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 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.     

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.     

Decrease in helper (T4+) lymphocytes following cimetidine treatment for duodenal ulcer.

We studied the possible in vivo influence of cimetidine on peripheral blood lymphocyte (PBL) subpopulations defined with monoclonal antibodies (MoAb) in eight haematologically normal patients with uncomplicated duodenal ulcers before cimetidine treatment, 1 week after the start, and finally 1 week following cessation of therapy. After cimetidine had been given for 3-5 weeks there was a significant decrease, compared with pretreatment numbers, in the proportion of T3+ cells (64.6 +/- 8.1 (mean +/- s.d.) v 51.0 +/- 7.8%) and in T4+ cells (47.3 +/- 4.3 v 30.8 +/- 4.7%). The number of T8+ cells was not affected (20.3 +/- 4.3 v 20.1 +/- 6.7%). These changes resulted in a significant reduction in the T4/T8 ratio (2.46 +/- 0.8 v 1.67 +/- 0.6). The total numbers of lymphocytes and monocytes as well as the percentage of B1+ lymphocytes did not change significantly. The observed decrease in T4/T8 ratio after cimetidine treatment is explained by a reduction in the number of T4+ cells and the appearance of a new subpopulation of T3-, T4-, T8-, B1-lymphocytes. The underlying mechanism, however, is not clear. Cimetidine does not seem to have a direct receptor-modulating effect, since in vitro exposure of normal lymphocytes to the drug did not change the proportions of the T cell subsets.     

Antacid treatment of duodenal ulcer

Sixty-seven consecutive outpatients with endoscopically verified duodenal ulcer were randomised to a double-blind treatment with either 10 ml of an antacid suspension (buffering capacity 85 mmol/10 ml, packed in single dosage pads) 1 and 3 h after each meal and at bedtime or cimetidine 400 mg b.i.d. The double-dummy technique was employed. Endoscopy was performed after 4 weeks treatment and, if the ulcer had not healed, after 8 weeks treatment. When ulcer healing had occurred, the patient entered a 1 year follow-up study. The cumulative healing rates after 4 and 8 weeks treatment were 83 and 97% vs. 69 and 94% in the antacid and cimetidine groups respectively. No significant differences were observed between the treatment groups regarding ulcer healing, symptom relief or compliance. Adverse reactions were few and only 3 (9%) patients in the antacid group had to discontinue the treatment due to diarrhoea. Of the cimetidine treated patients, 61% had symptomatic relapse during the 1 year follow-up compared to 71% of the antacid treated patients. There were no significant differences in recurrence rate or time to relapse. The moderate dose antacid treatment used here is efficient, well tolerated, safe, convenient and is a good alternative treatment of the duodenal ulcer patient.     

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.     

Effect of epinephrine, propranolol, and verapamil on the chemiluminescence of neutrophils in duodenal ulcer patients

To answer the question whether beta-adrenergic receptor agonists or antagonists and calcium channel blocking agents affect activation of neutrophils in vivo, the chemiluminescence (CL) test was employed. The intensity of emitted photons was amplified by luminol. The effect of investigated agents was measured after stimulation of isolated peripheral blood polymorphonuclear leukocytes (PMNLs) with opsonized zymosan particles. The investigations were performed on 9 duodenal ulcer patients, aged 19-23 years, after informed consent. Single subcutaneous dose of epinephrine (0.014 mg/kg) induced a marked increase in PMNL number and a moderate, but significant, decrease in CL 30 min after injection. Verapamil (0.15 mg/kg intravenously) diminished CL, propranolol (0.1 mg/kg intravenously) enhanced CL, but 150 min after injections CL was approaching the initial values. The obtained results suggest that the investigated compounds may modify the PMNL function in vivo.     

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.     

Medical treatment of gastric and duodenal ulcer

Summary Antacids prove ready if only temporary relief of the symptoms of ulcers. Physicians have been able to increase the rate of healing of gastric ulcers by advising patients to stop smoking and then either admit them to hospital for bed-rest, or use carbenoxolone sodium as an outpatient therapy. The early trials of some other drugs have shown increase in rate of healing of gastric ulcer, but there is no medical treatment which will prevent the high recurrence rate of benign gastric ulcer. The limited data indicate that adequate medical reduction in acid secretion and enhancement of mucosal resistance may benefit patients with duodenal ulcer.Presented at the meeting on Gastric and duodenal ulcer disease: Basic principles and clinics of treatment by drugs and operations, Marburg, November 22, 1975     

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.     

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