One hundred and fifty subjects were studied in a double blind fashion to determine the relationship between lactose malabsorption and milk lactose intolerance. Each participant received 250 ml of a different type of milk on 3 consecutive days. Milk A contained no lactose, milk B had 12.5 g, and milk C contained 37.5 g of lactose. After the experiment was completed each subject was classified with a lactose tolerance test as having "sufficient" or "insufficient" lactase activity. Milk A produced no gastrointestinal symptoms in either sufficient or in insufficient persons. Milk B produced symptoms in 3.8% of sufficient and 37.1% of insufficient individuals, and Milk C induced symptoms in 7.6% of sufficient and 83.5% of insufficient subjects. These differences are very highly significant (P less than 0.0001). It is concluded that lactose-intolerant subjects are indeed milk-intolerant and that the frequency with which symptoms occur in persons with lactose malabsorption increases in direct relation to the lactose content of the milk.

The effectiveness of prophylactic ingestion of a commercial preparation of lactobacilli (Lactinex) for the prevention or modification of traveler's diarrhea was tested in a randomized double blind clinical trial in 50 volunteer travelers to Mexico from the United States. Twenty-six subjects received the lactobacilli preparation and 24 received placebo. The incidence of diarrhea and its duration during the 4 weeks of observation were quite similar for the two preparations: 35% for lactobacilli-treated subjects and 29% for placebo subjects. Typically, the diarrhea was mild, lasting 2 days. From the observations during this study we conclude that prophylactic ingestion of lactobacilli for 1 week does not reduce the incidence or duration of traveler's diarrhea either during the period of ingestion or during the following 3 weeks.

The efficacy of cimetidine (1.6 g per day) was evaluated using a double blind placebo-controlled trial in 24 patients with moderate or severe peptic reflux esophagitis. The results show that cimetidine is superior to placebo when using endoscopic and histological criteria. Improved patient symptomatology and lower antacid comsumption failed to reach statistical significance. No change in the abnormally low lower esophageal sphincter pressure was observed at the end of the trial. No clinical side effects or significant biochemical changes were noted during the trial.

Glucagon has been claimed to be an effective treatment for pancreatitis, but the studies reporting this were either uncontrolled or did not use concurrent controls, and none were double blind. To evaluate the efficacy of glucagon for alcohol-related pancreatitis, we performed a controlled, randomized, double blind study. Twenty-six patients with pancreatitis associated with alcohol ingestion received either glucagon or placebo in addition to intravenous fluids, nasogastric suction, and meperidine as needed. There were no statistically significant differences between the group which received glucagon and the group which did not in any of 12 parameters which included symptoms, signs, laboratory tests, and requests for analgesia. We conclude that glucagon in addition to conventional therapy is no better for the treatment of alcoholic pancreatitis than conventional therapy alone.

Cimetidine therapy in gastric ulcer disease has been evaluated in four complete and one incomplete controlled, double blind trials. A sixth trial, still under way, is partially blind. Treatment duration ranged from 2 to 6 weeks; doses ranged from 0.8 to 1.2 g daily. Two studies also evaluated the influence of hospitalization on ulcer healing and symptoms. Relatively large doses of antacid taken with cimetidine confounded the evaluation of cimetidine efficacy in two of the trials, without answering the question of antacid efficacy. Cimetidine was more effective than were small doses of antacid in healing ulcers in one study but was not significantly superior to treatment with larger quantities of antacid in two other trials. Preliminary results indicate that cimetidine is more effective than carbenoxolone in healing ulcers. Hospitalization for 2 and 3 weeks conferred no advantage, but patients were not randomly assigned to hospitalization. Definitive studies on whether cessation of cimetidine therapy is followed by accelerated ulcer recurrence have not been reported. The efficacy of chronic or intermittent cimetidine therapy has not been studied in gastric ulcer disease.

The gastric emptying of the liquid phase of a meal and the fasting antral contractility were studied in 13 patients with reflux esophagitis and in 9 age-matched control subjects. Gastric emptying half-time (t 1/2) in reflux esophagitis patients was no different from that of control subjects (P less than 0.30). Antral contractility (number of antral contractions and the cumulative antral activity), however, was lower in reflux esophagitis patients than in control subjects (P less than 0.001). Oral metoclopramide (15 mg) accelerated gastric emptying, increased the number of antral contractions as well as the cumulative antral activity in patients with reflux esophagitis (P less than 0.001). However, it only increased the cumulative antral activity in normal subjects (P less than 0.01). These results suggest that metoclopramide may be potentially beneficial to reflux esophagitis patients by reducing the volume of gastric contents available for gastroesophageal reflux.

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.