During the last decade, the effects of anaesthetics on cerebral blood flow, cerebral metabolic rate of oxygen and intracranial pressure have been studied experimentally and clinically. In this review studies of CBF and CMRO2 during craniotomy have been performed with the classical technique described by Kety and Schmidt. In chapter 1 general considerations concerning the effects of anaesthetics on cerebral blood flow and metabolism are reviewed. In chapters 2 and 3 the effects of inhalation agents and hypnotics on flow and metabolism are considered. Chapters 4 and 5 cover the effects of central analgetics, and neuromuscular blocking agents. In chapter 6 the effects of other drugs in common use in neuroanaesthetic practice are summarized. Chapter 7 considers the effects of drugs used for controlled hypotension. In chapter 8 the application of Kety's method in studies of CBF and metabolism is reviewed, the studies of cerebral circulation and metabolism during nine different techniques of anaesthesia for craniotomy are presented, and other studies of cerebral circulation during neuroanaesthesia are reviewed. In chapter 9 considerations concerning central and cerebral hemodynamics during anaesthesia in the sitting position are considered. This review is primarily addressed to anaesthetists, but it will also be of interest to those working within neurosurgery, neuroradiology and clinical neurophysiology.

Ventilator-associated pneumonia (VAP) continues to be one of the greatest challenges to critical care practitioners and one of the greatest threats to the survival of our patients. The choice of this topic for an issue of the PERSPECTIVES IN CRITICAL CARE INFECTIOUS DISEASES Series is therefore quite appropriate. Despite its importance, many areas of the management of ventilator-associated pneumonia remain controversial. We therefore are pleased to include contributions from experts and investigators offering different perspectives on some of these controversial areas.

A cutting-edge review of the fundamental biological principles underlying the more common inflammatory disorders of the nervous system. The authors provide extensive updates on the latest findings concerning the mechanisms of inflammation and introduce such new concepts and methodologies as "endothelial and leukocyte microparticles" and "gene microarray technology" to help explain important links between the central nervous system (CNS) and general inflammatory processes. Among the diseases examined from an inflammatory perspective are multiple sclerosis, acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, CNS vasculitis, neuropsychiatric systemic lupus erythematosis, Alzheimer's disease, and Parkinson's disease. The role of the immune system in neuroinflammation is also explored in such disorders as neurosarcoidois, HIV-Associated dementia, and HTLV-associated neurological disorders.

Ake Nygren Karolinska Institute, Sweden would like to welcome you on behalf of Karolinska Institute, I one of the organizers and initiators of this series of confer- ences on traffic safety. The conference we are opening today is the fourth in the series. Karolinska Institute is the largest medical university in Sweden. It is dedicated to improving health through research, educa- tion and dissemination of information and ideas. The series on traffic safety is one of the ways in which we are disseminating information and ideas on an international front. Karolinska Institute is 190 years old. The Medico Chirurgiska Institute was originally established in 1811 by royal decree after wars and cholera epidemics. In 1822, it became known by the name "Carolinska" . Amongst many other international endeavors, Karolinska Institute is perhaps best known for the nomination and appointments of Nobel Prize winners in medicine and physiology. Under the terms of Alfred Nobel's will, the prize winners are nominated and chosen by the Nobel Assembly of Karolinska Institute. During the hundred years that the prize has been in existence, several researchers from Karolinska Institute have become laureates. These are Hugo Theorell in 1955; Ragnar Granit in 1967; Ulf von Euler in 1970; and Sune Bergstrom and Bengt Samuelsson in 1982. In 1987, the medicine prize was awarded to Tonegawa from v Japan and in 1994 the literature prize was awarded to Oe Kenzaburo.

This volume contains selected works from the 25th Anniversary of the International Conference on Intracranial Pressure (ICP) held in Williamsburg, Virginia. The theme of the meeting was Intracranial Pressure and Neuromonitoring and focused on all the current state of the art brain monitoring methodologies and their application to brain injury. The brain monitoring techniques covered a wide spectrum from neurochemical monitoring of the injured brain to specialized techniques for assessing shunt function in normal pressure hydrocephalus. It also includes the most recent advances in monitoring of the brain oxygen levels using electrodes or the less invasive Near Infrared Sprectroscopy devices. Controversial issues regarding the management of ICP and CPP or both are also addressed and there are several works dealing with this topic. Of particular interest is the group of papers describing diagnosis and outcome in normal pressure hydrocephalus. It is the first compilation of papers which covers all the latest brain monitoring studies in both ischemia, trauma and hydrocephalus. The manuscripts in this volume have been selected from over 300 abstracts submitted to this international symposium. The abstracts are also published in order to provide the most comprehensive view of the progress made in brain injury research.

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.

Infectious Complications in Transplant Patients has been uniquely designed and formatted to address issues and trends pertaining to pathogens deemed important in critically ill transplant patients. The chapters have been carefully selected so as to direct the focus of the book towards current approaches to controversial, emerging or topical problems in these patients. Each chapter has been authored by a North American and a European specialist. This format serves to impart an added dimension reflective of the diversity of opinions and practices pertaining to unresolved or controversial issues. The authors are recognized experts in their respective fields.

Drug dosage in renal insufficiency has become an toxication. In 1975, his Poison Index was pub important facet of nephrology, a subspeciality of lished, first in German, and two years later in internal medicine which is only 30 years young but English, with supplements in 1979 and 1983. This constantly growing in scope and importance. Two volume has become an obligatory reference in more thirds of all drugs are partially, mainly, or exclu than 2500 dialysis units. sively excreted by the kidneys. In the presence of Based on GOnter Seyffart's experience and renal insufficiency, dose adjustments are therefore knowledge in this field, the plans for this book obligatory. In patients on dialysis, drug elimination matured in 1984, a logical step in view of his by this route must also be considered. untiring effort and diligence. In order to deal with As the reader of this book will discover, 20 more than 1200 different drugs and almost 4000 percent of currently used drugs are contraindicated references, 21 contributors were sollicited, while it where there is any degree of renal insufficiency, took six years to complete the work. The major and for at least another 60 percent a dose reduc share of the effort was thus left to the main author tion is required. It is obvious, therefore, that the and editor and he has produced a concise work of detailed knowledge required can never be com impressive clarity.

Much research over the past 30 to 40 years has shown that the inflammatory response, while critical for host defense during microbial infection, may itself play a central role in the pathogenesis of sepsis. Although key mediators responsible for this injury have been identified, efforts clinically to augment our conventional antimicrobial and supportive therapies during sepsis with agents modulating the inflammatory response have been unsuccessful. As a result, the mortality associated with this lethal syndrome, especially when complicated by shock, has remained persistently high. Unfortunately, during this same period of time, the incidence of sepsis has accelerated as other fields of medicine have relied increasingly on therapies that predispose to infection. While frustrating, overall this experience in the field of sepsis has not been without value. Most importantly, it has helped define on several different levels the complexity of the septic patient. Recognizing and addressing this complexity as discussed by each of the contributors to Evolving Concepts in Sepsis and Septic Shock may now provide new inroads into the treatment of sepsis.

Information is provided from the basic and clinical sciences on the mechanisms damaging the brain from trauma or ischemia. New aspects involve the endoplasmic reticulum, mitochondrial failure, pathobiology of axonal injury, molecular signals activating glial elements, or the emerging therapeutical role of neurotrophins. Experimental issues involve a better analysis of the ischemic penumbra, the salvagable tissue. Therapeutic contributions reach from the environmental influence to gene expression, including neuroprotection, such as hibernation - mother nature's experiment - or hypothermia which is reported to induce cell swelling. Treatment issues deal also with thrombolysis and combination therapies, or with the clearance of adverse blood components - LDL/fibrinogen - by a novel procedure using heparin. Other highlights are discussing the specificities of pediatric vs. adult brain trauma, or the evolving role of the Apolipoprotein-E e4 gene in severe head injury. An update is also provided on an online assessment of the patient management during the pre- and early hospital phase in Southern Bavaria. The empirical observation of neuroworsening is analyzed in further details, whether this is a specificity autonomously driving the posttraumatic course. Finally, the unsolved question why drug trials in severe head injury have failed so far in view of the promising evidence from the laboratory is subjected to an expert analysis.

During the past twelve years, a course on critical care medicine has been sponsored by the Post Graduate Division of the University of Southern California School of Medicine in association with its Center for the Criti cally Ill. The content of each of the symposia has paralleled the evolution of critical care medicine as a recognized service specialty. The annual program was planned as a teaching session for physicians and allied medical personnel who sought to advance their involvement in this rapidly advancing field. A panel of highly regarded authorities on sub jects bearing on critical care medicine, faculty members of the USC School of Medicine, and staff members of our own Center for the Critically 111 at the Hollywood Presbyterian Medical Center serve as faculty of these symposia. Although the primary commitment of the organizers to maintain this as a teaching and demonstration session was not abandoned, the number of annual registrants progressively increased from fewer than 100 to more than 1200, gradually outstripping local hotel facilities in central Los Angeles. The symposium for the past two years has been held in the large and at tractive Anaheim Convention Center adjacent to Disneyland."

Infection Control in the ICU Environment provides the details of the most common infection control problems facing intensive care units. Authors include noted scientists, intensivists and epidemiologists from the United States and Europe as well as infection control experts from the Centers for Disease Control and Prevention. Acinetobacter, methicillin resistant staphylococcus aureus and vancomycin resistant enterococci are examined in detail. This volume also includes cutting edge information regarding the potential for prophylactic and pre-emptive therapy of fungal infections in intensive care units. Innovations in vascular catheter care and prevention of bloodstream infections are discussed in this volume as well as the newest information in mathematical modeling to understand the epidemiology and control of infections in intensive care units.

th It is a great pleasure for me to open the jubilee 25 International Symposium on Blood Transfusion here in Groningen. This symposium is co-sponsored by the World Health Organization and is being held under the auspices of the ISBT and the Secretary General of the Council of Europe, Mr Walter Schwimmer. The patronage was granted with great pleasure for several reasons. First of all, Dutch experts are very active in our Committees and have largely contributed in developing the Council of Europe principles in the blood area. Secondly, the Council of Europe is active today in the area of blood transfusion due to a tragic event, which occurred in 1953 in the Netherlands; following a flooding many of the blood products given for assistance' could not be used due to incompatibilities and differences in labelling. Some words to present the Council of Europe since the organisation is sometimes confused with institutions ofthe European Union: The organisation has been founded in 1949 to establish the principles of democracy and rule of law all over Europe. Since 1989, the year of the fall of the Berlin wall and the opening up of the iron curtain, these principles could be extended to the countries of Central and Eastern Europe. Today this makes the Council of Europe the only pan-European organisation with 41 Member States thus representing more than 750 million people.

How are people and communities able to prevail despite challenge? What helps them bounce back from adversity and even grow in knowledge and understanding? And can this resilience be taught? During the past decade, exciting scientific advances have shed light on how resilience operates from neurons to neighborhoods. In The Resilience Handbook, experts in the science of resilience draw on human and animal research to describe the process of resilience and follow its course as it unfolds both within individuals and in social networks. Contributors also highlight the promise of new interventions that apply what we know about resilience processes to bolster positive health, and raise some of the pressing questions and issues for the field as it matures. This handbook is designed to be used by students as an invitation to a burgeoning field; by researchers, as a framework for advancing theories, hypotheses, and empirical tests of resilience functions; and by clinicians, as a comprehensive and up-to-the-minute integration of theory and practice.

The international interdisciplinary gathering of top of secondary brain damage in brain trauma, as ac- level clinical and laboratory scientists in Mauls, Italy knowledged from the beginning of these workshops in has developed from its beginning in 1984into a fruitful Mauls, the significance of inflammation is all but clear. tradition where worldwide experts active and knowl- Although inflammatory phenomena are seen in trauma edgeable in cerebral ischemia and trauma convene for and ischemia ofthe brain, as activation ofwhite blood update and exchanges of their most recent clinical and cells with emigration into the tissue presumably en- experimental findings and concepts. These meetings hancing damage, inflammatory cells may have benefi- have, of course, experienced shifts in emphasis from cial properties as well. Thechapter on the Janus-faceof the past until now, corresponding to the most actual inflammation isanalyzing this ambiguity. developments, which were fascinating clinicians and The exploration of novel cell-biological mechanisms laboratory scientists alike. The current Supplement of on a molecular or more systemic basis causing apop- Acta Neurochirurgica is an example in case. Its virtue totic cell death, inflammation, or regeneration, provide as before is that authors contribute articles in a review- useful objectives for therapeutical interventions ex- like manner on their own field of research, according pected to be more specific than the present treatment to the platform presentations at the meeting as indis- modalities.

The small neck of the aneurysm afforded an easy surgical attack. An ordinary flat silver clip was placed over the sac and tightly compressed obliterated it completely. The clip was flush with the wall of the carotid artery. The sac, lateral to the silver clip, was then picked up with the forceps and thrombosed by the electocautery. Walter Dandy reporting his successful operation of a posterior communicating aneurysm on March 23, 1937. Walter Dandy's patient left the hospital in good health 2 weeks later, and from his report one may gain the impression that the operation was an easy task. Despite continuous developments during the following decades, it was not until the introduction of the operating microscope and microsurgical techniques that surgical treatment was generally accepted. During the microsurgical era surgical results have continued to improve due to diagnostical, neuroanaesthesi ological, and microsurgical refinements, and improved neurointensive care. Endovascular obliteration has become an important treatment alternative but this has not been included in this particular volume. The purpose of the present supplement of the ACTA NEUROCHIRURGICA is to review some of the elements in the neurosurgical management of patients with aneurysmal subarachnoid haemorrhage that are important for a successful outcome. Professor Helge Nornes has been a major force in the development of new techniques and research strategies in this area for a number of years and has recently retired from the National Hospital in Oslo."

Transmediastinal gunshot injuries present the risk of immediately life threatening injuries. Stable patients have been evaluated by a combination of esophageal swallow and endoscopy, aortography and bronchoscopy. There is an increasing trend favoring CT scan. Unstable patients require immediate exploration, being prepared to enter both hemi-thoraces. Selected References: * Bergsland J, Karamanoukian HL, Soltoski PR, Salerno TA. Single suture forcircumflex exposure in coronary artery bypass grafting. Ann Thorac Surg.1999;68: 1428-1430. * Fedalen PA, Bard MR, Piacentino V, et al. Intraluminal shunt placement and off- pump coronary revascularization for coronary artery stab wound. J Trauma 200 1;50: 133-135 * Hanpeter DE, Demetriades D, Asensio JA, Berne TV, Velmahos G, Murraygunshot wounds. J Trauma 2000;49(4):689-695. * MacPherson D. Bullet Penetration: Modeling the dynamics and the incapacitation resulting from wound trauma. Ballistics Publications, EI Segundo, CA, 1994 * Wall MJ, Soltero E. Damage control for thoracic injuries, Surg Clin North AmI997;77(4):863-878. * Rozycki GS, Feliciano DV, Oschner MG, Knudson MM, Hoyt DB, Davis F, Hammerman D, Figueredo V, Harviel JD, Han DC, Schmidt JA. The role ofUltrasound in patients with possible penetrating cardiac wounds: aProspective multicenter study. J Trauma 1999; 46(4):543-552. * Roussseau H, Soula P, Bui B, D'Othee BJ, Massabuau P, Meites G, Concina P,Mazzerolles M, Joffre F, Otal P. Delayed treatment of traumatic ruptureof the thoracic aorta with endoluminal covered stent. Circulation 1999 Feb2; 99(4): 498-504.

At the Sixth Wiggers Bernard Conference, a group of scientists from various disciplines discussed new findings relating to nitric oxide synthase inhibitor in shock, sepsis, and organ failure. Dedicated to the presentation and discussion of both positive and negative findings related to the use of NOS inhibitors, the meeting served as a forum for issues relating to specific and non-specific inhibitors, as well as the role of nitric oxide-oxygen radical interactions. Both experimental and clinical data were presented in the trauma and sepsis field.

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."

The terrorist use of diseases as bioweapons has been one of the major security concerns in recent years, particularly after the anthrax letter attacks in the USA in 2001. This uncertain threat of intentional outbreaks of diseases exists side by side with the constantly changing very real threat from diseases, epidemics and pandemics as recently illustrated by the H1N1 influenza pandemic, SARS, and H5N1 bird influenza events. This publication contains case studies on the public health planning for (un)usual disease outbreaks for 11 large and small countries with a focus on South Eastern Europe. In many countries, military entities traditionally play an important role in emergency response to disease outbreaks. In smaller countries, very little exists, however, in terms of specific biopreparedness efforts (in both the military and civilian area), which is at least partly due to a relatively low bioterrorism threat perception, and serious resource constraints. The uncertainty associated with the bioterrorism threat makes public health preparedness planning for such events politically and financially very difficult. The similarity of responding to bioterrorism events and natural disease outbreaks from a public health point of view suggests the merit of looking at biopreparedness as a part of overall health emergency planning, not as a separate effort.

In recent years much enthusiasm and energy has been directed toward the development of human gene therapies, especially for inherited conditions and cancers. However, current gene transfer technology is limited in its transduction efficiency and ability to permanently and safely correct genomic defects. Thus the promise of gene therapy for these conditions is as yet unrealized. The progression of gene transfer technology will eventually surmount these limitations. Gene Therapy for Acute and Acquired Diseases includes selected examples of ongoing studies in molecular genetics that have the potential to evolve into human therapies for acute illnesses. These chapters are intended to highlight lesser known applications of gene therapy for acquired disorders. It is expected that human gene therapy trials for these conditions will be forthcoming in the near future, leading to previously unimaginable therapies. Thus, this first-ever book about gene therapy for acute and acquired diseases is intended to serve as a glimpse into the future.

Acute lung injury (ALI) impacts patient care in every ICU in the world. Our collective understanding of this condition has grown immensely over the past decade but morbidity and mortality remain unacceptably high. To enhance the understanding of clinicians and researchers, this book addresses the pathophysiology of acute lung injury from a molecular and cellular standpoint; includes animal models of acute lung injury and points to potential therapeutic advances based on scientific findings. It is a concise compendium of the multiple pathways, mechanisms and molecules involved in the pathophysiology of acute lung injury and is intended to help caregivers understand the process and thus care for patients more effectively.

Currently blood is a volatile issue. The safety of blood and the quantification of transfusion risks have been dominant themes that have stimulated the development of alternative approaches in this rapidly developing area. In clinical medicine conventional blood and its components are used in supportive therapies dependent on the choice of apparent uncritical trigger factors. A compounding factor is depth of prospective clinical trials for evidence. Such trials in critical care areas would be of enormous value, not only in recording adverse effects and under-transfusion, but also indicating the value of decision analysis and cost-effectiveness in transfusion practice. Alternative approaches include the use of cytokines, growth factors, humanised monoclonal antibodies, recombinant plasma factors, and buffy coat derived natural human interferons. These are being increasingly implemented in the clinic. Solutions for oxygen transport are being developed and fibrinogen coated microcapsules are being investigated for thrombocytopenia. In surgical patients, various crystalloid and colloid combinations are explored as volume replacements. To avoid allogeneic transfusions, beneficial blood saving methods include various strategies, such as autologous deposits, normovolemic haemodilution and various agents including aprotinin, tranecamic acid, desmopressin and erythropoietin, but their use in hospital shows considerable variations. That umbilical cord blood could be a significant source of allogeneic stem cells in related and unrelated transplantation is illustrated by the increasing number of cord blood banks in Europe and elsewhere. Future blood resources are likely to face several challenges: immediate challenges relate to increased regulatory and political oversights; intermediate solutions would offer some improvements in public health and alleviate public fear but probably not address the economic challenges thrust upon the medical care system. As we approach the year 2000, the major concerns about transfusion medicine remain its logistics, safety and effectiveness. This theme is presented in the proceedings of the 22nd International Symposium on Blood Transfusion, developed in 21 up-to-date topics, collected and discussed in four sections. This book will be of timely value to students, professionals and all others interested or involved in the field of transfusion medicine, whether clinical or related.

With the introduction of new post-graduate Medical training in the UK, virtually all doctors will be exposed to some form of surgical training prior to specialization. Many of these doctors will have little exposure to surgical emergencies in medical school. Thus, they may unnecessarily refer to a senior doctor when not needed, or catastrophically neglect a patient needing urgent surgical opinion. Surgical Emergencies in Clinical Practice is a compact resource which allows any clinician, without previous surgical knowledge, to be able to make an accurate diagnosis and have a treatment plan for the whole spectrum of surgical emergencies. The essential steps of initial management of all surgical emergencies is outlined in a manner that can be used on a day-to-day basis for clinical management. Written by experts in the field, Surgical Emergencies in Clinical Practice is a valuable tool for all junior doctors and medical students in the UK, Europe, Asia and North America. It will also be of interest to nurse practitioners, general practitioners and allied health professionals managing these patients.

Rodney E. Slater Secretary of Transportation, U. S. Department of Transportation know many of you have traveled great distances to be here. I To me, that shows not only your dedication to the cause, but demonstrates how very important transportation safety is becoming throughout the world. So I am very thankful to the main organizers of this third annual conference -- all of whom are from Sweden: Dr. Hans von Holst of the Royal Institute of Technology; Dr. Ake Nygren of the Karolinska Institute; Dr. Ake E. Andersson of the Institute for Futures Studies; and finally, Dr. Arne Witt16v and Lars Anell from AB Volvo. And let me give a special welcome to our friends from Africa. I will be visiting a number of African nations in January. And while my main mission is to promote trade and investment with the United States, we will be talking about safety, too. Airline safety, for example, is a big concern, as Africa grows and prospers and the demand for air travel expands. We discussed it during recent meetings of the International Civil Aviation Organization in Montreal several weeks ago. And we will do so again during my trip. plan to talk about how my department can help the Also, we many nations of Africa improve highway safety. Africa relies heavily on road transportation. But highway fatalities are very high. And the economic costs are very steep, especially for Africa's fragile, emerging v market economies.