Primary care medicine is the new frontier in medicine. Every nation in the world has recognized the necessity to deliver personal and primary care to its people. This includes first-contact care, care based in a posi tive and caring personal relationship, care by a single healthcare pro vider for the majority of the patient's problems, coordination of all care by the patient's personal provider, advocacy for the patient by the pro vider, the provision of preventive care and psychosocial care, as well as care for episodes of acute and chronic illness. These facets of care work most effectively when they are embedded in a coherent integrated approach. The support for primary care derives from several significant trends. First, technologically based care costs have rocketed beyond reason or availability, occurring in the face of exploding populations and diminish ing real resources in many parts of the world, even in the wealthier nations. Simultaneously, the primary care disciplines-general internal medicine and pediatrics and family medicine-have matured significantly."

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.

Decision making is the physician's major activity. Every day, in doctors' offices throughout the world, patients describe their symptoms and com plaints while doctors perform examinations, order tests, and, on the basis of these data, decide what is wrong and what should be done. Although the process may appear routine-even to the physicians in volved-each step in the sequence requires skilled clinical judgment. Physicians must decide: which symptoms are important, whether any laboratory tests should be done, how the various items of clinical data should be combined, and, finally, which of several treatments (including doing nothing) is indicated. Although much of the information used in clinical decision making is objective, the physician's values (a belief that pain relief is more important than potential addiction to pain-killing drugs, for example) and subjectivity are as much a part of the clinical process as the objective findings of laboratory tests. In recent years, both physicians and psychologists have come to realize that patient management decisions are not only subjective but also prob abilistic (although this is not always acknowledged overtly). When doc tors argue that an operation is fairly safe because it has a mortality rate of only 1 %, they are at least implicitly admitting that the outcome of their decision is based on probability."

Volume 5 of Contemporary Nephrology summarizes major advances in 15 different areas of nephrology. As in previous volumes the different chapters constitute up- of the discipline contributed by individuals dates in both basic and clinical aspects with in-depth expertise in their respective areas. We are grateful to the authors for their outstanding contributions to this fifth volume. Drs. Reuss and Cotton review in Chapter 1 new advances in our understanding of water transport in epithelial tissues responsive to antidiuretic hormone. In Chap- ters 2 and 3 Dr. Knox and Dr. Schoolwerth and their associates summarize respec- tively new information in the areas of renal hemodynamics and electrolyte excre- tion, and renal metabolism. Chapter 4, written by Drs. Laski and Kurtzman, updates recent developments in the regulation of acid-base balance in health and disease. Chapter 5, contributed by Drs. Sutton and Cameron, provides the reader with a detailed account of progress in the area of mineral metabolism. In Chapter 6, Dr. Campese examines the contribution of sodium, calcium, and neurogenic factors in the pathogenesis of essential hypertension. The immunological aspects of renal disease are clearly discussed by Dr. Couser in Chapter 7. New developments in this field are emphasized and should provide the reader with a clear understanding of the direction in which this field is moving. Drs. Humes and Messana (Chapter 8) discuss selected areas in which new developments have occurred in our understand- ing of acute renal failure and toxic nephropathy.

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.

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."

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.

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 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."

This fourth edition of Common Diseases comes just over 10 years after the first. There has been change and counterchange in the primary health care (PHC) field. One change has been the tendency to replace 'general practice' by 'PHC'. Vocational training has become compulsory. With larger group practices have come formalized teams and teamwork, increasing con cern with the business side of general practice and attempts to achieve best values for money and maximal profits. On the clinical side there have been enthusiasms for prevention, early diagnosis, anticipatory care, screening and quality initiatives. As a counterchange it is necessary to remind ourselves that the real essence of general practice, PHC, or whatever title we give it, is 'personal doctoring' of people as individuals in family units. All the changes mentioned will achieve less than expected without good continuing doctor/ patient personal care. But even this is not enough. Good general practice demands a sound knowledge of the nature of disease in the community. Not only are traditional diagnostic and therapeutic skills necessary, but also application of an understanding of the frequency and distribution of the diseases and an awareness of their likely natural history - their course and outcome."

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."

Decoding the significance of proteinuria as an indicator of severity or prognosis in kidney disease is a stimulating challenge to students and practitioners of nephrology. Sir Richard Bright in 1827 associated pro with the disease that bears his name. In the subsequent more teinuria than a century and a half, however, the meaning of the linkage between proteinuria and renal disease remains elusive. Proteinuria is discovered on routine urinalysis in about 10 million Americans, most of whom express no symptoms of kidney disease, each year. From the studies of Robinson (updated in these pages), we know that proteinuria, per se, can be present for 20 years without change in re nal function, as described in orthostatic proteinuria. By contrast, pro teinuria may be the harbinger of swift kidney destruction, rarely cul minating in clinical collapse, a syndrome typifying "malignant proteinuria" as detailed herein by Avram. Although proteinuria is ubiquitous, an orderly management strategy for rational handling of proteinuria of less than nephrotic range is lack ing. Separation of tubular proteinuria and transient proteinuria of fever is now possible routinely. This book provides a record of the contribu tions of investigators and clinicians whose work forms the substrate for production of understanding and, ultimately, marching orders for prac titioners seeking optimized management for their proteinuric patients."

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."

Primary care medicine is the new frontier in medicine. Every nation in the world has recognized the necessity to deliver personal and primary care to its people. This includes first-contact care, care based in a positive and caring personal rela tionship, care by a single healthcare provider for the majority of the patient's prob lems, coordination of all care by the patient's personal provider, advocacy for the patient by the provider, the provision of preventive care and psychosocial care, as well as care for episodes of acute and chronic illness. These facets of care work most effectively when they are embedded in a coherent integrated approach. The support for primary care derives from several significant trends. First, technologically based care costs have rocketed beyond reason or availability, occurring in the face of exploding populations and diminishing real resources in many parts of the world, even in the wealthier nations. Simultaneously, the primary care disciplines-general internal medicine and pediatrics and family medicine-have matured significantly. They have become viable alternatives to the specialty approach to care with its potential dehumanization, coordination problems, and increased cost."

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.

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.

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."

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."

The Fourth International Congress of Peritoneal Dialysis was held in Venice, Italy, June 29 to July 2, 1987. By this time peritoneal dialysis had emerged as a treatment for a substantial fraction of patients with end-stage renal disease and countless numbers of patients with acute renal failure. This treatment is now practiced worldwide and is the life-sustaining treatment for about 40,000 patients with chronic renal failure, representing 15 to 20% of dialysis therapy in about 1000 centers. It is not surprising, therefore, that the number of health professionals engaged in the investigation and the application of the treatment has also grown exponen tially. The First International Symposium on Peritoneal Dialysis, organized by Dr. A. Treviiio-Be cerra in Chapala, Mexico, in 1978, brought together a group of pioneers when continuous ambulatory peritoneal dialysis was in its infancy. In 1981, Dr. G. M. Gahl chaired the Second Symposium, in West Berlin, when the technique and professional interest were growing con siderably. By 1984, when Dr. 1. F. Winchester and I organized the Third Symposium, the pre sented papers exceeded 100 and there were about 1000 attendees. At that time, it was deemed appropriate to form a more organized group and the International Society for Peritoneal Dialy sis was founded. One of the first actions of the Society was to choose from among several applicants Dr."