The effect of an infusion of natural motilin on the rate of gastric emptying of a standard breakfast was studied in 5 subjects using Caesium 129-tagged resin particles. Emptying rates were measured on 4 separate days. On 2 days, the subjects receive only saline (controls), while on the other 2 days a motilin infusion of 0.34 pmol/kg/min for 60 min, followed by 0.68 pmol/kg/min for 60 min, was given. All infusions were blind and given in random order. At the end of the low-dose motilin infusion 31 +/- 4% of the meal had emptied, compared with 17 +/- 2% with saline infusion (P less than 0.01). A similar effect was also seen with the high-dose infusion. Plasma motilin concentrations rose from a basal of 68 +/- 13 pmol/liter to 126 +/- 10 pmol/liter during low-dose motilin infusion and to 170 +/- 11 pmol/liter during the high dose. No significant change in basal or postprandial levels of glucose, gastrin, pancreatic glucagon, pancreatic polypeptide, gastric inhibitory peptide, enteroglucagon, or vasoactive intestinal peptide was noted, but postprandial insulin release was greater during motilin infusion.

Obese subjects are prone to supersaturated bile, which is maintained or increased during weight loss. In this report, two related studies were carried out on obese subjects to investigate effects of bile acid feeding on biliary lipid metabolism before and during weight reduction. In one study, chenodeoxycholic acid (CDCA), 750 mg/day, was given to 12 obese subjects during weight maintenance (1st mo) and during weight reduction (2nd mo). In the second study, effects of two bile acid preparations, CDCA and Bilron (containing mostly cholic acid and deoxycholic acid), randomly administered, were compared in another 12 obese subjects undergoing weight reduction. The results show that obese subjects had large pools of bile acids during weight maintenance which decreased on caloric restriction (1,000 kcal/day). CDCA increased pool size only modestly during weight maintenance, from 3,536 +/- 1,267 (SD) mg to 4,735 +/- 1,434 mg. Both CDCA and Bilron markedly reexpanded the contracted pool of bile acids in obese subjects on weight reduction. However, significantly reduced saturation of bile occurred only in those on CDCA and weight reductions, whereas supersaturation was unaltered when weight was maintained constant in these patients, or when Bilron was given. No significant side effects were noted during bile acid feeding for any of the subjects. Thus, CDCA given to obese subjects on weight reduction will reduce bile saturation and could protect against gallstones.

The effect of aluminum-magnesium hydroxide tablets (800 mg seven times per day) and that of sulpiride, a hypothalamic neurolaptic, were studied in 101 patients with duodenal ulcer in a double-blind controlled 4-wk trial. Significantly more of the patients treated with antacid, sulpiride, or antacid-sulpiride combination showed a greater than 50% reduction in ulcer size than did the patients treated with placebo. However, only in the antacid- and antacid-sulpiride-treated groups did the ulcer, with and without residual inflammation, disappear statistically more often than in the placebo-treated group. Furthermore, only in the antacid-sulpiride-treated group did complete healing, with no trace of inflammation, occur statistically more often than in the placebo-treated group. Disappearance of ulcer pain was likewise statistically more frequent in the antacid-sulpiride group than in the placebo-treated group. Antacid therapy with aluminum-magnesium hydroxide tablets appears to accelerate the rate of ulcer healing. Sulpiride appears to have a minor but definite synergism with antacids. Cigarette smoking affected ulcer healing adversely; on the other hand, factors favorable to healing were the early onset age of ulcer symptoms and acid hypersecretion. Male patients also healed more favorably than females.

The relationship between alcoholic liver disease and circulating thyroid hormones was investigated in 124 hospitalized patients treated with placebo or propylthiouracil (PTU) for a maximum of 46 days in a double-blind study. Serum triiodothyronine (T3) levels on admission were significantly (P less than 10(-6) and inversely correlated with the severity of alcoholic liver disease. After hospitalization, changes in T3-levels in patients with low admission T3 significantly correlated (P less than 0.001) with the degree of spontaneous improvement of liver function (placebo group). Treatment with 300 mg of PTU daily (Orrego et al. Gastroenterology 76:105--115, 1979) markedly increased the rate of improvement in severely ill patients with low T3 on admission. In this group, serum T3-levels were also increased after PTU, but this increase did not correlate with the change in the patient's condition. It is suggested that the known inhibitory effect of PTU on peripheral deiodination of T4 to T3 is marked by a more marked improvement in liver function in this group. PTU treatment in this group reduced the free T4-index and increased TSH levels markedly (16%; P less than 0.02) toward levels found in hypothyroidism. PTU did not improve the condition of mildly ill patients with normal admission T3-levels, nor did it alter free T4-index or serum TSH levels in these patients. Serum T3-levels provide a sensitive indicator of the severity of alcoholic liver disease and of its response to conventional treatment. Serum T3-levels also distinguish between a group of patients, in whom low-dose PTU administration results in a beneficial effect, and another group, in whom no therapeutic effect of PTU is observed.

The effect of propylthiouracil (PTU; 300 mg/day) on alcoholic liver disease was evaluated in 133 patients in a short-term randomized double-blind trial. Severity of the disease was assessed by a composite clinical and laboratory index (CCLI). A normalization rate (NR) representing the rate of improvement in CCLI was calculated. Patients with alcoholic hepatitis, with and without cirrhosis, showed a significantly higher NR on PTU (43.6 +/- 4.6) than on placebo (19.8 +/- 3.3; P less than 0.001). A similar effect was observed in patients with abnormal prothrombin (no biopsy): NR was 32.9 +/- 6.9 on PTU and 2.6 +/- 3.7 on placebo (P less than 0.005). The effect of PTU on each clinical and laboratory component of the CCLI was also compared in these two groups. In 38 patients with alcoholic hepatitis and in 25 with abnormal prothrombin, those on PTU showed a greater improvement in 15 of 15 items (P less than 0.001) and 14 of 15 (P less than 0.01), respectively. When patients were divided according to the severity of the disease into those in the lower and upper halves of the CCLI range (81 and 52 patients, respectively), PTU was shown to have a significant effect only in the latter: The NR was 41.4 +/- 3.8 on PTU and 22.5 +/- 4.2 on placebo (P less than 0.005). PTU was ineffective in patients with inactive cirrhosis.

To investigate the effectiveness and safety of the Sengstaken-Blakemore (SB) tube compared with the Linton-Nachlas (LN) tube, a randomized clinical trial was carried out between both types of balloon. Seventy-nine patients suffering from gastrointestinal bleeding attributed to esophagogastric varices were included in the study. Both types of esophageal tamponade showed great effectiveness in obtaining primary hemostasis (86%), but when the bleeding was from esophageal varices, the SB tube achieved permanent hemostasis more frequently (52%) than did the LN tube (30%). In bleeding gastric varices the SB tube failed in all of the cases, but primary hemostasis was obtained with the LN tube in 50% of them. Better tolerance and greater effectiveness were obtained when the SB tube was applied without external traction. The usefulness of esophageal tamponade for bleeding varices was higher when performed within 6 hr of the onset of hemorrhage.

Fifty-five patients with alcoholic hepatitis were studied in a 28- to 32-day randomized double blind treatment trial comparing prednisolone (40 mg per day) with placebo therapy. Of 31 placebo-treated patients, 4 died during the study interval and 2 more died within 5 days of study completion. Only 1 of 24 prednisolone-treated patients died during the same interval (Fisher exact test; P = 0.10). Stepwise discriminant analysis of laboratory factors associated with death revealed independently significant associations with prolongation of prothrombin time and height of serum bilirubin at the initiation of the study. When treatment was included as a variable in this discriminant analysis, it was found that corticosteroid therapy significantly decreased mortality (P less than 0.05). The corrected wedged hepatic venous presure decreased to a similar extent in the two groups. These studies suggest that corticosteroid therapy does decrease early mortality in patients with severe alcoholic hepatitis, but has no short term effect on the development of portal hypertension.

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.

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).

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.