Experimental gerontological research is necessary to obtain optimal information and thus ensure proper drug therapy for the elderly. Most older persons acquire multiple diseases, first of all chronic diseases. They involve complex problems of a physical, social, and psychological nature. The multimorbidity of the elderly raises many questions in drug therapy. By contrast with our extensive knowledge of pharmacokinetics and pharmacodynamics in younger age groups, few facts are available in respect of the elderly. A variety of factors may influence drug therapy. Physiological and pathological age-related changes of molecules, cells, organs, and the total organism may interact to enhance or inhibit drug therapy in higher age groups. It is well known that elderly patients are overmedicated and therefore the incidence of adverse drug reactions increases with age. Elderly patients with multimorbidity often have a diminished body clearance of drugs; age-related changes of the kidney seems to be one of the most important factors in this regard. Far less important than the elimination of drugs through the kidney is their excretion in the bile. So far results have disclosed that oxidative steps in drug clearance are more likely to be disturbed than phase II reactions. Furthermore; changes in distribution volume and age-related alterations in receptor sensitivity also influence the clearance of drugs in the elderly.

This book brings together a range of academic, industry and practitioner perspectives on translational medicine (TM). It enhances conceptual and practical understanding of the emergence and progress of the field and its potential impact on basic research, therapeutic development, and institutional infrastructure. In recognition of the various implications TM has for public health policy and commercial innovation, the book addresses the major systemic aspects of the field. The contributors explore the dynamic interactions and key challenges in translating new science into viable therapies for the clinic, which includes recognizing the importance of social, commercial, and regulatory environments in addition to good science.

When I was about fifteen, my Biological Seiences teacher, Prof. N. Benacchio, lent me a book by Paul de Kruif "The Microbe Hunters" and I remained fascinated by infectious diseases. I was intrigued by the potency of virulent bacteria which are constantly trying to invade our bodies and often overcome what today we call innate and adoptive immunity. Indeed, shortly after that, I was struck by his tragic death due to peritonitis. Later, while studying medicine (although medical knowledge in the 1950s was almost primordial compared with today), I soon realised how the various biological systems were wonderfully organised but at the same time frail and how our life could end in a few minutes. Slowly it became obvious that our "wellness" was the result of a dynamic and very unstable equilibrium between health and disease. This unstable equilibrium could be broken forever if the body's response could not reverse the pathological state. I stuck a sort ofposter on the wall ofmy room with these three words and connecting arrows: HEALTH -? DISEASE -? DEATH As I don't believe in another world after death, it became obvious to me that we should make every possible effort not only to delay death, but to try always to shift the equilibrium to the left. In this book, I will try to show that this can be achieved, as a last resort, even with ozonetherapy.

Our aim in this volume, as in Volume I, HormonaI Correlates of Behavior: A Life Span View, has been to provide a critical assess ment of the state of behavioral endocrinology as weIl as the more usual summary of extant data. Each contributor was asked to probe the strengths and weaknesses of his area as candidly as possible. As aresult, we hope the reader will find this Volume useful as a reference source and as an honest evaluation of our present know ledge of the interaction between hormones and behavior. R. L. Sprott Bar Harbor, 1975 B. E. Eleftheriou v CONTRIBUTORS Robert Ader, Ph.D., Department of Psychiatry, University of Rochester Schoo1 of Medicine and Dentistry, Rochester, New York 14642. F. R. Brush, Ph.D., Experimental Psychology Laboratory, Syracuse University, Syracuse, New York 13210. Robert M. Benson, M.D., Pediatric Endocrine Clinic, Children's Medical and Surgical Center, The Johns Hopkins Hospital and University, Baltimore, Maryland 21205. John J. Christian, Sc.D., Department of Biological Sciences, Univer sity of New York at Binghamton, Binghamton, New York 13901. David A. Edwards, Ph.D., Department of Psychology, Emory University, Atlanta, Georgia 30304. Carl Eisdorfer, Ph.D., M.D., Department of Psychiatry and Behaviora1 Sciences, School of Medicine, University of Washington, Seattle, Washington 98101. Basil E. Eleftheriou, Ph.D., The Jackson Laboratory, Bar Harbor, Maine 04609. Merri11 F. Elias, Ph.D., Department of Psychology and All-University Gerontology Center, Syracuse University, Syracuse, New York 13210.

Clinical research represents an integration of many procedures from the social, biological, and natural sciences. Critical examination of the spectrum of medical inquiries will reveal the full gamut of research activities. Under standing the processes involved in the integration of these investigative and cognitive functions may lead to further advances in creative behavior. The purpose of this book is to formalize this process by identifying, collecting, and organizing the elements and issues involved. During the past thirty years, there have been significant advances in research methodology, many of them stimulated by multi-disciplinary collabo ration. The anticipated barriers to communication were not realized in prac tice. Scientists engaged in mutual problem-solving could accomplish more than their colleagues working in relative isolation. In the, r productive fashion, these multi-disciplinary teams, by pooling their knowledge sets and by devel oping communication mechanisms, created the interfaces between the clini cal, analytical, and communication sciences. These interfaces, while neither complete nor perfect, represent the methodology of interest in accomplishing the capture, evaluation, and utilization of information, or Information Process ing. The list of contributors to this methodology is virtually endless and we acknowledge their enormous and significant efforts."

PATIENT FLOW: Reducing Delay in Healthcare Delivery is dedicated to improving healthcare through reducing the delays experienced by patients. One aspect of this goal is to improve the flow of patients, so that they do not experience unnecessary waits as they flow through a healthcare system. Another aspect is ensuring that services are closely synchronized with patterns of patient demand. Still another aspect is ensuring that ancillary services, such as housekeeping and transportation, are fully coordinate with direct patient care. Past experience shows that effective management of healthcare delays can produce dramatic improvements in medical outcomes, patient satisfaction, and access to service, while also reducing the cost of healthcare. The 15 chapters of this book exposes the healthcare community of researchers, practitioners and administrators to a set of techniques and strategies that can be used by clinicians and administrators to substantially reduce delays in healthcare delivery. It is the first book treatment to have reduction in patient delay as its sole focus, and therefore, provides the foundation by which hospitals can implement change. Reflecting the highly interdisciplinary and practitioner nature of this book, the chapters have been written by doctors, nurses, industrial engineers, system engineers and geographers, and thus, these perspectives provide the comprehensive view needed to address the problem of patient delay.

The book provides a "hands-on" discussion and methods for solving a variety of problems that inhibit prompt and swift health care delivery. Some examples are:

• presents a set of breakthrough strategies that use "real-time" monitoring systems for continuous improvement;
• offers techniques for scheduling staff needs to match patterns in patient demand, and thus reduce predictable delays;
• utilizes simulation modeling techniques for both healthcare design and process improvement;
• provides methods for forecasting the demand for healthcare on a region-wide basis;
• presents queueing theory as a general method for modeling patient waits in healthcare;
• outlines rapid delivery of medication in the event of a catastrophic event, such as a pandemic or terrorist attack;
• demonstrates the importance of optimizing care as patients transition from one care setting to the next care setting with an emphasis on clinical outcomes and the business case;
• provides project management tools to guide the implementation of patient flow projects.

This book is the result of several years of enthusiastic planning and effort. Much of this enthusiasm came from the experience of devel{)ping Critical Care Consultant, a large BASIC program for critical care applications (St. Louis, C. V. Mosby, 1985). Working with clinicians showed me that many were interested in learning about clinical applications of computers (and even programming in small doses) but were faced with a paucity of clinical application software. Few had the time or training to develop any such software on their own. After a search through the existing medical literature unearthed relatively little in the way of usable programs, I decided that a series of small clinical applications programs would be of use to the medical community. At the onset a number of strategic decisions were made: (1) the programs would be written in BASIC, in view of its universal popularity, (2) the units used for clinical laboratory tests would be those in common use in the United States, (3) the programs would be simple and easily understood and employ no exotic tricks that were not easily transported across computers, (4) references to the literature would be provided to allow the clinician to critically assess the algorithm or method used himself or to follow up on subsequent criticisms that may have been published, and (5) the programs would demonstrate reasonable standards of software engineering in terms of clarity, trans portability, documentation, and ease of modification."

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."

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.

The Fifth World Congress of the International Society for Diseases of the Esophagus was held in the historic city of Kyoto, Japan, from August 5 through 8, 1992. Approximately 40 countries throughout the world participated and roughly 500 presentations were made. Excellent authors were selected and they were requested to send in their manuscripts for publication of this book. It is our ardent hope that this book will prove to be beneficial to the doctor interested in the esophagus and that it will provide the reader with first-hand information from leading scientists and clinicians in this field. The incidence of esophageal diseases vary greatly from country to country and in recent years, worldwide interest in these diseases has resulted in various international studies. The International Society for Diseases of the Esophagus was inaugurated by Professor Komei Nakayama in 1979 and since that time it has actively contributed to the exchange of information regarding these diseases and has made endeavors in bringing about advancement in the struggle against diseases of the esophagus in every way possible.

The seventeenth annual symposium sponsored by the Texas Research Institute of Mental Sciences was held October 23-26, 1983, in Houston, Texas. The theme was Aging 2000: Our Health Care Destiny. This volume on biomedical aspects and a companion volume on psycho social aspects include edited versions of the presentations by about 80 speakers. Their papers were directed at practitioners, researchers, and medical educators who will be active and productive in the year 2000, and we focused on those who would influence the evolution of care of elderly persons during the next 17 years. We chose topics that would be of particular interest to teachers and current planners in the disciplines concerned with delivery of health and social services. We believe that having a core of more qualified and better trained practitioners will help the population of aged persons achieve a higher level of physical and mental health, life satisfaction and happiness, to find better coping techniques and control of environmental stresses, and to attain personal and social goals. Our Goals While preparing for the symposium we knew that the status of the art in 1983 obviously would be the base from which we would work, but we asked our speakers to give priority to future planning and directions."

Why anDther series .on infectiDus disease? The questiDn is a fair .one in view .of the proliferatiDn .of mDnDgraphs, texts, and periDdicals .on the vast subject .of infectiDus disease. The gDal .of this series is tD provide an additiDnal service tD the clinician in the fDrm .of clinical infDrmatiDn nDt usually assembled in .one convenient vDlume. One type .of mDnDgraph presented in this series will CDver a specific infecti.on, detailing microbi.ol.ogic research and clinical aspects. It is h.oped that such a cDmpilati.on will be helpful in bDth its thDroughness and breadth tD the clinician interested in this particular problem. The .other type .of mDnDgraph that this series will pr.ovide will discuss a clinical presentati.on that c.omprises many pDssible specific etiDI.ogies. V.olumes in the series will be multiauthDred, giving us the DppDrtunity tD invite auth.orities in each specific area t.o cDntribute their expertise and experience. Regular revisions are planned SD that each v.olume will remain as current as it is thorDugh. We hDpe that .our gDals are met and that the present series .of mDn.o graphs establishes its .own identifiable and valuable niche in the growing cDmpendium .of resDurce material available tD the clinician. Contents Series Preface ....................................................... VB Contributors .......................................................... Xl Introduction ......................................................... xv 1. Acute Osteomyelitis FRANCIS A. WALDVOGEL ...................................... ."

This timely and important work looks at the collaborative health care model for the delivery of mental health care in a primary care setting. This has become the ideal model for the treatment of comorbid medical and psychiatric or psychological disorders. There is also an increased awareness that pharmacological intervention, the most frequently delivered intervention for psychological disorders, is often of limited effectiveness without concurrent specific psychological intervention. The book includes more than two dozen case studies, co-written by clinical psychologists and primary care physicians. It is essential reading for any psychology practitioner in a clinical setting, as well as for health care administrators.

The Yearbook compiles the most recent developments in experimental and clinical research and practice in one comprehensive reference book. The chapters are written by well recognized experts in the field of intensive care and emergency medicine. It is addressed to everyone involved in internal medicine, anesthesia, surgery, pediatrics, intensive care and emergency medicine.

I opened my series editor manuscript of The Handbook of Contraception: A Guide for Practical Management, edited by Drs. Donna Shoupe and Siri Kjos, on a tiny plane on the way to giving a lecture in Albany, NY. I expected to peruse the ma- script, and found that I could not put it down. The Handbook of Contraception: A Guide for Practical Management is an incredibly informative and enjoyable read. In keeping with the objective of this series for primary care clinicians, there is a quality in this title that is uncommon among medical textbooks. The chapters of this book are written with extraordinary intelligence and und- standing, and with attention to practical considerations in the selection and mana- ment of contraceptive options. The authors have reviewed the science behind contraception, including the chemical structure and effects of hormonal contraception, physiology of contraception, efficacy rates, and side effects, as well as the practical considerations that are relevant in helping patients choose between different cont- ceptive options. They do this with a clarity of language and intent that lets the book cover with sufficient detail the full range of questions that any primary care clinician will have regarding any of the traditional or new contraceptive options. Also included in each chapter is a section on "counseling tips," which explicitly answers many of the questions that clinicians and their patients often have when discussing contraceptive options. For a book so useful and well done, the editors and authors deserve our thanks.

Recent publications have addressed specific aspects of the endothelins, such as their roles in disease or the importance of endothelin receptors. However, in this book the entire field of endothelins is covered. This includes the pathways of endothelin production and their regulation, the local and systemic actions of endothelins, receptors for the endothelins and the signalling pathways employed, and the involvement of endothelins in a range of diseases. Attention is also paid to the development through chemistry, pharmacology and toxicology of endothelin antagonists and endothelin-converting enzyme inhibitors, with mention of all the important members of these drug classes. This leads to well-rounded discussions of the potential therapeutic benefit of endothelin inhibitors.

Almost 50 million persons visit another continent each year. It is mainly those 15-18 million travelers from industrialized nations who visit or reside in developing countries that are at increased health risk. To develop effective health protection advice, the health risks of travel and the benefits of prophylaxis (vaccines, new and old drugs, behaviour modification, etc.) should be assessed systematically. The purpose of this book is to improve the protection of the travelers' health by more effective and more uniform recommendations. It contains many data on recent research and represents the first comprehensive account on travel medicine for professionals.

The proliferation of information on rotaviruses in the twenty years since their description as human pathogens has made it difficult to keep up with the latest developments in the field. Numerous aspects of rotavirus biology have been addressed in reviews, but these have been infrequent and quite selective in the material covered. The time appeared right to attempt to gather, into a single source, an overview of what we have learned. This volume is the result of that attempt. I hope that the reader will find in this single source, the core of information covering our current state of knowledge. I acknowledge my debt to the authors of the various chapters, for it is they who performed the tedious process of reviewing the literature and synthesizing and organizing it into concise works. R.F. RAMIG Contents Introduction and Overview R.F. RAMIG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Structure of Rotavirus B.V.V. PRASAD and W. CHIU .................... 9 The Rotavirus Genome U. DESSELBERGER and M.A. MCCRAE . . . . . . . . . . . 31 . . Rotavirus Protein Structure and Function G.W. BOTH, AR. BELLAMY, and D.B. MITCHELL 67 Rotavirus Replication J.T. PATTON . . . . . . . . . . . . . . . . . . . . . . .. . . . 107 . . . . . . .

The decisive factor in trauma is that many processes first occur at the cellular level before they can be determined in laboratory tests, and recognition of them has only recently found its way into intensive care practice. Yet knowledge of the pathophysiology of these processes is essential for an early diagnosis of multiple organ failure and the implementation of adequate therapy, which ultimately make the patient's survival possible. Professor Schlag, an internationally renowned scientist and clinician, has been concerned with the basic pathophysiological principles of shock for many years. In this book he has brought together for the first time an international team of authors primarily from the USA and Europe, who present their collective findings of trauma, shock, development of the organ in shock and early failure and of sepsis-like syndrome, and development of septic multiple organ failure. Patienten mit Multiorganversagen haben immer noch eine schlechte Prognose in der intensivmedizinischen Behandlung, insbesondere wenn sie noch zusatzlich in einen septischen Schock geraten. Hier hilft auch oft eine breite Abdeckung mit modernsten Antibiotika nicht weiter. Neue Ansatze fur eine Therapie dieser problempatienten haben sich in den letzten Jahren durch Erkenntnisse der pathophysiologischeen Vorgange die zum Schock fuhren ergeben. Herr Professor Schlag hat als anerkannte Kapazitat auf dem Gebiet der Traumatologie und Schockforschung fur dieses erste umfassende Werk zu den Grundlagen des Multiorganversagens eine beeindruckende Liste von mehr als 50 international renommierten Autoren zusammenbekommen. Das Buch ist nicht nur eine Aufarbeitung aller Grundlagen des Schocks und Multiorganversagens sondern zudem ein ausgezeichnetes Nachschlagewerk fur jeden intensivmedizinisch tatigen Klinikarzt, egal ob er aus der Anasthesie, der Inneren Medizin oder der Unfallchirurgie kommt."

Nutritional support of critically ill patients is a major treatment modality which will enhance recovery and shorten convalescence. New knowledge has emphasized that much of the organ dysfunction associated with sepsis and altered blood flow is related to oxidative injury. Specific nutrients are highly effective in counteracting these effects and their early administration may attenuate cellular damage and multi-organ failure. Patient outcome may also be enhanced by the route of feeding, administration of newer nutrient combinations, utilization of evolving methods of monitoring and the use of growth factors. This new knowledge has evolved to a new area of metabolic support which is addressed for the first time by a group of international experts. The topics presented and general conclusions are of major importance to the practitioners in this field, for they show, for the first time, a departure from the more traditional approaches of nutritional support in patients with life-threatening diseases.

Six members of the Herpesviridae family are human pathogens, including herpes and 2 (HSV-I and 2), Epstein-Barr virus (EBV), varicella zoster simplex virus I virus (VZV), human cytomegalovirus (HCMV), and human herpesvirus 6 (HHV 6). Each of these viruses is capable of causing distinct diseases of varying severity in children, young adults, and the aged. The diseases range from infection of epithelial tissue to the infection of internal organs and white blood cells. A common feature of the six pathogenic human herpesviruses is their ability to latently infect different cell types in which the viral DNA is not integrated and is unable to express its pathogenicity. Reactivation of the herpesviruses is a result of cellular processes which reactivate viral genes, leading to virus progeny and to signs of infection. Due to their ability to become latent after initial infection, once the pathogenic herpesviruses infect children they are maintained throughout life, having the potential of cause various diseases upon reactivation.

In spite of a long history of intense investigation the transmissible spongiform encephalopathies remain a poorly understood family of neurodegenerative diseases. This group of diseases has been described in a wide variety of animal species and includes kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler syndrome in humans, and scrapie, bovine spongiform encephalopathy, and related syndromes in ruminants and rodents. In all cases spongiform degeneration and astrocytosis are seen in specimens of brain and a filterable transmissible agent is present in the brain and some other tissues of affected individuals. However, the precise nature of this agent remains unknown. Agent infectivity, which can so far only be assayed by serial transmission to new individuals, be remarkably resistant to inactivation has been shown to by heat, chemicals, and irradiation. These properties create significant biohazard possibilities during exposure to infected tissues. Transmission between humans was originally reco gnized in the unique epidemiology of kuru in New Guinea tribesmen, and concern about transmission from animals to humans has re-emerged as a result of the current epidemic of bovine spongiform encephalopathy in dairy cattle in Great Britain. Although interspecies transmission has often been achieved experimentally, its efficiency is highly variable. There fore, the possibility of spread of bovine spongiform encephalopathy from cattle to humans or various animal populations cannot be accurately predicted at this time. This volume presents a comprehensive update of know ledge concerning the transmissible spongiform encephalo pathies."

An up-to-date overview of acute and chronic pancreatitis. The two authors with special interests in this field deal with the aetiology, pathophysiology, and clinical features of these diseases, as well as complications, treatment strategies, and prognostic factors. Two chapters on congenital abnormalities and hereditary pancreatic diseases round off this book. Intelligently-structured for everyday practice, this can also be used as an actual reference book. For gastroenterologists in clinic and practice.