Notizen: 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.

Notizen: In patients with ulcer disease the optimal dose and duration of Helicobacter pylori treatment containing omeprazole (O), metronidazole (M) and clarithromycin (C) has yet to be established. The efficacy might be influenced by metronidazole- and clarithromycin-resistance.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To study the effect of duration of OMC treatment on its efficacy and influence of metronidazole-resistance and clarithromycin-resistance on the optimal duration.〈section xml:id="abs1-3"〉〈title type="main"〉Materials and methods:Ulcer patients (n=76) were randomized to three double-blind treatments of 10 days: OMC 4 consisted of 4 days b.d. 20 mg omeprazole, 400 mg metronidazole and 250 mg clarithromycin switched over to 6 days b.d. 20 mg omeprazole and placebo antibiotics (n=27); OMC 7 consisted of 7 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg and 3 days b.d. omeprazole 20 mg and placebo antibiotics (n=25); OMC 10 consisted of 10 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (n=24). H. pylori was assessed by biopsies for culture and histology pre- and 4–6 weeks after OMC therapy. Metronidazole-resistance and clarithromycin-resistance were assessed by the E-test.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Intention-to-treat-eradication rates were: OMC 4, 96%; OMC 7, 92%; and OMC 10, 96% (N.S.). All of the three per protocol eradication rates were 100% (95% CI: 85.2–100). Of 75 isolates, 16 were metronidazole-resistant and one was clarithromycin-resistant.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusion:In H. pylori-positive ulcer patients, OMC 4 is highly efficacious and as effective as OMC 7 and OMC 10. No influence of metronidazole-resistance or clarithromycin-resistance was observed.

Notizen: Antimicrobial treatment of Helicobacter pylori is the proper management strategy in patients with ulcers. A high rate of H. pylori reinfection after successful eradication therapy however, may give rise to ulcer recurrence. The risk of reinfection, depending on the prevalence and the rate of acquisition of H. pylori infection, varies with socioeconomic status, age and geographical location. The rate of reinfection may vary in a similar way. The available data in the literature reveal that reinfection by H. pylori is low or absent in developed countries and may be lower than the initial rate of acquisition. In addition, reported cases of H. pylori reinfection are often cases of recrudescent H. pylori infection. Acquisition rate in developing countries is high, so the reinfection rate is expected to be higher than in developed countries. However, studies discriminating reinfection from recrudescence are lacking and therefore more data from developing regions are needed to settle if ‘cured once, cured forever’ holds true.

Notizen: Thirty-three dyspeptic patients with colonization of Helicobacter pylorl in the gastric antrum were treated with tripotassium dicitrate bismuthate 120 mg q.d.s. for 28 days and metronidazole 250 mg q.d.s for 10 days starting on day 19. Five weeks after cessation of this treatment regimen H. pylori was eradicated in 23 patients. In 8 of the remaining 10 patients, H. pylori had become resistant to metronidazole. In this study resistance was significantly associated with smoking habits, but not with age, bacterial load, gastritis score or alcohol consumption.

Notizen: 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.

Notizen: In this overview, medical advice for routine clinical practice regarding peptic ulcer haemorrhage (PUH) is given, based on the extensive literature about Helicobacter pylori and the controversial results about the interaction of H. pylori infection and nonsteriodal anti-inflammatory drug (NSAID) use. PUH remains an important emergency situation with an incidence between 32 and 51/100 000 persons per year. There is a high association between H. pylori infection and peptic ulcer disease. The association between H. pylori infection and PUH is less clear, but a strong argument for the aetiological role is the fact that eradication of H. pylori decreases recurrence of bleeding. NSAID use is another important risk factor for PUH. H. pylori infection and NSAID use seem to act independently, although some studies show a synergistic interaction while other studies report that H. pylori is protective against the development of PUH in NSAID users. All patients with PUH should be tested for H. pylori infection, regardless of the use of NSAIDs. Because invasive tests are less sensitive in PUH patients, negative tests in patients with no other risk factors should be confirmed by serology or urea breath test (UBT). Eradication therapy with a proton pump inhibitor or ranitidine bismuth citrate-based triple therapy should be given to all H. pylori-positive patients. Only for nonaspirin–NSAID users does the effect of eradication therapy on the healing of gastric ulcers remain controversial, but currently we also advise eradication of H. pylori in this subgroup. After eradication therapy, acid-suppressant therapy is advised to heal the ulcer. The success of eradication should always be confirmed because of the risk of recurrence of peptic ulcer disease and bleeding in H. pylori-infected patients.

Notizen: 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.

Notizen: Aim : To determine the in vivo anti-microbial activity of a high-dose itraconazole and omeprazole regimen against Helicobacter pylori. Methods: In an open pilot study, 10 H. pylori positive dyspeptic patients were treated with itraconazole 200 mg b.d. and omeprazole 200 mg b.d. for 7 days. Follow-up upper gastrointestinal endoscopy was performed 4–5 weeks after completion of therapy. Eradication of H. pylori infection was determined by histopathological examination and culture of biopsies from the antrum and corpus. Results: Eradication was not observed in any patient. Conclusion: This combination of itraconazole with omeprazole does not eradicate H. pylori infection.

Notizen: Background: Cure rates of H. pylori infection, using dual therapy with omeprazole and amoxycillin, vary considerably and the efficacy of retreatment with this regimen in the case of initial failure is controversial. Therefore, we conducted a large prospective double-blind randomized trial, studying the efficacy of low vs. high dose omeprazole in dual therapy and of early retreatment with the same regimens. Methods: One hundred and sixty-eight consecutive H. pylori-positive patients, suffering from either peptic ulcer disease or functional dyspepsia, were enrolled. Group I (n=84) received omeprazole 20 mg b.d. plus amoxycillin 750 mg t.d.s., for 2 weeks. Group II (n=84) received omeprazole 40 mg t.d.s. plus amoxicillin 750 mg t.d.s., for 2 weeks. Results: The H. pylori eradication rate was 60.2% in group I and 64.3% in group II (P=0.59). Cure of H. pylori infection was significantly better in patients with peptic ulcer disease, compared to non-ulcer dyspeptics (P=0.016). Retreatment, given in 54 patients, was successful in 21.4% patients in group I and in 28% patients in group II (P=0.58). Conclusions: High dose of omeprazole has no advantage compared to low dose in terms of eradication efficacy. Early retreatment with the same regimen offers limited improvement in cure rate. Presence of peptic ulcer disease influences cure rates significantly.

Notizen: The oesophago-gastric junction functions as an anti-reflux barrier preventing increased exposure of the oesophageal mucosa to gastric contents. Failure of this anti-reflux barrier results in gastro-oesophageal reflux disease, and may lead to complications such as oesophagitis, Barrett’s oesophagus and eventually oesophageal carcinoma.Recent studies have suggested that transient lower oesophageal sphincter relaxation is the main mechanism underlying gastro-oesophageal reflux. It involves a prolonged relaxation of the lower oesophageal sphincter, mediated by a vago-vagal neural pathway, synapsing in the brainstem.Several drugs, such as atropine, baclofen and loxiglumide, have been shown to reduce the rate of transient lower oesophageal sphincter relaxations and concomitantly the number of reflux episodes. These findings illustrate that transient lower oesophageal sphincter relaxations may represent a potential new target for the pharmacological treatment of gastro-oesophageal reflux disease.It is possible that the reduction in the number of transient lower oesophageal sphincter relaxations may also contribute to the beneficial effect of fundoplication and new endoscopic anti-reflux procedures. It should be emphasized, however, that other factors, such as low lower oesophageal sphincter pressure, the presence of a hiatal hernia and impaired oesophageal peristalsis, are also of great importance. Therefore, whether the targeting of transient lower oesophageal sphincter relaxations is the ‘golden bullet’ in anti-reflux therapy remains to be proven, as evidence of an effective control of gastro-oesophageal reflux in reflux patients is still lacking.