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.

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."

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).

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.

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 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.

A practical, clinically-oriented handbook of iron overload disorders giving a compact guide to normal iron metabolism, iron-related pathobiology, and the diagnosis and management of heritable and acquired iron overload disorders. Many of these disorders were discovered and characterized only in the last decade, and are unmentioned or inadequately described in most texts. Written by clinicians for clinicians, this handbook summarizes information on diverse iron overload conditions, including their history, signs, symptoms, and physical examination findings, genetics, genotype-phenotype correlations, pathophysiology, differential diagnosis and treatment. Most physicians, regardless of specialty, encounter patients with systemic or organ-specific iron overload conditions. This book contains essential information for practising adult and pediatric medical specialists in the fields of hematology, gastroenterology, hepatology, rheumatology, endocrinology, diabetology, neurology, oncology, dermatology, and internal medicine. Pathologists, pharmacologists, geneticists, genetic counselors, and epidemiologists will also find substantial, up-to-date sections in this handbook that are pertinent to their respective fields of interest.

"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.

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.

This book explores the pathophysiology, clinical assessment and management of the obese patient in the context of serious chronic disease, as well as the political and environmental aspects, including prevention. The book's approach of arriving at an exploration of these issues through the vehicle of assessing the controversies is unique and interesting, attempting to debunk the myths and explore the genuine science whilst demonstrating areas where healthy debate is rife.

xii a second edition might be in order, and readily agreed. Although the basic principles remain the same, discussions with analysts, laboratory supervisors, and managers indicated many areas where improve ments could be made. For example, new chapters have been added on sampling and quality assurance; laboratory facilities and quality assurance; and auditing for quality assurance. Very little of the first edition has been discarded, but many topics have been expanded considerably. The chapter on computers has been completely rewritten in view of the rapid changes in that field. The chapter in the first edition on planning and organizing for quality assurance has been split into two chapters, one on planning for quality assurance and the other on organizing and establishing a quality assurance program, and new material on mandated quality assurance programs has been combined with the material on laboratory accreditation. Numerous examples, especially those involving mathematical calculations, have been added at the suggestion of some readers. In short, this edition is very nearly a new book, and I can only hope it is as well received as the first edition. CHAPTER 1 Quality, Quality Control, and Quality Assurance One of the strongest trends in modem society is the continuing ev olution from a manufacturing to a service-oriented economy."

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.

1. Renal failure following circulatory shock develops because of per- sistent vasoconstriction which is just sufficient to prevent glomerular filtration. Hypoxia of renal tissue has not been demonstrated in surviving cases. 2. During the low-pressure phase in circulatory shock the remaining blood flow through the medullary regions washes out the osmotic gradient built up by the countercurrent system of Henle's loops, so that a concentrated urine cannot be formed. 3. During recovery from circulatory failure the osmotic gradient of the medullary region can only be built up if sufficient fluid from the glomerular filtrate reaches the countercurrent system. The greater the GF, the faster the gradient is built up. References 1. BoYLAN, J. W. , and E. AssHAUER: Unpublished data. -2. DEETJEN, P. , and K. KRAMER: Pfliigers Arch. Physiol. (G. ) (in press). - 3. KRAMER, K. , and K. ULLRICH: Pfliigers Arch. Physiol. (G. ) 267,251 (1958). -4. KRA- MER, K. , K. THURAU and P. DEETJEN: Pfliigers Arch. Physiol. (G. ) 270, 251 (1960). - 5. KRAMER, K. , and P. DEETJEN: Pfliigers Arch. Physiol. (G. ) 271, 782 (1960). -6. KRAMER, K. , and P. DEETJEN: Unpublished data. - 7. KuHN, W. , and A. RAMEL: Helv. chim. acta 42,628 (1959). - 8. LASSEN, N. A. , 0. MuNcK and J. H. THAYSEN: Acta physiol. Scand. IJ1, 371 (1961). - 9. MUNCK, 0. : Renal Circulation in Acute Renal Failure. Oxford 1958.

HOW DO I USE THIS BOOK? This book is organized to answer specific questions about the metabolic and nutritional problems of critically ill patients. Thc questions are listed under five chapter headings in the Contents. Each question is self-contained with its own charts, tables, and references, although, in some instances, you may be referred to another section of the book for additional information. A detailed subject outline appears on the first page of each chapter, and there is an index for cross-reference to specific subjects. A metabolic support plan and accompanying metabolic and nutritional worksheet are locatcd in the Appendix. This plan pro vides the best estimates available for predicting the metabolic requirements of patients, and outlines approaches to feeding the hospitalized patient which will satisfy these nutritional needs. Clin ical cases are presented in this section to help you get started using the support plan. This volume is a handbook organized for frequent use - place the appropriate tables and nomograms on the bulletin board of the intensive care unit or in your office for convenient reference. Use the metabolic and nutritional support plan and establish the habit of assessing the metabolic requirements of your patients. Refer to the references cited to explore in further detail specific questions or areas of interest. By applying our knowledge of the metabolic and nutritional alterations which occur following disease, we can improve our care of the critically ill."

This was an important Symposium in a rapidly developing field of interest. It was designed to draw attention to areas which have been neglected in standard hepatology textbooks and to review areas of controversy. It was also meant to help bridge the communication gap between hepatologists'caring for children and adults as well as between some areas of clinical and basic research. The Symposium was a substantial success. Unfortunately two of the twenty participants did not deliver a manuscript. The result is a publication which is late and which is not as complete as it should be. For this lateness and incompleteness the editors apolo gize most sincerely--especially to those participants who delivered their manuscripts on time but even to those who delivered their manu scripts late. perhaps the most noteworthy feature of this publication is the fact that material presented in May 1980 is by no means out of date. Apart from the section on Viral Hepatitis, one of the most rapidly evolving fields of medicine, the context of the Symposium remains disturbingly current. The neglect continues, the controversies remain. We hope that this publication will help draw investigators into liver research, provide a useful point of reference for. those in the field and stand as a monument to editors past, present and future, who have chased, are chasing and will chase manuscripts in vain."

Although a strikingly modem account of multiple (disseminated) sclerosis was given by Charcot more than one hundred years ago, we are still not sure of the precise nature of the disease, still less of any precise mode of management. Even diagnosis is at best 'probable'. This collection of essays examines the particular difficulties which beset the problem and have mili tated against the solution-problems of data collection and evaluation; clinical and biochemical vagaries and unanswered questions ; laboratory test prediction of the disease, etc. Experts in their fields have set out the difficulties and way forward as ther see them, and there must necessarily be overlap or contradictions which underline our lack of knowledge. Clearly no attempt can be made to cover more than a very few aspects of the problem (a further volume is planned to review other areas not covered here, in particular the relationship between multiple sclerosis and experimental allergic encephalo myelitis)-but it is hoped that the 'softness' of much of the data we have to work upon will become appan!~nt. It is intended that this volume should clearly differ from the large number of monographs and reports of symposia dedicated to multiple sclerosis in bringing out the shortcomings of our approaches, and in some respects our naivities rather than our individual brilliancies.

Clinical biomechanics is a rapidly changing field with an increasingly wide appeal. While the core subjects of biomechanics remain the behavior of bones, joints, ligaments, and muscles, this book focuses on more clinical aspects such as artificial joints, tissue transplantations, and the effects of disease on biomechanical properties. Also featured are special studies of the hand, spine, vascular system, and the analysis of three-dimensional motion.
Based on the 20th Annual Meeting of the Japanese Society for Clinical Biomechanics and Related Research, this book provides an overview of the subject as well as describing many exciting new concepts and innovative methods for analyzing biomechanical systems. It should appeal across a wide spectrum of professions, proving indispensable to everyone from orthopedic surgeons to engineers with an interest in biology.

People with intellectual disability often have health needs that go unrecognised and untreated; this may be because of difficulties in communication, diagnostic overshadowing, discrimination or indifference. There is concern that public health measures aimed at reducing the main health killers in the population will not address these issues for people with intellectual disability and may preferentially widen the inequality that already exists. This book is a comprehensive and systematic review of physical and mental health co-morbidities in people with intellectual disability. Such an evidence base is vital in shaping public health policy, healthcare commissioning and the development of more effective healthcare systems, as well as supporting better understanding and practice at an individual clinical level. This is essential reading for policy makers and commissioners of services, as well as individual practitioners across mainstream and specialist health and social care, in considering not only service developments but practice at the coalface.

Jaundice is much more than a clinical sign of liver disease. It is also a pathophysiological disorder. Through studying it we have come to a much better understanding of how the liver functions under normal and abnormal circumstances. In spite of several important advances in this field, it has not recently been the subject of a comprehensive and interdisciplinary review. This Symposium was held in Montreal on May 31 and June 1, 1974, and the experts who participated in it came together for the purpose of reviewing the current status of Jaundice. The Editors sincerely appreciate the outstanding contribution which these experts made to the Second International Symposium of the Canadian Hepatic Foundation. They are also particularly indebted to Valerie M. Price, Executive Director, Canadian Hepatic Foundation, for her invaluable role in the preparation of this publication. Carl A. Goresky Murray M. Fisher v Contents BILIRUBIN CHEMISTRY An Overview of Bilirubin Chemistry 1 A. F. McDonagh The Conjugates of Bilirubin 19 E. R. Gordon Discussion Period. * * 39 R. Schmid, Char:imm BILIRUBIN PRODUCITON 43 Bilirubin Metabolism: An Overview * * * R. Schmid Bilirubin Production fram Non-Erythroid SoUI"Ces * * * * * * * * * * * * * * * * 57 S. H. Robinson Bilirubin Production fram Erythroid Sources 69 U. Muller-Eberhard and E. F. Johnson Induction Mechanisms for Bile Pigment Formation 85 B. A.

In 1960, Dr. Van R. Potter and Dr. Henry Pitot (at McCardle Laboratory in Madison, Wisconsin), Dr. Tetsuo Ono (then at McCardle Laboratory and now at the Japanese Foundation for Cancer Research in Tokyo, Japan) and Dr. Harold P. Morris (then at the National Cancer Institute and now at Howard University, Washington, D. C. ) decided that an experimental cancer model would be an invaluable tool to examine neoplastic changes in cells. Since they were study ing the various highly specific metabolic processes which are unique to liver tissues, they determined that a transplantable liver cancer model would be the ideal system to work with. This system would provide for comparison of normal liver tissue of the non-tumor bear ing animal, the tumor bearing animal's (host) liver and the liver cancer. Dr. Morris undertook a series of rat studies employing several chemicals known to cause liver cancer. Soon the first Morris hepatomas (#3683, 3924A, 5123) were being studied by several labs. During the next 18 years, Dr. Morris developed and transplanted numerous strains of hepatomas of which no two were identical. These tumors ranged from the very slowly-growing, highly differentiated cancer tissues, e. g., 96l8A which is a diploid tumor containing gly cogen and a "nearly normal" complement of enzymes, to a large group of rapidly-growing, poorly differentiated cancer tissues, e. g."

In spring this year it will be 23 years since I began to study rotation technique as applied to radiology. In applying this technique to roentgenography the name Rotation Radiography was adopted publicly in 1946. Since then this study has revealed that the technique is valuable not only in diagnosis but also in radiotherapy, and the name Conformation Radiotherapy was publicly an nounced in 1960. Through these studies it became clear that it is possible to show the axial transverse cross section of the human body roentgenographically, which could be of great value medically, but it was realized that no detailed roentgenograms of the axial transverse cross section covering the whole of the normal human adult have been published so far. To prepare an atlas was therefore considered basic for the practical application of this method, since without it further developments of this type of roentgenography cannot be expected. Conse quently it was decided first to prepare the atlas. In addition, the clinical application of this method to the diagnostic and therapeutic field was described with brief notes on the essential features of the method."

Herbal Medicines Offer Hope for Combating Hepatitis C

More than 500 million people worldwide carry the deadly hepatitis C virus (HCV), and hepatitis C poses a public health crisis far greater than the AIDS epidemic. This deadly disease, which can go undetected for years, eventually attacks the liver, causing cirrhosis, cancer, and even liver failure. Conventional medical treatments for hepatitis C have limited effectiveness. In Herbs for Hepatitis C and the Liver, Stephen Buhner examines the most recent research on how hepatitis C affects the body. He offers important information, practical guidance, and hope. This book includes:

* Clear descriptions of the common medical tests and treatments for hepatitis C -- what they mean and how effective they are.

* A guide to knowing and using the top herbal medicines that work to protect the liver and stregthen the immune system.

* A protocol for cleansing and strengthening the body with a combination of diet, herbs, and lifestyle changes.

The updated bestselling guide to human metabolism and metabolic regulation The revised and comprehensively updated new edition of Human Metabolism (formerly Metabolic Regulation - A Human Perspective) offers a current and integrated review of metabolism and metabolic regulation. The authors explain difficult concepts in clear and concise terms in order to provide an accessible and essential guide to the topic. This comprehensive text covers a wide range of topics such as energy balance, body weight regulation, exercise, and how the body copes with extreme situations, and illustrates how metabolic regulation allows the human body to adapt to many different conditions. This fourth edition has been revised with a new full colour text design and helpful illustrations that illuminate the regulatory mechanisms by which all cells control the metabolic processes necessary for life. The text includes chapter summaries and additional explanatory text that help to clarify the information presented. In addition, the newly revised edition includes more content on metabolic pathways and metabolic diseases. This important resource: Is a valuable tool for scientists, practitioners and students across a broad range of health sciences including medicine, biochemistry, nutrition, dietetics, sports science and nursing Includes a full colour text filled with illustrations and additional diagrams to aid understanding Offers a companion website with additional learning and teaching resources. Written for students of medicine, biochemistry, nutrition, dietetics, sports science and nursing, Human Metabolism has been revised and updated to provide a comprehensive review of metabolism and metabolic regulation.

The meeting which took place in Rome on November 19th and 20th of 1982 is easily the best meeting on hepatic coma that I have ever attended, and I have attended many. It was an exceedingly we- planned meeting with prolonged opportunity for discussion, and there was genuine interplay and exchange of ideas (not the usual picture of a rushed meeting with investigators presenting their own point of view and talking past each other without a meaningful ex change) which took place in Rome. My co-editors and I hope that the published transcript, which of course can only reflect what transpired in Rome on those two days, does justice to a very intellectually exciting and gratifying ex change of ideas. L. Capocaccia, J. E. Fischer and F. Rossi-Fanelli v CONTENTS Introduction 1 SECTION 1: PATHOGENETIC PROBLEMS IN HEPATIC ENCEPHALOPATHY Ammonia: The old and the new * * . * * * . * . * * * . * . * 5 L. Zieve Role of synergism in the pathogenesis of hepatic encephalopathy * * * * . * * . . . . * 15 L. Zieve y-Aminobutyric acid receptors in experimental hepatic encephalopathy *. *. * * 25 M. L. Zeneroli, ~. Baraldi,and E. Ventura A possible role for excitatory neurotoxic amino acids in the pathogenesis of hepatic en 41 cephalopathy * * * * * * * * * * * * * * * F. Moroni, G. Lombardi, G. Moneti, D. Pellegrini and C.