This volume contains the papers presented at the Inter- national Symposium on "Cirrhosis, Hepatic Encephalopathy and Ammonium Toxicity", held in Valencia, Spain, November 27-29, 1989. Hepatic cirrhosis as well as other liver failures usual- ly lead to hepatic encephalopathy which is an important cause of death in occidental countries. However the molecular bases of the pathogenesis of hepatic encephalopathy remain unclear and several hypotheses have been proposed. Hyperammonemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy. Therefore, a part of the book is devoted to the effects of hyperammonemia on cerebral function, ammonia and amino acid metabolism, brain microtobules, astrocytes and synaptic trans- mission and their possible role in the pathogenesis of hepatic encephalopathy. Carnitine has a remarkable protective effect against acute ammonium intoxication. Thus some results regarding this effect are also presented, as well as the clinical use of car- nitine. The alterations of the metabolism of ammonia and of seda- tives in liver diseases and their clinical implications are also discussed. The possible role of altered GABA-ergic neurotransmission on the pathogenesis of hepatic encephalopathy has received considerable attention recently. Results of these studies and those on benzodiazepine receptor ligands are presented as well as those on the hypothesis of the role of altered synaptic plasma membrane on the pathogenesis of hepatic encephalopathy.

In an attempt to attain the best possible delimitation of all the problems posed today by benign diseases of the esophagus, 181 authors each agreed to answer one or more of 210 questions that had been drawn up on the subject. These questions, each one deliberately limited and difficult, mostly concerned reflux esophagitis: its natural history, the means of its diagnosis, all existing treatments, and its eventual degeneration. The authors approached are today's most reputed specialists in the fields of epidemiology, gastroenterology, endoscopy, pathology, and surgery of esophageal diseases. The authors were all assigned one or more questions in their own field, none of which was simple: all did their best to synthesize in their replies their own experience on the precise point under review and included all the most useful bibliographical references on the topic. The book is thus the result of an original, individual approach to try to pinpoint the heart of a problem. The 210 answers succeed one another in logical progression according to the different diagnostic and therapeutic stages, specifying, at each step, the degree of precision sought. Consequently, the reader has at his disposal an exceptional synthesis of facts and concepts. Opening the book at random he will find at once the detail he is looking for, the professional opinion he is lacking, or the development of a question he had perhaps not yet asked himself.

Ever since the emergence of the concept of catharral jaundice by Virchow, viral hepatitis has eluded scientists as a pathogenetic enigma. A tremendous new impetus was given to hepatitis research by Baruch Blumberg's discovery of his 'Australia Antigen', now known as hepatitis B surface antigen. This led to an unheard-of outburst of research activity to elucidate the nature of the virus, its chemical and antigenic composition, its epidemiology, and pathogenetic mechanisms in the causation of liver disease. Coinciding with this period, modern medical science witnessed impressive progress in the analysis of the extraordinarily complex mechanism of immunological reactions. Immunohistochemical techniques for the detection of hepatitis B viral components are a product of this scientific progress in both areas. The application of such tech niques forms the core of this work. It represents a vast amount of work, performed during the course of several years, with meticulous application of advanced immunohisto chemical techniques, combined with histopathology and clinical-patho logical methods. This has resulted in the compilation of original results and new insights into the cellular and tissular localization of the anti genic components of the hepatitis B virus in different forms of chronic liver disease. The most outstanding results are the demonstration of the superior sensitivity of the applied immunohistochemical technique in the search for viral components in chronic hepatitis patients. and the differ ential distribution patterns of hepatitis B surface antigen in the various forms of chronic liver disease."

We have been privileged to start our academic careers at the begin ning of the decade in which the immunological roles and hypersensitivity diseases of the gastrointestinal tract and liver have been defined. In the early 1960s IgA was reported to be the main secretory immunoglobulin, immunoblasts were shown to home to the intestinal mucosa and certain serum autoantibodies were described in patients with chronic liver disease. Shortly thereafter IgE and Australia antigen were discovered. Parallel advances in clinical investigation, in particular closed biopsy techniques, facilitated correlation of morphological changes with im munological mechanisms in disease of the gastrointestinal tract and liver. Only 10 years later, the concepts of immunity and hypersensitivity are regularly applied to the pathogenesis, diagnosis, treatment and prog nosis of many chronic diseases in these organs. In designing this book we have attempted to integrate theorectical and clinical immunology as they pertain in 1975; our ultimate aim is aptly described by Brachet as quoted by Professor Paronetto (page 319). We would like to think that this review provides a basis for the next major advances in the fields of gastrointestinal and hepatic immunology. As we see it, the outstanding problem in both sites is how to produce protective immunity without hypersensitivity."

The pathogenesis of cell death and necrosis in the liver is a central topic of research in liver disease. A molecular understanding of events and sequences leading to cellular death provides the basis for preventive and therapeutic efforts. This volume originates from a "Workshop on Experimental Liver Injury" held on November 9 and 10, 1974, in Freiburg, Germany. Recent progress in the elucidation of the mode of action includes agents inducing liver cell necrosis by a primary dis- turbance of nucleotide and nucleic acid metabolism as well as hepa- totoxins characterized by a primary attack on cellular membranes. I hope that this book will contribute to an increasing understanding of disease mechanisms. Freiburg im Breisgau Dietrich Keppler June 1975 Acknowledgments The generous support from Dr. H. Falk, Freiburg, has been a prereqUIsite for the organisation and publication of the meeting on "Pathogenesis and Mechanisms of Liver Cell Necrosis". I wish to express my sincere thanks for this sponsorship. I am indebted to those who acted as chairmen during the meeting: Professors H. Remmer (Tilbingen), M. Frimmer (Giessen), W. Gerok (Freiburg), H. Popper (New York), H. Schimassek (Heidelberg), and K. Decker (Freiburg).

The literature of medicine continues to expand at a remarkable pace. The number of papers and monographs published has increased dramatically in the past five years. Nowhere has this increase been as dramatic as in the field of acute and chronic hepatitis. Why then should there be still another book? Despite the sheer volume of words published, it is still difficult to find in anyone volume a compilation of all of the most significant work. Most mono graphs have considered either chronic or acute hepatitis, not both. Few works have addressed both the clinician and the basic scientist. This book addresses both of these audiences and considers both of these diseases. It was designed to provide an authoritative but concise assessment of our changing concepts of acute and chronic hepatitis. It covers what is currently known and, based on the most convincing research, believed about these diseases. To fulfill this ambitious goal, only authors with international reputations in their fields of expertise were invited to contribute. In the evolution of our current thoughts on the pathogenesis and manage ment of acute and chronic hepatitis, our ideas have changed several times. This book presents the facts as they are known today and, in areas where all the facts are not established, presents the well-founded opinions of those considered to be authorities. The authors present established and usually confirmed data and do not deal extensively with areas of speculation or unconfirmed material."

Inflammatory dieseases of the pancreas occur with increasing incidence in western industrialized countries. This volume deals with all aspects of CHRONIC PANCREATITIS including epidemiology, etiology, morphology and pathophysiology, dia- gnostic imaging as well as conservative and operative treat- ment. Very recent data based on experimental and clinical research projects are presented. The contributions have all been written by a team of internationally well recognized authorities in the various fields involved. Topics of parti- cular interest include feed-back regulation, new aspects of conservative and interventional treatment as well as modern surgical approaches including organ-preserving procedures.

Material for this book was gathered in the early 1980's in Manchester, where a higher incidence than usual of complications in the gastro-intestinal and urinary tract was observed. Part I describes the principles and methods of radiotherapy for pelvic tumours, pathological features and radiological analysis of bowel and urinary tract changes. Parts II and III are devoted to clinical assessment and management, where the need for a multi-diciplinary approach is emphasized.

In the rapidly evolving field of Helicobacter infection new data on pathogenetic and pathophysiological mechanism have appeared. New methods which will be more sensitive and specific in the diagnosis of the infection are being developed and in this proceedings the first attempt using PCR technology is published. From the clinical point of view, a challenging aspect that needs clarification, is the observation which suggests an appearance of a correlation between the presence of the bacteria and abdominal pain and other symptoms in children whereas in old age no such correlation is evident. The relationship of H. pylori and gastric cancer is studied with histopathological data and epidemiological approaches. On the treatment side schemes using short courses and new antibiotic combinations are being investigated and preliminary data are reported.

The larvae of Anisakis, whose adult form lives on sea mammals such as whales, seals, and dolphins, are parasitic upon many species of salt-water fish. When the final host animals eat paratenic hosts, the larvae grow to adulthood in the hosts' stomach. However, when hu mans eat these infested fish, the larvae die instead, causing a disease called anisakiasis. In 1960, in the Netherlands, van Thiel et al. found a worm in the intestinal wall of a patient who had eaten raw herring and had suffered symptoms of acute abdomen. The impact of this report was tremendous among Japanese parasitologists because of the Japanese habit of eating raw fish. In 1964, the Special Research Group from the Ministry of Education was established to investigate the disease, stimulating progress in the study of anisakiasis. Three types of worm, Anisakis simplex larva (previously known as Anisakis larva type I), Anisakis physeteris larva (Anisakis larva type II), and Pseudoterranova decipiens larva type A, are believed to cause anisakiasis. As many as 165 kinds of fish and squid in the seas near Japan are hosts to Anisakis simplex, and 9 species are hosts to Pseudoterranova decipiens larvae. Contra caecum has experimentally been observed to invade the gastrointestinal tract, but no infection by this larva has been reported in humans. A case of infection by Pseudoterranova decipiens type B has been described. In Japan, the name Terranova decipiens (Shiraki 1974) has been adopted instead of Phocanema decipiens (Mozgovoi 1953)."

This study assembles current and new information on the mechanisms involved in intracellular calcium regulation and their actual or potential relationship to cellular calcium transport. Topics discussed in detail are calcium channels, cellular calcium extrusion, sodium/calcium exchange, calcium-binding proteins with special reference to the vitamin D-induced calbindin, calcium transport and disorders thereof. Each topic is introduced with an overview followed by research papers dealing with relevant topics in each category. New information deals with calcium channels which are not voltage-sensitive, the structure and function of the plasma membrane Ca ATPase, the role of the Na/Ca exchanger in intracellular Na and proton regulation, a comprehensive overview of calcium transport with quantitative analysis of the role of the intestinal and renal calcium-binding proteins, description of the structure and function of the calbindin genes, and identification of calcium transport defects in diabetes and hypertension. Readers will be brought up-to-date on current knowledge and concepts in this rapidly expanding field and be directed to the relevant primary and secondary literature.

It is now more than 40 years since Drs. Wild and Reid published their first experience with rectal ultrasonography from the Surgery Department at the University of Minnesota. Professor Owen H. Wangen steen, in whose laboratory the studies were carried out, recognized at that time the need for early detection in the treatment of cancer. Technical improvements over the past 20 years have made endoscopy the procedure of choice for examination of the hollow organs of the genital, urinary and gastrointestinal tracts. The simultaneous development of endosonography has had an equally dramatic impact on the practice of medicine and surgery. The technology has been demonstrated to be helpful in both benign and malignant conditions. One of the so-called benign conditions of the anorectum is fistula-in-ano. Fistula surgery has always relied on excellent anatomic delineation of the intramuscular tracts. There is hope that adaptation of ultrasonographic technology will aid in the surgical management of this malady. Clearly, rectal ultrasonography has considerable potential in the management of rectal carcinoma. Accuracy rates in the range of 90% for the depth of neoplastic invasion have been reported. This ability for accurate assessment will undoubtedly lead to a better definition of the population of patients that can be managed by local therapeutic means.

Provides findings on acute pancreatitis in the fields of morphology, epidemiology, pathophysiology, enzymatic and in- strumental diagnosis, clinical aspects and pharmacological and surgical treatment. Emphasis on clinical implications on the local release and vasoactice and toxic substances, the high rate of bacterial infection in the necroses, and the causes of impairment of cardiocirculatory, pulmonary and re- nal organs.

A new presentation of physiological regulatory mechanisms and therapeutic applications is given in this book. It represents a collection of the most up-to-date information in cholecystokinin (CCK) research, especially focusing on the development and characterization of CCK antagonists. The book contains chapters on the synthesis, biochemical and pharmacological characterization of potent and selective CCK antagonists as well as physiological applications of these compounds. The last section of the book is devoted to the involvement of CCK in pathological states and potential clinical applications of CCK antagonists.

Imaging of Gastrointestinal Tract Tumors describes current imaging practice for the most commonly encountered benign and malignant digestive tract tumors and gives a review of the literature for less frequent tumors. General features (anatomic data, frequency, clinical and biologic signs, treatment) are discussed for all pathologies prior to description of imaging techniques, which include barium studies, ultrasonography and angiography, and above all CT. MRI appears particularly indicated for esophageal carcinoma and pelvic recurrences of colorectal cancers. The book is divided into three main section - benign tumors, malignant tumors, and tumors with an indeterminate prognosis - reflecting the value of different imaging strategies as a function of a tumor's natural history. The thorough analysis of literature for both frequent and less common tumors allows global evaluation of the diagnostic possibilities of imaging techniques, making Imaging of Gastrointestinal Tract Tumors a reference work for all specialists concerned with digestive tract pathologies.

For the first time four crucial aspects of gastrointestinal endoscopy are combined in a single text. Drugs for sedation and monitoring of the patient are addressed with particular reference to safety issues and comfort and acceptability for the patient. Resource management and health economic techniques are applied to endoscopy to determine quality and outcome. Problems of negligence and informed consent form the basis of a medico-legal examination of endoscopic practices.

The most comprehensive and conceptual one-volume treatment of this field available and the first to emphasize the cellular and molecular aspects of gut peptide biology. Authored by an array of internationally distinguished scientists, it deals with issues of peptide localization and biosynthesis in gastrointestinal cells, mechanisms of peptide release and inactivation and the nature of peptide receptors. The breadth and readability make it an invaluable reference source for scientists in all disciplines interested in any aspect of brain-gut peptides.

Only a few years ago, most treatises on sonography covered all the diagnostic applications of ultrasound, de scribing organs from the brain down to the placenta. Dr. Bruneton and his associates must be thanked for pre senting this book devoted to the spleen. It probably offers the most complete presentation of details and the richest images available in its field. This book will thus become the ultimate reference in most libraries of books on son ography. March 1988 F. Weill The authors wish to thank Christine Rostagni, Fran ise Fein, and Bernard Fontaine for their assistance in the preparation of this book. Contents 1 Sonographic Anatomy of the Normal Spleen, Normal Anatomic Variants, and Pitfalls B. Senecail . . . . . . . . . . . . . . . . . . . . . . 1 1. 1 Anatomy of the Spleen. . . . . . . . . . . . . . . . 1 1. 1. 1 Morphology and Structure . . . . . . . . . . . . . 1 1. 1. 2 Location and Relations of the Spleen. . . . . . . . 3 1. 1. 3 Average Dimensions of the Cadaver Spleen . . . . 5 1. 1. 4 Congenital Anomalies and Normal Variants. . . . 5 1. 1. 4. 1 Fissured Spleen. . . . . . . . . . . . . . . . . . . . 5 1. 1. 4. 2 Lobulated Spleen. . . . . . . . . . . . . . . . . . . 5 1. 1. 4. 3 Spleen with Two Hili. . . . . . . . . . . . . . . . . 5 1. 1. 4. 4 Wandering or Ectopic Spleen . . . . . . . . . . . . 6 1. 1. 4. 5 Numeric Anomalies . . . . . . . . . . . . . . . . . 6 Ultrasonography of the Spleen . . . . . . . . . . . 1. 2 6 1. 2. 1 Equipment . . . . . . . . . . . . . . . . . . . . . . 6 1. 2. 2 Patient Examination . . . . . . . . . . . . . . . . . 7 1. 2. 3 Scanning Technique . . . . . . . . . . . . . . . . . 7 1. 3 Sonographic Features of the Normal Spleen. . . . 7 1. 3. 1 Splenic Contour . . . . . . . . . . . . . . . . . . . 7 1. 3. 2 Echo Pattern of the Splenic Parenchyma. . . . . ."

The aim of this symposium was to provide a framework for fruitful discussion on intestinal transport, not only for advanced scientists but also for younger people starting in this field of research. Invited lectures, communications and poster presentations were focused on four central themes, all treating the prop erties of the sole intestinal epithelium, deliberately leaving aside problems dealing with more integrative functions of the whole intestine. The importance of motility or blood circulation, for instance, is certainly capital in the overall intestinal function, but these aspects by themselves deserve another meeting. This volume has compiled the manuscripts of the invited lectures which sub stantially comprised the four sessions of the Symposium. Part 1 is designed to emphasize actual knowledge of the transport of water, inorganic as well as organic ions and molecules across the isolated intestinal epithelium. An enormous wave of investigations has emerged from studies per formed with "Ussing chambers," which roused interest in studies on absorption mechanisms and subsequently on secretory processes. This has triggered off a trend to research on isolated cells as absorption and secretion are the main func tion of the different cell types constituting the intestinal epithelium. In this first session not only the importance of the parallel arrangement of these different cellular entities is stressed, but also the role played by the paracellular route."

In July, 1988, more than 300 scientists from 29 different countries gathered at Tiibingen, W. Germany, in order to spend 4 days discussing their favourite trace element, selenium. This meeting continued the good tradition of three previous meetings held in Corvallis/Oregon, 1976, in Lubbock/Texas, 1980, and in Beijing/China, in 1984. Incidentally, the University of Tiibingen provided a unique historical background for a Symposium devoted to recent advances in biochemistry, pharmacology, human nutrition and human health; here, the first independent depart ment of Physiological Chemistry in Germany was founded in 1845. Pro fessor H9Ppe-Seyler elucidated here the hemin structure and his student Friedrich Miescher discovered the nucleic acids. This book contains one-half of the oral or poster presentations which were selected before the meeting was held on the basis of a one page abstract. It is the reader who will have to decide whether this time consuming policy of quality assessment was warranted or not."

Dr. Raymond Pederson, Dr. Jill Dryburgh and I commenced work on GIP in 1968, when, with the generous help of Professor Viktor Mutt and Professor Erik Jorpes of the Karolinska Inst, itute, Stockholm, we were able to establish that there existed an inhibitory material for acid secretion in cholecystokinin-pancreozymin prepara tions. Once the physiological evidence for the inhibitor was established it seemed appropriate to seek help in its isolation. Dr. J. Dryburgh and Dr. R. Pederson were left to bioassay fractions in Vancouver whilst I enjoyed the company of Professor Mutt at the Karolinska for one year, as a Medical Research Council of Canada Visiting Scientist. Purification of the inhibitory factor proceeded rapidly due, in no small measure, to Professor Mutt's untirmg efforts on my behalf. Later that year, Dr. Dryburgh joined us in Stockholm to begin the sequence work on GIP. This was completed late in 1970 in Vancouver. In Stockholm in June 1970, I met a fellow Canadian Dr. John Dupre (McGill University) at a cocktail party who kept commenting about the possibility of GIP being an insulinotropic hormone, the "incretin" of earlier days. At that time, gastrointestinal physiologist as I was, I did not recognize the importance of his comment. This became apparent two or three years later when Dr. Dupre demonstrated that GIP was insulinotropic in man. In 1972, Maryanne Kuzio and Dr."

Congenital hip dysplasia and dislocation are common diseases of newborns and small infants, with frequently severe consequences if orthopaedic therapy is not initiated at an early stage. Therefore many clinicians have been looking for a simple method for the investigation of the hip joint in the early neonatal period. Up to 1980 the diagnosis of hip dysplasia could usually not be made before the 3rd month of life, by means of pelvic roentgenography. Only incomplete or complete unilateral dislocations were diagnosed in the neonatal age group. In 1980, however, Graf, an Austrian orthopaedic surgeon, began using ultrasound investigation ofthe hip joint in newborns and small infants in order to make an early diagnosis and to avoid radiation exposure. The intention of the present study was to compare ultrasound of the hip joint with other established diagnostic procedures and to establish whether it is suitable as a screening procedure in newborns. 2 Incidence of Congenital Hip Dysplasia and Dislocation In 1972 Barlow reported that 90 % of hips which are unstable at birth develop to normal joints spontaneously without any therapy. Visser (1984) thus suggested determining the percentage of hip dislocations after the 2nd - 3rd month of life so that children with spontaneous stabilisation would be excluded.

Hepatology has come of age in the last decades. Biology of the liver has flour ished long before. As the largest homogeneous organ of the body the liver served as useful model in the development of biochemistry and related discip lines. Only gradually were these biological investigations applied to the clinical study of liver disease. This was particularly stimulated by the recognition that in the greater part of the world, the developing countries and what we now call the Third World, liver disease represents a major threat to overall public health. It leads to morbidity and mortality of persons in their productive years from liver cancer, cirrhosis and parasitic disease, particularly, schistosomiasis. Moreover, the growing emphasis on the social impact of diseases focused on disorders of the liver because malnutrition, poverty, and drug addiction contrib ute greatly to their spread. This is compounded by the increase of alcohol abuse, recently on the rise even in the developing countries. Concern with envi ronmental pollution has also raised the interest in liver diseases, in part because the liver acts as a guardian against polluting chemicals and in part because it is considered, possibly to an exaggerated degree, a vulnerable target of such chemicals.

Studies on the colon not only serve medical interest or clinical purposes, but are also a highly interesting subject of comparative physiology, from which we can learn much about the basic principles in physiology. Presented here are examples of research on colonic ion transport of each vertebrate group, including the classical models of epithelia, rat and rabbit, and also on the special and unique features in fish, amphibians, reptiles, birds, and selected mammals such as the guinea pig. Physiology and pathophysiology of ion transport in the human large intestine are as well covered as the use of colonic cell cultures as model systems for crypt cell properties.

Continuing progress has been made since the first edition of Artificial Liver Support was published. Liver transplantation has however become an estab lished therapy for a relatively small number of patients who remain patients for life. There therefore continues to be a great need for the development of other forms of artificial liver support. Improved intensive care utilizing improved plasma exchange, dialysis, sclerotherapy, and intracranial pressure monitoring have improved survival in fulminant hepatic failure. Progress has also been made in lipid membrane detoxification, in cell cultures, and in cell transplantation, and the isolation of various liver cell growth factors has led to deep insight into the mechanisms of liver regeneration. This book gives the clinician and the researcher detailed information about established new methods of clinic work and laboratory research, and describes new experimental approaches indicating the direction of future research. G. BRUNNER M. Mno Preface to the First Edition The regenerative capacity of the liver cell is almost unlimited. Therefore after acute liver damage, be it viral, toxic, hypoxic, or surgical in origin, restitutio ad integrum is the usual outcome. In two forms of liver disease, however, this is not the case: in fulminant hepatic failure, liver regeneration often is not fast enough to keep the organism alive; in end-stage cirrhosis, regeneration is disturbed by a hypertrophic architecture of fibrotic tissue. For these extreme forms of liver disease and for critical situations before and after liver surgery, artificial liver support is needed.