Patients with suspected portal hypertension must first be evaluated by physical examination, upper digestive endoscopy and ultrasonography with Doppler. Moreover, the evaluation of patients with portal hypertension depends on the cause of portal hypertension, the presence of complications and the specific treatment considered. Haemodynamic assessment with measurement of the hepatic venous pressure gradient is useful in confirming the origin of portal hypertension. This technique is the 'gold-standard' for evaluating haemodynamic treatments. Splanchnic and systemic circulation must also be measured. Quantitative evaluation of the splanchnic territory by Doppler sonography and other non-invasive investigations, may be performed. Further clinical studies are, however, needed to determine their interest in portal hypertension.

Portal hypertension is a common clinical syndrome associated with chronic liver diseases and is characterized by a pathological increase in portal pressure. Increase in portal pressure is because of an increase in vascular resistance and an elevated portal blood flow. The site of increased intrahepatic resistance is variable and is dependent on the disease process. The site of obstruction may be: pre-hepatic, hepatic, and/or post-hepatic. In addition, part of the increased intrahepatic resistance is because of increased vascular tone. Another important factor contributing to increased portal pressure is elevated blood flow. Peripheral vasodilatation initiates the classical profile of decreased systemic resistance, expanded plasma volume, elevated splanchnic blood flow and elevated cardiac index. The elevated portal pressure leads to formation of portosystemic collaterals and oesophageal varices. Pharmacotherapy for portal hypertension is aimed at reducing both intrahepatic vascular tone and elevated splanchnic blood flow.

Esophagitis healing proportions are often incorrectly called the healing rate. The aim of this study was to compare different drug classes by expressing the speed of healing and symptom relief through a new approach.

Over the last decade, the role of visceral sensitivity has been largely recognized in the pathophysiology of functional digestive disorders, particularly in the irritable bowel syndrome. These studies have highlighted the role of afferent pathways arising from the gut as a possible target for new treatments intended to relieve pain or modify altered reflexes present in such patients. These pharmacological targets have been identified mainly by studies on animal models of visceral hyperalgesia of various origins including local inflammation. Locally, several mediators are of paramount importance for sensitization of nerve endings: 5-hydroxytryptamine, bradykinin, tachykinins, calcitonin gene-related peptide, and neurotrophins. Selective antagonists to various subtypes of their receptors are currently available and have been shown to be active in these animal models. Other substances, such as somatostatin, opiold peptides, cholecystokinin, oxytocin, and adenosine, modulate the transmission of nociceptive inputs from the gut to the brain and are of clinical interest. This article reviews the current understanding of these mediators. Although these agents seem to be promising tools for the treatment of visceral hyperalgesia and its consequences (abdominal pain and disturbed reflexes), their clinical efficacy remains to be shown. A better understanding of the nature and the location of the defect in the sensory pathways may permit the selection of subgroups of patients for treatment according to the pharmacological properties of these new therapeutic agents.

In nonhuman mammals, lactase activity declines during or after weaning. In contrast, about one half of the human species maintains high lactase activity even in adulthood. To clarify this difference, this study examined some parameters for which contrasting observations have been reported in connection with lactase decline.

Most macrophages in the normal intestinal mucosa have a mature phenotype. In inflammatory bowel disease (IBD), a monocyte-like subset (CD14+ L1+) accumulates. The aim of this study was to characterize its potential with regard to cytokines.

Ileal pouch-anal anastomosis (IPAA) has become the operation of choice following proctocolectomy for ulcerative colitis (UC) and familial adenomatous polyposis. Functioning ileal pouch mucosa undergoes histological changes resembling the colon (colonic metaplasia). The possible role of stasis and luminal factors--bile acids, short-chain fatty acids and bacteria--are discussed. It seems likely that colonic metaplasia is an adaptive response to the new luminal environment in IPAA. Inflammation in the ileal reservoir ('pouchitis') is the most significant late complication in IPAA. It occurs in 20-30% of patients and is virtually confined to those with prior UC. The clinical picture in pouchitis is highly variable; however, it can be easily categorized into three groups. Nevertheless, in most cases it is likely to represent recurrent UC in the ileal pouch. Current treatments and possible preventative strategies for pouchitis have been outlined.

The role of diet in the aetiology and pathogenesis of ulcerative colitis (UC) remains uncertain. Impaired utilization by colonocytes of butyrate, a product of bacterial fermentation of dietary carbohydrates escaping digestion, may be important. Sulphur-fermenting bacteria may be involved in this impaired utilization. Oxidative stress probably mediates tissue injury but is probably not of causative importance. Patients with UC are prone to malnutrition and its detrimental effects. However, there is no role for total parenteral nutrition and bowel rest as primary therapy for UC. The maintenance of adequate nutrition is very important, particularly in the peri-operative patient. In the absence of massive bleeding, perforation, toxic megacolon or obstruction, enteral rather than parenteral nutrition should be the mode of choice. Nutrients may be beneficial as adjuvant therapy. Butyrate enemas have improved patients with otherwise recalcitrant distal colitis in small studies. Non-cellulose fibre supplements are of benefit in rats with experimental colitis. Eicosapentaenoic acid in fish oil has a steroid-sparing effect which, although modest, is important, particularly in terms of reducing the risk of osteoporosis, but it seems to have no role in the patient with inactive disease. gamma-Linolenic acid and anti-oxidants also are showing promise. Nutrients may also modify the increased risk of colorectal carcinoma. Oxidative stress can damage tissue DNA but there are no data published at present on possible protection from oral anti-oxidants. Butyrate protects against experimental carcinogenesis in rats with experimental colitis. Folate supplementation is weakly associated with decreased incidence of cancer in UC patients when assessed retrospectively. Vigilance should be maintained for increased micronutrient requirements and supplements given as appropriate. Calcium and low-dose vitamin D should be given to patients on long-term steroids and folate to those on sulphasalazine.

Prompt diagnosis and exclusion of infection requires a minimum of rigid sigmoidoscopy, rectal mucosal biopsy and stool culture. Admission to hospital is mandatory for patients with features of severe disease, or who are in their first attack of ulcerative colitis and have bloody diarrhoea, even if the criteria for severe disease are not met. Once admitted, the patient should be monitored by plain abdominal X-ray, full blood count, serum albumin and C reactive protein on alternate days; temperature and pulse rate should be recorded four times per day. Treatment should be instituted as soon as the diagnosis is made with an intravenous corticosteroid (hydrocortisone 100 mg intravenously, four times daily, or equivalent). Antibiotics may be included if infection cannot be confidently excluded. Free diet can be allowed but attention should be given to nutritional, fluid and electrolyte status with intravenous replacement if necessary. Any evidence of colonic dilatation occurring despite maximal therapy should be regarded as an absolute indication for colectomy. The patient should be kept fully informed from an early stage about the likely natural history of the condition and about the possible therapeutic options including surgery. Cyclosporin therapy should be reserved for patients who have a poor response to the first 3-4 days of corticosteroid therapy, particularly those with serum C reactive protein > 45 mg/l and who do not yet have absolute indications for colectomy. Most patients who have not convincingly responded within 10 days of starting full medical therapy should undergo colectomy, although partial responders who are afebrile may reasonably continue for up to 14 days before a final decision. Approximately 30-40% of patients with severe colitis will need colectomy within the first 6 months. With optimal management, mortality should be zero, but better medical therapies are urgently needed to reduce the colectomy rate.

For many years, corticosteroids have been the mainstay for treating acute ulcerative colitis. In patients with refractory disease, immunosuppressive therapy may be indicated, including azathioprine or its metabolite 6-mercaptopurine, cyclosporin and possibly methotrexate. Their benefits in ulcerative colitis must be weighed up against their possible adverse effects, the availability of surgical cure for this condition, and the long-term risk of carcinoma complicating colitis that applies in patients with chronic extensive disease. Information about the safety of corticosteroids and immunosuppressive agents has accumulated as a result of their extensive use in inflammatory bowel disease, organ transplantation and various other disorders.

Topical therapy can be considered the standard treatment for distal ulcerative colitis. The group of drugs of first choice are the aminosalicylates which are effective in inducing remission in acute disease as well as in preventing relapse. Corticosteroids appear to be slightly less effective and have no proven benefit in maintenance therapy. With new topical steroids, such as budesonide, systemic effects can be minimized. The major role of corticosteroids is to complement aminosalicylates, when necessary. The new topical compounds appear to be especially valuable when there is a long-term requirement for corticosteroids. With the vast majority of patients obtaining remission with standard treatment, it is difficult to make the case for alternative substances. Short-chain fatty acids, local anaesthetics and bismuth compounds seem to be the most promising innovations in topical therapy although their equivalence or even superiority to mesalazine has not been established.

About one-half of patients with ulcerative colitis develop abnormal liver function tests at some time during the course of the illness. This should prompt an investigation for primary sclerosing cholangitis and other common hepatobiliary diseases. Primary sclerosing cholangitis occurs in 2-10% of patients with ulcerative colitis. The diagnosis of primary sclerosing cholangitis is most often made by endoscopic retrograde cholangiography. Liver histopathology is often inconclusive but magnetic resonance cholangiography shows promise as a useful non-invasive diagnostic tool. Cholangiocarcinoma complicates 20-40% of patients with end-stage primary sclerosing cholangitis and is now one of the most common causes of death in patients with ulcerative colitis. Distinction between benign and malignant strictures can be difficult and is best done with a combination of clinical suspicion, repeated imaging for mass lesions, cholangiography, and endoscopic brushings and/or biopsies. Dominant lesions of the common bile duct or common hepatic duct produce progressive jaundice and liver damage. Early treatment may improve prognosis. Single strictures can be dilated endoscopically. If the stricture is more complicated and extends into the intrahepatic ducts or there is suspicion of cholangiocarcinoma, surgical resection may be more appropriate. Liver transplantation should be considered in end-stage disease.

The place of colonoscopy in the management of ulcerative colitis is restricted to clinical situations where the information provided will change clinical management. The information provided will be answers to the questions?inflammatory bowel disease, o r, in the patient with known colitis: inflammatory bowel disease?type?activity extent?dysplasia. Biopsy is pivotal to the diagnosis and provides the certainty of tissue diagnosis, assessment of activity and detection of dysplasia. Sigmoidoscopy is sufficient for providing information for clinical management in most circumstances, but colonoscopy is important where clinical features are disproportionate to sigmoidoscopic findings and systemic parameters of inflammatory activity; to determine type and extent of inflammatory bowel disease and when surveillance needs to start; and for biopsy to detect dysplasia. Ileoscopy is an important aspect of colonoscopy for differential diagnosis, and is the unique definer of total colonoscopy.

The majority of patients with ulcerative colitis (UC) will run a typical chronic, relapsing course. The proportion with chronic, continuous symptoms diminishes with time. The greatest impact of the disease is in the first few years after diagnosis, especially in patients with extensive or severe colitis. After this time, the likelihood of requiring surgery declines rapidly, and survival is no different from that of the general population. The long-term course can be best predicted by the course in the preceding period. Most patients are able to lead an essentially normal lifestyle, at work and at home, with either medical or surgical treatment. Awareness of how the patient feels the disease affects his or her life is important. Educating the patient about their illness will also help in management.

Ulcerative colitis is an inflammatory disease of the large intestine of unknown aetiology. The nature of the inflammatory infiltrate together with the response to corticosteroids suggests that an abnormal immune response is at work. The key question of whether the immune system is responding to an abnormal breach in the mucosa due to another primary abnormality or whether the primary defect lies within the immune response itself has not been answered. Thus far, it is clear that both T and B cell compartments are involved in the persistence of inflammation but the initial interactions that take place in the mucosa in terms of antigen processing and presentation have not been adequately investigated. Those critical steps and potential defects that push T cells and B cells into a heightened state of activation need to be identified.

There is now considerable evidence that abnormalities of the structure and function of the colonic epithelium are present in patients with ulcerative colitis and that many of these may occur independently of mucosal inflammation. It is proposed that epithelial abnormalities are the central defect that underlie the development of mucosal inflammation and its chronicity. A simple model for pathogenesis is proposed in which inflammation develops only when epithelial barrier function is impaired to an extent which permits the influx of luminal pro-inflammatory molecules to the lamina propria. Several candidate hypotheses regarding the molecular basis for the abnormality are addressed. The mechanism by which the barrier function is critically impaired involves the interaction of the abnormal epithelium with luminal, mucosal and systemic factors. Focusing on the epithelium would potentially lead to a conceptually different management approach and the development of novel therapeutic strategies.

A number of lines of evidence support the hypothesis that ulcerative colitis is an inherited disorder in a proportion of cases. First, there is a pattern of familial aggregation. Second, there are differences in the prevalence of the disease in different ethnic groups. Finally, the concordance rate in monozygotic twin pairs is higher than that of dizygotic twin pairs, although not as high as the concordance rates observed in Crohn's disease. Genetic models of the inheritance patterns suggest that ulcerative colitis is probably caused by one major gene, although that gene (or genes) remains to be identified. While at least one localization for susceptibility to Crohn's disease now seems certain, efforts to localize and characterize the susceptibility genes involved in the inheritance of ulcerative colitis are still underway. While the genes of the major histocompatibility complex have been imputed as causal in susceptibility to ulcerative colitis, a consensus of proof continues to elude us.