The International Society on Oxygen Transport to Tissue (ISOTT, www. isott. info) is an interdisciplinary society comprising about 250 members worldwide. Its purpose is to further the understanding of all aspects of the processes involved in the transport of oxygen from the air to its ultimate consumption in the cells of the various organs of the body. The annual meeting brings together scientists, engineers, clinicians and mathematicians in a unique int- national forum for the exchange of information and knowledge, the updating of participants on latest developments and techniques, and the discussion of controversial issues within the field of oxygen transport to tissue. Founded in 1973, the society has been the leading platform for the presentation of many of the technological and conceptual developments within the field both at the meetings themselves and in the proceedings of the society. These have been published first by Plenum Publishing (1973), then by Kluwer Academic/Plenum Publishers and presently by Springer Publishing, all in the Advances In Expe- mental Medicine and Biology Series. The 36th Annual ISOTT conference was held in Sapporo, Japan during August 3-7, 2008. It was the second occasion that the ISOTT meeting was held in Japan; the first one was held in the same place in 1987 organized by Professor Masaji Mochizuki.

The measurement of cardio-circulatory and gas-exchange parameters during phy sical exercise - the so-called ergo spirometry or cardiopulmonary exercise testing (CPX) - as a basis of pathophysiological and clinical research has a long tradition in Cologne. Knipping and his coworkers, especially Hollmann, performed basic re search work in healthy subjects. In the area of sports medicine, bicycle or treadmill exercise testing with parallel serial lactate determinations has gained increasing im portance for the assessment of cardiac functional capacity. Also, in other medical disciplines, ergospirometry lost its importance. K. Wasserman in Los Angeles is to be credited for having further improved the method to its present standard, a computerized, on-line measuring and practicable cardiopulmonary exercise testing procedure. The prerequisites were technical innovations, such as continuously measuring gas analyzers and personal computers. Thereby, the knowledge about physiology, pathophysiology, and clinical circumstances of cardiocirculatory and re spiratory regulation during exercise were significantly extended. The working groups of W. Hollmann, Cologne, and K. Wasserman, Los Angeles, determined normal values for the gas-exchange parameters and derived values for healthy normals in large populations. Wasserman and coworkers were able to introduce a differential diagnostic concept for patients suffering from various cardiovascular and cardio pulmonary diseases. Many cardiologists, working, for example in myocardial failure or with rate-adaptive pacemakers, belong to those who recommended the modem, computerized ergo spirometry. Furthermore, this method is controversely discussed* by colleagues working in sports medicine and pulmonary function.

Cryosurgery is a method of therapy that uses treatment could be viewed easily and at frequent freezing temperatures to achieve specific effects intervals. Though endoscopic cryosurgical tech on tissues. Depending upon the technique of niques were used for the treatment of prostatic treatment, the tissue response varies from an in disease and of laryngeal disease, the restricted flammatory reaction, which is associated with a visualization of the lesion, as well as some limi minor freezing injury, to the destructive effect tations in apparatus, precluded continued de which is characteristic of severe freezing injury. velopment at that time. In the following years, some early uses of Cryosurgical treatments require the use of special apparatus cooled by cryogenic agents to produce cryosurgery have fallen into disfavor, mostly be the freezing temperatures necessary in the tissues. cause of effective competing methods of thera As with any other method of therapy, the physi py, but other uses of cryosurgery have become cian must place emphasis on the selection of ap part of standard medical practice, as demonstrat propriate patients, on the careful determination ed by incorporation into textbooks of surgery and its specialities. Today, the commonly accepted of the nature and extent of disease, and on pre cise cryosurgical technique in order to achieve uses of cryosurgery are for the treatment of many types of skin disease, including cancer, for the good results."

The scientific literature has expanded dramatically in recent years, making entry into the structure of any given area extremely difficult; concurrent with this explosion more people are required to become acquainted with information outside their main line of expertise. For this reason there is a need for review articles which give an overall review of circumscribed areas. This volume reviews the subject of respiratory control mechanisms; the authors of each chapter are active research workers engaged in the area covered by their chapter. The first four chapters are concerned with the basic physiological mechanisms which sense changes in the respiratory system, in the standard physiology textbook parlance chemical and neural sensory receptors. The peripheral arterial chemoreceptors sense changes in arterial oxygen tension, carbon dioxide and pH. The first chapter describes the basic responses in the organ produced by changes in blood chemistry. Later chapters discuss changes in activity produced by exercise, chronic hypoxia and the possible role of the chemoreceptors in initiation of respiration in the new-born. In Chapter 1, a section considers the action of drugs on the peripheral chemoreceptors, and finally there is a discussion of the possible mechanisms whereby the organs sense changes in blood chemistry. This pattern is followed in subsequent chapters wherever possible; first a discussion of the basic physiological properties, followed by any clinical application and dis cussion of the mechanism whereby the receptor might operate. The remaining chapters are of a more applied nature.

As I reflect on the evolution of this book, I am struck by the differences be tween my early conceptions and the final product. When I was first ap proached by Springer-Verlag regarding a monograph on my interests in the area of fetal lung development, I imagined that it would be relatively easy to summarize my contributions, plus the work of other investigators as needed for proper perspective. This rather naive idea was abandoned as I prepared my initial outlines for the monograph. I quickly realized that con tributions from my laboratory are not sufficient for telling the story of "hormones and lung maturation." The result of this decision is a longer and more heavily-referenced book than I originally envisioned. Although I have attempted to discuss in considerable detail most aspects of hormones and the fetal lung, I know with certainty that I have not in cluded all relevant references in each area. In most of these instances this reflects my impatience or lack of diligence, and I offer my apologies to those investigators whose work has been so omitted. In some situations published work has not been cited in a deliberate decision to limit the breadth of discussion or, rarely, due to my judgment of major shortcom ings in experimental design or execution."

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 . . . . . . . . ."

High pressure in the lungs, or pulmonary hypertension, is most commonly due to smoking-related lung disease and conditions affecting the left heart, for example, high blood pressure in the arteries, faulty heart valves, and a weakened heart muscle. Pulmonary arterial hypertension (PAH), is a rare and complex disease, associated with many different medical conditions, which is caused by a growth of cells lining the inside of the lung arteries, resulting in high pressure in areas of the body. Both conditions lead to strain and potential failure of the right heart, and therefore awareness and early diagnosis of the condition is needed to lead to better outcomes: however this depends on education of all specialists and primary care clinicians about PAH. This practical handbook covers both PH and PAH, providing information required by the wide range of clinicians who will encounter these conditions, including cardiologists, respiratory physicians, rheumatologists, specialists in liver and AIDS medicine, and haematologists. It covers what it is, who it is likely to affect, how it is diagnosed, including the pitfalls of the various diagnostic tests, the different and evolving forms of treatment, long term management of this often devastating chronic disease, and the crucial role of multidisciplinary management in optimizing clinical care of these patients who usually have multi-system diseases. It also covers the up new classification for both PH and PAH, and new drugs that have recently become available.

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."