A. Walan

Effect of omeprazole, a substituted benzimidazole, on 24-h intragastric acidity in patients with peptic ulcer disease.

Intragastric pH was measured during physiological conditions over 24-h periods in patients with peptic ulcer disease. After single oral doses of 20, 40, and 80 mg omeprazole we found a dose-dependent reduction in mean intragastric acidity ranging from 38% to 99%. After treatment for 1 week with omeprazole, 40 mg daily, with or without an initial loading dose of 80 mg, intragastric acidity was decreased by more than 99%. This is a more pronounced decrease in acidity than can be achieved even with very high doses of histamine H2-receptor antagonists.

The effect of 20 Mg omeprazole daily on serum gastrin, 24-h intragastric acidity, and bile acid concentration in duodenal ulcer patients.

Serum gastrin, 24-h intragastric acidity, and bile acid concentrations were measured during physiologic conditions in 10 patients with duodenal ulcer disease. Omeprazole, 20 mg daily, for 8 days reduced acidity by greater than or equal to 99% in six patients and by 47-54% in four patients. The degree of acid reduction was related to the area under the plasma omeprazole concentration time curve (AUC). Serum gastrin levels were not significantly increased by omeprazole. Intragastric bile acid concentrations were increased by omeprazole, but this seems to be of little importance for the healing of duodenal ulcers.

Results of Short- and Long-Term Cimetidine Treatment in Patients with Juxtapyloric Ulcers, with Special Reference to Gastric Acid and Pepsin Secretion

One hundred and seven patients with active juxtapyloric ulcers and a history of chronic ulcer disease were treated with cimetidine. After ulcer healing 67 patients were selected for medical management, testing the value of cimetidine maintenance treatment. Time to healing was shorter for patients with duodenal ulcers when compared with those with active prepyloric ulcers. Recurrences were fewer for patients with pure duodenal ulcer disease (DUD) when compared with those with active or previous prepyloric ulcer disease (PUD). Patients whose ulcers were slow to heal and those with active or previous prepyloric ulcers (PUD) required a higher dose of cimetidine for effective control of their disease. All patients with slowly healing ulcers (more than 6 weeks) relapsed with 400 mg cimetidine at night. Among patients with relapse 46% with DUD and 31% with PUD were controlled by increasing cimetidine to 400 mg twice daily. Tests of acid secretion were of no value in predicting the rate of ulcer healing or relapse rate. Pepsin secretion studies, however, were of predictive value for patients with DUD but of indeterminate value for patients with PUD. Long-term cimetidine produced a significant decrease in pentagastrin-stimulated pepsin secretion (without treatment) in both patients with and without relapse. No significant changes in acid secretion were observed. As a result of these studies we recommend a cimetidine maintenance dosage of 400 mg twice a day for all patients whose ulcers are slow to heal on 1 g cimetidine a day and in patients with prepyloric ulcer disease regardless of rate of healing.

High gastric bile acid concentration in prepyloric ulcer patients.

The intragastric concentrations of bile acid (BAC) and pH were measured over 24 h in 13 patients with duodenal (DU), in 11 with prepyloric (PU) ulcer disease, and in 12 healthy controls. Large fluctuations in bile acid concentration occurred for individuals from all three groups. PU patients had BACs higher than DU patients and controls both during the day (p less than 0.01 and p less than 0.001) and at night (p less than 0.001 and p less than 0.05). Controls had a significantly higher BAC during the night than the day (p less than 0.001). The acidity was significantly higher in DU patients than in controls both during the day and night (p less than 0.05). Compared with PU patients, the DU patients had higher acidity at night (p less than 0.01).

Serum Folate Determinations in Tracing Adult Coeliacs

A simple screening test would be helpful in tracing adult coeliacs in medical practice. Results from a gastroenterological routine practice with a high detection rate of coeliac disease showed that a low concentration of serum folate was the commonest abnormality in the serum of adults with this disorder unaccompanied by dermatitis herpetiformis. It occurred in 85%, ranking with steatorrhoea in frequency, and suggests that a serum folate determination could help to refer subjects for jejunal biopsy to detect coeliac disease. In patients found to have a low serum folate recording without a known cause, the predictive value of the low value for adult coeliac disease was examined, and the findings indicate that the investigation of such patients should include jejunal biopsy.

Variation of Disaccharidase Activities in Duodenal Biopsy Specimens

Multiple biopsy specimens were taken from the duodenal cap and/or from the descending part of the duodenum in patients admitted for routine upper endoscopy, to determine the degree of variation in disaccharidase activity. Four specimens were taken from each site and assayed in pairs. The mean coefficients of variation (CV) of enzymatic activities between duplicate measurements in the same pair of specimens were less than 3.5% and between two pairs of biopsies about 30%. The large variation in disaccharidase activity between assays performed on simultaneously biopsied specimens from the same area of the bulb and the descending part of the duodenum in the same individual implies that single values for enzyme activity must be interpreted with caution.

Metabolic consequences of reduced gastric acidity

A review of the effect on metabolism of antacids, anticholinergics and histamine H2-antagonists is given. It is stated that long-term treatment with antacids by a variety of mechanisms can cause severe metabolic complications such as the milk-alkali syndrome and phosphorus depletion. The interaction with other drugs can also be marked. There is very little known of the effect of anticholinergics on metabolism. Clinical experience has not indicated that any serious consequences will occur. The authors have investigated the effect continuous treatment with cimetidine 400 mg at night or twice daily for three years on weight, haemoglobin, plasma iron, plasma folate, plasma vitamin B12, albumin and plasma calcium. The only significant difference that occurred was a slight decrease of plasma calcium within the reference values. In conclusion it is stated that there is very little indication that the moderate and inconstant reduction of acidity over 24 hours which can be achieved by anticholinergics or twice daily administration of presently available H2-antagonists will result in metabolic consequences arising from reduced acidity. Higher doses given more frequently might give a risk for bacterial overgrowth with metabolic consequences.

Effect of Cimetidine and Oxmetidine on 24-h Gastric Acid and Pepsin in Patients

The 24-h intragastric pH, titrated hydrogen ion concentration, and pepsin concentration were studied in nine peptic ulcer patients during administration of placebo and of 800 mg cimetidine given as two or four equal doses. Cimetidine, 400 mg twice daily, was more effective in reducing acidity during morning (p less than 0.05) and overnight (p less than 0.01) than cimetidine, 200 mg four times daily, which, however, was the most effective regimen during the afternoon (p less than 0.05-0.01). During the 24-h period pH values equal to or above 5 were observed for less than 1 h with placebo treatment, for 1.8 h with cimetidine, 200 mg four times daily, and for 4.7 h with cimetidine, 400 mg twice daily. A new histamine H2-receptor antagonist, oxmetidine, was studied in six other patients, also during a 24-h period. Both 400 mg twice daily and 200 mg four times daily of oxmetidine were superior to placebo (p less than 0.05) in reducing intragastric acidity during the entire 24-h period.

Prevention of Ulcer Recurrence—Medical vs Surgical Treatment the Physician's View

What factors should be considered in the choice between medical and surgical treatment of peptic ulcer disease? We would suggest the factors included in Table I. It is our opinion that we have concentrated too much on the recurrence rate, that is on how many of the patients who have a recurrence and not so much on the severity of recurrences in terms of symptoms, duration and influence on ability to work. It is also our firm belief that with regard to costs too much attention has been paid to one small part of the total cost, namely the cost for drugs. The strategy in the choice of the treatment for patients with a peptic ulcer depends on many factors as shown in Table II. At our department, the pharmacological part of the treatment of the first episode of an active duodenal ulcer as well as the first recurrences will usually consist of cimetidine 800 mg as a single nocturnal dose or in divided doses, for 4-6 weeks. Antacids are often given for relief of pain. The treatment will be continued for another 2 weeks if the patient is not symptomless after 4 weeks. The patient is then instructed to make further contact in the event of new symptoms suggesting a recurrence. Personally, we usually perform another endoscopy at that time as a guidance for the decision whether to give maintenance treatment or not. If we find an ulcer or signs of duodenitis, we give another 4-6 weeks course of cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of food on the effect of propantheline and L-hyoscyamine on salivation.

The absorption of a quartenary (propantheline, 30 mg) and a tetiary (1-hyoscyamine, 0.8 mg) anticholinergic compound was studied in 8 healthy volunteers by measuring the effects on salivation. Both compounds were administered as rapidly disintegrating tablets, 1-hyoscyamine also in a slow-release formulation (Egazil Durules). The three preparations and placebo were administered under fasting conditions and with a standardized light meal using a randomized cross-over design. Salivation measurement were performed with a citric acid stimulation method every hour for 10 hours. In the fasting patient, all three anticholinergic test preparations decreased the salivation significantly. When taken with food, the effect of propantheline was almost abolished, while the effects of the 1-hyoscyamine preparations were uninfluenced. It was concluded that the clinical effects of proprantheline might be extremely varying depending how the drug is taken in relation to meals. In contrast the clinical effects of 1-hyoscyamine seem to be independent of food intake.