The philosophy of this NATO Advanced Research Workshop and the monograph it has yielded is that if you put a small number of very talented and creative scientists of different backgrounds and documented accomplishments together in a cloistered place for a few days to consider a very important and timely topic, many new ideas will be generated. The keynote of this conference was the Future. By this we mean the expected future developments of highly reliable sequential quantitative measurements of atherosclerotic plaque size and components in living human subjects. Some of the best minds and the most experienced and talented individuals at the leading edges of imaging of arteries were involved; some of the best scientists and students of the atherosclerotic plaque and its components participated; and some of the leading investigators of the cell biology or, as we call it in the USA, the pathobiology of atherosclerosis, contributed important new information. All of these individuals were actively involved in the conference and each obviously had carefully prepared and was able to communicate effectively.

Most of us spend at least two-thirds of our lives either sitting or standing. It is somewhat surprising, therefore, to find not a single book devoted to disorders caused by derangements of the normal physiological adjustments to changes in posture. In fact, until very recently, medical students have not even been advised to measure the blood pressure and heart rate in the upright posture as part of the routine physical examination. Although Bradbury and Eggleston first described orthostatic hypotension as a consequence of autonomic insufficiency in 1925, interest in orthostatic disorders has been slow to develop in the subsequent years. It is well known that the change from recumbency to the standing posture stimulates neurological, endocrine, and cardiovascular adjustments that ensure maintenance of a normal circulation despite the effects of gravitational forces. The mechanisms of these physiological responses to orthostasis have been stud ied by many investigators. Some of the defects to which antigravitational com pensatory mechanisms are subject, such as postural hypotension resulting from autonomic failure, have been studied intensively and have become part of the general knowledge of most medical practitioners. Other orthostatic disorders such as various other postural abnormalities of blood pressure control, and orthostatic edema-have received far less attention and have been unable to compete with the more dramatic and life-threatening ailments of humankind for a place in our standard medical texts. These disorders often give rise to distressing symptoms and may lead to severe impairment of health.

Since the apoE4 allele is a risk factor or susceptibility gene in late-onset familial and sporadic AD, the mechanism of disease expression may involve metabolic effects that are isoform specific. Isoform-specific interactions of apoE therefore become critical in the mechanism of AD pathogenesis. Detailed characterization of the binding of the apoE isoforms with proteins and peptides relevant to the pathology of the disease may be critical in understanding disease pathogenesis. These critical isoform-specific interactions of apoE may involve interactions with proteins and pep tides in the defining neuropathologic lesions of the disease, the neurofibrillary tangle and senile plaque. Other possible critical isoform-specific interactions include the mechanism of internalization, intracellular trafficking, and subsequent metabolism. In addition, differential post-translational modifications of apoE isoforms may determine differences in metabolism contributing to the pathogenesis of the disease. Oxidation of apoE may confer several isoform-specific, biochemically distinct properties. Since {3A peptide binds apoE in the lipoprotein binding domain of the protein and not in the receptor-binding domain, apoE could target bound {3A4 peptide to neurons via the LRP receptor. Internalization of the apoEI {3A peptide complex into the cell, by the same route as the apoE-containing lipoproteins, would result in incorporation into primary lysosomes and pH dependent dissociation. The demonstration of apoE in the cytoplasm of neurons, with isoform-specific interactions of apoE with the microtubule-binding protein tau demonstrated in vitro, suggest additional, testable hypotheses of disease pathogenesis.

The topics in this book represent the presentations given at the Fifth Annual Meeting entitled "Cardiac Surgery: Current Issues" held at the Frenchman's Reef Beach Resort, St. Thomas, U.S. Virgin Islands, November 18-20, 1993. This symposium was sponsored by the Division of Cardiothoracic Surgery, the School of Cardiovascular Perfusion and the Department of Nursing Education and Quality Assurance of Cooper Hospital/University Medical Center, the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Camden, New Jersey, as well as the Academy of Medicine of New Jersey. Chapter authors were charged with the task of writing brief overviews of major issues related to the field of cardiac surgery. The book is specifically tailored to the needs of cardiothoracic surgeons, cardiovascular perfusion ists, allied health professionals and nursing personnel involved in all phases of caring for the cardiac surgical patient. Although intended as a reference source with emphasis on up-dated approaches applied in cardiac surgery, it is hoped that the discussion of these topiCS will compliment other texts and manuscripts. Obviously, a book of this length cannot cover the whole multidisciplinary and complex field of cardiac surgery. However, co-editors are certain that the annual appearance of this text will highlight comprehensive, new and Interesting approaches to the field of cardiac surgery."

The primary purpose of this book is to bridge the gap be tween the practice of clinical medicine and diagnostic radi ology. It is intended primarily for utilization by medical students in training and by nonradiologist physicians. In this world of rapidly expanding knowledge in the many specialties of medicine, it is becoming increasingly difficult for many physicians to stay abreast of the newer and constantly changing modalities of diagnosis as well as the therapeutic regimens of the common as well as the less common disease processes within their realm of practice. This book will enable the busy clinician to utilize the consultative services offered by his or her colleagues in diagnostic radiology with maximum effectiveness. The most common clinical applications of the more recent imag ing modalities (i. e. , nuclear medicine, ultrasound, comput erized tomography, and magnetic resonance imaging) have been categorized and condensed into a format that will be both comprehensible and useful on a daily basis for those physicians routinely requesting these diagnostic examina tions for their patients. For simplicity, the book is divided, whenever feasible, into organ systems and subdivided into the multiple classifications of pathologic states (i. e. , con genital, trauma or iatrogenic, inflammatory, and neo plasm). In addition, there are brief comments related to the vii specific advantages and disadvantages as well as the cost effectiveness of each modality.

This volume is the third in the Contemporary Geriatric Medicine series. As in previous volumes, information is presented in the form of easy-to read essays to bring the reader up to date on state-of-the-art develop ments in the area of geriatric medicine. Once again, a system approach is utilized. In addition, several new topics-including alcoholism, throm boembolic disease, and decubitus ulcer management-have been intro duced to enhance this volume's usefulness to the busy clinician and student. Each chapter is not meant to be an exhaustive review of all topics in the field, but rather to focus on issues currently receiving a great deal of attention. Our goal continues to be to create an exciting approach to contemporary issues in geriatric medicine. The editors are once again appreciative for having been given the opportunity to develop this series. Appreciation is also expressed to our professional colleagues, families, and administrative assistants, who have enabled this volume to reach fruition. As in the past, we thank, most of all, our elderly patients for providing the inspiration and impetus to improve our knowledge and understanding of the health care needs of the elderly. Steven R. Gambert, M.D. V alhalla, New York ix Contents Chapter 1 Geriatric Cardiology and Blood Pressure 1 Edmund H. Duthie, Jr., and Michael H. Keelan, Jr."

A solution to the protein folding problem has eluded researchers for more than 30 years. The stakes are high. Such a solution will make 40,000 more tertiary structures available for immediate study by translating the DNA sequence information in the sequence databases into three-dimensional protein structures. This translation will be indispensable for the analy sis of results from the Human Genome Project, de novo protein design, and many other areas of biotechnological research. Finally, an in-depth study of the rules of protein folding should provide vital clues to the protein fold ing process. The search for these rules is therefore an important objective for theoretical molecular biology. Both experimental and theoretical ap proaches have been used in the search for a solution, with many promising results but no general solution. In recent years, there has been an exponen tial increase in the power of computers. This has triggered an incredible outburst of theoretical approaches to solving the protein folding problem ranging from molecular dynamics-based studies of proteins in solution to the actual prediction of protein structures from first principles. This volume attempts to present a concise overview of these advances. Adrian Roitberg and Ron Elber describe the locally enhanced sam pling/simulated annealing conformational search algorithm (Chapter 1), which is potentially useful for the rapid conformational search of larger molecular systems."

This book is written for medical students and house officers working on the wards, in the intensive care unit, and in the emergency room. It is intended for use by all whose work involves the daily evaluation and management of medical emergencies. The material is a compilation of information gained from our personal experiences in clinical practice, from participation in professional meet ings and conferences, and from searching the medical literature. The introductory chapters in Part I form a foundation that is devel oped in the subsequent parts where specific topics are discussed. When possible, we have simplified complex approaches to diagnosis and man agement by formulating algorithms and handy reference tables. Since this is a handbook and not a textbook, we have limited our discussion of pathogenesis and pathophysiology in order to concentrate on practical aspects and specific details that are useful in the diagnosis and management of pulmonary emergencies. Our aim is to alert young physicians to common pulmonary emergencies and guide them through their initial management."

Why another series on infectious disease? The question is a fair one in view of the proliferation of monographs, texts, and periodicals on the vast subject of infectious disease. The goal of this series is to provide an additional service to the clinician in the form of clinical information not usually assembled in one convenient volume. One type of monograph presented in this series will cover a specific infection, detailing microbiologic, research and clinical aspects. It is hoped that such a compilation will be helpful in both its thoroughness and breadth to the clinician interested in this particular problem. The other type of monograph that this series will provide will discuss a clinical presentation that comprises many possible specific etiologies. Volumes in the series will be multiauthored, giving us the opportunity to invite authorities in each specific area to contribute their expertise and experience. Regular revisions are planned so that each volume will remain as current as it is thorough. We hope that our goals are met and that the present series of mono graphs establishes its own identifiable and valuable niche in the growing compendium of resource material available to the clinician. Preface to the Second Edition Since the first edition of Infectious Mononucleosis was published, we have seen exciting advances in our understanding of this disease."

Cells have evolved multiple strategies to adapt the composition and quality of their protein equipment to needs imposed by changes in intra- and extracellular conditions. The appearance of pro teins transmit ting novel functional properties to cells can be controlled at a transcrip tional, posttranscriptional, translational or posttranslational level. Extensive research over the past 15 years has shown that transcriptional regulation is used as the predominant strategy to control the production of new proteins in response to extracellular stimuli. At the level of gene transcription, the initiation ofmRNA synthesis is used most frequently to govern gene expression. The key elements controlling transcription initiation in eukaryotes are activator proteins (transactivators) that bind in a sequence-specific manner to short DNA sequences in the of genes. The activator binding sites are elements of larger proximity control units, ca lied promoters and enhancers, which bind many distinct proteins. These may synergize or negatively cooperate with the activators. The do novo binding of an activator to DNA or, if already bound to DNA, its functional activation is what ultimately turns on a high-level expression of genes. The activity of transactivators is controlled by signalling pathways and, in some cases, transactivators actively partici pate in signal transduction by moving from the cytoplasm into the nuc1eus. In this first volume of Inducible Gene Expression, leading scientists in the field review six eukaryotic transactivators that allow cells to respond to various extracellular stimuli by the expression of new proteins."

This book has been designed, as its title implies, as a practical book for medical practitioners, although it should be of interest to medical students and nutritionists. It attempts to provide essential information about this important group of substances rather than be an all embracing monograph on the subject. For this reason biochemical and physiological considera tions have been kept to a minimum, and aspects of animal disorders and animal husbandry have not been considered. The material is often presented in a rather dogmatic fashion and, with rare exceptions, references are not included since this makes reading more difficult. The exceptions, where references are provided, are the therapeutic claims, and the series of recent studies which have indicated that vitamin deficiencies are still widely present among certain groups of the population of many industrially developed countries. To add to this reference list there is a reading list which has been selected to give key books, reviews with extensive bibliography and important articles over the past 10 years. From this reading list it is possible to trace most of the literature on the vitamins since they were first described over half a century ago."

In their second year in medical school, students begin to learn about the differences between "disease" and "illness." In their studies of pathology they learn to understand disease as pertubations of molecular biological events. And we clinicians can show disease to them by our scans, lay it out even on our genetic scrolls, and sometimes even point out the errant nucleotide. Disease satisfies them and us; at Yale, lectures on the gastrointestinal tract run from achalasia to proctitis. There is, alas, little mention of functional bowel disease or of the irritable or spastic colon, for that is not easy to show on hard copy. Functional bowel disease represents "illness," the response of the person to distress, to food, to the environment, and to the existential problems of living. In real life such matters are most important. Richard Cabot first found out at the Massachusetts General Hospital almost a century ago that 50% of the patients attending the outpatient clinic had "functional" complaints. The figure had grown to over 80% when the very same question was reexamined 60 years later.

DDDDDDDDDDDD Effective management logically follows accurate diagnosis. Such logic often is difficult to apply in practice. Absolute diagnostic accuracy may not be possible, particularly in the field of primary care, when management has to be on analysis of symptoms and on knowledge of the individual patient and family. This series follows that on Problems in Practice which was concerned more with diagnosis in the widest sense and this series deals more definitively with general care and specific treatment of symptoms and diseases. Good management must include knowledge of the nature, course and outcome of the conditions, as well as prominent clinical features and assess ment and investigations, but the emphasis is on what to do best for the patient. Family medical practitioners have particular difficulties and advantages in their work. Because they often work in professional isolation in the com munity and deal with relatively small numbers of near-normal patients their experience with the more serious and more rare conditions is restricted. They find it difficult to remain up-to-date with medical advances and even more difficult to decide on the suitability and application of new and rela tively untried methods compared with those that are 'old' and well proven. Their advantages are that because of long-term continuous care for their patients they have come to know them and their families well and are able to become familiar with the more common and less serious diseases of their communities."

In the last two years, a wealth of new information has accumulated regarding both clinical and research aspects of health care for the elderly. Although many controversial issues have been resolved, many still remain. Volume 2 of Contemporary Geriatric Medicine is once again dedicated to the clinician who cares for the elderly on a continuing basis. Although, for the most part, general topics first introduced in Volume 1 have been retained, all infor mation in this volume is new and represents the current state of the art. In addi tion, several new topics-including falls, interpretation of laboratory data, and oral health care-have been introduced to enhance this volume's usefulness to the busy clinician. Through these easy-to-read essays, we attempt once again to keep the non geriatrician abreast of the current state of the art regarding the special needs and problems of the elderly. Each chapter is not meant to be an exhaustive review of all topics in the field, but rather to focus on issues receiving a great deal of atten tion. Our goal is to create an exciting approach to contemporary issues in gerIatric medicine."

The contributions to this volume were presented at a Symposium entitled "Current Topics in Muscle and Nonmuscle Motility" held in Dallas 19-21 November 1980 under the auspices of the A. Webb Roberts Center for Con tinuing Education, Baylor University Medical Center Dallas, and the Univer sity of Texas Health Science Center at Dallas. This very useful opportunity for a group of active investigators in motility to meet and discuss their latest findings was made possible in part by the income from an endowment fund established by a generous gift from Dr. Albert P. D'Errico in the Baylor University Medical Center. Dr. D'Errico was the first formally-trained neurosurgeon to practice in the Dallas area, the first Chief of Neurological Surgery, and a member of the Medical Board of the Baylor University Medi cal Center Dallas (1947 -1964). The income from this fund is used to promote the dissemination of up-to-date information in the Neurosciences, to provide intellectual stimulation, to add to the fund of knowledge, and improve the skills of neurosurgeons, neurologists, internists, and others in specialized fields of medicine. We are all indebted for this generous gift that made this enriching educational experience possible. We are also grateful for support the Symposium received from Electron Microscopy Sciences, Forma Scien tific, J. E. O. L. USA, Inc. , Ladd Research Industries, M. J. O. Diatome Co. , Or ganon Co. , Upjohn Co. , G. D. Searle & Co. , and Smith, Kline and French. Robert M.

During the past five years there has been a reawakening of interest in the psychotherapy of patients with medical disorders characterized as psychosomatic. For three decades, psychoanalysis and psychoanalytic psychotherapy were used extensively to treat and study psychosomatic disorders. Early in the 1960s, interest in this approach to these conditions faded, and the .Psychosomatic Service. in most hospitals became the .Consultation Liaison Service. (Lipowski, 1967). The recent focus of biofeedback on psychosomatic conditions provides a new technique with which the physician or psychiatrist may treat these patients (Rickles, 1981). In addition, the successful application of biofeedback training to a variety of complaints such as those presented in this volume has heralded the addition of biofeedback to the treatment modalities used for medical complaints. Frequently, psychological factors can still be seen; for example, when biofeedback treatment may require lifestyle changes on the part of the patient, the exploration of secondary gains or resistances before the disorder can be success fully treated, and the establishment of rapport and empathy which is so important for truly effective biofeedback training. Aside from certain psychological dimensions that are always present in biofeed back training, in this case biofeedback is being used in a primarily medical setting for primarily medical complaints."

Few diagnostic methods in Cardiology have heralded such revolutionary developments as the introduction of coronary arteriography. When, in the early 1960's, Dr. F. Mason Sones demonstrated that visualization of the coronary anatomy in living humans was not only feasible but sufficiently safe and reliable to be used as a clinical tool in the evaluation of patients with known or suspected ischemic heart disease, the thus far somewhat neglected area of coronary circulation became the focus of interest. Naturally, for a considerable period of time a great deal of emphasis was placed upon coronary anatomy. Simple relations between narrowing lesions, impediment to flow, and prognosis were assumed to exist. Spectacular results of surgical coronary revascularization seemed to confirm this concept. Gradually it has become evident that the pathophysiology of coronary artery disease is considerably more complex. Diagnostic methods were introduced to assess and quantify exercise-induced myocardial ischemia. At first, these tests were used mainly to achieve a more discriminative selection of candidates for coronary arteriography and the coronary arteriogram remained the gold standard. Currently, these techniques have evolved to the point where they provide valuable functional and metabolic information. They have become powerful independent tools in clinical investigations and evaluation of individual patients.

The recent interest in the pharmacology of the skin and the treatment of its diseases has come about for two reasons. The first is a realisation that many aspects of pharmacology can be studied as easily in human skin as in animal models, where they may be more relevant to human physiology and disease. Examples of this are the action of various vasoactive agents and the isolation of mediators of inflammation after UV irradiation and antigen-induced dermatitis. The second reason is the fortuitous realisation that a pharmacological approach to the treatment of skin disease need not always await the full elucidation of aetiology and mechanism. For example, whilst the argument continued un resolved as to whether the pilo-sebaceous infection which constitutes acne was due to a blocked duct or to a simple increase in sebum production, 13-cis retinoic acid, was found quite by chance totally to ablate the disease; again, whilst cyclosporin, fresh from its triumphs in organ transplantation, has been found able to suppress the rash of psoriasis, it has resuscitated the debate on aetiology. We are therefore entering a new era in which the pharmacology and clinical pharmacology of skin are being studied as a fascinating new way of exploring questions of human physiology and pharmacology as well as for the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.

Prevention of disease and injury, including early identification of risks and disease and optimal control of potentially debilitating or fatal complications of chronic conditions, is the area of clinical medicine that holds the greatest promise for improving human health. Each year a long list of major, but potentially preventable health problems exacts a terrible human and financial toll. These problems urgently need our attention, especially as major advances in curative medicine become more complex and costly. Prevention of disease and injury may well be the central health issue of our time, an issue of vital concern to every quarter of our society. Now is a very good time to promote prevention. Citizens and some social groups are increasingly aware of and interested in health and fitness issues. There is great enthusiasm about-even obsession with-health, and we are seeing an astonishing proliferation of health publications and media presentations for laymen, fitness and weight control cen ters, exercise programs, health food stores, disease support groups, health education programs, and do-it-yourself diagnostic kits. All of this betokens an increased health consciousness on the part of public and perhaps signals greater individual accountability for health."

Starting in 1986, the European School of Oncology has expanded its activities in postgraduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meetings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminating the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It wa& decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a common problem in medical literature: that of the material being outdated even before publication.

The Sclera is the definitive text on the diagnosis and treatment of scleral diseases, with in-depth chapters on non-infectious scleritis, infectious sclertitis, non-inflammatory diseases of the sclera, and systemic implications of scleral disease. Basic physiology, anatomy, and biochemistry are addressed as well. Written for the ophthalmologist, the revised and updated new edition of The Sclera contains the most current information available on newer characterizations of the composition of the sclera, immune derangements of it, and success in medical and surgical treatment of the inflammatory diseases of the sclera.

As 'seasoned campaigners' we offer our readers more than 60 joint practice years of commonsense experience on children and their prob lems. Child care is a large and fascinating part of general family practice. More than any other discipline it is a mix of understanding the wide range of normal and abnormal development, of skilful diagnosis and treatment of treatable conditions, of long-term care for handicapped children, and of organizing and carrying out prevention. F or all this and more the physician has to rely on sound knowledge and understanding of the child, parents, family, social and community conditions, available services and the likely natural history of the condition - and to dispense all this with humanity, sense and sensi bility. We have divided the book logically into 6 sections: (I) Factual background. (2) Universal problems of behaviour and development. (3) Common clinical disorders, so frequent and yet often so dif ficult to manage. (4) Social, family and community factors that create and influ ence many problems of childhood. (5) How to use available services and resources with discrimina tion and sensitivity. (6) The importance of understanding and managing the whole child. We have no single group of readers in mind. We hope that our views will be appreciated, for example, by parents, nurses, health visitors, general practitioners, community physicians and paedia tricians - in fact all who care for children."

Having the privilege of editing the English language version of this book I have found the detailed thought, explanation and step-by-step instruction that this book provides most refreshing and stimulating. There are few publications indeed that provide a completely reliable companion to bedside and out-patient instruction for the medical student - and even fewer that enhance the established physician's techniques. Medical skills in the art and science of patient examination are normally learnt experimentally - time, personal instruction and constant repetition are necessary for them to be acquired. Even then it must be admitted by many that there are some techniques that are never fully understood, properly learnt or correctly concluded - and these errors are liable to a lifetime's repetition. This volume with its excellent photographs and illustrations takes the reader clearly and incontrovertibly step-by-step through every detail of all the procedures necessary for the standard forms of examination of a patient. It is a companion for every student and doctor who wishes to learn fully and completely these necessary skills and to improve the ones they already have. Dr Alexander D. G. Gunn, Director, University Health Service, Reading, Berks, UK 1982 Preface to the Dutch edition The idea of writing this book coincided almost them a superficial acquaintance with five or six exactly with the establishment of a 'skills 'fashions' and proficiency in none of them.

This book is addressed to all professionals concerned with the health care of children. It is, first and foremost, a teaching tool. It can be used for class discussion or case conferences with medical students or residents, nurses, and other staff in pediatrics or family medicine. It can also be used for self-teaching or continuing education by those already in practice. No one who reads this book is a beginner at moral reasoning. However, many may well be beginners at discussions that focus sharply on the ethical issues in medicine and introduce philosophical analysis. The goal is to clarify, conceptualize, and guide reasoning in order to come to conclusions that can be defended with good reasons. Case studies provide the most successful method of teaching medical ethics, posing the issues as they arise in real-life situations. The cases in this book are brief and rather skeletal in nature. This is partly to deflect the natural curiosity of those who are driven to seek more and more medical details, hoping thus to resolve the ethical issues or avoid them entirely. It also allows the reader to concentrate on one ethical issue at a time. In real life, of course, the hard questions arise often several at a time, embedded in a rich and complex medical and psychosocial background. As one must learn to walk before one can run, so it is wise to practice on cases where the key issue is highlighted.

There is now widespread recognition that emotional problems, to say nothing of the interactions of emotions with other manifestations of illness and disease, constitute a substantial component of all human suffering. For too long the pro vision of medical care has been restricted to the physical aspects of that suffer ing while the psychological aspects have been shunned. Whether through igno rance about the nature of emotional illness and its clinical management, or through uncertainty about the legitimacy of their ministrations, physicians and many other health professionals have left the care of psychiatric problems to psychiatrists and other mental health professionals. For a variety of reasons this strategy is no longer feasible and substantial changes are required. The extent of the needs, the nature of the presenting problems, the ex pectations of the patients, the prohibitive costs of alternative approaches, and the lack of trained mental health professionals make it imperative that general health workers learn to cope with the psychological and behavioral health prob lems of their patients. There are no other alternatives if the realities of comtem porary suffering, limited resources and psychobiological knowledge are accepted. It is to the pragmatic knowledge base for this essential component of contemporary health care that this book makes a seminal contribution. Dr."