This second International Symposium on Mucus in Health and Disease once again brings together basic scientists such as Biochemists, Anatomists, Biologists and Clinicians who are dealing with aspects of mucus in the various tracts of the body where it is of such great functional importance. It is fitting that the meeting should take place at Manchester University where there is so much activity in this field and our grateful thanks are due to Or Eric Chantler for his untiring efforts in organising this meeting. At the first Mucus meeting, Sir Francis Avery Jones stated "this is a subject which will justify further Symposia, both local and international." As he predicted, this meeting succeeds the first and adds further to our progress in understanding the complex and unique structure and function of the mucus secretion in its various sites of the body. Much was learned from the first meeting and it is hoped that the second will be an appropriate successor to it. The emphasis in this meeting has been to encourage discussion and the presentation of research material. In this respect, review articles have been kept to a minimum. The structure of the Conference has been organised around eight keynote addresses: one on the biosyn thesis of the general mucus glycoproteins and another on its physical properties. Other keynote papers are on the biochemical and clinical aspects of mucus in the respiratory, gastrointestinal and urogenital tracts by recognised authorities in these subjects."

The Sapporo International Symposium on "Recent Advances in Nitric Oxide Research" was held in Sapporo, Japan, in 1997, following the Fifth International Meeting on the Biology of Nitric Oxide in Kyoto, Japan, organized by Dr. Salvador Moncada, Dr. Noboru Toda, and Dr. Hiroshi Maeda. The field of nitric oxide research continues to expand rapidly, and our understanding of the physiological and pathophysiological roles of NO has increased greatly. The Kyoto Meeting was stimulating and informative, providing impetus for the Sapporo Symposium, which I had the great honor to organize. To communicate the information from these events, Dr. Ichiro Sakuma and I decided to publish this book. The contents of its chapters were contributed by the participants who were active at the Sapporo symposium and cover the majority of the presentations made during that symposium. Dr. Csaba Szabo of Children's Hospital Medical Center in Cincinnati (U. S. A. ) reviews the roles of peroxynitrite and poly(ADP-ribose)synthetase in shock, inflammation, and reperfusion injury, and Dr. David A. Geller and his colleagues of the University of Pittsburgh (U. S. A. ) review the regulation and function of NO in the liver. As contributions from the Hokkaido University School of Medicine (Sapporo), Dr. Hiroko Togashi and colleagues present their data on transient cerebral ischemia and NO production, Dr.

Read with two objectives: first, to acquaint yourself with the current knowledge of a subject and the steps by which it has been reached; and secondly, and more important, read to understand and analyze your cases. William Osler, The Student Life What follows is a collection of cases-or more aptly, the stories of our patients and friends who have been seen at The Ohio State University Hospitals where our faculty have provided their care and about whom this volume is written. Today many fear that our patients are being moved from center stage while we are being distracted by the technology of medicine. This volume was written with patients in mind. The idea is that the most intriguing questions and the most rewarding answers begin and end at the bedside. This is a story of our patients, told by expert clinicians and spiced with commentary along the way. This volume in no way at tempts to be comprehensive. Instead, it is like the practice of medicine, scattered, somewhat disjointed, while at the same time intensely personal and focused upon whatever problem the patient brings to us. The discussions are not so much about disease entities as they are about patients with problem." The two are uniquely dif ferent. For instance, when the physician suspects hepatitis, not every imaginable cause can be actively investigated. Instead, tests and procedures are discriminate ly chosen, a part of medicine that is still more art than science."

Computing and information management technologies touch our lives in the environments where we live, play and, work. High tech is becoming the standard. Those of use who work in a laboratory environment are faced with an obvious challenge. How do we best apply these technol ogies to make money for our companies? The first level of deliverable benefits is achieved through task automation. The second level is ob tained by integrating the individual islands of automation. The third, or top level, of benefits is related to applying intelligence to computing applications. The use of computing technology, at level one, to automate lab pro cedures, methods, and instruments has been profitable for many years. We can easily find yearly returns in the range of 10-50% for investments at this level. For level two, the integration of some applications has evolved and has led to data management systems and local area net working in the lab environment. Investment paybacks at level two are substantially higher, in the range of 200-400%. Examples of applications at the top level, that of intelligent systems and applications, are few and far between. And what about the payback for investments at this level? With such limited experience at level three, we can only estimate the benefits. But again, they appear to be much higher, in the range of 2000- 4000%."

Bone is a sex hormone-dependent organ, which has important implications for current therapeutic strategies in the prevention and possible treatment of bone loss in the elderly. This book contains the proceedings of the Schering Workshop on "Sex Steroids and Bone." The various chapters by leading experts give and overall view of current knowledge on the control of bone hemostasis by sex steroids and new ideas on how this controlcould be exerted. It was also of particular concern to integrate a general survey of in vivo experimentation and histomorphometric evaluation of bone tissue. The organizers of the workshop and editors of this volume hope that it will contribute to a better understanding of the role of sex steroids in bone and thus pave the way for a better experimental approach instudying drug effects on bone with the ultimate goal of improving therapy in bone diseases.

It is a pleasure to present the book, Evaluation and Treatment of Obesity, for reference and textbook use. The text is an outgrowth of the Obesity Weight Control Track of the 1982 La Crosse Health and Sports Science Symposium, sponsored annually by the La Crosse Exercise Program, Uni versity of Wisconsin-La Crosse. With versatile faculty, topics, and attend ing professionals, the Obesity-Weight Control Track stimulated an effort to produce interdisciplinary resources on obesity. Out of this effort, three books have been compiled and edited. This book, Evaluation and Treatment of Obesity, introduces an interdis ciplinary, practical approach to obesity management. The other two books, Nutrition and Exercise in Obesity Management and Behavioral Management of Obesity, expand on the basic theories introduced in this book, providing in-depth information of value to the practicing profes sional. These three books apply the latest information from the fields of medicine, nutrition, exercise, and psychology to the problem of obesity. The information is intended to guide health professionals in the inter disciplinary management of obesity. In 1983 the Obesity-Weight Control Track focused on controversial issues of theoretical and practical concern. The speakers from this track contributed their expertise to the compilation of two additional books. Thus, Trends and Controversies in Obesity Research and Innovation in Obesity Program Development will complete the series. Consider the five volumes a consolidated, comprehensive reference related to the growing, interdisciplinary field of weight control."

The present volume is one of a series concerned with topics considered to be of growing interest to those whose ultimate aim is the understanding of the nutrition of man. Volumes on Sweetness, Calcium in Human Biology and Sucrose: Nutritional and Safety Aspects, have already been published, and another, on Dietary Starches and Sugars in Man: A Comparison, is in preparation. Written for workers in the nutritional and allied sciences rather than for the specialist, they aim to fill the gap between the textbook on the one hand and the many publications addressed to the expert on the other. The target readership spans medicine, nutrition and the biological sciences generally and includes those in the food, chemical and allied industries who need to take account of advances in these fields relevant to their products. Funded by industry but with an independent status, the Inter national Life Sciences Institute (ILSI) is a non-profit organization founded to deal objectively with the numerous health and safety issues that today concern industry internationally. ILSI sponsors scientific research, organizes conferences and publishes monographs relative to these problems. London Ian Macdonald March 1988 Series Editor Preface This volume has been prepared at a time when interest in both the biological roles of zinc and its nutritional significance is growing rapidly.

Teach us to live that we may dread Unnecessary time in bed Get people up and we may save Our patients from an early grave. A most revealing paraphrase by Asher* of a verse by Bishop Thomas Ken more than adequately summarizes the plight of the immobilized patient, who often lies dormant and de pressed for years on end. In this volume, Dr. Steinberg has offered the reader a unique opportunity to share his many years of experience in caring for the immobilized patient. His careful attempt to explore the pathophysiologic effects of immobilization on a number of organ systems, combined with a host of practical aspects with regard to patient care, is unique and refreshing. This text should command the re spect of any physician faced with the vicissitudes and frus trations of caring for the immobilized. The final chapter de tailing "The Psychological Aspects of Immobilization," by Hammer and Kenan, offers the reader considerable insight into the essentials and value of occupational and physical therapy. It should prove most valuable to physicians as well "Asher, R. A. ]. Dangers of going to bed. Br. Med. J. 2:907, 1947. v vi FOREWORD as social workers, paramedical personnel, and the many physical therapists who come into daily contact with the nonambulatory patient. L. V. Avioli St. Louis Preface It may be a paradox that the importance of disability and immobilization has been enhanced by the very progress of medical science."

Historical Introduction The Marfan Syndrome: From Clinical Delineation to Mutational Characterization, a Semiautobiographic Account VictorA. McKusick l n 1876, E. Williams, an ophthalmologistin Cincinnati, Ohio, described ectopia lentis in a brother and sister who were exceptionally tall and had been loosejointed from birth. I Although there is a Williams syndrome that has aortic manifestations (supravalvar aortic stenosis), the name Williams was never associated with the disorder we now call Marfan syndrome. The reason is clear: Williamswas geographically removed from the leading medical centers and published in the Transactions of the American Ophthalmological Society; surely his report attracted little attention and the non-ocular features were not emphasized. 2 The case report that brought the disorder to attention was provided by a prominent Pari- sian professor of pediatrics, Antoine Bernard-Jean Marfan (1858-1942), who did much to establish pediatrics as a specialty in France and elsewhere. He was the author of widely read textbooks and monographson pediatrictopics and waseditor of Le Nourrisson for a great many years. In addition to the syndromeunder discussion here, his name is often attached to "Marfan's law" (that immunity to pulmonary phthisis is conferred by the healing of a local tuberculous 3 lesion) and Marfan's subxiphoid approach for aspiratingfluid from the pericardial sac. (Please pardon my use of the possessive form of the eponym in these two instances!) Pictures of Marfan (Fig.

"Infection in the Compromised Host" has become a classic chapter in textbooks devoted to infectious diseases and internal medicine. The numbers of compromised hosts are increasing in the era of modem medicine because of our expanded capabilities to deal with difficult diseases, especially neoplasms. As a consequence, microbiologic complications related to the intensive care administered to these patients are increasing as well. Under these circum stances, not only does the underlying illness create conditions favorable for the development of unusual infections, but often the therapy contributes to the acquisition of potential pathogens that turn into agents responsible for severe and frequently fatal disease. Granulocytopenia and immunosuppression have been the two key fac tors in predisposing patients with cancer and other serious diseases to severe bacterial infections. Colonization by hospital-acquired pathogens and breaks in the anatomic barriers-as a result of disease or medical intervention-have contributed to the high incidence of infectious diseases in these patients. Although there is some overlap between the types of infection in granulocytopenic and immunosuppressed hosts, each ofthese clinical entities has distinctive features thatjustify considering them separately, reserving the term immunocompromised hosts only when refer ring to patients who are predisposed to opportunistic infections. For about two decades, infections in granulocytopenic patients have attracted the atten tion of clinicians because they represent a model for the study of antimicrobial drugs in hosts deprived of an essential element of defense against bacterial infection, that is, an adequate number of normally functioning granulocytes.

One of the fascinations of psychiatry is that it is amenable to many different approaches. In seeking to account for mental disorder, for example, it is pos sible to explore the meaning and significance of symptoms in the psychody namic sense, to examine the social determinants of illness, or to adopt an es sentially biological viewpoint in investigating links between physiological and psychological dysfunction .. As a clinical discipline it may be practiced in the community, in the specialized clinic or hospital, or shoulder-to-shoulder with other medical practitioners in the general hospital. This richness and diversity are at once a strength and a weakness, attracting practitioners with a wide range of talents and interests, yet sometimes leading to polarizations and false an titheses. The so-called "medical model" of psychiatry has come under a good deal of attack, and deservedly so when claiming an exclusive provenance over all types and aspects of mental disorder. What cannot be gainsaid, however, is the central role of medicine in relation to many parts of the field, and the success in terms of understanding and therapy that has resulted from medicine's in volvement. Nor can it be doubted, after the most cursory acquaintance with the physically or mentally ill, that the relationship between these two forms of suffering is often so close and so mutually reinforcing that distinctions are drawn somewhat arbitrarily. This last is perhaps the cardinal reason for the alliance between medicine and psychiatry."

nd This book stems from the 2 Parkinson's Disease Symposium on "Neurotoxic Factors in Parkinsons disease and related disorders", held on August 6-7,1999 at the University ofUlm Medical School in Ulm at the Danube, Germany. The symposium wasalso asatellite ofthejointmeetingofthe InternationalSocietyfor Neurochemistry (ISN) and the European Society for Neurochemistry (ESN) that followed immediately afterwards in Berlin. The specific topic, neurotoxic factors in Parkinson's disease (PD), was chosen in light of accumulating neurobiological and epidemiological evidence indicating that the causes of this second most common neurodegenerative disorder, and possibly of related conditions such as multiple systems atrophy, in some manner involve environ- mental (xenobiotic) and even endogenous toxic agents. This volume brings together much of that neurobiological evidence; and in epidemiology, several recent major studies ofPD - for example, a study of20,000 twins published in the Journal of the American Medical Association in 1999 - conclude that environmental and life style than genetics, appear to be critical in the idiopathic disease. However, factors, rather the precise roles of neurotoxic factors in the pathogenesis of PD and related basal ganglia disorders remain uncertain, despite the cascade of research resulting from the discovery of the prototype MPTP in the early 1980's, and frankly, we have been surprised by the paucity of concentrated attention on specific environmental agents other than MPTP.

In the front material of this book both a foreword and a preface appear. What the content of a preface should be is well understood. It is the author's retrospective account of intent, of the labors to accomplish that intent, and of the content of the book that resulted. What a foreword should be is less obvious. Most properly, it is perhaps the brief testimony of one who knows the accomplishments of the author and the scope of the field and who may direct readers to the book. On some basis, the writer is assumed to have earned the right to undertake such a task. To undertake the writing of a foreword for so considerable a researcher, teacher, and scholar as Alfred Evans can be seen not only as an honor but also as a daunting one. My first thought, in truth, is that this wine needs no blush and that no foreword is needed. As John Rodman Paul Professor of Epidemiology at Yale, Alfred Evans has an established reputation in the field of causality. We have learned from his insights about the evolution of causal thinking as epidemiology passed from the era of the germ theory into that of the search for causes of chronic noncontagious diseases. It was he who drew attention to the effect of specific context in that evolution.

Since its launch in 1998 the European Society for Intravenous Anaesthesia (EuroSIVA) has come a long way in providing educational material and supporting the research and clinical application of intravenous anaesthesia. After the first two annual meetings held in Barcelona and Amsterdam in 1998 and 1999, three other successful meetings took place in Vienna, Gothenburg and Nice in 2000, 2001 and 2002. Next to these main meetings, starting in the year 2000, a smaller winter meeting has been organised every last week of January in Crans Montana, Switzerland. Both the main summer and the winter meetings breathe the same atmosphere of sharing the latest on intravenous anaesthesia research in the presence of a friendly environment and good company. Since the first meetings the educational tools of EuroSIVA have increased in quantity and technical quality allowing digital slide and video presentation along with the use of the computer simulation program TIVAtrainer during the speaker sessions and the workshops. Furthermore, EuroSIVA now exploits a website www. eurosiva. org that allows for continuous exchange of information on intravenous anaesthesia, the TIVAtrainer, the EuroSIVA meetings and online registration for these meetings. The EuroSIVA is currently engaged in friendly contacts with the Asian Oceanic Society for Intravenous Anaesthesia (AOSIVA), the United Kingdom Society for Intravenous Anaesthesia (UKSIVA), the Korean Society for Intravenous Anaesthesia (KSIVA), the European Society of Anaesthesiology (ESA) and the International Society for Applied Pharmacology (ISAP).

The availability of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) sold over-the-counter (OTC) to the public without prescription has become an issue of major concern in recent years. The problem has been highlighted in the UK, USA and other countries because of the continuing high rates of cases of poisoning and the influence of switching from prescription-only status for many NSAIDs to OTC sale brought about, in a large part, by governments and health maintenance organisations (especially in the USA) anxious to save on costs of these drugs. Concern in the UK about poisoning from paracetamol and the appreciable morbidity and mortality from aspirin was such that a major review was initiated in 1996 by the UK government's Medicines Control Agency (MCA). Doubtless, many other governments have also undertaken reviews of the safety issues concerning OTC analgesics and NSAIDs. In the UK the situation has culminated in the decision announced in August 1997, as this book was going to press, that the number of tablets/capsules of the solid dosage forms of paracetamol and aspirin would be limited for sale OTe. This decision was essentially based on the need to limit the unit quantity of these drugs so as to reduce the likelihood of poisoning with paracetamol and the development of gastrointestinal and other more serious side-effects from aspirin. Time. will tell whether these new regulations will influence the occurrence of these adverse events.

At the Sixth Wiggers Bernard Conference, a group of scientists from various disciplines discussed new findings relating to nitric oxide synthase inhibitor in shock, sepsis, and organ failure. Dedicated to the presentation and discussion of both positive and negative findings related to the use of NOS inhibitors, the meeting served as a forum for issues relating to specific and non-specific inhibitors, as well as the role of nitric oxide-oxygen radical interactions. Both experimental and clinical data were presented in the trauma and sepsis field.

This collection of contributions on the subject of the neural mechanisms of sensorimotor control resulted from a conference held in Cairns, Australia, September 3-6, 2001. While the three of us were attending the International Union of Physiological Sciences (IUPS) Congress in St Petersburg, Russia, in 1997, we discussed the implications of the next Congress being awarded to New Zealand. We agreed to organise a satellite to this congress in an area of mutual interest -the neuroscience of movement and sensation. Australia has a long-standing and enviable reputation in the field of neural mechanisms of sensorimotor control. Arguably this reached its peak with the award of a Nobel Prize to Sir John Eccles in 1963 for his work on synaptic transmission in the central nervous system. Since that time, the subject of neuroscience has progressed considerably. One advance is the exploitation of knowledge acquired from animal experiments to studies on conscious human subjects. In this development, Australians have achieved international prominence, particularly in the areas of kinaesthesia and movement control. This bias is evident in the choice of subject matter for the conference and, subsequently, this book. It was also decided to assign a whole section to muscle mechanics, a subject that is often left out altogether from conferences on motor control. Cairns is a lovely city and September is a good time to visit it.

In this book, the discussion of the normal and pathological aspects of anxiety is critically examined. A chapter on the molecular basis of anxiety is included, outlining the potential of such approach in the discovery of novel effective pharmacological interventions. The face validity, predictability and usefulness of animal models in the design of valid new efficacious products are discussed. Separate chapters dedicated to each particular type of anxiety such as generalized anxiety disorder, social phobia, posttraumatic stress disorder, panic and obsessive-compulive disorder are included. This book should be of benefit to psychiatrists, clinical psychologists, general practitioners, nurses, students and all those engaged in neuropsychiatric research.

One of the major features that distinguishes vertebrates from invertebrates is the presence of a complex immune system. Over millions of years, many novel immune genes and gene families have emerged and their products form sophisticated pathways conferring protection against most pathogens. The Human Genome Project revealed that the immunoglobulin gene superfamily was one of the largest in the genome, containing more than 20f all known human genes. High-throughput technologies for the study of DNA, mRNA and proteins, such as microarrays and real-time gene amplification technologies, as well as biobank facilities, are enabling the investigation of these genes and pathways in ever more detail. The parallel development of databases and bioinformatics tools to store and interpret this information will also contribute to greater understanding of the function of the immune system.

Genomics is finally changing from an academic discipline to one with real clinical relevance. The study of immune regulation in response to pathogen invasion, to the presence of malignant or allogeneic tissue and, in some cases, to normal autologous tissue requires techniques that study the behaviour of whole systems in parallel. A genome-wide, systems biology approach is needed to understand the genetic and environmental factors that regulate the healthy immune system and its response to pathogens as well as to malignant cells arising within the body. It will also facilitate determining what goes wrong when the immune system attacks normal host cells, as in autoimmune diseases such as Type 1 diabetes.

Finally, greater knowledge of the immune system will enable us to use it to promote health and curedisease, through vaccine development - targeting both pathogens and tumour cells - and by manipulation of cellular and humoral defences.

This book provides an overview of key conceptual and molecular technologies being deployed in immunogenomics, followed by detailed evaluations of the impact of genomics and systems biology on important areas such as cancer immunology, autoimmunity, allergy and the response to infection. It will be of interest to all those working in immunology, as well as to bioinformaticians and specialists such as oncologists and microbiologists.

In the previous two volumes of this series, we presented classic problems in internal medicine as illustrated by actual cases cared for in our institution. It has been gratifying for us to see the interest that these volumes have generated with students and trainees. We remain committed to the case method of instruction, and believe that there is no better method to learn medicine than to have an individual patient problem as the basis for study of pathophysiology, natural history, diagnosis and management. We hope that our readers find this third volume as enjoyable and instructive as the editors found it. Juan M. Bowen, MD Ernest L. Mazzaferri, MD, FACP xiii Acknowledgement The editors are grateful to Jeff Smith and Jenny Riegler for their unflagging professionalism and patience. xiv Contents Case 1 Mitral Regurgitation - Chronic Versus Acute: Implications for Timing of Surgery * . * * * . . * . . . . . * . . . . . . . . . . . 1 Harisios Boudoulas, MD Charles F. Wooley, MD Advances and diagnostic imaging in a surgical technique have changed the approach to mitral valve regurgitation. This chapter provides an expert's perspective. Case 2 Cystic Fibrosis in Adults .. * ************ 36 Andrew Libertin, MD John S. Heintz, MD As children with cystic fibrosis grow into adulthood, the internist assumes a greater role in their care. Case 3 Thrombotic Thrombocytopenic Purpura . . . . . . . . . . 51 . . . Donald E. Thornton, MD Earl N. Metz, MD, FACP Patients with ITP continue to present difficulties in diagnosis and management. Two experts discuss the current approach to ITP.

This volume contains the proceedings of the ninth "Colloque medecine et recherche" of the Fondation IPSEN devoted to research on Alzheimer's disease. This symposium was held in Lyon on June 21, 1993, on the topic, "Amyloid Protein Precursors in Development, Aging and Alzheimer's Disease". The choice of this venue and of this particular subject was not a matter of chance. As far as the history of medicine and neurology is concerned, Lyon is doubtless one of the most famous cities in France and the F ondation IPSEN had to organize one of its meetings in this city which has been regarded for centuries as a major crossroads. Regarding the topic, the amyloid story is at the center of the debate in the field of Alzheimer's studies. For nearly 10 years, "alzheimerology" has more or less been intertwined with "amyloidology". The purification and the sequencing of the beta/ A4 peptide in amyloid congophilic angiopathy (Glenner and Wong 1984) and in Alzheimer's disease (Masters et al. 1985) were the first steps toward the numerous successes realised in the last few years. The discovery of the amyloid precursor protein (APP), the localisation of its gene on chromosome 21 and the sequencing of its cDNA in 1987 (Kang et al. 1987; Goldgaber et al. 1987; Robakis et al.

"Methods in Pulmonary Research" presents a comprehensive review of methods used to study physiology and the cell biology of the lung. The book covers the entire range of techniques from those that require cell cultures to those using in vivo experimental models. Up-to-date techniques such as intravital microscopy are presented. Yet standard methods such as classical short circuit techniques used to study tracheal transport are fully covered. This book will be extremely useful for all who work in pulmonary research, yet need a practical guide to incorporate other established methods into their research programs. Thus the book will prove to be a valuable resource for cell biologists who wish to use organs in their research programs as well biological scientists who are moving their research programs into more cell related phenomena.

What disease is and how it affects humans is the focus of this primer. Designed to cover the basics of communicable and non-communicable diseases, the book provides a framework for understanding the major health problems in our society. Hurster uses the Biological Laws of Disease to frame each discussion and to demonstrate how these laws relate to the prepathogenesis and pathogenesis stages of the natural history of any disease. Considerable attention is given to the roles of the individual, the community, and the government in bringing about behavior change with respect to disease prevention, detection, control, and management.

A detailed description of a new approach to perceptual analysis and processing of medical images is given. Instead of traditional pattern recognition a new method of image analysis is presented, based on a syntactic description of the shapes selected on the image and graph-grammar parsing algorithms. This method of "Image Understanding" can be found as a model of mans' cognitive image understanding processes. The usefulness for the automatic understanding of the merit of medical images is demonstrated as well as the ability for giving useful diagnostic descriptions of the illnesses. As an application, the production of a content-based, automatically generated index for arranging and for searching medical images in multimedia medical databases is presented.