Phagocytic and bactericidal activities of neutrophils in duodenal ulcer patients during cimetidine treatment

Phagocytic and bactericidal activities of neutrophils relative to Staphylococcus aureus 209 P strain were studied in 16 duodenal ulcer patients who were intravenously administered cimetidine in doses of 4 X 200 mg for 8 days and in a group of untreated healthy subjects. The investigations were made before the treatment on the last day of cimetidine administration, and one week after drug withdrawal. The bactericidal activity of neutrophils was found to be higher in duodenal ulcer patients than in the healthy controls. Cimetidine does not have a significant effect on the phagocytic activity of neutrophils and it has a moderately inhibitory effect (p less than 0.05) on the bactericidal activity relative to the ingested intracellular bacteria. This shows that cimetidine may modify some of the neutrophil functions in duodenal ulcer patients.     

Ranitidine and cimetidine in renal transplantation: a clinical trial

Sixteen patients were randomized for treatment with ranitidine and seventeen for treatment with cimetidine to prevent the appearance of upper gastrointestinal (UGI) complications after renal transplantation. The two operated groups were comparable with regard to age, sex, number of pre-operative blood transfusions, and HLA match. All patients were treated with a similar immunosuppressive regime, consisting of azathioprine and methylprednisolone, and underwent endoscopic examination ten and thirty days following surgery. In the second endoscopy an entirely normal condition was observed in 11 and 12 cases in the oesophagus, 4 and 4 cases in the stomach and 13 and 12 cases in the duodenum in the two groups of 16 and 17 patients respectively. Except for one uncomplicated prepyloric ulcer in the cimetidine group, the remaining endoscopic findings were mild in intensity. There were, however, significantly more rejection episodes in the cimetidine group than in the ranitidine group. Ranitidine seems to be a safe drug in transplant patients, but the high incidence of rejection episodes in the cimetidine group is a cause for concern.     

Long-term management of duodenal ulcer with pirenzepine and cimetidine: a double-blind controlled clinical trial

The effectiveness of pirenzepine in the prevention of duodenal ulcer relapses was assessed by means of a double-blind controlled trial versus cimetidine. Seventy duodenal ulcer out-patients endoscopically healed after a 6-week treatment with either pirenzepine or cimetidine were admitted to the trial. The former pirenzepine patients were treated again with pirenzepine: 1 tablet at breakfast and 2 tablets at bedtime (75 mg daily). The former cimetidine patients were treated again with cimetidine: 2 tablets at bedtime (400 mg daily). They received one placebo tablet at breakfast. Both treatments lasted 12 months. Tablets of a mild antacid were permitted only if necessary to relieve severe ulcer pain and heartburn. Patients underwent clinical and endoscopic assessments after 4, 8 and 12 months of treatment and whenever ulcer symptoms lasted more than 4-5 consecutive days. Only 47 out of the 70 patients that entered the trial underwent all clinical and endoscopic controls. Sixteen out of 23 patients on pirenzepine (70%) and 17 out of 24 patients on cimetidine (71%) did not relapse after 12 months. The difference is not statistically significant. Both treatments were well tolerated. The results show that pirenzepine was as effective as cimetidine in the prevention of duodenal ulcer relapses when administered at a dosage of 75 mg daily (of which 50 mg at bedtime) for one year.     

The effect of cimetidine treatment on suppressor T cells in duodenal ulcer patients

Changes in the suppressor T-lymphocyte activity were studied in 11 patients with duodenal ulcer during treatment with cimetidine. The drug was administered intravenously in a dose of 200 mg four times a day for a fortnight. Suppressor T-cell activity was determined by the Shou et al. method using two-stage culture before treatment, after 4 days of the treatment, just before drug withdrawal, and 2 days and 2 wk after the treatment. Suppressor T-cell activity significantly decreased soon after starting the treatment, remained low throughout the treatment, and rapidly and significantly increased following drug withdrawal.     

Effect of omeprazole and cimetidine on duodenal ulcer. A double-blind comparative trial

We conducted a double-blind randomized study of 132 patients to determine whether the new, investigational proton-pump inhibitor, omeprazole (30 mg per day), would accelerate healing and pain relief, as compared with cimetidine (1 g per day), in patients with duodenal ulcer. After two weeks of treatment, which was completed by all patients, the healing rates were 73 per cent in the omeprazole group and 46 per cent in the cimetidine group (P less than 0.01). After four weeks of treatment, which was completed by 118 patients, the corresponding figures were 92 and 74 per cent (P less than 0.05). In the omeprazole group 55 per cent of the patients were free of pain after the first week, as compared with 40 per cent of those treated with cimetidine (P greater than 0.05). No major clinical or biochemical side effects of omeprazole or cimetidine were noted. A six-month follow-up study revealed no significant difference between the recurrence rates after omeprazole and after cimetidine treatment. In May 1984 clinical trials with omeprazole were temporarily suspended, since a study of long-term toxicity in rats had shown the development of gastric carcinoid tumors.     

Inhibition of gastric acid secretion by cimetidine in patients with duodenal ulcer.

Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer. Oral doses of 100, 200, and 300 mg were tested. Each dose significantly inhibited basal and meal-stimulated secretion. After 300 mg, basal acid secretion was essentially zero for at least five hours. The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01). Cimetidine did not affect meal-stimulated gastrin release. No toxicity was observed after serial doses given during these tests. Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing.     

Changes in the interleukin-1 and interleukin-2 generation in duodenal ulcer patients during cimetidine treatment

The effect of cimetidine treatment on the generation of interleukin-1 (IL-1) and interleukin-2 (IL-2) was studied in 11 duodenal ulcer patients. The results obtained were compared with those for untreated healthy subjects. The drug was administered intravenously in a dose of 200 mg four times a day for 8 days. The investigations were performed before, during and 1 wk after cimetidine therapy. IL-1 generation was determined by the ability of supernatants from 2-day cultured adherent cells stimulated by lipopolysaccharide to enhance proliferation of PHA-stimulated mice thymocytes. IL-2 generation was determined by the ability of supernatants from 2-day cultured, PHA-stimulated mononuclear cells to proliferate autologous 17-day cultured T cells. In all ulcer patients IL-1 generation diminished during cimetidine treatment (P less than 0.005). It continued to decrease in 4 subjects and increased in the other 7 ones following drug withdrawal. All the values were higher than those in healthy controls. IL-2 activity in ulcer patients was similar to that in healthy subjects and it increased significantly in all ulcer patients following the onset of the treatment (P less than 0.005) and decreased nearly to the initial values 1 wk after termination of the treatment (P less than 0.005). The present studies indicate that cimetidine, a selective histamine H2-receptor antagonist, deeply changes mechanisms of immunoregulation in patients with duodenal peptic ulcer.     

The role of stressful life events in duodenal ulcer recurrence: A prospective study

This study prospectively assessed whether stressful life events (LE) were predictive of duodenal ulcer (DU) recurrence during remission of disease. We administered Paykel's Interview for Recent Life Events to 80 patients to assess events that occurred 12 months prior to the first interview and again 6 to 12 months later for LE that occurred during the interval. Upper gastrointestinal endoscopy detected DU recurrence in 11 patients. Prospective data analysis showed no significant difference in LE between relapsing and relapse-free groups, whereas retrospective analysis showed significantly more LE (p > .03) among relapsing patients. LE seems to have played a marginal role in DU recurrence.     

Gastric acid and serum gastrin response to sham feeding, and the effect of cimetidine on the response to sham feeding in duodenal ulcer patients

Sham feeding resulted in a significant increase of gastric acid secretion in 12 male patients with duodenal ulcer. No significant change in serum gastrin concentration was produced by sham feeding. Reproducibility of gastric acid response to sham feeding was very good (r = 0.74). The mean peak 30 min acid output amounted to 9.5 +/- 1.0 mmol/30 min following sham feeding. That was 46.5% of the 30 min peak acid output elicited by pentagastrin infusion administered in a dose of 1.5 micrograms/kg/h. Cimetidine in a dose of 2 mg/kg/h almost completely reduced (by 85%) the gastric acid secretion induced by sham feeding. Cimetidine did not cause any change in serum gastrin concentration during and after sham feeding.     

A randomized study of maintenance therapy with ranitidine to prevent the recurrence of duodenal ulcer

After an active duodenal ulcer has healed in response to medical therapy, the rate of recurrence during the subsequent year is relatively high. We therefore enrolled 140 patients with healed duodenal ulcers in a two-year randomized, double-blind trial comparing maintenance therapy (ranitidine, 150 mg nightly) with placebo for the prevention of recurrent duodenal ulceration. We performed endoscopy annually and when symptoms suggested the recurrence of ulcers. Verified recurrent ulcers in either group were treated for four or eight weeks with open-label ranitidine (150 mg twice a day). Patients whose ulcers healed within eight weeks resumed randomized treatment. Prophylactic therapy with ranitidine reduced the rate of ulcer relapses from 63 percent in the placebo group to 37 percent in the ranitidine group (P less than 0.05). Treatment with ranitidine extended the median ulcer-free interval from one to two years (P less than 0.05). The first recurrences of ulcer were asymptomatic in half the ranitidine group and in a quarter of the placebo group. Prophylactic therapy with ranitidine also reduced the frequency of recurrent ulcers that were unhealed by eight weeks, that were bleeding, that were in the stomach, or that were the second recurrent ulcer within six months, from 43 percent in the placebo group to 21 percent. Patients who drank alcohol, smoked, had a history of ulcer disease, or had duodenal scarring or erosion at the time of entry into the study were at the greatest risk for recurrence and benefited the most from prophylactic ranitidine. We conclude that prophylactic treatment with ranitidine is effective in preventing the recurrence of duodenal ulceration.     

Gastrin-producing cells of the stomach in duodenal ulcer before and after selective proximal vagotomy

Morphofunctional state of the gastrin-producing cells in the antral gastric mucosa depending upon the gastric secretion and serum gastrin was investigated in patients with duodenal ulcer before and after the selective proximal vagotomy (SPV). Morphometric analysis of the hormone containing granules in G-cells showed the increase of their functional activity after SPV. It was demonstrated that serum basal gastrin reflects morphofunctional state of the gastrin-producing cells. Functional capabilities of the gastrin regulation of the gastric secretion after the vagus denervation of the acid-producing part of the stomach must be taken into consideration in duodenal ulcer surgery.     

Antacids in the treatment of duodenal ulcer

Fifty patients with endoscopically proven pyloric-prepyloric ulcers (PU/PPU) and 50 with duodenal ulcers (DU) completed a six-week double-blind clinical trial initially comprising 124 patients. The antacid-treated patients received 10 ml of an antacid suspension seven times a day (buffering 367.5 mmol acid). Healing rate after three weeks of treatment was 74% in the antacid and 42% in the placebo group (p less than 0.01). After six weeks the corresponding figures were 96 and 68% (p less than 0.001). Regarding the PU/PPU and DU subgroups we found significant differences compared to placebo in the PU/PPU group only. Antacids caused a significantly faster and more perceptible pain relief than placebo. We found no significant correlation between ulcer healing and smoking habits. Regression analyses showed that, besides antacids, ulcer size and peak acid output influenced the healing rate significantly.     

Food intolerance in duodenal ulcer patients,non ulcer dyspeptic patients and healthy subjects

Summary In 50 duodenal ulcer out-patients and 50 non ulcer dyspeptic patients suffering from low to moderate epigastric painful symptoms the intolerance of 39 foods were significantly increased compared to a group of 50 healthy subjects. Food intolerance was not different between duodenal ulcer and non ulcer dyspeptic patients. Intolerance was related in the majority of nutrients to aversion and pain or to an increased incidence of aversion alone in patients and normals. In duodenal ulcer, coffee and fruit juice were associated with an elevated incidence of pain.Abbreviations DU Duodenal ulcer - NUD Non ulcer dyspepsia - N Normal Dedicated to Professor Dr. N. Zöllner on the occasion of his 65th anniversary