The application of molecular techniques to gastroenterology continues to yield important advances in the development of drugs to treat gastrointestinal disorders. Important new drugs have emerged through the collaborative and complementary efforts of basic scientists, clinicians, and clinical researchers in academia and the pharmaceutical industry. The challenge has been exciting, with a few surprises along the way. Consider peptic ulcer disease as an example. The discovery of H receptors and the availability of potent and 2 selective H-receptor antagonists signaled the beginning of a new era 2 in the treatment of gastric hypersecretory states and peptic ulcers. Introduction of proton pump inhibitors offered another therapeutic option. Though H-receptor antagonists and proton pump inhibitors 2 are important and useful drugs, the discovery of the link between H. pylori infection and peptic ulcer disease has led to even more effective pharmacotherapeutic regimens. Our intent in Drug Development: Molecular Targets for GI Diseases is to bring together hands-on experts to review promising areas of gastrointestinal pharmacology. The contemporary topics covered, from a mechanistic viewpoint, are relevant to gastrointestinal inflammation and motility disorders. Authoritative opinions are offered on both future research directions and potential applications for new therapies.

Based on the 20th edition of Harrison’s Principles of Internal Medicine, this book is dedicated to the field of gastroenterology in all its scope. It caters to medical professionals at all levels. Not only can this be used by aspiring doctors to prepare for medical entrance examinations, but also by seasoned physicians to update knowledge long after it has been acquired. It is sign-posted with references and contains over 2,500 questions. A comprehensive and authentic question bank on gastroenterology. Designed for postgraduate and superspecialty medical entrance examinations. Based on the 20th edition of Harrison’s Principles of Internal Medicine. Contains 2,500+ multiple choice questions. Caters to medical professionals at all levels.

Although pancreatic cancer is one of the most serious forms of cancers, the outlook for patients could be improved. The lack of clinical symptoms of early, surgically removable disease most often limits curative treatment options. The aggressive tumor cell biology, leading to a locally advanced nature of the disease and to early metastases, allows curative resection in only 20% of patients at the time of diagnosis. Patients are therefore often faced with a dreadful prognosis from a state of almost full physical health. Furthermore, because there is a high recurrence rate after curative resection, treatment of this tumor entity becomes a great challenge.

This book gives insight into the current understanding of the management of pancreatic cancer and considers recent findings in cancer research. It provides answers to questions of how to know when cancer is respectable, how to proceed when the diagnosis comes too late for a curative approach, and how to assess different study results. Moreover, it highlights new upcoming therapeutic options and experimental approaches, which might further improve the future prospects for patients with pancreatic adenocarcinoma.

Alessandro Condivilla of Bologna first attempted a resection of the head of the pan creas in 1898, but several decades of further trial-and-error attempts ensued before the prototype procedure of pancreatoduodenectomy (PD) was established by Whipple in 1935. In the half-century following that landmark, refinements of surgical technique, including pancreatico-and bilio-entero anastomosis as well as develop ment of new technology to support perioperative management and patient care have contributed to the decrease in mortality and morbidity rates for obstructive jaundice and pancreatic fistula. The improvement in mortality and morbidity rates associated with PD has led to an increase in the number of patients undergoing the procedure and in the number of institutions performing it. Indications for PD have also been expanded. In the early years after PD was established as a viable procedure, periampullary carcinoma was the most common indication; now PD is indicated for a number of benign and malignant diseases. Some surgeons believe that PD is the procedure of choice for certain types of chronic pancreatitis, pancreatico-biliary maljunction, and pancreatic and duodenal trauma. Other surgeons have reported the necessity of PD for lymph node dissection of gallbladder carcinoma. Consequently, the basic procedure has been greatly modi fied to accommodate the specific conditions of each disease. For patients with malig nancy, extended procedures have been developed to improve the curative resection rate and ensure complete lymph node dissection.

This book is the proceedings of the Falk Symposium No. 127 on Autoimmune Diseases in Paediatric Gastroenterology' (IV International Falk Symposium on Paediatric Gastroenterology), held in Basel, Switzerland, on November 8-9, 2001. The symposium focused on the role of the immune system, both the acquired and the innate systems, in inflammatory bowel disease (IBD) in children and adolescents. The innate system has an important fundamental role in host defence by initiating immune responses against potentially deleterious matter. However, a mutation within the innate system may elicit an immune response against the host: hence, an autoimmune response.

Chronic autoimmune hepatitis occurs predominantly in young people, and especially in women. Immunological changes are conspicuous. Tissue antibodies are found in a large number of patients. This is a disease of disordered immunoregulation marked by a deficit in suppressor T cells causing the production of autoantibodies against specific hepatocyte surface antigen. Liver membrane protein is found in the sera of patients with autoimmune chronic acute hepatitis and with primary biliary cirrhosis (PBC). The latter condition of progressive granulomatous destruction of intrahepatic bile ducts is, in many respects, analogous to the graft-versus-host syndrome where the immune system has become sensitized to foreign HLA-molecules.

Primary sclerosing cholangitis (PSC) is another condition of unknown origin. All parts of the biliary tree can be involved in a chronic, fibrosing, inflammatory process that results in obliteration of the biliary tree and ultimately in biliary cirrhosis. About half of the patients also suffer from ulcerative colitis and rarely from Crohn's disease. Circulating antibodies to some antigens are found in obstructed portal tracts, as well as increased concentrations of biliary immune complexes in patients with PBC.
In all three previous Falk symposia on paediatric gastroenterology, attention was focused on the role of the innate immune system in the aetiology of IBD. It has become increasingly clear in recent years that the innate system has a much more important and fundamental role in host defence. The decision to initiate an immune response is one of the major roles of the innate system. Mutations within this system could transform it into becoming constitutively active, resulting in an inflammatory reaction and thus eliciting an autoimmune response.

Following an introduction to the basic phenomena of autoimmunity, the proceedings discuss clinical aspects of autoimmune diseases. In particular, current knowledge and the state of the art about the diagnosis and treatment of the autoimmune diseases of the gastrointestinal tract are described by world-renowned experts. The book also contains the short presentations on selected topics, as well as abstracts of the mini-posters read by title, which were included in the symposium.

Gastroparesis is an increasingly recognized disorder. Treatment can be difficult due to the several mechanisms for symptom production. Gastroparesis: Pathophysiology, Presentation and Treatment serves as a concise reference on this disorder that allows clinicians to quickly access and evaluate the necessary information for treating and managing patients with gastroparesis. Each chapter is written byexperts in their respective area. The volume will enable the reader to better understand all aspects of this disorder. The book presents current concepts in a variety of areas opening with the epidemiology, clinical presentation and pathophysiology of gastroparesis. The natural history of patients is explored as well as evaluation of patients with suspected gastroparesis. This section includes chapters on Wireless Capsule Motility, Electrogastrography and Antroduodenal Manometry. This important resource concludes with a full section on treatment including dietary, prokinetic, antiemetic, sensory, electric stimulation, and surgical methods. New developments include the use of gastric electric stimulation for treatment, the use of SmartPill for diagnosis, and a number of new agents in development for this disorder. Gastroparesis: Pathophysiology, Presentation and Treatment is the ideal reference for gastroenterologists, and also for surgeons, endocrinologists, primary care physicians and nutritionists looking to keep pace with the latest information treatment options for their patients. "

There is currently an explosive growth of basic and clinical research in inflammatory bowel diseases. The extensive interest of the medical community in these diseases is largely explained by the devastating impact the illnesses have on the quality of life, their high prevalence in the community, and the fact that so many medical disciplines are involved in tackling the immensely complex studies on pathogenesis, clinical expression and treatment possibilities. The Falk Symposium No. 85 held in The Hague, the Netherlands, 29 June-1 July 1995 brought together over 80 speakers and 1000 participants from all over the world. Plenary sessions and workshops allowed the discussion of basic and clinical research, enabling appropriate choices to be made. Topics reflected areas of high current basic research interest, clinical importance, and actual or future treatment potential. Audience: An important work for all disciplines involved in research and therapy of inflammatory bowel diseases.

Neural Mechanisms of ingestive behaviour has long been one of the most intensively investigaged areas within neuroscience. Drug studies have been introduced to develop anti-obesity compounds and, more recently, to identify nerotransmitters which might be involved in the control of ingestive behaviour.
The current focus within this field is towards neurotransmitter receptors as it has become known that there are multiple receptor subtypes for each identified neurotransmitter.
The study of drug receptor subtypes and ingestive behaviour is growing very rapidly, and has become quite complex. This unique volume is designed to guide students and investigators through a number of different neurotransmitter systems and provide them with the latest information on the identities of receptor subtypes most relevant in the study of ingestive behaviour. As such, it will prove enormously useful to all engaged in studies on appetite and obesity treatment.
*
* Provides up-to-the-minute reviews of the most exciting new developments in the study of ingestive behavior.
* Includes contributions from leading experts in the field.
* Tackles the complex issues of relating neurochemical transmission to the neural and behavioral controls of feeding.
* The first book of its kind to deal explicitly with drug receptor subtypes in relation to ingestive behavior.

La salud y la enfermedad son parte de la vida, y la enfermedad es una entidad opuesta a la salud. Los sintomas son el aviso del cuerpo que algo no esta bien. El dolor es el principal sintoma que lleva al individuo a solicitar atencion medica. Todas estas enfermedades estan relacionadas con habitos alimenticios. Una de las base de una buena salud es una buena alimentacion. El cancer no se contagia ni se hereda, se hereda las costumbres alimenticias. El des balance en el cuerpo son las que causan enfermedades, el extremo de este des balance produce un cuerpo acido tambien, como es posible que una persona de 55 a 60 anos muera por causa natural y otra persona de 90 a 95 anos muera de causa natural tambien. La explicacion cientifica es que el paciente muere de una acidosis, su cuerpo esta completamente acido. Y esto esta relacionado con los alimentos que se consume.

This book, the proceedings of Falk Symposium No. 125 on 'Cytokines in Liver Injury and Repair' (Progress in Gastroenterology and Hepatology Part II), held in Hannover, Germany, on September 30 - October 1, 2001, provides an update of our current knowledge on the role of cytokines in various human and experimental liver diseases and on their present and prospective use in therapeutic trials.

Developments in recent years include: Since the first report of a cytokine knockout mouse for IL-2 in 1991 a large number of cytokine and cytokine receptor genes have been inactivated in mouse germlines and the corresponding mutant mice have provided a wealth of novel information. In addition, targeted-gene disruption techniques (e.g. cre-loxP) and liver-specific overexpression of certain cytokines have provided clues for the understanding of their role in the pathophysiology of liver diseases.

The number of well-characterized cytokines, chemokines, and growth factors is ever growing and it becomes increasingly evident that they are effective in a complex network of positive and negative signals. A disruption of this homeostatic balance is a direct cause of disease, determines its complications, and is related to its progression, e.g. in inflammation and fibrogenesis.

Signaling pathways from receptors to target genes have been dissected and now we are beginning to recognize highly complicated cross-talks between various signal transduction pathways and interferences with non-cytokine mediators such as reactive oxygen metabolites (ROS), lipid mediators, physical factors, and others leading to an almost incomprehensible vastness of agonistic and antagonistic signals.

Today, we understand in greater detail the extracellular control mechanisms of cytokine and growth factor bioavailability and its importance for pathophysiological mechanisms. During these processes the secretion of (latent) proforms of cytokines, their extracellular or transmembraneous immobilization and sustained proteolytic activation and their release into the immediate environment of cells play major roles and the possibility of autocrine, paracrine, juxtacrine, and endocrine signal transfer.

Finally, experimental and beginning clinical uses of proteins or gene transfer technologies for cytokine antagonism, scavenging, receptor blockade, and inhibition of signal cascades in therapeutic trials offer hopeful perspectives in the treatment of malign and benign liver diseases. Gene-therapeutic application of molecular-engineered 'designer cytokines', e.g. of hyper-IL-6, promises clinical benefit for the treatment of fulminant hepatic failure.

The book contains chapters by most well-known experts in the field who have contributed significantly to our present knowledge on cytokines in liver injury and repair.

Falk Symposium No. 82, held in Halle, Germany, November 1994, focuses on the advances made in understanding the aetiology and pathogenesis of inflammatory bowel disease (IBD). Sections of this book, the Proceedings of the conference, are devoted to extraintestinal manifestations, cancer development, IBD in the context of pregnancy, and the assessment of disease activity, prognosis and quality of life. The second half of the book is devoted to the discussion of standards and new developments in diagnosis, conservative management and surgery. Audience: All clinicians and basic scientists working in the field of IBD.

Despite recent advances, the pathogenesis and therapy of various forms of chronic inflammatory diseases of the gastrointestinal tract remains problematical. Especially threatening is the possible complication of the development of a malignant growth, but the role of the chronic inflammatory process in this is not known. Three examples are: H. pylori-induced gastritis is associated with gastric lymphomas and carcinomas; there is an increased incidence of intestinal T-cell lymphomas in tropical sprue; and chronic inflammatory bowel diseases, particularly ulcerative colitis, are associated with an increased incidence of carcinoma. In this book, the Proceedings of Falk Symposium No. 81, held in Berlin, November 3-5, 1994, an extensive exchange of information and opinions between international experts yields a state-of-the-art consensus on practical procedures in diagnostics, prophylaxis and therapy.

Helicobacter pylori is an important human pathogen that infects up to 50% of the human population. As the leading cause of peptic ulcers, gastritis, and gastric cancer worldwide, the organism has been the subject of intensive research to unravel the mysteries of its genetics and cellular biology. In fact, the number of publications in this field has risen dramatically in recent years making it extremely difficult for even the most diligent reader to stay abreast of progress. This book distills the most important cutting-edge findings in the field to produce a timely and comprehensive review. With contributions from leading international helicobacter researchers, topics include: lipopolysaccharides, outer membrane proteins, motility and chemotaxis, type IV secretions systems, metal metabolism, molecular mechanisms of host adaptation, genomotyping, and proteonomics. As a useful introduction to the subject for new researchers and as an invaluable reference for the experienced researcher, this book is essential reading for all researchers working with Helicobacter and related organisms.

Diseases of the gastrointestinal tract are common. There is increasing appreciation of the importance of the immune system in the pathogenesis of a number of these diseases. This book covers basic aspects of innate and adaptive immunity in the gastrointestinal tract, oral tolerance, and cellular and molecular mechanisms of acute and chronic inflammation. Specific disease covered include bacterial infections, human immunodeficiency virus (HIV) infection, coeliac disease, and inflammatory bowel disease. Other topics include mucosal immunisation and intestinal transplantation immunology. The readership of this book includes clinicians, scientists, and students interested in the gastrointestinal tract.

Basic research discusses the implication of pancreatic stress protein in acute pancreatitis and pancreatic cancer and their possible role as therapeutic targets. Also, very original results show the unexpected role of lipids as mediators during acute pancreatitis. Gene screening strategies allow the detection of the genes responsbile for gemcitabine resistance of pancreatic cancer cells. They lead to the selection of several target genes, in order to suppress the resistance of cells to gemcitabine treatment. The mechanism by which tetrahydrocannabinol is anti-tumoral in pancreatic cancer cells is presented and the use of THC as a promising new therapeutic agent is discussed.

Genetic data are shown concerning hundreds of families with hereditary chronic pancreatitis and their possible role in the pathogenesis of the disease. Another very original study addresses the prevention and treatment of pancreatic diseases with diat.

In clinical research, convincing data about the use of endoscopic sphicterotomy in the management of acute bilary pancreatitis is presented, based on the experience of a Center highly specialized in pancreatic diseases.

The aetiology of the chronic inflammatory bowel diseases - Crohn's disease and ulcerative colitis - is still enigmatic. The therapeutic approach has therefore traditionally focused on anti-inflammatory principles, including corticosteroids and aminosalicylates. Since a significant proportion of patients is steroid-dependent or refractory and because of the problematic side-effects of long-term systemic steroids, active immunosuppression has gained acceptance in the field. The classical immunosuppressants azathioprine and 6-mercaptopurine have long been evidence-based in IBD, but underused. Recently, methotrexate and cyclosporine have also been proven to be effective in certain situations. Newer drugs like tacrolimus, mycophenolate and others may be similarly useful but their potential is still unclear. Finally, the immune modifiers including IL-10 and TNF-antibodies have been successfully subjected to controlled trials. Other experimental drugs discussed in this book are on the horizon. This volume is the Proceedings of Falk Symposium 119 held in Freiburg-im-Breisgau, Germany, October 3-4, 2000, and covers systematically the field of immunosuppression in inflammatory bowel diseases. It is hoped that it will further the prudent use of these drugs in the proper clinical situations by increasing our understanding of both the mechanisms of action and the clinical benefit to the patient.

Beginning in 1970, the International Bile Acid Meeting has taken place every two years and each time new progress in our understanding of the complex role of bile acids in many metabolic processes of the liver and the intestine has been revealed by a selected group of leading scientists from all over the world. Although originally mainly physiological data on bile acid synthesis and transport were emphasized, and later on also the therapeutic benefit of bile acids in gallstone disease and cholestasis was discovered, we have come now to the molecular biology and genetic era with major discoveries in transport defects and related diseases. This book is the proceedings of Falk Symposium No. 120, held in The Hague, The Netherlands, on October 12-13, 2000 - the 16th International Bile Acid Meeting. One of the main discoveries recently has been the identification of nuclear receptors for bile acids, which gives them a much broader perspective than previously anticipated. It even suggests that bile acids can regulate their biosynthesis and enterohepatic circulation transcriptionally. It will therefore not be surprising that this topic, together with the molecular regulation of cholesterol 7alpha-hydroxylase and cholesterol homeostasis, has a dominant place in these proceedings. Another important topic is the progress in our molecular understanding of hepatic (both at the basolateral and canalicular sites), cholangiocytic and intestinal bile acid transport processes. Further insights into genetic defects causing cholestasis or intestinal malabsorption in animal models and in human diseases are also discussed by a number of well-known authors. Finally the last section deals with new findings on the role of bile acid therapy in cholestatic syndromes or chemoprevention and with the potential benefit of bile acid inhibitors. All contributors provide an update on the most recent developments in their field.

The pancreas is about the size and shape of the hand; the tail points to the spleen, and the head is nestled in a loop of the duodenum. Loss of the exocrine (digestive) func tions commonly leads to severe gastrointestinal disturbances, malabsorption, a cata bolic state, and weight loss in the face of an adequate diet. Loss of endocrine pancreatic function leads to a large spectrum of disorders associated with the loss of hormone secretions; the most common and most severe is diabetes mellitus. Loss of the entire pancreas owing to trauma, surgery, atherosclerosis, or other medical problems leaves the patient in a digestive and metabolic crisis. The correct diagnosis of pancreatic disorders remains a challenge given the multi faceted function of the pancreas. The clinical laboratory plays an important role, and other tools such as CAT scans, ultrasound, radiographs, biopsies, and even surgery are used to make a diagnosis. The emphasis of Clinical Pathology of Pancreatic Disorders is on the clinical laboratory definition of pancreatic pathology. Disorders of the endocrine pancreas can be highly complex, and sophisticated tests are needed to determine the nature of the disease, its prognosis, and its optimal treat ment. Diabetes is the most common of the endocrine diseases; it presents in many ways, and has varied etiologies. We now know that the diabetes of childhood is usually an autoimmune disease, and this has a major effect on the treatment of these individuals."

This book contains the proceedings of the XIIIth International Bile Acid Meeting (Falk Symposium 80), an official satellite meeting of the World Congress of Gastroenterology, held in San Diego, California, U.S.A., September 30--October 2, 1994. It begins with presentations of major advances in bile acid chemistry, biology and pharmacology. The new structure proposed for the mixed micelles present in bile is reviewed, as are the properties of new synthetic analogues of bile acids. The mechanisms by which bile acids interact with cell membranes are discussed in order to provide insight into the hepatotoxic effects of bile acids in cholestatic liver disease. The book further shows the exciting progress in the molecular biology of bile acid transport by the hepatocyte and enterocyte, and concludes with a consensus on the use of ursodeoxycholic acid in cholestatic liver disease and as an adjunct to immunosuppressive therapy after liver transplantation, and to interferon therapy in chronic viral hepatitis.

The Second International Symposium on Inflammatory Bowel Diseases was held in Jerusalem from September 8-11, 1985, under the auspices of the Israel Academy of Sciences, the Israel Gastroenterological Society and the Hebrew University-Hadassah Medical School. Five hundred physicians and researchers from 26 countries attended. The symposium was organized into six panels devoted to state of the art reviews and presentations of the latest findings and approaches on etiology, pathogenesis, medical and surgical management of IBD and clini cal assessment of disease. In addition, 89 abstracts were presented as posters during the symposium, all of which were published in the book of abstracts. The concluding panel outlined new directions for future re search on IBD. The organizing committee gratefully acknowledges all the contributors who presented their work in a clear and concise manner, and to all the participants whose active role in the discussions contributed to the suc cess of the meeting. In view of the great interest in the symposium and the tradition es tablished following the first, in 1981, it was decided to convene a third international symposium on IBD in Jerusalem in September 1989."

Hardly any other part of the human body is of such interdisciplinary interest as the anal, perianal and rectal region. Gastroenterologists, dermatologists, urologists, general practitioners and surgeons specialising in proctology, phlebology, and coloproctological surgery are involved in this region between the ectoderm, transitional zone, and entoderm. Diagnostic procedures, such as endoscopy, radiology, sonography, manometry, electromyography, and histopathology are even more diverse, in particular where the differential diagnosis of non-neoplastic conditions of the anorectal region is concerned. The Falk Symposium No. 118, held in Freiburg, Germany, on October 1-2, 2000, focused on the morphology and function of the pelvic floor and its dysfunction, radiation damage in proctology, haemorrhoidal complaints, and chronic inflammatory rectal diseases, as well as conditions of the anal and perianal region. These proceedings will be of interest to all research physicians and colleagues working in hospitals or in their own practice who are involved in the diagnosis and treatment of anorectal pathologies.