Gastric secretions contain hydrogen ions at a concentration that is more than one million times higher than their intracellular concentration. This phenomenal gradient as well as the demonstrated ability of gastric juice to digest tissues has motivated clinicians and investigators alike to emphasize acid secretion and acid ablation in studying the pathogenesis and therapy of peptic ulcer disease. Conse quently, over the past 150 years, we have made considerable progress in under standing the mechanisms and regulation of acid secretion by the stomach. Not surprisingly, therapy for both peptic disease and mucosal injury has also been predominantly directed at either neutralizing acid or suppressing its production. During the past 10 years, attention has been focused on factors other than acid in the genesis and therapy of ulcer disease. Work done worldwide demon strated that acid hypersecretion is not a common event in peptic ulcer disease. Therefore, we began realizing that factors other than acid secretion may be important in the genesis of ulcer disease or in gastroduodenal mucosal damage. In addition, new physiological information has established that the gas troduodenal mucosa is normally protected by a complex series of events includ ing mucus and bicarbonate secretion, cell renewal, surface mucosal restitution, and preservation of the microvasculature and mucosal proliferative zone.

By 1977 it was clear that the thermophilic campylobacters were a major cause of acute bacterial enteritis. In response to that observation an international workshop was convened in Reading, England, and attracted over 130 participants. Many of these individuals resolutely returned for the eighth in the series of biennial international workshops, this time held in Win chester, England, in July 1995. All were surprised at the continued, and even expanding, re search effort in this narrow microbiological field. Such a lasting interest is undoubtedly a reflection of a consistent rise in the incidence of infection, the growing number of closely re lated organisms and disease associations, and an ever-increasing awareness by the public and government agencies of public health and food safety issues. The second workshop in Brussels in 1983 was a forum that demonstrated the growing awareness in the campylobacter community of the existence of campylobacter-like organisms and provided the platform for presentations describing the association of these organisms, now classified in the genus Helicobacter. with gastroduodenal disease. The clinical aspects of the research into helicobacters is now thoroughly covered in several other meetings, and the remit of the international workshop has been expanded to provide a forum for the presentation of the basic microbiological research carried out on these bacteria. In a continuation of this ap proach the remit of the workshop has been further extended to other related organisms, reflect ing that there are many other campylobacter-like organisms still to identify and characterize."

HepatitisE (HEV) is a viral infectious disease that infects humans and domestic, wild, and synanthropic animals alike. In developing countries, the disease often presents as an epidemic, transmitted primarily through the fecal-oral route. In recent years, sporadic cases have also been documented in industrial countries, including Europe. The identification and characterization of animal strains of HEV from pigs, wild boar, and deer, and the demonstrated ability of cross-species infection by these animal strains raise potential public health concerns for foodborne and zoonotic transmission of the virus. This Brief will provide a thorough overview of HEV. It will discuss the epidemiology and pathogenesis of the virus in both humans and animals, review detection methods, and provide methods for its control and prevention."

In the past 15 years much evidence has accumulated which indicates the paramount importance of sensory nerves in reg ulating functions of the gastrointestinal tract. In parallel, the attention of researchers in this field has been increas ingly attracted to the role played by neuropeptides in the normal and diseased gut. Basic research on the peculiar properties of capsaicin, the pungent ingredient from plants of the genus Capsicum, has allowed the gap between these two areas of research to be bridged. Sincethen, the study of gut afferents and neuropeptides has become more and more interconnected and recognized as a major avenue to understand ing the pathophysiology of various human diseases. It is widely recognized that a certain subset of primary afferents synthesize, store and release neuropeptides (such as tachykin nins and calcitonin gene-related peptide) from their central and peripheral endings, the latter being widely distributed in the alimentary canal and related organs (liver, pancreas). The First International Meeting on Sensory Nerves and Neuropeptides in Gastroenterology, held in Florence from December 4-5, 1989, sponsored and organized by Fondazione Internazionale Menarini, aimed to focus the current status of research in this field. The contributions presented at the meeting and in this book delineate a suggestive scenario in which sensory nerves of the gut, and the multiple messages they carry through the release of neuropeptides, are to be considered as a major target for the development of new drugs potentially useful in a number of diseases of the gastro intestinal tract."

The meeting that provided the material for this book was the 58th Symposium of the Federation of European Microbiological Societies (FEMS) entitled MOLECULAR PATHOGENESIS OF GASTROINTESTINAL INFECTIONS which was held in Helsingor, Denmark from 2nd to 4th September, 1990. The aim of this meeting was to bring together scientists from a range of discipline- microbiology, cell biology, molecular biology and immunology - to consider how microbes, including parasites, colonize and infect the gastrointestinal tract. The programme was designed to focus particular attention on the range of strategies whereby enterovirulent bacteria and parasites colonize the gastrointestinal mucin layer, how they adhere to and penetrate the epithelial layer by entering the cells or passing between them, and how various protein toxins may facilitate these processes. Speakers were especially encouraged to highlight the recent expansion in our knowledge of the molecular mechanisms by which enterotoxigenic and enteropathogenic Escherichia coli, shigellae, salmonellae and Yersinia enterocolitica cause intestinal disease. There were also discussions of recently-discovered gastrointestinal pathogens such as Clostridium difficile and Helicobacter pylori as well as accounts of how virulent determinants can be used to develop new diagnostic methods based on DNA gene probes and the polymerase chain reaction (PCR). These presentations provided the basis for the chapters in this book.

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.

Primary liver cancer is the third most deadly and fifth most common cancer worldwide (~500,000 deaths annually), with a sharp increase of incidence in the United States in recent years. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major types of primary liver cancer. Risk factors include gender, hepatitis B virus (HBV), hepatitis C virus (HCV), cirrhosis, metabolism diseases, diabetes, obesity, toxins, excess alcohol consumption and smoking. Liver cancer arises most frequently in inflammatory livers with extensive oxidative stress due to viral hepatitis which causes over 80% of HCC cases worldwide. Currently, survival remains dismal for most HCC and CC patients, largely due to the tumor's aggressiveness at the time of diagnosis and the lack of effective therapy.

Chronic liver failure is a frequent condition in clinical practice that encompasses all manifestations of patients with end-stage liver diseases. Chronic liver failure is a multiorgan syndrome that affects the liver, kidneys, brain, heart, lungs, adrenal glands, and vascular, coagulation, and immune systems. Chronic Liver Failure: Mechanisms and Management covers for the first time all aspects of chronic liver failure in a single book, from pathogenesis to current management. Each chapter is written by a worldwide known expert in their area and all provide the latest state-of-the-art knowledge. This volume is specifically designed to provide answers to clinical questions to all doctors dealing with patients with liver diseases, not only clinical gastroenterologists and hepatologists, but also to internists, nephrologists, intensive care physicians, and transplant surgeons.

Since 1998, the Japanese Society of Hepatology has campaigned to fight hepatocellu lar carcinoma (HCC). Because the mortality rate for this disease has reached more than 30 per 100,000 population, the organizing committee chose HCC as the main topic of the 1999 Yamaguchi Symposium on Liver Diseases. Regarding hepatocar cinogenesis, we know that HCC often develops secondary to liver cirrhosis; thus liver cirrhosis must be recognized as a prevalent pathological condition leading to HCC. If we can control liver fibrosis, we can reduce the risk for HCC among patients with chronic hepatitis. To achieve this goal, we must know more about hepatic fibrosis. Professor Michael J. P. Arthur is familiar as a leading scientist in this field. We were fortunate that he accepted our invitation to speak. His lecture titled "Mechanisms of the Progression and Regression of Liver Fibrosis" provided important advice for developing antifibrotic agents. We also invited Professor Mark A. Zern, who has been studying hepatic fibrosis for some time. In the symposium he talked about novel approaches, including gene therapy, to treat acute and chronic hepatic diseases in the 21st century. In addition to the informative talks by those guests from abroad, the lecture by Dr. J. Fujimoto was very impressive. He revealed that gene therapy using hepatocyte growth factor (HGF) could inhibit progression to liver cirrhosis in rats repeatedly injected with dimethylnitrosamine (DMN). Dr. Fujimoto has already pub lished his finding that administration of HGF reduced hepatocarcinogenesis in rats."

Experts from Europe, Japan and the United States have contributed to this in-depth volume on digestive disease pathology. Each chapter contains numerous electron micrographs, often supplemented byline drawings, and extensive references to the literature.The clear illustrations and text are an excellent aid for the diagnosis of pathological entities in the gastrointestinal tract.

Quick Reference Dictionary for GI and Hepatology is a unique, pocket-sized reference designed specifically to provide a magnitude of terms and their definitions, guidelines, and references essential to the gastroenterology profession. Led by Dr. Jonathan Fenkel and his contributors, this compact, concise, and informative reference contains over 1000 commonly used GI and hepatology terms and definitions. Additionally, Quick Reference Dictionary for GI and Hepatology offers more than 20 quick reference appendices related to common GI and liver diseases. Some appendices include: * Causes of acute liver failure * Approach to elevated liver enzyme tests * Peptic ulcer disease: therapy and re-bleeding rates * Colorectal cancer surveillance guidelines * Scoring of acute pancreatitis * Types of gallstones Quick Reference Dictionary for GI and Hepatology provides an at- your-fingertips guide for anyone who works in the gastroenterology profession, including gastroenterologists, medical students, residents, fellows, nurse practitioners, physician assistants, office staff, and industry sales representatives.

Acute and chronic viral hepatitis infections are serious public health threats around the world. The different infections have different epidemiology and natural his- ries, and children play important roles in each of these. For example, children are important reservoirs for acute hepatitis A, childhood infections are responsible for most of the global morbidity associated with chronic hepatitis B, and perinatal transmission of hepatitis C continues to occur, even as the overall incidence of new infections wanes. Some non-A through E viral hepatitis infections are seen p- dominantly in infants and young children, while others have specific implications for this population. Therapeutic options for children with chronic viral hepatitis are limited when compared to those available for adults, especially for hepatitis B, and considerations given to long-term therapy have dramatic implications when dealing with the long life expectancy of these young patients. With these issues in mind, this unique volume has been created to address the special considerations regarding viral hepatitis in children. It includes the latest information and recommendations specifically directed at the pediatric population, and highlights the knowledge gaps which will need to be filled to improve our understanding of these infections and treatment of this special group. Experienced practitioners from around the world have contributed these reviews, incorporating the latest studies, the current recommendations, and the distinctive pediatric issues that shape clinical care, and will determine the research agenda for this field going forward.

The contents of this book represent papers which were presented at the Third International Meeting on "Side-Effects of Anti-Inflammatory and Analgesic Drugs" which was held under the auspices of the University of Verona, Institute of Pharmacology in Verona on 8-11 May 1991. This meeting was held in conjunction with the 13th European Workshop on Inflammation and although publications from this part of the meeting are not published here (they appear in Agents and Actions), we were fortunate in having a group of people interested in inflammation from varying backgrounds. The success of the third meeting followed previous meetings held in Cambridge and Verona respectively and continue a tradition which has now become well established. The meeting brought together physicians, scientists and those concerned with the production and use of anti-inflammatory drugs to a very stimulating conference to discuss basic issues affecting all aspects of side-effects of anti-inflammatory and analgesic drugs as well as their detection and treatment. The meeting was held in the Auditorium of Glaxo Italy and we are very grateful to that company for use of their facilities as well as to the University of Verona, Institute of Pharmacology, for valuable secretarial and administrative help. The success of the conference would not have been possible without valuable financial assistance of the companies listed separately (under Acknowledgements) as well as to the organizers of the 13th European Workshop on Inflammation who collaborated with us.

Portal hypertension is the most important complication of a great variety of both acute and chronic liver diseases. Nevertheless, hepatic cirrhosis is the most frequent cause of portal hypertension. Gastrointestinal bleeding due to rupture of oesophageal varices is, without doubt, the most severe complication of portal hypertension. At present, great advances are being made in the pathophysiology and in the development of new therapeutic tools for controlling and preventing this severe clinical event.

This book contains the papers presented and discussed during the Symposium on 'Portal Hypertension in the 21st Century', held in Montreal, Canada, in April 2004, and sponsored by Axcan Pharma Inc. and NicOx S.A. There are eight sections covering basic mechanisms, new drugs, prevention and current treatment of variceal bleeding, prevention of recurrent bleeding and hepatic hemodynamic monitoring.

An international faculty of authors have contributed chapters at an outstanding scientific level which will be vital reading for scientists and clinicians alike."

Recent advances in gastroenterology and hepatology as well as new findings in biliary and pancreatic diseases are presented in the proceedings of the 86th annual congress of the Japanese Society of Gastroenterology. From the hundreds of papers delivered at the congress, 70 were selected for inclusion here. Opening with special lectures on gastroenterology in the new millennium, ulcerative colitis-pathophysiology and therapy, and life style-related diseases and gastroenterology, the volume is divided into sections reflecting the major concerns of researchers in the science of digestive diseases in Japan today: apoptosis in digestive organs, nitric oxide, transcription factors in digestive organs, antigen-presenting cells, pathology of inflammatory bowel disease, NSAID-induced gastric lesions, microcirculation in digestive diseases, hepatic regeneration, and hepatic fibrosis.

Since the 1st Yamaguchi Symposium on Liver Diseases in 1989, this series of symposia has provided opportunities for exchanges of information on the topic between leading Japanese hepatologists and internationally renowned scientists. Somewhat unusually for meetings held in Japan, the official language of the symposium is English. The pro ceedings of these symposia are published under the title Frontiers in Hepatology and distributed worldwide. The 12th symposium was held on December 9 and 10,2000, at the ANA Hotel, Ube, Japan. The theme selected by the Organizing Committee was "Growth, Proliferation, and Apoptosis in Hepatocytes;' each of which is important in the understanding of the pathophysiology of intractable liver disease. Nine Japanese hepatologists were invited to give presentations, as was leading u.S. researcher Professor D.A. Brenner, recently elected editor-in-chief of the journal Gastroenterology. The reports given at the two-day meeting were valuable in furthering our under standing of the complicated signaling system involved in hepatocyte differentiation, proliferation, and apoptosis. Progress in this field is rapid, and another symposium on the same theme will be held in the near future. We believe that these proceedings are useful in summarizing current information on this important topic. The Organizing Committee would like to express special thanks to all participants and to the Viral Hepatitis Research Foundation of Japan for its continuing financial support."

Presenting patient- and problem-oriented review articles, this series is designed to keep the internist, general surgeon, and specialist in gastroenterology and hepatology abreast of the latest advances in the field.

According to a recent report from the Japanese Ministry of Health and Welfare, the mortality rate for hepatocellular carcinoma (HCC) is more than 30 per 100000 pop ulation. In addition, epidemiologists predictan increase in this figure by the year 2015, because of the rather high incidence of chronic liver diseases caused by HCY. The same situation has been observed in other Asian countries. It seems that HCC is likely to be an endemic disease, because of the higher preva lence of chronic hepatitis and liver cirrhosis caused by HBV, HCV, and/or aflatoxins in Asian and African countries. We also note that an interesting paper appeared in a recent issue of the New England Journal of Medicine describing the increase in younger HCC patients in the United States as compared with past decades. At present, silent hepatitis C infection is now smoldering in 4 million mostly unsuspecting Americans. Those carriers will be candidates for chronic liver disease, which is a pre disposing factor for the development of HCC. In Europe there are an estimated 5 million carriers. Accordingly, it is important to do all we can to reduce the prevalence of HCC not only in African and Asian countries, but also in the United States and Europe. With this perspective, last year the Japanese Society for Hepatology, in cooperation with the Ministry of Health and Welfare, initiated a national campaign to fight HCC."

This volume contains the papers presented at the International Symposium on "Cirrhosis, Hyperammonemia and Hepatic Encephalopathy," held in Valencia, Spain, De- cember 2nd_4th, 1996. Liver cirrhosis is one of the main causes of death in occidental countries. There are other hepatic dysfunctions such as fulminant hepatic failure, Reye's syndrome, or congenital deficiencies of urea cycle enzymes which can also lead to hepatic encephalopathy, coma and death. However, the molecular bases ofthe pathogenesis of hepatic encephalopathy remain unclear. One ofthe consequences of hepatic failure is the reduced ability to detoxify ammonia by incorporating it into urea. This leads to increased blood ammonia levels. Hyperam- monemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy and classical clinical treatments are directed towards reducing blood ammo- nia levels. Altered neurotransmission is an essential step in the pathogenesis of hepatic encephalopathy. The first part of the book is devoted to the discussion of the recent advances in the understanding of the alterations of different neurotransmitter systems in hepatic encephalopathy. The alterations of tryptophan metabolism and neurotransmission in hepatic encephalopathy and the implications for the clinical use of neuropsychoactive drugs are reviewed. The alterations in glutamate transport and neurotransmission in hepatic encephal- opathy due to acute liver failure are also reviewed. The role of NMDA receptors in the molecular mechanism of acute ammonia toxicity is discussed as well as its modulation by metabotropic glutamate receptors and muscarinic receptors.

Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin disease, and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. In addition, products of the biotechnology industry - monoclonal antibodies, cytokines, cytokine antagonists, and other products of genetic engineering that target key molecular pathways in disease pathogenesis - have either already made, or are on the verge of making an important impact on treatment. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. Gene therapy offers considerable promise for suppressing pathogenic processes in either transplantation or autoimmune disorders. The possibility of combining these important new advances to maximize benefit to the patient, and to minimize possible untoward effects (which are also given extensive coverage in this book), is one of the most exciting challenges of contemporary medicine. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area. Each chapter is contributed by one or more experts in the field. There was a need to bring this information together in a single volume, as much of the key recent developments have been dispersed throughout the biomedical literature, largely in specialized journals. Since, as in the past, important developments in immunosuppressive therapy in one branch of medicine (i.e. transplantation) are likely to benefit another (e.g., dermatology, rheumatology, gastroenterology), cross-disciplinary coverage of the mechanistic basis of the various therapeutic strategies in a single volume is likely to convey the potential of advances in therapy in the most coherent manner possible.

The aim of this Atlas is to present the three-dimensional arrangement of the liver structures, which should be familiar to those who diagnose and treat diseases of the liver, particularly in an era when the methods of diagnostic imaging and surgical treatment are becoming increasingly sophisticated. For this purpose a series of corrosive preparations of the blood vessels and bile ducts of the liver was made and photographed. In addition to the normal situations, many frequent and rare variations are shown. The Atlas also shows some blood vessels that have not been adequately described or are not well-known in the reference literature, but are nevertheless of great importance in performing segmental liver resections.This Atlas takes a fresh approach to the subject. The method used allows the size, three-dimensional arrangement and structure of the blood vessels and bile ducts of the liver to be preserved. The majority of photographs were taken from the direction from which surgeons see the liver during an operation. This, together with the schematic presentations complementing most of the photographs, gives a further instructional value to the work. With colour photographs and explanatory text, the Atlas forms a basic guide to orientation inside the liver parenchyma, to understanding and diagnosing certain pathological processes and to planning surgcial procedures.

Cellular therapy with liver stem cells and their progeny, including bone marrow cells, is a promising new approach that will contribute significantly to the treatment of liver diseases. The existence of the liver stem cell had long been debated, but it is now generally accepted that the liver contains cells with stem-like properties and that these cells can be activated to proliferate and differentiate into mature hepatocytes under certain conditions. There is also a substantial body of evidence to suggest that oval cells are involved in liver regeneration as they differentiate into hepatocytes and biliary cells. This book is a collection of work on stem cell and liver regeneration, initially delivered at the 14th Yamaguchi (Japan) Symposium on Liver Disease. Its nine chapters present the most recent data about basic and clinical research in hepatology in Japan and other countries, providing a valuable resource for researchers and practitioners alike.

International researchers summarize the current understanding of peptic disease and trace the development of a novel new drug for peptic disease therapy-sucralfate. Contributors present laboratory research along side data from clinical trials as well as from the practice of medicine. Articles discuss the history of sucralfate's development, mechanisms of action, clinical efficacy, and future directions for research. This volume will be of interest to scientists and clinicians working in gastroenterology and gastrointestinal physiology.

Needle biopsy of the liver is now an accepted procedure in most large hospitals, and surgeons and laparoscopists are more likely to biopsy the liver under direct vision than in the past. Consequently, increasing demands are being made on pathologists for rapid diagnosis. This full colour atlas provides a practical guide to the histopathological diagnosis of liver disorders, with particular emphasis on clinicopathological correlation and the need for the pathologist to be in full possession of all the available clinical information. Although containing over 350 colour illustrations, the book is more than just an atlas and each section includes a brief description of the main clinical and pathological features of the subject under discussion. For this second edition, many chapters have been rewritten - e.g. on viral hepatitis - and many new illustrations added. The book is intended for the practising and trainee pathologist and the clinician who performs liver biopsies, but will also be of value to postgraduates, residents and students in other branches of medicine.