Spiramycin is comparable to oxytetracycline in eradicating H. pylori when given with ranitidine bismuth citrate and metronidazole.

BACKGROUND: We have consistently achieved about 90% eradication of H. pylori with liquid bismuth, metronidazole and oxytetracycline. AIM: To test eradication and adverse events of ranitidine bismuth citrate (RBC) when given with metronidazole and either oxytetracycline or spiramycin. METHODS: One hundred and eighty-three patients were randomized to one of four 10-day regimens: RBC400OM: RBC 400 mg b.d., oxytetracycline 500 mg q.d.s.; RBC400SM: RBC 400 mg b.d., spiramycin 1 g q.d.s.; RBC200OM: RBC 200 mg q.d.s., oxytetracycline 500 mg q.d.s.; RBC200SM: RBC 200 mg q.d.s., spiramycin 1 g q.d.s. Additionally, all patients received metronidazole 400 mg q.d.s. A 14C-urea breath test was performed at 8 weeks. RESULTS: Intention-to-treat eradication rates were 94%, 91%, 94% and 89% with RBC400OM, RBC400SM, RBC200OM and RBC200SM, respectively (P = 0.81). Eradication was significantly higher in ulcer patients (97%) than in those with diagnoses other than ulcer (86%) (P = 0.009). There was a strong tendency to better eradication among those who had never smoked (100%) compared with ex-smokers (93%) and smokers (89%) (P = 0.06). Fifty-three per cent experienced at least one moderate or severe adverse event, and women had more adverse events than men (P = 0.0002). CONCLUSIONS: All four regimens had comparable efficacy and adverse events. Eradication was significantly better in ulcer patients but there was a trend to better eradication in those who smoked less, used less alcohol and exercised more. Adverse events were frequent, perhaps because of the large dose of metronidazole used, but few patients stopped treatment.

Effect of glyceryl trinitrate on gastric accommodation and symptoms in functional dyspepsia.

The purpose of this study was to investigate whether sublingual glyceryl trinitrate influences the size of the proximal stomach and postprandial symptoms in patients with functional dyspepsia. Twenty patients with functional dyspepsia were included in a double-blind, placebo-controlled crossover study with sublingual glyceryl trinitrate. All patients were scanned twice on consecutive days, receiving either placebo or 0.5 mg glyceryl trinitrate randomly 5 min prior to ingestion of 500 ml meat soup. Total symptoms, pain, nausea, and bloating were scored on a visual analog scale before and after the meal. Standardized ultrasonograms were obtained 1, 10, and 20 min postprandially of the proximal and distal stomach. The proximal stomach was larger in the sagittal section at 1 min postcibally (26.5 +/- 3.9 vs 24.8 +/- 4.9 cm2, P = 0.036) and 10 min postprandially (22.0 +/- 5.1 vs 19.8 +/- 5.3 cm2, P = 0.009) after administration of glyceryl trinitrate compared with placebo, whereas a tendency was observed after 20 min (18.7 +/- 5.5 vs 17.3 +/- 5.7 cm2, P = 0.076). The corresponding changes in the frontal diameters were 8.3 +/- 1.1 vs 7.8 +/- 1.2 cm (P = 0.067) after 1 min, 7.2 +/- 0.9 vs 6.4 +/- 0.8 cm (P = 0.001) after 10 min, and 6.3 +/- 1.1 vs 5.6 +/- 1.2 cm (P = 0.016) after 20 min. The area of the distal stomach was not different (P > 0.31) in the two groups. After administration of glyceryl trinitrate, the patients reported less pain (P = 0.048) and nausea (P = 0.023) 5 min postprandially, but this effect was reduced 15 min later. Total symptom score was improved by glyceryl trinitrate treatment (P < 0.042). Sublingual glyceryl trinitrate improves accommodation of the proximal stomach to a meal and reduces postprandial symptoms in a group of patients with functional dyspepsia.

Bismuth-based combination therapy for Helicobacter pylori-associated peptic ulcer disease (metronidazole for eradication, ranitidine for pain).

OBJECTIVES: 180 Helicobacter pylori-positive patients with peptic ulcer disease were randomly allocated to double-blind placebo-controlled treatment with one of four anti-H. pylori regimens consisting of bismuth subnitrate suspension (B), oxytetracycline (OT), metronidazole (M)/metronidazole placebo, or ranitidine (R)/ranitidine placebo. METHODS: Regimen 1: B 150 mg q.i.d., OT 500 mg q.i.d., M 400 mg t.i.d. for 10 days and R 300 mg b.i.d. for 4 wk. Regimen 2: same as regimen 1 except ranitidine. Regimen 3: same as regimen 1 except metronidazole. Regimen 4: same as regimen 1 except metronidazole and ranitidine. Gastroscopy and 14C-urea breath test were performed 4 wk after cessation of therapy, and breath test six months after cessation. RESULTS: According to intention-to-treat analysis, H. pylori eradication rates were 96%, 91%, 20%, and 9% with regimens 1, 2, 3, and 4, respectively. Comparing regimens 1+2 and 3+4, the eradication rates with and without metronidazole were 93% and 14%, respectively (p < 0.0001). Metronidazole increased the occurrence of diarrhea and abdominal pain. Comparing regimens 1+3 with 2+4 ranitidine did not influence H. pylori eradication (58% with and 50% without ranitidine; p = 0.37) or ulcer healing (93% with and 90% without ranitidine; p = 0.72) significantly, but reduced the occurrence of pain (p < 0.01). Six months after treatment, three patients who were H. pylori negative at 4 wk had become positive. These three had all received metronidazole placebo. H. pylori status remained negative in the other 85 patients. CONCLUSIONS: H. pylori eradication with this triple therapy is critically dependent on metronidazole. Adding ranitidine reduces the occurrence of abdominal pain during such therapy.

Lansoprazole capsules and amoxicillin oral suspension in the treatment of peptic ulcer disease.

BACKGROUND: Lansoprazole is a potent antisecretory drug also possessing anti-Helicobacter pylori activity in vitro. It is a candidate drug for combination regimens with antibiotics for treating H. pylori infections. METHODS: In a semiblind study, 65 patients with duodenal and/or gastric ulcer and pathologic 14C urea breath test results were treated with either 60 mg lansoprazole every morning only for 14 days or combined with 500 mg amoxicillin oral suspension four times daily between meals, given for 11 days. Endoscopy and breath test were repeated after 6 weeks and 6 months. Patients with unhealed ulcers were withdrawn. RESULTS: Eradication of H. pylori infection was attained in 46% of patients receiving lansoprazole and amoxicillin but in no patient receiving lansoprazole alone. Ulcers healed significantly more often in those who were H. pylori-negative (18 of 19 (95%)) than in those who were H. pylori-positive (20 of 41 (49%)). Adverse events, particularly stomatitis/sore throat and diarrhea, occurred significantly more often when amoxicillin was combined with lansoprazole. CONCLUSIONS: Lansoprazole eradicated H. pylori infection only when combined with amoxicillin. Eradication rates in this study are hardly acceptable, and further studies are necessary to define optimal doses and duration of treatment. Using amoxicillin as an oral suspension may not be of any substantial benefit and may cause stomatitis and sore throat.

Follow-up on 242 patients with peptic ulcer disease one year after eradication of Helicobacter pylori infection.

BACKGROUND/AIMS: From Dec. 1990 to Jan. 1993 we treated 306 patients with chronic peptic ulcer disease and gastric Helicobacter pylori infection with one of three triple therapy regimens comprising bismuth subnitrate suspension (B) 15 mg/ml, oxytetracycline (OT), and metronidazole (M). METHODS: Treatment I (101 patients): B 5 ml, OT 500 mg, and M 200 mg, all q.i.d. for 14 days. Treatment II (60 patients): B 10 ml and OT 750 mg q.i.d., M 400 mg t.i.d. for 7 days. Treatment III (145 patients): B 10 ml and OT 500 mg q.i.d., M 400 mg t.i.d. for 10 days. Gastroscopy and 14C-urea breath test were performed 4 weeks and 1 year after cessation of therapy. RESULTS: According to the urea breath test, H pylori eradication rates at 4 weeks were 87.9%, 81.9%, and 95.0% for Treatment I, II and III, respectively. At one year, 4 out of 242 patients, who were H pylori negative at 4 weeks, had become H pylori positive, i.e., H pylori reinfection rate 1.7%, 95% CI 0.5-4.2%. Only one of these "reinfected" patients had ulcer recurrence. Another patient had duodenal ulcer recurrence shortly after cessation of treatment in spite of being H pylori eradicated, i.e., ulcer recurrence rate 0.8%, 95% CI 0.1-3.0%. CONCLUSIONS: During the first year after H pylori eradication by triple therapy, recurrence rates of H pylori infection and peptic ulcer are very low (below 4.2% and 3.0%, respectively).

[10 days of triple treatment of Helicobacter pylori infection and peptic ulcer. Status after treatment of 4 weeks and of one year]. / Ti dagers trippelkur for Helicobacter pylori-infeksjon og magesår. Status fir uker og ett år etter.

We treated 143 Helicobacter pylori positive ulcer patients (duodenal ulcer 81, gastric ulcer 24, pyloric ulcer nine, previous duodenal ulcer 27, others two) with a ten days regimen of bismuth subnitrate, oxytetracycline and metronidazole. Four weeks after cessation of treatment the 14C-urea breath test showed that the infection was eradicated in 133 out of 140 patients (95%). The ulcer had healed in 129 (97%) of the H. pylori negative patients. Status at one year after treatment showed that 121 (98.4%) of 123 patients who had become H. pylori negative had remained negative. None of the H. pylori negative patients experienced ulcer relapse. The results show that the treatment is effective and that the rate of recurrence of H. pylori during the first year is very low.

Haemorrhagic effect of enoxaparin, a low molecular weight heparin. Comparison with unfractionated heparin in humans.

The haemorrhagic effects of unfractionated heparin (UFH) and the low molecular weight heparin (LMWH) enoxaparin were investigated and compared in the gastric mucosa (haemorrhage induced by biopsy) and skin (haemorrhage induced by Simplate) of 12 healthy volunteers. Administration of UFH and LMWH (given in a dose of 75 anti-Xa U/kg intravenously) increased median gastric bleeding time (3.5 min) and geometric mean blood loss (11.5 microliters) to 19 min (p = 0.00003) and 54.1 microliters (p = 0.0021) after UFH and to 13 min (p = 0.008) and 29.0 microliters (p = 0.275) after LMWH. Median skin bleeding time (4.25 min) increased to 6.0 min after UFH (p = 0.003) and to 6.75 min after LMWH (p = 0.0008). Mean heparin activity in plasma was 20% higher after LMWH than after UFH. The calculated gastric bleeding time to heparin activity ratio was significantly lower for LMWH than for UFH (p < 0.05).

Interaction between heparin and acetylsalicylic acid on gastric mucosal and skin bleeding in humans.

The haemorrhagic effect of unfractionated heparin and of the low molecular weight heparin, enoxaparin, on gastric mucosal bleeding induced by acetylsalicylic acid (ASA) and on skin bleeding induced by the Simplate technique was investigated in healthy human volunteers. Endoscopic estimation of gastric bleeding by visual analogue scores was more sensitive than biochemical quantitation of blood in the gastric washing by a modified HaemoQuant method. Contrary to what was expected, the ASA-induced gastric mucosal bleeding was not increased by heparin pretreatment, whereas heparin in combination with ASA, but not ASA alone, significantly increased the skin bleeding time. In the interaction with ASA, enoxaparin and unfractionated heparin appeared to act similarly.

Incomplete reversal of enoxaparin-induced bleeding by protamine sulfate.

The neutralizing effect of protamine sulfate on enoxaparin-induced bleeding was compared in two rat models: one employing the gastric mucosa, and the other the tail skin, using a 2:1 ratio of protamine sulfate to enoxaparin on a weight basis. Whereas protamine sulfate reduced the median bleeding time (from 20 to 9.5 min) and blood loss (80%) in the gastric mucosa, and apparent 'all-or-none' response was seen in the tail skin, in agreement with a different hemostatic mechanism in the two bleeding models. In both models, protamine sulfate incompletely reversed the bleeding induced by enoxaparin.

Haemorrhagic effects of unfractionated and two low molecular weight heparins, enoxaparin and fragmin, in rats.

The effects on primary haemostasis of unfractionated heparin and of the two low molecular weight heparins, enoxaparin and fragmin, were compared in two rat models, one employing the gastric mucosa and the other the tail skin. All three heparin preparations prolonged the bleeding time and increased the blood loss dose dependently. The prolongation of the bleeding time per unit dose caused by unfractionated heparin was significantly greater than the prolongation caused by either one of the two low molecular weight heparins. In the gastric mucosa, but not in the tail skin, enoxaparin prolonged the bleeding time significantly less than fragmin (p less than 0.05).

Gastric mucosal bleeding after unfractionated and low molecular weight heparin in rats.

The bleeding from an induced gastric mucosal lesion was monitored after intravenous administration of unfractionated heparin and enoxaparin, a low molecular weight heparin. The gastric mucosa was exposed in a chamber, which was superfused with saline and emptied at 1-min intervals for quantitation of bleeding. Both heparins prolonged the bleeding time and increased the blood loss dose-dependently. Five to ten times higher doses of enoxaparin (in terms of anti-Xa units) were required to achieve similar prolongation of the bleeding times as with unfractionated heparin. The results indicate a more favourable antihaemostatic effect of enoxaparin than of unfractionated heparin.

A new model to assess the haemorrhagic potential of various heparin preparations.

In the gastric mucosa, haemostasis is hampered by the acidity and peptic activity of the gastric juice and by the fibrinolytic activity of plasmin. The hostile intragastric environment may be responsible for the unsecure haemostasis, with episodes of rebleeds often seen in gastroduodenal haemorrhage. Secondly, the haemostatic mechanisms of the gastric mucosa are largely independent of platelet aggregation and thus rely mainly on the coagulation system, making the gastric mucosa a unique model to test haemorrhagic effects of anticoagulants. Using a rat gastric chamber technique, we studied bleeding times from induced gastric mucosal lesions after intravenous administration of unfractionated and low molecular weight heparins. The bleeding times were dose-dependently prolonged by all heparins. With unfractionated heparin, significant prolongation of the bleeding times was seen already at a dose of 75 anti-Factor Xa U/kg, proving that the present model is more sensitive than previous models. The bleeding time per unit dose of both Kabi 2165 (p less than 0.05) and enoxaparin (p less than 0.001) was significantly less than that of unfractionated heparin.

[Reflux esophagitis. Diagnosis and treatment]. / Refluksøsofagitt. Diagnostikk og behandling.

Refluxoesophagitis was the topic of a meeting of gastroenterologists in Bergen this year for the purpose of working out consensus guidelines on the diagnosis and treatment of this common disease. To day upper gastrointestinal endoscopy is the most important diagnostic procedure. There was a general agreement on using Berstad's staging scheme, which comprises only three stages of oesophagitis. Twenty-four hour pH-monitoring may provide useful information on the reflux pattern, but the practical consequences of the examination are still uncertain. H2-receptor antagonists are indicated in mild cases of oesophagitis. However, omeprazol is the only drug having a significant effect on endoscopic healing and therefore the drug of choice in severe oesophagitis. At present, there is no established maintenance treatment. Surgery is therefore recommended in patients with severe oesophagitis which does not respond to medical treatment, in patients with strictures, and in patients with severe Barrett's oesophagus. The Nissen-Rosetti fundoplicatio is recommended as the standard operative procedure.