E. J. S. Boyd

Smoking impairs therapeutic gastric inhibition.

Cigarette smoking reversed the inhibition of nocturnal gastric secretion produced by the H2-receptor antagonists cimetidine and ranitidine and by the phenothiazine derivative LM 24056. As a consequence of smoking, nocturnal secretion of acid increased by 91.5% and of pepsin by an average of 59% when compared with control studies when patients did not smoke. The inhibition of pentagastrin-stimulated gastric secretion produced by cimetidine or poldine was not affected by cigarette smoking. Since control of nocturnal secretion may be important in promoting ulcer healing and maintenance of remission, patients receiving antisecretory drugs should be advised not to smoke after having taken their nocturnal dose of the drug.

Safety of Ranitidine Maintenance Treatment of Duodenal Ulcer

During maintenance treatment with nocturnal ranitidine (150 mg) for 1 year, 38% of duodenal ulcers relapsed. Twenty-one patients whose ulcers remained healed after maintenance treatment for 1 year continued to receive ranitidine (150 mg at night) for a further year, while 26 patients with healed ulcers received placebo in a randomized double-blind study. The rate of recurrence of duodenal ulcers during the 2nd year of follow-up study was 18% in ranitidine-treated individuals and 87% in those receiving placebo. The ulcer recurrences of patients receiving ranitidine tended to be asymptomatic and were clinically mild in the rest. Recurrences in patients receiving placebo were usually symptomatic and significantly more likely to be associated with bleeding. We conclude that ulcers that remain healed after 1 years maintenance treatment with ranitidine tend to remain healed if maintenance treatment is continued. Moreover, this type of continuous treatment of duodenal ulcer is clinically safer than no treatment of the ulcer disease.

The fate of asymptomatic recurrences of duodenal ulcer.

Thirty-six patients in whom an asymptomatic duodenal ulcer had been detected endoscopically were followed up clinically and endoscopically during the following months. Ten of the patients were receiving either no treatment or placebo, and 26 patients were receiving maintenance treatment with either 150 mg ranitidine or 400 mg cimetidine at night. Treatment remained unchanged during the follow-up period. The cumulative annual rate of spontaneous healing was approximately one quarter, whether or not patients were receiving active maintenance therapy. However, the likelihood of developing symptoms during the year after detection of the asymptomatic ulcer was significantly greater in those patients receiving no treatment or placebo (77%) than in those receiving active maintenance therapy (27%). One patient, receiving no treatment, bled from his ulcer during the follow-up period. We conclude that routine endoscopic reexamination, to detect asymptomatic ulcer recurrences in patients receiving maintenance treatment for duodenal ulceration, is probably unnecessary, since the recurrences rarely cause clinical problems, despite prolonged failure to heal.

Effects of treatment compliance and overnight gastric secretion on outcome of maintenance therapy of duodenal ulcer with ranitidine.

Eighty-seven patients with endoscopically healed duodenal ulcers received continuous maintenance treatment with a standard dose of 150 mg ranitidine at night for 6-12 months. The cumulative annual rate of symptomatic reulceration was 24%, whereas a further 25% of asymptomatic relapses were detected with routine endoscopic examination. Compliance with drug therapy was assessed by urinalysis for ranitidine and by returned tablet count. Urinalysis appeared to provide the more accurate index of drug intake. Compliance was similar in patients whose ulcers remained healed after 1 years treatment and in patients with asymptomatic recurrence. Patients who developed symptomatic recurrences showed significantly poorer compliance in the period before development of symptoms. Overnight secretion of acid and pepsin during treatment did not differ between patients whose ulcers remained healed and those with relapses. Poor compliance was not implicated in the development of recurrence in patients who had good inhibition of overnight gastric secretion. We conclude that duodenal ulceration can recur during nocturnal maintenance treatment despite good compliance and satisfactory inhibition of nocturnal gastric secretion. However, symptomatic manifestation of the recurrences reflects poor compliance with treatment.

Pancreatic Synthetic Rates: A New Test of Pancreatic Function

Synthesis of pancreatic enzymes was measured in 7 patients with chronic pancreatitis and 10 patients with no pancreatic disease, on the basis of the incorporation of 75Se-methionine into pancreatic exocrine proteins. Two of the patients with chronic pancreatitis had normal exocrine function. Pancreatic secretion was stimulated by intravenous infusion of secretin (1 clinical unit x kg-1 x h-1) and cholecystokinin (1 Ivy dog unit x kg-1 x h-1). 75Se-methionine (3.0 microCi x kg-1) was added to the infusion. Synthetic rates were significantly greater in all the patients with chronic pancreatitis, including the two individuals with normal responses to stimulation with secretin and cholecystokinin. Studies of synthetic rates may therefore be able to confirm the diagnosis of chronic pancreatitis before exocrine insufficiency becomes manifest.

Omeprazole inhibits nocturnal and pentagastrin-stimulated gastric secretion in Man

The effect of omeprazole on the overnight and pentagastrin-stimulated gastric secretion of acid and pepsin have been studied in healthy male volunteers. After treatment with omeprazole, 30 mg or 60 mg daily for one week, overnight secretion of acid was reduced by 48 and 73%, respectively. During stimulation with pentagastrin, a single dose of 40 mg omeprazole reduced acid output by 98%, while after 80 mg, secretion of acid and pepsin was completely abolished. Omeprazole is one of the most potent gastric secretory inhibitors available at present, with potential for use in the therapy of ulcer disease.The effect of omeprazole on the overnight and pentagastrin-stimulated gastric secretion of acid and pepsin have been studied in healthy male volunteers. After treatment with omeprazole, 30 mg or 60 mg daily for one week, overnight secretion of acid was reduced by 48 and 73%, respectively. During stimulation with pentagastrin, a single dose of 40 mg omeprazole reduced acid output by 98%, while after 80 mg, secretion of acid and pepsin was completely abolished. Omeprazole is one of the most potent gastric secretory inhibitors available at present, with potential for use in the therapy of ulcer disease.

Pancreatic enzyme synthesis in pancreatic disease.

In a prospective evaluation of patients suspected of having chronic pancreatitis, synthesis of pancreatic enzymes was measured by means of the incorporation of selenium-75-labelled methionine into the proteins of duodenal aspirate during stimulation of pancreatic secretion with secretin (1 CU X kg-1 X h-1) plus cholecystokinin (CCK) (1 IDU X kg-1 X h-1). The rate of pancreatic enzyme synthesis was increased in patients with chronic pancreatitis. Measurement of pancreatic enzyme synthesis was more sensitive in the detection of chronic pancreatitis than either the bicarbonate or the trypsin secretory response to secretin plus CCK. A combination of the bicarbonate secretory response with measurement of the rate of enzyme synthesis provided a positive predictive power of 100% when both tests were abnormal and a negative predictive power of 100% when both tests were normal, so that the combined test can be recommended both for excluding and confirming the presence of chronic pancreatitis.

INHIBITION OF PENTAGASTRIN-STIMULATED AND OVERNIGHT GASTRIC SECRETION BY LM24056, A NEW PHENOTHIAZINE-DERIVED ANTISECRETORY DRUG

LM24056, a tricyclic drug, weakly inhibited pentagastrin-stimulated gastric secretion but was a powerful inhibitor of nocturnal gastric secretion in 5 healthy volunteers. In 23 patients with duodenal ulcer, LM24056 at doses of 100,200, and 300 mg inhibited overnight acid output by 31%, 70%, and 81%, and overnight pepsin secretion by 15%, 50%, and 69%, respectively. In view of its gastric inhibitory effects, LM24056 warrants clinical evaluation in the treatment of peptic ulcer disease.

Effects of some polycyclic drugs on gastric secretion and on the healing of duodenal ulcers.

Polycyclic drugs such as the dibenzazapine trimipramine have been shown to accelerate the healing of gastric and duodenal ulcers, possibly by inhibiting gastric secretion. We have therefore compared the effects of three polycyclic drugs (trimipramine, mianserin and quisultidine) on nocturnal and pentagastrin‐stimulated gastric secretion. The patterns of the effects of the three drugs on gastric secretion differed. Although pentagastrin‐stimulated secretion of acid was inhibited by trimipramine (13%), mianserin (38%), and quisultidine (29%), overnight gastric secretion was inhibited by mianserin (37%) and quisultidine (78%) but increased by trimipramine (16%). In view of its gastric inhibitory actions, the effects of mianserin on the healing of duodenal ulcers have been studied. In a pilot open trial seven out of eight duodenal ulcers healed after four weeks of treatment with mianserin 60 mg at night. A controlled, randomized long‐term study is now scheduled in order to assess the role of mianserin in the management of ulcer disease.

Effects of a mast cell stabiliser (FPL 52694) on human gastric secretion

The effects of a new monochrome mast cell stabilizer (FPL 52694) on gastric secretion have been studied in healthy volunteers. When administered orally for 3 days, FPL 52694 consistently reduced nocturnal and pentagastrin-stimulated secretion of acid by about 50%. Mealstimulated gastric secretion was not affected by the drug. Inhibition of the gastric secretory response to pentagastrin was not significant when single doses of the drug were administered either into the stomach or the duodenum, but administration of multiple doses resulted in significant inhibition. The drug does not inhibit gastric secretion by injuring the gastric mucosa, since the gastric mucosal barrier to back diffusion of hydrogen ions is not affected. We conclude that this mast cell stabilizer provides an interesting tool for studying aspects of the physiological control of gastric secretion and may have a therapeutic role in peptic ulceration.