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Notes: Gastro-oesophageal reflux disease is a common disorder and symptoms can be mild to severe. Management of the disease should be individualized. Life-style changes are important for all patients. Drug therapy is often necessary but only very few patients with severe disease need surgical treatment. The purpose of this article is to focus on drug therapy and to review the clinical trials of all the drugs used for gastro-oesophageal reflux disease. Thereafter, judged solely on the data derived from these trials, a practical approach to the management of gastro-oesophageal reflux disease is suggested.

Notes: It would be ideal to treat inflammatory bowel disease with topical corticosteroids that are either not absorbed through the mucosa, or have a substantial first-pass hepatic metabolism. The topical use of hydrocortisone, prednisolone-21-phosphate or betamethasone is often associated with systemic side-effects. Newer corticosteroid preparations (prednisolone metasulphobenzoate, tixocortol pivalate, fluticasone propionate, beclomethasone dipropionate and budesonide) are usually associated with minimal systemic corticosteroid activity. This article reviews the clinical activity and safety of these newer preparations.

Notes: Virtually all duodenal ulcers (DUs) and the vast majority of gastric ulcers (GUS) are the consequence of Helicobacter pylori-associated inflammation. In DUs, the inflammation is maximal in the antrum and is associated with gastric metaplasia in the bulb. Gastrin homeostasis is disturbed by H. pylori gastritis and there is robust acid secretion. Successful eradication of the infection cures the ulcer diathesis. Amalgamated figures for ulcer relapse per year in H. pylori-positive DUs are 〉 60% compared with 2.6% for H. pylori-negative DU patients. The corresponding figures for GU are 〉 50% for H. pylori-positive and 2.0% for H. pylori-negative individuals. This striking difference in relapse rate persists, as the re-infection rate in the developed world is 〈 1 % per year. Recurrent bleeding in bleeding-prone DUs is essentially abolished after cure of the infection.Proton pump inhibitors (PPIs) are increasingly used in eradication regimens. PPIs have intrinsic antimicrobial activity. MICs for lansoprazole (LAN) are lower than for omeprazole (OME). Two weeks of triple therapy (bismuth, tetracycline, imidazole) has, on average, a superior eradication efficacy (± 90%) compared with dual therapy (PPI, amoxycillin or clarithromycin) (± 80%). When a combination of PPI and two antibiotics has been used, results comparable to triple therapy have been reported. However, the side-effects profile and patient acceptability of PPI plus one or two antibiotic regimens are better than for traditional triple therapy. To date, published results with LAN-antibiotic combinations are limited, but may be expected to be comparable to those obtained with OME combinations.

Notes: Aim: To determine whether 4 days of quadruple therapy using bismuth, tetracycline and metronidazole combined with omeprazole is effective treatment for Helicobacter pylori infection. Methods. Non-ulcer dyspepsia, as well as chronic peptic ulcer patients with biopsy-proven H. pylori infection received 4 days of quadruple therapy. They were pre-treated with 3 days of omeprazole. At least 5–6 weeks later, endoscopy was repeated with 10 biopsies for urease test, histology and culture to establish cure of infection. Results: None of the 54 patients included was lost to follow-up but two had a 14C-urea breath test instead of endoscopy. Side-effects did not interfere with compliance. Forty-nine out of 54 patients (91 %; 95% Cl: 80–97 %) were cured. Metronidazole susceptibility data were available from 43 pre-treatment isolates. Of these 38/40 (95 %) with a metronidazole-sensitive strain, and one of three with a metronidazole-resistant strain were cured. Conclusions: Four days of quadruple therapy after omeprazole pre-treatment is a feasible, well tolerated, and effective treatment for N. pylori infection, especially in those carrying a metronidazole-sensitive strain. It seems that in quadruple therapy, cure rate and treatment duration have a non-linear relation. Our results need confirmation, but for patients suffering from side-effects with the 7-day regimen stopping treatment after 4 days is justified.

Notes: Aim: To perform a further Cox proportional hazards logistic regression analysis of data from two large-scale placebo-controlled trials with cisapride as maintenance treatment in reflux disease. Results: Analysis of each of the two databases, allowing the model to operate freely, led to the identification of a number of unexpected putative predictors of outcome in the 6 to 12 months following initial healing of oesophagitis with an H2-receptor antagonist or omeprazole. This allowed us to delineate more accurately the patient population that is likely to respond to long-term continuous treatment with low or standard dose cisapride.The analysis revealed that symptom severity may be more useful than endoscopic severity in predicting relapse or in guiding therapy. Reflux oesophagitis outcome is particularly poor in the presence of treatment-recalcitrant symptoms or severe mucosal damage.Analysis showed cisapride to be effective in the maintenance treatment of patients with non-refractory symptoms, irrespective of the initial severity of oesophagitis, the healing agent used, or a history of previous endoscopic relapses.

Notes: Healing the gastroduodenal mucosa through Helicobacter pylori eradication leads to a dramatic reduction in gastroduodenal ulcer relapse. Eradication of H. pylori proves to be difficult. Although the organism is sensitive to many antibiotics in vitro, the in vivo eradicating efficacy is often disappointing. This overview summarizes the most commonly used currently-available eradication schemes and the consequences of successful eradication in peptic ulcer disease.

Notes: There is an explosion of interest in the role of Campylobacter pylori as a cause of active chronic gastritis. This curved spiraled microorganism can readily be detected within the mucus gel covering the stomach mucosa, especially in patients suffering from peptic ulcer disease or non-ulcer dyspepsia. To what extent this intriguing microorganism is causally related to peptic ulcer disease remains to be elucidated, but all the evidence which is available so far supports a pathogenetically important role. There appears to be a striking discordance between in-vitro sensitivity and in-vivo efficacy of antibiotic therapy. At present, the combination of colloidal bismuth subcitrate and amoxycillin or tinidazole appears most effective in temporary elimination of these microorganisms.

Notes: Treatment of endosocopy-negative gastro-oesophageal reflux disease (s-GERD) should be directed towards rapid relief of symptoms and then maintenance of relief using minimum yet effective therapy. Responses to proton pump inhibitors are somewhat lower in s-GERD patients compared to GERD with overt erosive damage (e-GERD). The reasons for a lower response rate are not clear but may relate to the inclusion of patients who do not have reflux disease or patients with a lower oesophageal sensory threshold. Also poorly understood is the lower yield of complete heartburn relief when the number of associated dyspeptic symptoms is high. Some form of long-term therapy is needed in the majority of patients. ‘On demand’ proton pump inhibitor therapy to control reflux symptoms is a new and attractive option. Time to study discontinuation due to insufficient control of heartburn, or any other reason resulting in unwillingness to continue with on-demand therapy, is a pragmatic outcome that is well suited to definition of the efficacy of on-demand therapy. The goals of treatment of e-GERD should be to relieve symptoms and to heal lesions. Symptom severity and much less endoscopic abnormalities drives the therapeutic choices. When symptoms are mild or intermittent and when oesophagitis is of limited degree, standard dose proton pump inhibitor is usually instituted. Fewer and fewer clinicians would still opt for an H2-receptor antagonist. If there is moderate or severe oesophagitis or if symptoms are particularly troublesome, then the patient should start with standard-dose proton pump inhibitor therapy once a day, but not uncommonly a b.d. dosage maybe necessary. Once the dose of the acid suppressant that relieves symptoms is found, this dose should be maintained for a period of 3 months. After this time, an attempt should be made to reduce the dose. If symptoms recur, then the patients should go back to the full-dose proton pump inhibitor and a plan should be formulated for long-term treatment. The long-term treatment options vary between ongoing acid and suppressant therapy, with occasional attempts to reduce the dose, or to go for ‘on demand’ therapy and (rarely) includes consideration for surgery or endoscopic anti-reflux therapy.

Notes: Acute uncomplicated diarrhoea is commonly treated by self-medication. Guidelines for treatment exist, but are inconsistent, sometimes contradictory, and often owe more to dogma than evidence. An ad hoc multidisciplinary group has reviewed the literature to determine best practice.In general it is recognized that treatment of acute episodes relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. Self-medication in otherwise healthy adults is safe.Oral loperamide is the treatment of choice. Older anti-diarrhoeal drugs are also effective in the relief of symptoms but carry the risk of unwanted adverse effects. Oral rehydration solutions do not relieve diarrhoea, and confer no added benefit for adults who can maintain their fluid intake. Probiotic agents are, at present, limited in efficacy and availability. Antimicrobial drugs, available without prescription in some countries, are not generally appropriate for self-medication, except for travellers on the basis of medical advice prior to departure.Medical intervention is recommended for the management of acute diarrhoea in the frail, the elderly (〉 75 years), persons with concurrent chronic disease, and children. Medical intervention is also required when there is no abatement of the symptoms after 48 h, or when there is evidence of deterioration such as dehydration, abdominal distension, or the onset of dysentery (pyrexia 〉 38.5 °C and/or bloody stools).