Despite a worldwide reduction in its incidence, stroke remains one of the most common diseases generally and the most important cause of premature and persistent disability in the industrialized countries. The most frequent cause of stroke is a localized disturbance of cerebral circulation, i.e., cerebral ischemia. Less common are spon taneous intracerebral and subarachnoid hemorrhages and sinus ve nous thromboses. The introduction of new diagnostic procedures such as cranial computed tomography, magnetic resonance imaging, digi tal subtraction radiologic techniques, and various ultrasound tech niques has led to impressive advances in the diagnosis of stroke. Through the planned application of these techniques, it is even possible to identify the pathogenetic mechanisms underlying focal cerebral ischemia in humans. However, these diagnostic advances have made the gap between diagnostic accuracy and therapeutic implications even greater than before. This fact can be easily explained. In the past, therapeutic studies had to be based on the symptoms and temporal aspects of stroke; it was impossible for early investigations to consider the various pathogeneses of cerebral ischemia. Inevitably, stroke patients were treated as suffering from a uniform disease.

Over the last 10 years the syndrome of severe acute renal failure has progressively changed in its epidemiology. It is now most frequently seen in critically ill patients, typically in the context of sepsis and multiorgan failure. This epidemiologic change has meant that intensive care physicians and nephrologists must now work in close cooperation at all times and must take many com plex issues of prevention, pathogenesis, and management into account that they did not previously have to tackle. Simultaneously, the last 10 years have seen the development of major technical and conceptual changes in the field of renal replacement therapy. There are now previously unavailable therapeutic options that provide physicians with a flexible and rapidly evolving armamentarium. The nutrition of these patients, previously limited by the par tial efficacy of renal replacement therapies, has also become more aggressive and more in tune with the needs of critically ill patients. Increased understanding of the pathogenesis of the multi organ failure syndrome has focused on the role of many soluble "mediators of injury" (cytokines, leukotrienes, prostanoids etc.). These molecules are likely to participate in the pathogenesis of acute renal failure. Their generation and disposal is also affected by different techniques of artificial renal support."

This book reviews the most recent developments in the patho- physiology and therapy of ventilatory failure. It contains contributions by twenty-five internationally recognized aut- horities on respiratory muscle function and investigators actively contributing to our knowledge of the cause, diagno- sis and therapy of ventilatory failure. Of particular inter- estare the descriptions of new modalities of partial and complete ventilatory assistance as well as new knowledge re- garding ventilatory control and fatigue during stressful breathing. The reader will find here a state-of-the-art re- view of the latest research and practical applications in this most critical area of intensive care medicine.

The publication of the Vth International Symposium 1995 on "Mechanisms of Secondary Brain Damage" in Mauls/ltaly is a collection of focused reviews reaching from novel molecular- and cell biological findings to aspects of clinical management in head injury and cerebral ischemia. A specific purpose of these series of meetings introduced in 1984 is for an exchange on problems of mutual interest by international high ranking experts from the basic sciences and related clinical disciplines, such as intensive care medicine, neurology, or neurosurgery. The present volume covers three major areas: (a) Molecular and cell biological mechanisms including inflammation (b) Novel findings on mechanisms and treatment in cerebral ischemia (c) Secondary processes in head injury, regeneration and treatment Molecular-and cell biology is currently attracting attention towards activation of genomic processes associated with the demise of cells referred to as "programmed cell death" and "apoptosis" which, actually, might be distinguished from each other. Thus, the phenomenon of delayed neuronal death in selectively vulnerable brain areas following brief interruption of blood flow is scrutinized as to the contribution of the activation of suicide genes. The physiological role of such a response, among others, is removal of surplus neurons during ontogenesis of the brain. Yet, evidence is accumulating that similar mechanisms playa role in cerebral ischemia, probably also trauma, where nerve-and other cells demonstrate features of apoptosis. Observations on protection of neurons by administration of protein synthesis inhibitors in cerebral ischemia provide more direct support.

The International Brain Hypothermia Symposium 2004was the second time I have had the honor of opening such a gathering on brain hypothermia treatment. It was a great pleasure to greet the participants in the hope that their valuablecontributions would make the Tokyo meeting memorable. Brainhypothermia has long been seen as a promising method that may overcome current limitations on brain resuscitation in patients with severe brain damage. However, although excellentresults have been obtained in experimental animal models, for some reason brain hypothermia has not alwaysbeen successful clinically, and resolving this problem has been a major challenge facing physicians specializing in brain therapies. The ICUmanagement of recent research has uncovered newmechanisms ofbrain damage not seen in animal models, including brain thermo-pooling at temperatures above 40 C in severe brain damage, masking neuronal hypoxia even with normal cerebral blood flow. Stress-related hyper glycemia with brain hypothermia was expected to generate useful results in patients with external injuries, cerebral occlusive stroke, and cardiac arrest. In recent clinical studies of brain hypothermia treatment, many excellent results began being reported on the manage ment of severe brain injury, ischemic stroke, and post-resuscitation after cardiac arrest. However, in clinical brain hypothermia treatment many questions remained about appro priate treatment targets, leu management technique, prevention of complications, control of brain tissue temperature, management of hypothermia insult, and mechanisms underly ing the onset of vegetative states."

Sepsis is still the leading cause of death in surgical and general intensive care units. Although our knowledge of this complex syndrome has increased in recent years, it is still far from com- plete. New therapeutic approaches have been developed. Some did not fullfill the high expectations for their use in clinical prac- tice; others are still under clinical evaluation. is the aim of this monograph to offer basic information on the It etiology, definition, pathophysiology, prevention and therapy of sepsis and septic shock to both the clinician and the scientist. We believe that it presents an extensive overview that may help the clinician to better understand and treat sepsis and septic shock. We also hope that this work will give some directions for future research both in the clinical field as well as the laboratory. Jena, Berlin, Jerusalem, K.Reinhart February 1994 K.Eyrich C.Sprung TableofContents I.Definition/Prognosis Sepsis and Septic Shock: Update on Definitions (Jo-L.Vincent) 0 0 0 0 0 0 0 0 0 0 0 0 ******** 3 Clinical Manifestations and Prognostic Indicators in Sepsis (R.C.Bone) ...0 * * * * * * * * * * * * * * * * * * * 16 What Determines Prognosis in Sepsis? Evidence for a Comprehensive Individual Patient Risk Assessment Approach to the Design and Analysis of Clinical Trials (W.A.Knaus, D.P.Wagner, F.E.Harrell, Jr.

The period that followed World War II has witnessed a dramatic change in neurology. From being a discipline in which its partici- pants were castigated for being interested solely in diagnosis, usually of disorders of unknown causation without effective therapy, neurology has evolved into a highly active treatment- orientated subject. This transition is clearly reflected in the ap- proach to diseases of the peripheral nervous system, and to the Guillain-Barre syndrome (GBS) in particular. In a state-of-the- art review made in 1952, Elkington (1952) observed that no less than 56% of neuropathies remained undiagnosed, and amongst those of unknown causation he listed GBS. With intensive in- vestigation and follow-up, the proportion of neuropathies seen at tertiary referral centres which elude diagnosis is now as little as 13% (McLeod et al. 1984). Overall, of course, the proportion is even less. This change is partly because of the introduction of new diagnostic techniques and partly because of the application of the great expansion in knowledge evident throughout medicine. In this book, Professor Richard Hughes has assembled current information on GBS and related disorders, including chronic in- flammatory demyelinating polyneuropathy (CIDP), the existence of which was not appreciated until Austin's perspicacious study published in 1958. In the Introduction, Professor Hughes gives an account of the way in which recognition of the GBS emerged and matured, and shows that it followed, pari passu, with the realisation that paral- ysis and sensory loss may result from peripheral nerve disorders.

Individualized dosing regimens specific to the patient, infection, bacteria, and antibiotic can optimize outcome. Integration of pharmacokinetic and pharmacodynamic data, called dual individualization, can be accomplished through the use of AUIe. AUIC dosing has been shown to predict bacteriological outcomes, hasten clinical outcomes, reduce the emergence of resistance, and be cost-effective. MPC dosing has been shown to predict the emergence of resistant submutants. AUIC and MPC information can provide guidance as to when low doses can be used, and when higher concentrations are required. This strategy can ensure efficacy, minimize toxicity, reduce the opportunity for resistance to occur, and save money. REFERENCES I. Paladino JA. Streamlining antibiotic therapy: clinical application of pharmacokinetic and pharmacodynamic principles. J Osteopath Med 1991; 5: 16-25. 2. Liss RH, Batchelor FR. Economic evaluations of antibiotic use and resistance - a perspective: report of task force 6. Rev Infect Dis 1987; 9 (suppI3): S297-312. 3. Holmberg SO, Solomon SL, Blake PA. Health and economic impacts of antimicrobial resistance. Rev Infect Dis 1987; 9: 1065-78. 4. Sanders cc. Mechanisms responsible for cross-resistance and dichotomous resistance among the quinolones. Clin Infect Dis 2001; 32(Suppl I ):S 1-8. 5. Ballow CH, Schentag 11. Trends in antibiotic utilization and bacterial resistance: report of the NNRSG. Diagn Microbiol Infect Dis. 1992; 15(suppl):37S-42S. 6. Rice LB, Eckstein EC, DeVente J, Shlaes OM. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center. Clin Infect Dis 1996; 23: 118-24.

Nitric Oxide (NO) is a free radical, a gas, and a pluripotent product of mammalian cells. Only a few years ago, scientific discussions of NO were largely held in the context of the chemistry of air pollution. Now, however, the great significance of NO as a signalling and cytotoxic molecule has captured the attention of the biomedical community. This book provides a very up-to-date review of the role of NO in sepsis and ARDS. Consideration is given to NO both as a pathophysiologic mediator as well as a therapeutic agent. An internationally recognized group of scientists and clinicians have contributed chapters dealing with cutting-edge science and practical clinical strategies. Numerous tables and charts have been included to aid the reader in understanding this fascinating and important subject.

I am very happy and honoured to have so many famous contrib utors from around the world presenting their knowledge and experience in this book, including Dr. Rufer who, as early as 1967, attempted to improve the pressure-volume curve of a child dying from RDS using dried surfactant from dogs; Drs. Enhorn ing and Robertson who were the first to treat rabbit fetuses with surfactant replacement and impressively demonstrated that sur factant improved lung mechanics; and Dr. Fujiwara who at the end of the 1970's had already successfully treated the first babies with surfactant replacement and published this work al ready in 1980. Thus, the idea of surfactant replacement therapy is now more or less 20 years old and almost 10 years have passed since the first publication by Dr. Fujiwara of his impressive clinical results. Up to now (September, 1988) about 2,200 babies have been treated worldwide with tracheal instillation of surfactant, with most promising results. The type of surfactant used varies from pure natural extracts from bovine or pig lungs, to surfactant extracted from human amniotic fluid, to pure phospholipids. To date, however, there is still no surfactant commercially available (except in Japan), in spite of the fact that it is urgently awaited by neonatologists and intensive care doctors throughout the world. This volume is based on the contributions presented at the international congress on Surfactant Replacement Therapy which was held in Rotterdam, The Netherlands, in November 1987."

by E.K. ZSIGMOND, M.D. Department of Anesthesiology University of Illinois Chicago U.S.A. It is, indeed, a distinct honor and privilege to be invited by the authors to write a preface to this monumental monograph, Regional Opioid Analgesia. Regional Opioid Analgesia is a colossal undertaking by Drs. De Castro, Meynadier and Zenz shortly after the introduction of this revolutionary approach to pain relief which opened a new epoch in analgesiology. This is, indeed, the first authentic and comprehensive textbook encompassing the current knowl edge on this novel approach to pain relief. We are indebted to the authors for introducing the new opioids to regional analgesia with the scientists, who de veloped the potent short and ultrashort acting opioids with high therapeutic indices, which many researchers dreamt about but never before materialized. The side effect liabilities of these new opioids are minute as compared to morphine and meperidine. Regional Opioid Analgesia could not have been more authentically written than by Drs. De Castro, Zenz and Meynadier, who have conducted daily clinical investigations on all known opioids for regional analgesia as well as for neurolept analgesia. Therein lies the great value of this monograph: it is the most authentic work on this topic."

Perinatal medicine, which is concerned with the problems of the fetus and newborn, has rapidly developed in the last two decades as an important and challenging specialty. Rapid advances in the field, coupled with tech nological advances, now are making survival of infants with weights as low as 500 grams possible. Ventilator care for severe respiratory problems is on the verge of being replaced by surfactant replacement therapy; on the other hand, development of such technologies as extracorporeal mem brane oxygenation and jet ventilation has revolutionized the care of these sick infants. The advances taking place today in the field of perinatal medicine make periodic updates, like the one provided by this volume, a virtual necessity for clinicians and paramedical personnel alike. A distinguished group of specialists in various aspects of perinatal medicine has contributed to this book. Their wide-ranging experience and points of view should make this book a valuable reference for all physicians and allied health personnel involved in the care of the high-risk fetus and newborn. MANOHAR RATHI, M.D. Acknowledgements. I am grateful to the contributors for their cooperation in preparing the manuscripts, to my associates for their help and support, and to the publishers for their continued interest in this work. Above all, I thank Ms. Rose Aiello-Lech and Ms. MaryAnn Cichowski for their hard work in making this publication possible."

This monograph focuses on splanchnic function in health and disease. It represents a distillate of the communication that took place at the First International Symposium of Applied Physiol ogy of the Peripheral Circulation, "Splanchnic Circulation: No Longer a Silent Partner." The individual chapters roughly follow the individual presentations and display in durable form the con cepts and importance that this symposium achieved. The concept for this annual symposium was the child of An tonio Artigas, who not only recruited sponsorship but also Jean Francois Dhainaut and me to help with the organization and work. We chose the splanchnic circulation as the peripheral cir culatory system to be presented first for many important reasons. Much new information has become available which demon strates, as the title of the symposium implies, that splanchnic function has major influence on the overall expression of health and disease in humans. All aspects of splanchnic physiology, it seems, have been rediscovered to be dynamic, important, and complex in their interactions within individual tissues and among remote tissues and organs. It is hoped that after having reviewed this monograph the reader will agree that the splanchnic circula tion and its organ systems are emerging as important aspects of critical illness and host-defense homeostasis."

Intensive care in childhood is a relatively new field of medicine. Due to major differences in physiology, many disciplines are involved in the care of the critically ill child. Apart from specific disease patterns, morbidity in direct relation to the stay in the ICU or the underlying disease mainly determine long term morbidity. Today we understand that the treatment of the critically ill child can have a great impact on the quality of life in adulthood. This book covers the whole spectrum of intensive care in childhood. It is based on the experience of leading specialists from the various fields involved in the treatment of these children.

Assisted Circulation 4 is an authoritative review of the progress which has been achieved in the last 5 years since the publication of "Assisted Circulation 3" in 1989. The present book highlights the work of well-known experts on indications for assisted circulation, cardiac support devices such as bridges, devices for transplantation, devices for chronic mechanical support, biological energy sources, cardiomyoplasty, extracorporeal membraneoxygenation and an overview of cardiac devices support with a specific emphasis on xenotransplantation. Assisted Circulation 4 is the latest product of an ongoing effort by the editors to keep readers regularly informed of recent developments in the field. Assisted Circulation is a standard technology in cardiac surgery and especially in cardiac transplantation.

This supplement of Acta Neurochirurgica contains the proceedings of the Ninth Convention of the Academia Eurasiana Neurochirurgica held in Chateau St. Gerlach, Houthem, The Netherlands, 29 July - 1 August 1998. During this convention a three-day symposium on Neurosurgery and Medical Ethics was held. In this time of tremendous technical advancement in medicine in general and neurosurgery in particular, we are liable to lose sight of the sick patient as a human being, and the odds are that he will be the object rather than the subject of our action in the near future. It is a purpose and a task of the Academia Eurasiana Neurochirurgica to recognize this thread and to pay attention to tradition, morality and ethics in neurological surgery. The theme of this convention and the subject of the symposium met this purpose as no other. In the scientific sessions during the first day, the moral backgrounds of medical ethics in the most important cultures and religions in east and west were elucidated by invited experts in this field. A mutual respectful understanding of each other's conception of and belief in ethical principles is a growing necessity in our multicultural societies in both continents. On the second day, the ethical aspects of different fields of neurological surgery were discussed by members of the Academia. In this context, also the internationally much-discussed and much-criticized regulations on euthanasia in The Netherlands were explained.

C. Manni The focusing of general interest and of many disciplines on disaster medicine is an interesting and recent phenomenon in our society. Disasters have by now left the his torical and philosophical sphere and finally entered the operational arena. Modern man, in other words, no longer accepts disasters in a passive and fatalistic manner, but claims to be able to control them like so many other forces of nature. The new approach is aimed at preventing, containing, and remedying the invariably tragic consequences of these events. The role of medicine in this context is of fundamental importance and is charac terized by two main aspects: application of techniques of intervention appropriately and effectively, and collaboration with the general organization, assuming responsi bility for the protection of health and the treatment of injuries. Following a period of more or less chaotic growth, during which sectionalism and empirical interests prevailed, and localized aspects of this new discipline underwent considerable development, a need is now felt to propose and realize a more com prehensive scientific approach. It has become necessary to identify and to rationally analyze the individual components of this branch of medicine. As in any analysis, the recognition of the "object" of the research is of fundamental importance: hence the title of this first round table: "Types and Events of Disaster."

In January 1980, the First Symposium on the Measurement of Tis sue Oxygen Pressure in Patients was held in Frankfurt. After a 4-year "rest period," the organizers of the 1984 symposium, Profes sor R. Huch of Zurich and Dr. J. Hauss of Munster, together with myself, extended another invitation to come to Frankfurt to find out what had gone on in the field of oxygen pressure measurement and its application in clinical medicine. As the following presentations will show, the application of oxygen pressure measurements has been broadened considerably. Furthermore, technological advances have been made, particularly with the increased use of computers. For various reasons, including technical ones, these methods have not been adapted as widely as one would want. Although con gresses on tissue oxygen pressure have been held in the last few years, the clinical aspect of tissue P0 measurement has not been 2 dealt with in such a concentrated and comprehensive way since 1980. It therefore seemed necessary to hold such a symposium, not only for scientific reasons, but also to enable a larger group of clini cians to gain insight into the importance of the possibilities these methods offer."

The 1992 International Yearbook of Nephrology is the 4th in a successful series of yearly books updating practising nephrologists and nephrologists-in-training on rapidly changing areas of nephrology. We were encouraged to proceed in our editorial venture by reviews of the previous issues which have appeared in various Nephrology Journals. These reviews have pointed to the successful use of the International Editorial Board, the broad range of topics of current interest which have been covered and the comprehensive and practical nature of the reviews. The principal aim of the Yearbook remains to provide reviews which are more current than those which appear in Nephrology textbooks and which can be in the hands of the readers a few months after the authors have completed the manuscripts. The appointed authors are always experts in the field, who are asked to give an objective review of the topic, up-dating the readers on the world-wide literature and providing them with a complete, accurate and up-ta-date list of important recent references. We have decided to maintain the successful format of the first three issues. Thus, the volume will continue to be divided into sections; each section will continue to have a different primary focus every year, depending upon what is of greatest interest at the time.

Sepsis and Innovative Treatment: The Odyssey R. C. Bone The Odyssey by Homer, dates back to the 8th century, B. C. [1]. It is a great epic adventure of Odysseus's dramatic journey from Troy back home to Ithaca. Odysseus survives the ordeals of this journey and returns with new powers and insights. The study of the pathogenesis and treatment of sepsis has also been an odys- sey. I feel we will return from this odyssey with new insights and treatments. However, as with Odysseus, this will occur only after considerable struggle. In the 1980s we had a rather simplistic view of sepsis. It was a highly lethal complication caused by infection and often charac- terized by shock and multi-organ failure. Our knowledge of the inflammatory responses associated with sepsis was embryonic compared to today. The inflammatory response was often treat- ment with mega-dose corticosteroids along with fluid resuscita- tion, vasopressors and antibiotics. Because of the paucity of mul- ti-center controlled trials documenting the risk/benefit ratio of the treatment of sepsis with corticosteroids, two large multi-cen- ter controlled trials were organized to evaluate the role of corti- costeroids in sepsis [2, 3]. Because animal models showed bene- fits of corticosteroids only with pre-treatment or early treatment, a definition of sepsis was used that did not require positive cul- ture documentation or septic shock to be included in the studied population.

This book concentrates on problems generated by acute care in severely traumatized patients during the first 24 hours after injury. During this hectic period, highly complicated problems have to be solved at the site of the accident, during transport to hospital, and in hospital. Multiple medical and paramedical disciplines are involved in providing care to the severely injured. This book endeavors to present a problem-oriented approach to the diagnostic, therapeutic, and organizational aspects that may be encountered.

The acute abdomen is one of the most frequent, most dangerous and most difficult problems that the diagnostic radiologist has to deal with. This comprehensive manual presents a clinico-radiologic approach to the use of diagnostic imaging techniques for acute abdominal conditions. Imaging techniques, radiologic symptoms and clinical conditions are treated separately. This lucid format, together with a detailed subject index, offer the reader a quick and reliable reference aid in daily practice. The text is clearly structured and concise in style, and provides helpful practical hints, including discussion of diagnostic pitfalls. It is supported by a wealth of illustrations covering native diagnosis, ultrasonography, computer tomography and angiography.

The book is based on papers presented at the recently held international meeting on central-nervous-system monitoring in Hamburg, Germany. Experts inthe fields of neurophysiology, experimental and clincial anesthesia and intensive care discussed the state of the art in noninvasive central-nervous-system monitoring. Starting with the principles of CNS monitoring in humans, the topics covered include pharmacokinetic pharmacodynamic interactions, the usefulness of spontaneous and evoked brain electrical activity as an overall-control for afferent systems andfor the assessment of analgesic drug treatment, perioperative anesthesiological monitoring, and intraoperative awareness. Recently developed specific EEG and EP indices such as spectral edge frequency, median frequency, auditory and somatosensory evoked responses for the assessment of depth of anesthesia are evaluated for intraoperative monitoring. The surgical and anesthesiological perspective in intraoperativemonitoring during vascular surgery are presented, as is the state of theart in the monitoring of afferent central-nervous-system pathways by monitoring transcranial motor evoked potentials. Bispectral EEG analysis forthe assessment of anesthetic adequacy represents the future trend in intraoperative monitoring. In addition to neurophysiological methods, assessment of jugular bulb venous oxygen saturation and transcranial Doppler sonography may give additional information for the interpretation of brain fuction. In the field of intensive care, topics in multimodal long-term monitoring of brain function are presented. The application of an expert system supporting the diagnosis of brain death is also included.

Sepsis and infection are the major enemies of the intensive care patient in whom immunological defenses are severely impaired. This major problem is thefocus of attention in this book, based on the presentation of the First International Congress on the Immune Consequences of Trauma, Shock, and Sepsis, which is one of the first attempts to exchange ideas on the state-of-the-art in this area of immunology. Both basic and clinical research, including new centres of attention, are described. The growing role of immunology in medicine opens new avenues to the under- standing of trauma and sepsis and will allow the design of novel therapeutic approaches.