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.

Childhood obesity is one of the most serious problems facing the developed world. It is damaging to the medical and psychological well-being of the child and casts a shadow on their future health, leading to serious illness and ultimately premature death. Management of Childhood Obesity provides practical, realistic and easily implemented advice on sensitive approaches to children and their families in a very accessible form for all practitioners involved in the care of overweight children. Changes to diet and activity are reviewed in detail but also with the whole spectrum of eating within the family and community, including sedentariness and the significance of sleep in preventing overweight.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

Although in the last few years more experience in the field of epilepsy surgery with amygdalo-hippocampectomies was gained in several hos- pitals, a detailed microanatomical and microsurgical description meet- ing the requirements of the modern neurosurgeon has not been achieved so far. Recently the allocortex - the so-called "limbic system" - has doubtlessly received more attention, as can be gathered from the recently published monography by Duvernoy, which however only considers anatomical points of view. Lately not only epilepsies but also tumorsurgical operations on the border between temporal lobe and basal ganglia can be - thanks to modern MR-examinations - carried out more exactly. Here the tumor-conditioned deformations of the temporo-medial area and its connections with the adjacent basal gang- lia as well as their blood supply are of great importance. Using conven- tional techniques the postoperative morbidity was especially high until recently. The author has at the suggestion of his teacher G. M. Ya argil approached the problem first of all morphologically by developing his own techniques of brain dissection. After some developmental and topographic-anatomical descriptions he has described the vessel-supply by using injection-preparations. Particular aspects of A. chorioidea ant. with her lateral, medial and Tractus opticus penetrating perforat- ing arteries to the basal ganglia and Capsula into have never been described in such a convincing manner before. It is of great importance in the operative removal of the amygdalo- hippocampal area to realize that it is not sufficient to preserve the A.

The Interfaces of Perinatal Addiction Ira J ChasnofT In the last few years, problems associated with drug use in pregnancy have become endemic. As cocaine has become the drug of choice for millions of Americans, including pregnant women, as AIDS has become more commonly recognized in women and infants, and as legal cases have begun to raise the question of fetal abuse, no professional group has come forward to serve as advocate for this special population of substance abusers. Meanwhile, however, physicians, nurses, social service agencies and public health officials have all been faced with increasing numbers of infants showing the detrimental effects of their mothers' drug use. Although problems of substance abuse in pregnancy have received increasing attention in the medical literature since the early 1970s, there has recently been a very rapid increase in the number of articles published related to this field. The reasons for this new interest are easily understood when current statistics from the National Institute on Drug Abuse are reviewed 1. Although patterns of abuse of alcohol, marijuana, heroin and other substances by women of childbearing age have changed very little over the last ten years, the incidence of cocaine use in this special population has been rising rapidly, a reflection of cocaine's increasing popularity among the general population of the United States.

This book is addressed to all professionals concerned with the health care of children. It is, first and foremost, a teaching tool. It can be used for class discussion or case conferences with medical students or residents, nurses, and other staff in pediatrics or family medicine. It can also be used for self-teaching or continuing education by those already in practice. No one who reads this book is a beginner at moral reasoning. However, many may well be beginners at discussions that focus sharply on the ethical issues in medicine and introduce philosophical analysis. The goal is to clarify, conceptualize, and guide reasoning in order to come to conclusions that can be defended with good reasons. Case studies provide the most successful method of teaching medical ethics, posing the issues as they arise in real-life situations. The cases in this book are brief and rather skeletal in nature. This is partly to deflect the natural curiosity of those who are driven to seek more and more medical details, hoping thus to resolve the ethical issues or avoid them entirely. It also allows the reader to concentrate on one ethical issue at a time. In real life, of course, the hard questions arise often several at a time, embedded in a rich and complex medical and psychosocial background. As one must learn to walk before one can run, so it is wise to practice on cases where the key issue is highlighted.

Traditions are dangerous; doubly so in science. Traditions are unchanging; science is about change. This was the 4th International Colloquium on Carbohydrate Metabolism in Pregnancy and the Newborn to be held in Aberdeen, and by now the form is set. How much its content has changed is a matter of nice judgement and not under the control of the organizers. It is not within their power to bring news of revolution, if there has been no revolution. Certainly many of the speakers had kent faces from previous Aberdeen meetings, but so they would be at any meeting on diabetes anywhere in the world. The written proceedings of scientific conferences have purposes other than to record changes: sometimes they need to state a consensus. The 3rd Colloquium came to an agreement about the importance of prepregnancy recognition and control of abnormalities of carbohydrate metabolism. The 4th set out to examine what results it had achieved. Much of this book is taken up with follow-up studies of the applications of similar regimes in different parts of the world. Since the first Aberdeen meeting in 1973, progress in the manage ment of diabetic pregnancy has been slow and steady, but the change in the city and the society where the meetings took place has been fast.

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.

Clinical sono-encephalography, although a relatively new technique, is rapidly gaining acceptance in hospital and specialist practice. No problem was involved in its introduction, as the method is self-evidently suitable for the diagnosis of acute and chronic intracranial lesions. As an auxiliary exami nation it is, within its limitations, almost ideal: it requires no large invest ment in apparatus, it is rapidly done, the patient suffers no discomfort, and there is no risk of complications. In the hands of an experienced examiner, who has a solid grounding in neurological theory and practice to enable him . to interpret his findings, it yields important and reliable information. The use of this method in children requires special knowledge, covering the age of the child, the technique of examination, the range of normality and the interpretation of the pathological findings from the neuropediatric point of view. These special features of pediatric sono-encephalography are seldom discussed in the literature, wide as it is. This monograph is designed to bridge the gap. The book is based on the author's extensive experience acquired over a number of years in the neuropediatric department of the University Children's Hospital Heidelberg. Wisely used, pediatric sono-encephalography should provide a useful tool, not only for experts in highly specialized hospital de partments, but also for pediatricians, neuropediatricians, child psychiatrists, neurologists and neurosurgeons engaged in more routine clinical work. Heidelberg, February 1971 HORST BICKEL Preface Neuropediatrics has experienced enormous advances within recent years."

The Clubfoot: The Present and a View of the Future is a monumental source book of far greater magnitude and scope than has previously been written on this subject. It disseminates recent advances in basic and clinical research on the clubfoot. The introduction places the progress of the last 20 years in perspective. Papers present and evaluate the latest surgical techniques and the management of newly understood complications. The editorial comment section at the end of each chapter offers comparative analysis of the topics discussed in that chapter. This volume is a superb tool for pediatric orthopedists and orthopedists specializing in foot and ankle surgery who want to advance their knowledge of research, clinical management, and operative techniques in patients with clubfeet.

Endocrine glands may be involved in patients with thalassemia major. In the last 20 years, new therapies have significantly improved life expectancy, while several endocrine abnormalities have been described in children, adolescents, and young adults suffering from thalassemia major.
The practical objective of this book is to establish guidelines for the management of endocrine disorders underlying the various phases of thalassemic life. Internationally acknowledged experts give a state-of-the-art account of physiopathological and therapeutical approaches to endocrine disorders in thalassemia and focus on such topics as growth hormones, thyroid diseases, puberty, hypogonadism, diabetes, and bone metabolism.

In this book the current knowledge on human cytomegalovirus (HCMV) as a human pathogen is lucidly summarized, bringing the reader fully up to date with current knowledge concerning HCMV and all the known clincial and medical aspects of diseases caused by, and associated with, HCMV. The book is divided into four parts: (I) Human cytomegalovirus and human diseases; (II) human cytomegalovirus infections and the immunocompromised host; (III) diagnosis, treatment, and prevention of human cytomegalovirus and human diseases; and (IV) molecular aspects of human cytomegalovirus. Each part is put together from chapters written by experts in the respective fields, providing basic medical and molecular knowledge in addition to more specific understanding of HCMV infections.

The first of its kind, this book describes pediatric palliative care in more than 23 countries. Each region in the world is covered and countries included are both resource poor and rich. Authors are multidisciplinary and regarded nationally and internationally in their field. Clinicians, advocates, policymakers, funders, and researchers will learn how programs were developed and implemented in each country. Authors describe children for whom pediatric palliative care is needed and provided for in their country. When applicable, a brief history of pediatric palliative care is included noting especially policy changes and legislative acts. For example, the chapter on Poland describes how pediatric palliative care grew from the Catholic church into a national movement spearheaded by several health care workers. The Pole national spirit that brought them through a change in political regime has also been a driving force in the pediatric palliative care movement. The chapter on South Africa, for example, illustrates how a resource poor country has been able to leverage philanthropic and government funding to make its dream of having an infrastructure of pediatric palliative care a reality. These are just a few examples of the inspiring stories that are included in this book. Readers from countries who wish to start a pediatric palliative care program, or advance an existing program, will learn valuable lessons from others who have faced similar barriers. Introduction and concluding chapters highlight the strengths and weaknesses of the modern pediatric palliative care movement.

This book is based on the 20th Study Group of the Royal College of Obstetricians and Gynaecologists, which concerned the important topic of fetal growth. Basic scientific and both obstetric and paediatric aspects of the subject were addressed in contributions from many different disciplines. The deliberations covered the broad topics of normal fetal growth, fetal overgrowth and fetal undergrowth. Clinical implications of these entities, especially fetal undergrowth, played a large part in the proceedings as dictated by clinical concerns. Definitions, epidemiology, aetiology and screening were covered, as were technological developments, with special reference to blood flow and volume flow measurements, both fetal and placental. Other aspects of clinical fetal monitoring, including fetal activity measurements, and biophysical evaluation were rationalised and placed in context, and the important newly emerging areas of cordocentesis and therapy in IUGR addressed. Finally, neonatal management of the SGA baby, mortality and long-term morbidity were discussed.The formal papers presented by the members of the Study Group are given together with edited versions of the ensuing discussions and the Group's conclusions.

Today, individuals have greater access to information about their healththaneverbefore(Randeree,2009;Eysenbach,2008).Muchofthis changeisdue, inlargepart, toadvancesinbiotechnologyandtheseque- ing of the human genome (Manolio & Collins, 2009). It is now possible, forexample, forindividualstologontotheInternetand, forafeeofs- eral hundred dollars, order an at-home DNA collection kit and have the resultsofamyriadofgenetictestsdelivereddirectlytotheire-mailinbox (Gurwitz&Bregman-Eschet,2009).Insomecases, thesetestresultsmay indicatepersonalriskforcommonchronicdiseases, suchascertainforms ofcancer, diabetes, cardiovasculardisease, andseveralothers.Companies marketing these test kits often claim that promoting greater access to and awareness of the association between genes and health, and one's genetic susceptibilities to disease, leads to more proactive and insig- fulmethodsofindividualhealthmanagement(Hogarth, Javitt,&Melzer, 2008). Moreover, it is consistent with an emerging trend in medicine - that of consumer-oriented medicine - which places health information toolsdirectlyinthehandsofpatientsunderthepremiseoffosteringbetter patient-providercollaboration(Silvestre, Sue,&Allen,2009). Though the principles behind this direct-to-consumer approach to genetics seem laudable and perhaps even exciting, there is consid- ablecontroversyastowhat, ifany, utilitytheinformationactuallyholds (Geransar&Einsiedel,2008;Wasson, Cook,&Helzlsouer,2006).Unlike geneticteststhatarediagnostic(e.g., chromosomeanalysisforDowns- drome)orhighlypredictive(e.g., BRCA1andBRCA2testingforhereditary breast-ovarian cancer risk), this new wave of presymptomatic predictive genetictestsforcommondiseaseyieldsresultsthataremuchmoreunc- tainbecausethestatisticalmodelsonwhichtheyarepresentlybasedare imperfectandwithlimiteddata(Ng, Murray, Levy,&Venter,2009). Theabovescenarioraisesmanyquestionsfortoday'shealth-carec- sumers. For example, for whom is this information applicable, and for whatpopulationsorsubpopulationsisitnot?Underwhatcircumstances might this information be useful, and when should it be disregarded as irrelevant?Andperhapsmostimportantly, what, ifanything, canbedone inlightofinformationaboutpersonalgeneticrisktoeffectivelylowerthe oddsofbecomingsickandraisetheoddsofstayinghealthy? vii viii PREFACE Becausetheprevalenceofmostdiseasesvariesasafunctionofage, gender, race/ethnicity, and other personal characteristics, answers to these questions are complex and many are just beginning to be und- stood(Khouryetal.,2009).Someexpertshaveconcludedthattheanswers tosuchquestionsremainoutofreachatthepresenttimeandmayc- tinue to be elusive for another 5-10 years (Frazer, Murray, Schork, & Topol,2009).Yet, twenty-?rstcenturyhealth-careconsumers, providers, and policy makers face these choices now about incorporating personal genetic information into health management and often do so without a complete and accurate understanding of the potential impact of their decisionsonmultiplelevels(Carlson,2009).

Pediatric body CT began in earnest in 1976 when for the first time a body CT machine was installed in a pediatric institution, the Hospital for Sick Children in Toronto. The first images were received with great enthusiasm. More recently, newer equipment with faster scan times and better resolution has enabled us to delineate disease processes with even greater accuracy. In the past 9 years we have performed more than 5000 body scans in children. With this experience our examination techniques have changed and the indications for CT in children have been modified. CT has come to occupy an important and specific place in the management of pediatric patients. The performance of body CT studies in children is not always easy. Excellent diagnostic studies can be obtained only with a special understanding of the problems of pediatric patients and pediatric pathology. The information contained herein is a review of our experience with pediatric body CT, how we use body CT in children, and its relationship to other modalities in this department.

Wir berichten tiber 185 Kinder mit unterschiedlichen Erscheinungen, die her- kommlich als Riesenhamartom, Angiodysplasie, kongenitale Trophoedem, ort- licher Gigantismus (z. B. Macrodaktylie) usw. gekennzeichnet werden. Wir schla- gen vor, aIle diese Erscheinungen als eine Entitat zu verstehen: kongenitale Weich- teildysplasie (congenital soft-tissue dysplasia, CSTD. Nach jtingsten embryologischen und zellbiologischen Untersuchungen tritt die CSTD als Folge embryonaler oder fetaler biosynthetischer Zellfehlregulation auf. Das Konzept einer CSTD-Entitat fiihrt sowohl zu einem gemeinsamen Unter- suchungsprotokoll als auch zu einem gemeinsamen therapeutischen Vorgehen un- ter besonderer Berticksichtigung der "Stabilitat" und der Gutartigkeit des Zu- standes. Die Behandlung sollte auf die funktionelle Verbesserung beschrankt bleiben, anstatt die Korrektur kosmetischer Defekte zu versuchen. References 1. Andre JM (1973) Les dysplasies vasculaires systematisees, vol 1. L'expansion scientifique, Paris 2. Andre JM, Jacquier A, Picard L (1977) La neurofibromatose de Recklinghausen. Pathogenie - Conception actuelle. Ann Chir Thor Cardiovasc 16: 175-185 3. Andrews EJ, Ward BC, Altman NH (1979) Spontaneous animal models of human diseases, vols 1 and 2. Academic, New York 4. Azouz EM (1983) Hematuria, rectal-bleeding and pelvic phleboliths in children with Klippel- Trenaunay syndrome. Pediatr Radiol 13: 82-88 5. Barksy AJ (1967) Macrodactyly. J Bone Joint Surg 49A(7): 1255-1266 6. Berliner DL, Ruhmann AG (1966) Comparison of growth of fibroblasts under the influence of II-beta-hydroxy and ll-keto-corticosteroids. Endocrinology 78: 373 7. Chassaignac C (1959) Hypertrophie congenitale des 2 membres droits. Bull Soc Coo Paris 8.

Aspects of Lyme Borreliosis is a comprehensive scientific presentation of virtually all aspects of lyme borreliosis. It starts with a concise history of lyme borreliosis and its causative agent, Borrelia burgdorferi. The morphological and biological characteristics of B. burgdorferi are presented, followed by outlines on the ecology and histopathology of LB.The various aspects of the clinical manifestations of LB are systematically dealt with, starting with a clinical overview. A special chapter covers the microbiological diagnosis. After a presentation on the susceptibility of B. burgdorferi in vitro and in animals against a great variety of antibiotics, a thorough discussion on the treatment of LB including criticalremarks follows. The book closes with a chapter on the epidemiology of LB.

Neuroblastoma is the third most common malignancy of childhood. accounting for 8% of all cancers in patients under 15 years of age. In the majority of cases. by the time neuroblastoma is diagnosed. it has already spread from its site of origin to involve distant sites. Approximately 90% of cases of neuroblastoma can be diagnosed by a combination of techniques including detection of specific tumour markers in the urine. histopathological and immunocytological assessment of involved bone marrow and the 'characteristic' appearances of tumours dem- onstrated by computerised tomography and ultrasonography. However. despite this plethora of techniques. up to. 10% of cases of neuroblastoma are still difficult to diagnose and rely on excisional biopsy of a site of disease. It was against this background that the scintigraphic localisation of neuroblastoma with the radiolabelled guanethidine analogue. mIBG. became available. With mIBG scintigraphy it is now possible to demonstrate the presence of neuro- blastoma (and related tumours) at the primary site. soft tissue sites. in the bone marrow and in cortical bone. in a single investigation. The success of mIBG scintigraphy depends on many factors including the choice of isotope for labelling the mIBG. the equipment used to carry out the procedure. and the manipulation and interpretation of the information obtained. At the Royal Marsden Hospital we have performed over 100 mIBG studies in children. and our advice has frequently been sought by other centres who are. or intend to become.

"Child development" has always been a traditional component of well child care and a particular area of interest for pediatricians, child neu rologists, and psychologists. However, it was not until the early 1960s that children with developmental disabilities (i. e. , chronic handicapping disorders) became a major focus of public and professional attention. During this period, children with "special needs" were dramatically catapulted into the limelight and "exceptional" became the buzzword of the day. Public and professional awareness of these issues reached new peaks and recognition of the potential psychosocial impairments of chil dren with developmental disabilities created national anxiety. A variety of factors contributed to an unprecedented societal advocacy for chil dren with developmental problems: (1) a national concern generated by President Kennedy'S particular interest in mental retardation; (2) in creased activity and visibility of parent advocacy/lobbying groups (e. g. , the Association for Children with Learning Disabilities); (3) the enact ment of federal legislation designed to protect the rights of the handi capped (e. g. , PL94-142); and (4) the popularization of developmental behavioral disabilities by the various communications media. Cumulatively these events precipitated a redefinition of the real mean ing of "comprehensive health care for children," resulting in an empha sis on the child's neurodevelopmental, educational, psychological, and social needs. For the pediatrician, a myriad of new management respon sibilities were mandated, in addition to the traditional health care con cerns.

The purpose of this series of volumes is to present a comprehensive view of the complications that result from the use of acceptable diagnostic and thera peutic procedures. Individual volumes will deal with iatrogenic complications involving (1) the alimentary system, (2) the urinary system, (3) the respiratory and cardiac systems, (4) the skeletal system and (5) the pediatric patient. The term iatrogenic, derived from two Greek words, means physician-in duced. Originally, it applied only to psychiatric disorders generated in the patient by autosuggestion, based on misinterpretation of the doctor's attitude and comments. As clinically used, it now pertains to the inadvertent side effects and complications created in the course of diagnosis and treatment. The classic categories of disease have included: (1) congenital and developmen tal, (2) traumatic, (3) infectious and inflammatory, (4) metabolic, (5) neoplastic, and (6) degenerative. To these must be added, however, iatrogenic disorders a major, although generally unacknowledged, source of illness. While great advances in medical care in both diagnosis and therapy have been accomplished in the past few decades, many are at times associated with certain side-effects and risks which may result in distress equal to or greater than the basic condi tion. Iatrogenic complications, which may be referred to as "diseases of medical progress," have become a new dimension in the causation of human disease."

There has been increasing interest in neonatal neurology, especially since imaging techniques were introduced in the neonatal ward. Looking at the natural history of imaging techniques, we can identify three main axes of its development. Logically, it was first essential to image the brain morphologically. For this purpose, computed tomography was initially used, followed by ultra sound. However, to improve the quality of the images, magnetic resonance imaging was introduced. Major features of ultrasound and magnetic reso nance imaging are their safety and lack of ionization. Morphological imaging techniques have proved to be insufficient to ex plain the mechanisms underlying CNS injuries. Thus, it was essential to develop functional techniques to assess cerebral hemodynamics and oxy genation. The use of Doppler ultrasound, PET scanning, SPECT scanning and, more recently, NIRS have widened our knowledge of general neurolog ical problems. Finally, to achieve our goal of attaining a better understanding of CNS injuries, it is important to assess cerebral cellular metabolism. Magnetic resonance spectroscopy was introduced to achieve this goal. We hope that this book links these different techniques in order to widen our horizon. The future is promising and bound to provide further develop ments, which however can only be understood if we grasp the present level of development.

Over a mere 5 years, neonatal cranial sonography has evolved from an obscure and largely experimental imaging possibility to the modality of preference in the examination of the young brain. The almost immediate acceptance of the ultrasound examination of the neonatal brain was based on a number of coinci dent factors, the most important of which was the emergence of a burgeoning population of premature neonates who were, for the first time, surviving be yond infancy. These delicate patients were beginning to withstand the rigors of extrauterine life when not fully prepared for it; pulmonary, cardiac, and infec tious diseases no longer claimed most of them. With survival, a new specter reared its head: Would the eventual mental and neurologic status of these same children be worth the expense and time needed to bring them through their first months? This issue became increasingly pressing as evidence mounted through the 1970s that very premature neonates were at a high risk for intracranial hemor rhage and posthemorrhagic complications. An imaging modality that could evaluate the premature brain was sorely needed. The CT scanner with its proven ability to diagnose intracranial hemorrhage was of little value in this regard. So too were static gray-scale or waterpath ultrasound units. These modalities all had the same limitation, lack of portability. As neonatal intensive care units proliferated, so did the technology that would soon allow cribside neonatal neuroimaging, the real-time sector scanner."