The effect of glucagon on aspirin-induced damage to human gastric mucosa and its effect on gastric mucosal potential difference were studied in 27 healthy volunteers. Intragastric instillation of 600 mg of aspirin suspended in 100 ml of isotonic saline caused significant damage to 21 +/- 3% of surface epithelial cells and a marked reduction in gastric potential difference within 15 min of aspirin instillation. Glucagon, 2 mg given intravenously, caused hyperglucagonemia, hypophosphatemia, hyperinsulinemia, increased blood glucose levels and gastric pH, as well as significant prolonged elevation of gastric potential difference. Glucagon injection given 15 min before aspirin instillation effectively prevented surface epithelial cell damage, decreasing percentage of damaged cells to 3.5%. Glucagon did not prevent the drop in gastric potential difference evoked by aspirin, but did, however, prevent potential difference from falling below base line values after aspirin. This study showed in man that glucagon protects gastric mucosa against aspirin damage and suggests possible therapeutic value in clinical situations requiring prevention of aspirin-induced gastric mucosal damage.

Aspirin induces gastric mucosal damage and bleeding in the presence of acid. Cimetidine, the histamine H2-receptor antagonist, reduces basal and stimulated acid secretion. Arthritic patients taking fixed doses of aspirin who were found to have aspirin-induced occult gastrointestinal bleeding were given cimetidine in a randomized double blind, crossover study. Autologous 51Cr-labeled blood was measured in 4-day stool collections at the end of each 4-week period of placebo and cimetidine therapy in 22 acid-producing patients. Mean daily fecal blood loss was reduced during cimetidine therapy to 2.2 +/- 0.3 ml per day, compared with 4.1 +/- 0.7 ml per day during placebo therapy (P= 0.002).

The effectiveness of cimetidine for symptomatic relief in patients with chronic gastroesophageal reflux was studied in a multicenter, double blind clinical trial. Patients were entered into the study for a total of 8 weeks, receiving either cimetidine, 300 mg four times daily, or identical placebo tablets. Throughout the trial, frequent assessments were made of symptom severity and frequency, combined with careful measurement of antacid use. Esophagoscopy, esophageal acid sensitivity, and lower esophageal pressures were performed before and at the completion of the treatment period. Significant (P less than 0.05) decreases in symptom frequency and severity were noted throughout the study in the cimetidine-treated patients, as compared with the placebo group. This subjective improvement was corroborated by a concomitant decrease in antacid use, which was significantly (P less than 0.05) reduced in the cimetidine-treated group. In addition, significant improvement in esophageal acid sensitivity resulted from cimetidine therapy. No objective improvement in esophageal endoscopic appearance or sphincter pressures was noted. The results of this double blind trial indicate that cimetidine is more effective than the placebo for the relief of symptoms of gastroesophageal reflux.

Two hundred forty patients with benign gastric ulcer were treated in a controlled clinical trial to assess the effect on healing of cimetidine, antacids, and hospitalization. Inpatients and and outpatients were randomly assigned to one of three treatments: cimetidine plus antacid, cimetidine plus dummy antacid, or placebo tablet plus antacid. In 206 patients who met criteria for analysis, ulcer healing as shown by endoscopy occurred by 12 days in 11 to 26 percent and by 42 days in 58 to 76 percent. There were no significant differences in healing between hospitalized and nonhospitalized patients or between treatment subgroups. Symptomatic response was equivalent in all groups. The median antacid consumption was 328 mEq of in vitro buffering capacity per day. Patients taking antacids experienced significant diarrhea compared with those taking no antacid. This investigation suggests that the effect of cimetidine is equivalent to that of large amounts of antacid, but because a true placebo group was not studied it is not possible to conclude from this study alone whether either agent influenced healing. In contrast to widespread belief, initiation of treatment in the hospital did not enhance healing, but because patients were not randomly assigned to inpatient and outpatient status no final conclusion about the effect of hospitalization on healing can be drawn.

A randomized, prospective, multicenter trial of the effects of cimetidine on benign gastric ulcer was conducted in 60 outpatients. Endoscopic assessment was used as the criterion for healing. Although none of the differences was statistically significant, mean healing rates were higher and mean decreases in ulcer size were greater with cimetidine than they were with placebo. Twenty-four per cent of the ulcers healed completely in 2 weeks when cimetidine was administered, compared with a placebo healing rate of 14 percent. At 6 weeks in the incidence of healing increased to 60 percent in the cimetidine group and 41 percent in the placebo group. The mean percentage of decrease in ulcer size was greater at both 2 and 6 weeks in the cimetidine group than it was in the placebo group. In both, the cimetidine and placebo groups, relatively liberal intake of a potent antacids in treatment of gastric ulcers has not been defined definitively. Thus, a possible beneficial effect of cimetidine may have been obscured. For more clear discimination between the effects of cimetidine and placebo in healing of gastric ulcer, studies utilizing either no antacid or antacids of low neutralizing capacity will be needed.

The published world literature on the efficacy of cimetidine, a histamine H2-receptor antagonist, in the treatment of duodenal ulcer is reviewed. In eight prospective randomized double blind placebo-controlled studies, cimetidine was administered to 348 duodenal ulcer patients with an incidence of endoscopically verified healing incidence of 37 percent in 300 placebo-treated patients. Healing rates were similar in patients receiving cimetidine in doses ranging from 0.8 to 2.0 g per day. It appears that at least 3 to 4 weeks of cimetidine therapy are needed to achieve healing rates of about 70 percent. In most trials, cimetidine was superior to placebo in achieving symptom relief in patients with duodenal ulcer. The drug has not been shown to result in acid rebound after cessation of therapy. There are no published prospective studies on the question of whether treatment with cimetidine results in increased ulcer for the short term treatment of duodenal ulcer. More data are required for an assessment of long term therapy with cimetidine.

Sixty patients who had been referred for elective ulcer surgery, and in whom a remission had been induced, entered a prospective double blind controlled trial of a single daily dose of 400 mg of cimetidine given at bedtime, or placebo. Eighty per cent of patients receiving placebo suffered symptomatic relapse and recurrence of duodenal ulceration at endoscopy within 6 months. The mean interval to relapse was 10 weeks. On the other hand, only 27 percent of patients had a recurrence during the 6-month period on low dose cimetidine therapy. No significant toxic or other side effects which could be attributed to the drug were observed.

In a randomized double blind multicenter trial, patients treated with cimetidine (800 or 1200 mg daily) or an intensive regimen of Al-Mg antacid (210 ml daily) had similar rates of duodenal ulcer healing and pain relief. After 4 weeks of treatment, the proportion of patients with ulcer healing by endoscopy were: cimetidine (1200 mg), 21 of 33 (64 percent); cimetidine (800 mg), 19 of 32 (59 percent); and antacids, 15 of 29 (52 percent). These proportions did not differ significantly. Eighty per cent of cimetidine-treated patients became asymptomatic by week 4, as did 63 percent of antacid-treated patients (P greater than 0.1). No untoward effects were observed during cimetidine treatment. Twenty-seven per cent of antacid-treated patients reported diarrhea.

Eighty-five patients with endospcopically confirmed duodenal or pyloric canal ulcers entered a double blind trial with 1200 mg of cimetidine per day or placebo for 6 weeks. Eighty-four per cent of patients treated with cimetidine and 38 percent of those receiving placebo healed their ulcers (P less than 0.001). Measurement of basal acid output and maximal acid output before and after treatment showed no significant change but patients who failed to heal their ulcers had a higher basal acid output and maximal acid output than those who healed. Patients who smoked or drank alcohol had the same healing rate as abstainers. Sity-seven patients with duodenal ulceration healed by a 6-week course of cimetidine were randomly allocated to 400 mg of cimetidine twice daily or placebo in the maintenance trial. Actuarial analysis of the number of relapses in each group demonstrates that cimetidine is highly effective in preventing relapse.

A previous report from this institution demonstrated significant improvement of caloric intake and survival in patients with alcoholic hepatitis and hepatic encephalopathy given prednisolone when compared with placebo. The purpose of this study was to compare the effects of prednisolone with a regimen of 1600 calories per day without prednisolone. Fourteen patients with alcoholic hepatitis and encephalopathy were studied. All 7 on caloric supplementation and 2 of 7 given prednisolone died (p less than 0.01). These results suggest that prednisolone therapy reduces the mortality of those patients with alcoholic hepatitis and hepatic encephalopathy. This effect does not appear to be related to total caloric intake.

Cimetidine inhibits basal and nocturnal acid secretion and acid secretion stimulated by histamine, pentagastrin, caffeine, insulin, sham feeding, and food. Cinetidine (300 mg) inhibits basal acid secretion in duodenal ulcer patients by 95% for at least 5 hr. When taken at bedtime, cimetidine inhibits nocturnal acid secretion by greater than 80% for most of the night. Cimetidine markedly inhibits food-stimulated acid secretion and is more effective than anticholinergic drugs. However, to get adequate suppression of food-stimulated acid secretion throughout the day, cimetidine should be given with each meal. Cimetidine has no effect on nocturnal serum gastrin concentration, but, when stimulated by food, serum gastrin concentration is higher after cimetidine than after placebo.

A double blind trial involving 21 patients on carbenoxolone and 23 patients on placebo was conducted under endoscopic control to assess the healing of duodenal ulcers over a period of 6 weeks. The two groups were adequately matched with the exception that larger ulcers predominated in the carbenoxolone group. Relief of symptoms showed poor correlation with ulcer healing. Fourteen of the 21 patients in the carbenoxolone group and 7 of the 23 in the placebo group showed endoscopic evidence of complete healing. The result is highly significant (P less than 0.016) and confirms the therapeutic efficacy of carbenoxolone sodium positioned-release capsules in the treatment of duodenal ulcers. Side effects of carbenoxolone therapy in the form of weight gain, rise in diastolic blood pressure and hypokalaemia were observed, but with adequate monitoring and appropriate countermeasures, no patient suffered any ill effects.

To determine the amount of lactose that could be tolerated in a meal, 59 lactase-deficient American Indians, ranging in age from 5 to 62, were given graded doses of lactose. The diagnosis of lactase deficiency had beeen documented previously by showing increased breath hydrogen after an oral lactose load (2 g per kg, maximum 50 g). With this load, 88% of the subjects had symptoms. On 6 consecutive mornings, each subject was given a breakfast that contained graded doses of lactose ranging from 0 to 18 g. The order of the breakfasts was randomized and the contents were double-blinded. Symptoms, which were assessed by a "blinded" observer, were present after 9% of the breakfasts at all dosage levels, including the lactose-free breakfast. Thus, under the conditions of this study, a modest amount of lactose, equivalent to that present in 1 to 1 1/2 glasses of milk, when taken with a meal, is well tolerated by the lactase-deficient American Indian.

We have studied the gastric response to an ordinary solid-liquid meal in 12 patients with active duodenal ulcer and 8 healthy volunteers. Our method employs gastric and duodenal markers to quantify acid, pepsin, and volume outputs in response to the meal, without manipulating intragastric pH. Intragastric volume, rate of gastric emptying, delivery of acid into the duodenum, and serum gastrin response were also measured simultaneously. On a separate day, peak acid output in response to betazole (1.5 mg per kg subcutaneously) was determined. Our results indicate an inappropriately prolonged gastric secretory response to meals in duodenal ulcer disease, without a concomitant increase in peak postprandial secretory rates or an increase in serum immunoreactive gastrin levels. Further, the stomach in duodenal ulcer disease did not "retain" the additional acid secreted in the later postprandial period, and abnormally high rates of acid delivery into the duodenum occurred. Our data are consistent with a dual defect in the duodenal mechanisms regulating both acid secretion and acid delivery into the duodenum.