established syndromes and the means whereby they may be reversed. Drs Kox and Bihari are to be congratulated on bringing together within the covers of this volume many of the acknowledged European experts in these two fields of investigation. Each author has provided an up-to-date account of his current experimental and clinical research, and their com bined contributions makes fascinating reading. Undoubtedly, these are exciting times in the development of understanding of shock and ARDS. Inevitably, more questions are raised than answers provided, but the accumulated knowledge presented here adds significantly to our under standing of this complex biological jigsaw. From this corporate endeavour will come the clinically useful developments of the future and with them the ultimate hope that the term 'refractory' shock may be finally removed from our vocabulary.

Considerable progress in understanding how inhaled minerals cause disease in man has been made in the past two decades. This is mostly due to the great amount of human, animal and cell multidisciplinary studies carried out on silica, asbestos and asbestiforms all around the world. Two previous NATO Workshops on "In Vitro Effects of Mineral Dusts on Cells", have been published in the NATO ASI Series (1985 and 1989). The present NATO-INSERM workshop has focused specifically on a group of silicates, named phyllosilicates because of their sheet structure, of which health related effects have been poorly and sporadically investigated. These silicates are presently largely used as filling materials (kaolin, talc, chlorite), insulating materials (vermiculite, micas), adsorbants (sepiolite, attapulgite) and in many other industrial applications. The estimated annual world production is presently 5.5 million tons of talc (1.8 million for Europe) and only in the United Kingdom about 3.5 million tons of kaolin.

The simple reason for creating this book was my impression that the law is having an increasing impact on the practice of medicine. There is hardly a physician I know who has not been deeply troubled by legal problems professionally, economically, and most important of all, psychologically. The past decade has seen medical practice premiums steadily rising. Multimillion dollar verdicts have not been unusual. Having disregarded these vital issues for many years, physicians have suddenly become very aware of litigation-related problems. Having been interested for a long time in the logic ofthe law and the romance of legal research, I thought it would be useful to create a book that would result in the blending of great minds in law and medicine. It has been my long standing observation and belief that the approach of professors of medicine, and that of learned members of the bar and bench, when put together, produce unique results. Putting these views together has been the real challenge in editing this book."

The processes of distention and recoil have an essential role in the functions of arteries and lungs. In both organ systems, these processes involve to a great extent the connective tissues, in particular the manner in which the extracellular materials are arranged to afford such movements. This book concerns the microenvironment of the connective tissues in the walls of arteries and the stroma of lungs. Proteoglycans, collagen, and elastic fibers and their interrelationships are discussed by eight scientists who are established researchers in this area. Their reports include important findings on how this microenvironment is altered in diseases such as atherosclerosis, emphysema, and pulmonary fibrosis. The concepts developed result from studies at the biochemical, macromolecular, ultrastructural, and light microscopic levels. Taken col lectively, the reports focus attention upon the role of the connective tissues in arterial and lung distensibility and how alterations in the connective tissues result in the loss of this function. Medical researchers and physicians interested in arterial or lung functions or diseases will find the scientific approaches and findings of the authors innovative and provocative. Students of stereologic morphometry will be particularly interested in the quantitative studies of cells and fibers in arterial walls; histologists and pathologists will find the chapter on histochemical staining interesting from both a scientific and historic viewpoint.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology textbooks are generally out of date. Single papers in specialized journals are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good indepth reviews of cancer topics, and published symposium lectures are often the best overviews available. Un fortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes which aim to meet this need. It is an attempt to establish a critical mass of oncology literature covering virtually all oncology topics, revised frequently to keep the coverage up-to-date, easily available on a single library shelf or by a single personal subscription. We have approached the problem in the following fashion. First, by dividing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc. Second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more.

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. . . . . . . . . .

Most studies on autonomic innervation of smooth muscle have focused on the short-term mechanisms involved in neurotransmission in physiological and pathophysiological conditions. However recent obser vations of the long-term plasticity of this system, i. e. its capacity for regeneration and for compensatory change in pattern of innervation and expression of cotransmitters and receptors in ageing, following surgery, trauma or in disease, have indicated that an understanding of the mechanisms involved could influence the design of therapeutic regimes. There is increasing evidence for long-term communication between nerves and smooth muscle cells during development and throughout adult life. To date, the trophic interactions between nerves and airway musculature have attracted little interest, consequently, much of the information presented here is drawn from studies using other smooth muscles. However, the questions posed about trophic interactions dur ing development apply as much to airways smooth muscle neuroeffector systems as to other autonomic neuroeffector systems. These are: i) How do developing nerve fibres know where to go and how do they reach their target sites? ii) What determines the density and pattern of inner vation at reaching the effector? iii) How do the nerves survive and maintain their position once established? iv) What factors influence neurochemical differentiation such that genetically multipotential neu rones are triggered to synthesize one or combinations of neurotransmit ters? v) What influence do nerves have on the structure, function and receptor expression of their effector cells? vi) How do diseases interrupt these processes? - see 1]."

I organized this book because there is a need to put together in book form recent advances in our knowledge of how airway smooth muscle: works in health and in disease. After a period when it seemed that progress was very slow, there has been in the past few years an incredibly rapid gathering of knowledge in this area. In particular, our understanding has improved regarding the cascades of events that follow the initial binding of agonist to plasma membrane receptors and that lead to the cross-bridge movements that determine contraction. This advance in our knowledge was stimulated by use of single-and whole-cell channel recordings of plasma membrane currents and by description of the l3-receptor-GTP-binding protein-adenylate cyclase-cAMP coupling system, which serves as a model for other coupling mechanisms. The discovery of the receptor-activated inositol phospholipid transduction system has greatly stimulated research and led to advances in our understanding of mechanisms involved in smooth muscle con traction. Major advances were also triggered by the development of indicators for measuring free cytosolic calcium concentration and starting the unraveling of 2 the events involved in Ca + -dependent activation of contractile proteins. Al though most of the studies that led to our current understanding of these areas were performed on nonairway smooth muscle, these studies usually add to our understanding of airway smooth muscle, and there is an enlarging body of data that have been obtained on airway smooth muscle."

This volume deals specifically with those antituberculosis drugs which passed the preclinical phase and have been or are used in the treatment of tuberculosis and other mycobacterial diseases (except leprosy) in at least some parts of the world. Despite this restriction, there are 14 such drugs, and as a result this volume has reached rather large proportions. To prevent it from becoming even larger and more unwidely, most derivatives of antituberculotics have been omitted, especially where it is claimed that they provide only better bioavailibility or tolerability. Only in the chapter on the chemotherapy of diseases due to so-called atypical mycobacteria is the clinical use of the drugs described to a certain extent. In addition to antituberculotics, also discussed are antimicrobials which have been found to be effective against these mycobacteria. The sequence in which the drugs are described is historical, reflecting not the time of discovery but rather the first clinical application. This order was selected for reasons which are now no longer relevant. In this volume less emphasis is placed on detection, biological or synthetic production of antituberculotics, and structure-activity relationships. In contrast, emphasis is put on the degree, type, and mechanism of antimyco bacterial activity, pharmacokinetics, and biotransformation in animals and man, on experimental pharmacodynamics, and on the toxicity of antituberculotics used therapeutically.

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . xiii . . . . . . . . . . . . . Part I. Integrative Approach to Assessing Human Health Risk: Two Contemporary Problems Chapter 1. Integrating Diverse Data Sets to Assess the Risks of Airborne Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 R.o. McClellan, R.G. Cuddihy, w.e. Griffith, and J. L. Mauderly Chapter 2. Risk Assessment for Radon Inhalation Based on Animal Exposure Data and Human Epidemiology . . . . . . . 23 . F. Steinhausler Part II. Types of Evidence: General Strengths and Weaknesses Section 1. Epidemiological Chapter 3. Inhalation Hazards: The Interpretation of Epidemiologic Evidence. . . . . . . . . . . . . . . . . . . . 39 . . . . . . . J.e. Bailar Chapter 4. Problems in Interpreting Epidemiological Data 49 P.N. Lee Section 2. Animal Chapter 5. Rodent Carcinogenicity Studies: Their Value and Limitations. . . . . . . . . . . . . . . . . . . . . . . . . . 61 . . . . . . . . . .