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Notes: GERD prevalence continues to rise in contrast to peptic ulcer disease. The spectrum contains reflux esophagitis and so-called `endoscopy-negative GERD' or `non-erosive GERD' (NERD) or S-GERD and patients with `normal' overall 24-h esophageal acidification but with a high `symptom-index'.The majority of reflux patients will not need endoscopy initially. Prompt referral for endoscopy is indicated only if the patient has atypical symptoms or alarm symptoms such as dysphagia, anemia, weight loss, severe abdominal pain, or pain that does not respond to acid neutralization or suppression, or develops symptoms after the age of 50 years. Antireflux therapy consist of raising the head of the bed, maintaining normal weight, and avoidance of foods and drugs that precipitate symptoms, together with antacids or over-the-counter H2 receptor antagonists (H2RAs). If symptoms persist after these simple measures or if antacids or H2RAs are needed quite often, then a more formal first-line treatment should be started. Many experts feel that a stepdown approach instead of a stepup approach is clinically and economically a more appropriate way of installing such first-line therapy. Physicians increasingly consider prescribing a (low- or standard dose) once-a-day proton pump inhibitor (PPI) as firstline therapy. If symptoms recur after 4-week trial or are in sufficiently relieved, then the patient should be referred for endoscopy. Endoscopy may reveal no abnormalities (NERD) or evidence of reflux-induced damage.Treatment of endoscopy-negative reflux disease should be directed towards rapid relief of symptoms and then maintenance of relief using minimum effective therapy. Responses to PPIs are somewhat lower in endoscopy-negative patients compared to esophagitis. Some form of long-term therapy is needed in the majority of patients. `On demand' PPI therapy to control reflux symptoms is a new and attractive option.The goal of treatment of GERD should be to relieve symptoms and to heal lesions. Symptom severity and much less endoscopic abnormalities, drives the therapy. When symptoms are mild or intermittent and when esophagitis is absent or minimal, standard dose PPI is usually reinstituted. If there is moderate or severe esophagitis or if symptoms are particularly troublesome, then the patient should start again with standard-dose PPI therapy once a day, but not uncommonly a b.i.d. dosage maybe necessary. Once a 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. A plan should be formulated for long-term treatment.

Notes: The high mortality rate in patients with upper gastrointestinal bleeding appears to be particularly related to re-bleeding. The haemostatic mechanisms that may influence the re-bleeding of ulcers are largely unknown.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:We studied and analysed fibrinolytic activity in bleeding ulcer patients and the effect of acid suppression on this activity.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Fibrinolytic activity was analysed in mucosal biopsies from 29 bleeding gastroduodenal ulcer patients and six controls. We analysed levels of D-Dimer, fibrin plate lysis area, plasminogen activator activity, plasminogen activator inhibitor activity, and plasmin antiplasmin complexes.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Significantly more fibrinolytic activity was detected in biopsies from patients with bleeding ulcers compared to controls. Moreover, in patients with endoscopic stigmata of recent haemorrhage, mucosal fibrinolytic activity was higher compared to patients without stigmata of recent haemorrhage. In mucosal biopsies of patients that had used acid suppression before admission, a decreased fibrinolytic activity was found compared to patients without such therapy. This effect of acid suppression on fibrinolytic activity was confirmed in nine patients before and after a 24-h ranitidine infusion.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Fibrinolytic activity is enhanced in patients with bleeding gastroduodenal ulcers. Acid suppressive therapy decreases this increased activity, which may be one of the mechanisms explaining the potential beneficial effect of this therapy.

Notes: Ridogrel at low doses inhibits thromboxane synthase. Oral ridogrel, from 5 mg once daily to 150 mg twice daily, improves the endoscopic appearance of colonic mucosa and clinical manifestations in mild to moderate ulcerative colitis.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:One US trial and one international trial were conducted to determine the effect of ridogrel on mild to severe active ulcerative colitis.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Two 12-week, double-blind, randomized, parallel-group trials were conducted. A US trial compared 0.5 mg, 2.5 mg and 5 mg of ridogrel once daily with placebo. An international trial compared 0.5 mg of ridogrel once daily with 2.5 mg and 5.0 mg of ridogrel once daily and 800 mg of mesalazine (known as mesalamine in the USA) three times daily. The primary efficacy outcome measure was the rate of complete remission.〈section xml:id="abs1-4"〉〈title type="main"〉Results:In the US trial, complete remission was achieved in 20.8% of patients in the 0.5 mg ridogrel group, 17.9% in the 2.5 mg ridogrel group, 20.6% in the 5.0 mg ridogrel group and 13.6% in the placebo group. In the international trial, 14.4% of patients in the 0.5 mg ridogrel group, 19.6% in the 2.5 mg ridogrel group, 19.4% in the 5.0 mg ridogrel group and 16.4% in the mesalazine group experienced complete remission. In the international trial, rates of complete remission at the end-point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the 0.5 mg ridogrel group, but the differences were not statistically significant. In the US trial, rates of complete remission at the end-point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the placebo group, but the differences were not statistically significant. Approximately 30% of the patients in each group discontinued treatment before the 12-week end-point owing to a lack of therapeutic response. All doses of ridogrel were well tolerated and comparable with placebo or mesalazine in terms of safety.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:No significant differences in the primary efficacy outcome measure were found between either the 2.5 mg or the 5.0 mg dose of ridogrel and placebo in the US trial and between either the 2.5 mg or the 5.0 mg dose of ridogrel and the 0.5 mg dose of ridogrel, a surrogate dose for placebo, in the international trial. There was no clear indication in either trial of an effective dose of ridogrel in the treatment of ulcerative colitis.

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: 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: Methods: In a pilot study we have evaluated the clinical efficacy of bismuth sucralfate to eradicate H. pylori. Ten consecutive patients with chronic dyspepsia and H. pylori associated gastritis were treated with bismuth sucralfate (220 mg bismuth per tablet, 4 tablets per day for 4 weeks). If a 14C urea breath test immediately after the medication was negative, a gastroscopy was performed one month later to obtain biopsies for culture and histological examination. Results: Four patients experienced side effects. In none of the ten patients could eradication of H. pylori be demonstrated one month after treatment with bismuth sucralfate. Conclusion: Bismuth sucralfate is not effective for the treatment of H. pylori infection.

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: 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.