Proceedings of the NATO Advanced Study Institute, San Miniato, Italy, September 2-13, 1985

Here is a practical guide giving you systematic strategies for correctly diagnosing heart disease. The emphasis is on the patient's history and the physical examination, the two cornerstones of medical diagnosis. These are correlated with knowledge of the natural history of disease and the physical findings of subsequent examination techniques. The role of current examination technology - both invasive and noninvasive - is discussed. Important advances in the field, including procedures such as echocardiography, transesophageal probe, exercise electrocardiography, nuclear ventriculography and magnetic resonance imaging, are taken into consideration. The book covers all major heart diseases and is liberally illustrated.

Comprehensive Management of Menopause is a balanced, authoritative, and state-of-the-art approach to the treatment of all medical issues of the menopausal patient, strongly emphasizing clinical and practical applications for comprehensive care. The book is edited by leaders in the field and contains an impressive array of internationally recognized contributors. Divided into five easily referenced sections: Physiology, Diagnosis and Epidemiology; Medical Aspects of the Menopause; Gynecologic Aspects of the Menopause; Management and Therapeutic Guidelines; and The Future; this outstanding volume contains the most up-to-date information on diagnosis, treatment, and management of: - osteoporosis and musculo-skeletal pain; - cardiovascular disease and lipid and metabolism disorders; - all gynecologic aspects of menopause, including the newest technology and advances in hormone therapies; - breast problems and skin care. It also includes preventive medicine and general health care guidelines. Comprehensive Management of Menopause is the definitive text comprising all aspects of menopause and is indispensable to every physician providing medical care to women.

Thoroughly illustrated, this second edition provides the primary care physician with detailed information on the most commonly encountered clinical situations and the most frequently asked questions. The chapters address everything the primary care physician will regularly face and will need to know about the breast, pregnancy, sexually transmitted diseases, contraception, infertility, gynecologic cancers, urogynecology and gynecology.

The Tenth International Conference on Intracellular Protein Catabolism was held in Tokyo Japan, October 30-November 3, 1994. under the auspices of the International Committee on Proteolysis (lCOP). ICOP meetings have been held biennially in the USA, Europe, and Japan in turn. The previous three ICOP meetings (7th to 9th) were held in Shimoda, Japan, in 1988. in WildbadKreuth, Germany, in 1990, and in Williamsburg. Virginia, in 1992. Previous meetings were held in resort areas, this was the first meeting held in a large city. Attendance has grown every year so that nearly 400 participants from 19 different countries attended the Tokyo meeting. At the meeting, novel and updated results on the structure-function. physiology, biology, and pathology of proteases and inhibitors were discussed, together with cellular aspects of proteolysis and protein turnover. Thirty-nine invited papers and eight selected posters were presented orally and 171 poster presentations were discussed. This book documents almost all of the lectures and some selected posters. Since the world of proteolysis and protein turnover is expanding very rapidly. far beyond our expectations, it is impossible to cover all the new aspects of this field. However, this book will give an idea of the current status, trends. and directions of the field, and information necessary to understand what is and will be important in this field. Further. the editors hope that the novel ideas, approaches. methodologies, and important findings described in this book will stimulate further study on proteolysis and protein turnover.

Evidence-based Clinical Practice (EBCP) is the conscientious, explicit, and judicious use of current best external evidence in making decisions about the care of individual patients. In neurology, practice has shifted from a rich, descriptive discipline to one of increasingly diagnostic and therapeutic interventions. Providing a comprehensive review of the current best evidence, Neurology: An Evidence-Based Approach presents this type of evidence in a concise, user-friendly and easily accessible manner. The three co-editors of this important volume are linked in their passion for evidence-based clinical practice in the clinical neurological sciences, connected to a common historical origin at the University of Western Ontario (UWO), London, Ontario Canada and influenced directly by Evidence-Based Medicine teachings of McMaster University, Hamilton, Ontario Cananda. The book is organized in three sections: Basics of Evidence-Based Clinical Practice, with an introduction to the topic, a chapter on the evolution of the hierarchy of evidence, and another chapter on guidelines for rating the quality of evidence and grading the strength of recommendation. The second section, Neurological Diseases, provides an illuminating overview of evidence-based care in ten of the most common areas in neurologic practice. The final, third section provides an outstanding roadmap for teaching evidence-based neurology with a chapter on the Evidence-Based Curriculum. A superb contribution to the literature, Neurology: An Evidence-Based Approach offers a well designed, well written, practical reference for all providers and researchers interested in the evidence-based practice of neurology.

The widespread occurrence of the various forms of arthritis not only results in a great waste of manpower, but also causes immeasurable pain and suffering for the patients. Due to the limited understanding of its etiology, the currently available treatments are directed at the effects of the disease rather than its causes. The solutions available to the clinician at the advanced stages of arthritis are frequently surgical and include prosthetic replacement arthroplasty. Many advances have been made in the last decade in the basic understanding of the kinematics and kinetics of anatomical joints, as well as in the technology of joint replacement. The NATO Advanced Study Institute held in Portugal during June 20-July 1, 1983 addressed these topics and provided instruction on the advances in biomechanics of diarthrodial joints. The proceedings of this Institute are presented in this volume. Many different areas of specialization contribute to the field of joint biomechanics. Due to the complexity of each individual topic, it was not attempted here to present a complete treatise of each of these areas. Each chapter typically gives a review and a flavor of the subject matter, as well as discussing the state-of the-art advances in general or in specific research areas. Some of the chapters, such as those on lubrication and muscle mechanics, are more mathematically oriented than the others. Nevertheless, the reader with a non-engineering background, I trust, would still find most of the book informative and easy to read."

The secretion of bioactive products by tumors of the gastroenteropancreatic system results in the development of watery diarrhea that can lead to death in a very short period if not brought under control. Even if the consequences are less dramatic, the patients' ability to lead a normal daily life is seriously impaired, and they may become severely depressed. SandostatinR alleviates the condition by inhibiting peptide release, and its long duration of action makes it an effective and rational adjunct to therapy at all stages. Last year a consensus Round Table Meeting was held in Scottsdale, Arizona, to discuss the optimal use of SandostatinR in this indication. These guidelines offer the results of clinical research and the dosage recommendations arising from them, together with a critical summary of the points of view presented.

This volume comes from manuscriptscontributed by invited speakers to the NATO AdvancedStudyInstitute on Biopolymers, which was held in Izmir, during August 27th - September 5th, 1984. Many more detailshave been added to the manuscripts as a resultof the interchange of ideas during the symposium. This book includes 16 papers which were originallypresented at the meeting by some of the world'sforemostinvestigators. In this volume, the existing basic knowledgeacross the wholefieldof polymericbiomaterials is reviewed.Classification, structure, composition, synthesis, modification and fabrication of these novel materialsis included in detail. Fundamental phenomena involved in the interactionof polymers with the biological environmentand resultingresponses of blood and tissue components are discussed. Modification of polymers physically, chemicallyor biochemically, in order to improve their biocompatibility is included. Selected applications of polymeric biomaterialsin Medicine, Dentistry, Biotechnology, Pharmacology and otherrelated fieldsarealsocovered. We stronglyhope thatthis book will be agreatcontribution to the rapidly expanding field of biomaterialsand willhelp to stimulate an even more excitingfuturefor th is field. ErhanPiskin AllanS. Hoffman VI ACKNOWLEDGEMENTS NATO Advanced Study Institute on "Biopolymers" was held in Izmir during August 27th - September 5th, 1984. I would like to ex press my deepest appreciation and gratitude to NATO Scientific Affairs Division, that our meeting has been accepted as a NATO ASI, and has been supported by their programmes. I wish to thank also to all the other supporting firms and organizations, especially to Hacettepe University and Turkish Scientific and Technical Research Council."

The very first international working discussion on slow infections of the nervous system was entitled "Slow, Latent, and Temperate Virus Infec tions" and was held at the National Institutes of Health (NIH) in December 1964. The primary impetus was the discovery and investigation of kuru in New Guinea by D. Carleton Gajdusek, M. D. This working discussion brought together investigators in human and veterinary medicine, virolo gists, microbiologists, and neuropathologists actively engaged in laboratory work with viruses that illustrated properties of latency, masking, slowness, or temperateness, with emphasis on subacute and chronic neurologic dis eases of unknown etiology. In the Preface to the monograph of published papers presented at the working discussion, Gajdusek and Gibbs wrote the following: After microbiology had given solution to the etiology of most acute infections of the central nervous system and after fungi and bacteria had been incriminated in impor tant chronic disorders of the nervous system such as torula and tuberculosis men ingitis, we have been left, in neurology, with a wide range of subacute and chronic affections of the central nervous systems of unknown etiology. Some of these diseases, still listed as idiopathic, are among the most prevalent afflictions of the central nervous system. Many others with familial patterns of occurrence do not yet have their basic pathogenesis or underlying metabolic defect elucidated, although we tend to think of them as genetically mediated."

Sudden death is probably the greatest challenge facing modem cardiology today. This is mainly due to the impact of its brusque appearance and the socioeconomic implications. The incidende is presently decreasing somewhat, mainly due to the decline in new cases of ischemic heart disease on one hand, and to better preven tion in risk patients on the other. Nevertheless, the figures are still high and represent over 300.000 patients per year in the United States alone. This book is an updating of the problem of sudden death from a multifactorial standpoint. It includes not only electrophysiologic data but also covers aspects ranging from epidemiology to prevention. Risk markers and triggering mechanicsms of sudden death are reviewed, with special emphasis on the role of electrical instability, ischemia and depressed ventricular function. The book includes the contributions from many experts, often pioneers in their respective fields. It is our hope that the book serves as an Updating for those cardiologist who are not specialized in these subjects, but may also be of interest to the expert. We wish to express our sincerest gratitude to the authors for sending in their work so promptly, and also Kluwer Academic Publishers for their exactitude and perfection in this edition."

Why yet another book on clinical diagnosis? The profusion ofmedical text booksfor studentsand young postgraduates is known to all ofus, and so also is the time-consuming and frequently frus- trating search in these books for the relevant facts we need, so often sub- merged in a mass of information which we do not really require. The traditional textbook that most clinicians have used in their training may well be written in the leisurely, discursive and unstructured style much loved by our teachers of old, but perhaps out of place in modern medical education where knowledge is so rapidly expanding and time available for its assimi- lation rapidly contracting. It iswith these considerationsinmindthat wefelt itwould beusefulto pro- vide a clear, concise, easily readable and well-illustrated book on the essen- tials of clinical diagnosis. Each chapter deals with a medical problem commonly encountered in dailyclinicalpracticeand beginswith alistofthepossiblecausesand apracti- cal perspective of their prevalence in general practice and in hospital prac- tice; the age distribution and the clinicalsignificanceofthe various disorders is also pointed out. The majorpartofthe chapter isconcernedwith thediag- nostic approach to the particular problem and emphasizes the importance of symptomsand signsin reachingthecorrectdiagnosis, as well asthe value and limitation of the investigational approach to the diagnosis. The book emphasizes the fundamental clinical skills ofhistory-taking and clinicalexamination in diagnosis, so frequently and mistakenlysubordinated to the investigational approach which is often disappointing in the limited diagnostic help which it does provide.

This volume contains the proceedings of the XVth North American Testis Workshop, held in Louisville, Kentucky, April 7 to 10, 1999, to describe current advances in testis biology. The first two chapters provide a useful historical perspective of testis physiology and formulate compelling research questions about important aspects of sperm formation and function. This prologue sets the scene for the remainder of the volume that follows a logical progression, as the title implies, from stem cell to cell function, but that is necessarily preceded by sex determination, the quintessential requirement for there being a testis in the first place. The program for this XVth Testis Workshop evolved from recommenda tions of the scientific committee and their advice on the selection of invited speakers. The XVth Testis Workshop has a strong comparative flavor with contributions on worms (Caenorhabditis), flies (Drosophila), and chickens, which are models that permit and thereby reveal the power of genetic analy ses of the molecular mechanisms involved in spermatogenesis. A glimpse into the future is provided with information from EST, protein, and genome databases that already have an impact on progress in our understanding of the male germ cell. Although there is heavy emphasis in these chapters on cellular and molecular e, Yents, database mining and translational profiling relevant to testis function and dysfunction and assisted reproduction tech nologies are not overlooked."

Clinicians spend their working lives making decisions. such decisions are usually made in interlocking streams rather than in the discrete circumscribed contexts so beloved of scientists. When the clinician encounters a patient a complex interactive process is initiated in which the clinician searches his memory to match the symptoms and signs indicated by the patient with the complex disease models which he carries in his head. He then makes choices about further questions or tests in order to clarify his understanding of the patient's problem and to formulate a management or treatment plan. In recent years there has been increasing interest in how clinicians make such decisions and a realization that decision-making in clinical medicine is virtually the same as that in many other professional contexts. The scientific study and formal teaching of clinical decision-making is a relatively young discipline. Less than 20 books have so far appeared which take explicit account of the theoretical and experimental decision-making literature in medicine and other related disciplines. This book is a distinctive and important contribution to this growing field. It combines a comprehensive critical analysis of a wide range of relevant philo sophical, statistical, psychological and medical literature with an interesting set of experimental observations of primary care physicians. Dr. Ridderikhoff shows great erudition and wide command of a large reference literature. Dr. Ridderikhoff takes a firmly descriptive rather than prescriptive viewpoint on understanding clinical decision-making."

Preventing Disease, the offspring of an extraordinary collaboration between the U.S. and Canadian Preventive Services Task Forces, presents a meticulous and objective review of the published evidence on preventive measures. Examining such diverse and relevant topics as screening for endometrial cancer, exercise counselling for healthy adults, and the evidence for a causal relation between dietary lipids and coronary heart disease, this volume reflects the editors' shared conviction that recommendations for preventive action should rarely exceed what is well justified by the evidence. In the current period, characterized as the Second Public Health Revolution, the authors' hard-nosed approach leads them to ask the tough questions. Are preventive measures cost-saving? Does preventive screening actually lead to treatment in clinical practice? Does the treatment do more good than harm? To what extent does our desire to eliminate causes of serious disability, ill health and premature death cloud our objectivity? All concerned about preventive medicine, community health, and primary care will find valuable stimulation for thought and action in this book: the contributions have gone beyond the rhetoric.

An ever greater number of our contemporaries will reach a very much greater age than their ancestors. Longevity is one of the most fertile fields for paradoxes: it is clear that the same causes do not produce the same effects at the age of ten and at the age of one hundred! On the subject of longevity, the "recipe book" is far from having been written. Nevertheless, the Fondation IPSEN has chosen a few of these paradoxes to discuss and try and explain them.

The author has organized basic, core information on the diagnosis, treatment and prevention of chemical dependence into a readily understandable format. His approach teaches the physician what steps to take from a practical point of view: how to prevent addiction in the first place, how to diagnose the condition, how to aid the family get the addict into treatment, and how to increase the chances of long-term recovery. The book is divided into three sections. The first section covers basic definitions and concepts. The second section describes the pharmacology of the various psychoactive substances: depressants, opioids, stimulants, cannabinoids, hallucinogens, phencyclidines, and inhalants. The third section discusses chemical dependence in special groups: women, adolescents, the elderly, ethnic minorities, dual diagnosis patients, HIV- positive patients, and impaired physicians.

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.

Pelvic pain in the female patient is common in gynaecological practice, but the specialties of general surgery, urology and orthopaedics provide a significant number of patients and problems. These patients may suffer a multitude of symptoms, and only careful analysis and investigation of each individual problem by the doctor concerned will lead to correct diagnosis and management. The subject matter of this book lies in the practice of many specialties, and all are combined here in a coherent whole. This emphasises the close collaboration necessary between family practitioners, junior hospital staff and consultants. The authors are consultants who work together in a busy district general hospital, and their experience and collaboration is evident in the approach to the diagnosis and management of pelvic pain in the female. Emphasis is laid on the careful evaluation of history and examination and the correct interpretation of diagnostic investigations. Full details of radiology, ultrasound scanning, endoscopy, peritoneoscopy and bacteriological investigation are given. Full consultation between members of staff who have special experience in these investigative procedures is of paramount importance. Details of treatment for relief of pain are important to all doctors concerned with this aspect of clinical management. and this section will be of particular value. The blending of these specialties allows full consideration of the problems affecting the patients. Careful management leads to better treatment for the patient and better satisfaction for the doctor.

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."

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.

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."

Migraine is a debilitating disorder, it is essential that it is diagnosed accurately and swiftly in patients. This book covers, in-depth, the key diagnostic criteria and treatments that pediatricians and other primary care providers must be aware of in order to treat pediatric migraine effectively.

Written by an expert on the subject of pediatric migraine/headache
A refresher for GPs and hospital doctors with practical diagnostic and treatment advice
Reviews clinical developments and guidelines, and places them into everyday clinical practice
Stresses the importance of early intervention, therapies and patient education
Concise but comprehensive"

Following an introduction to the philosophical and theoreti- cal background of traditional Chinese medicine, the dia- gnostic system is presented: the Chinese system of channels and functional organs, the significance of pointsand point categories, methods of needling and moxibustion. There is a chapter on treatment based on western diagnosis.

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, where they may be more relevant to human physiology and diseases, as in animal models. 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 etiology and mechanism. For example, whilst the argument continued unresolved 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 etiology. 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 an important step in the development and study of new drugs, use of which will improve disease control and at the same time help to define pathological mechanisms.