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.

Heptadecapeptide gastrin I (G-17) contrast the lower esophageal sphincter (LES) in man and animals. Previous studies in man found that atropine infusion (12 microgram kg-1hr-1) inhibited the effect of gastrin on the LES, suggesting that this effect of gastrin is mediated by a cholinergic mechanism. Studies in the opossum have not shown similar inhibition. To reevaluate the interaction of atropine and G-17 on the LES, 5 normal males were studied. Submaximal and maximal effective doses of G-17 were used with both atropine infusion (12 microgram kg-1hr-1) and rapid intravenous injection (1 mg). There was a small decrease in basal LES pressure with atropine infusion. However, neither atropine infusion nor rapid intravenous injection inhibited LES stimulation by submaximal and maximal doses of G-17. The results do not support the hypothesis that LES responses to gastrin are mediated by an atropine-sensitive cholinergic mechanism.

We tested whether human duodenojejunal mucosa is able to synthesize apoproteins from amino acid precursors because lipoprotein-like particles are visualized by electron microscopy in human absorptive cells and because apoproteins are synthesized by the perfused rat intestine. Duodenojejunal biopsies from 21 normal fasting volunteers were incubated with L-[U-14C]leucine; 15.6 +/- 3.3 nmoles of the [14C]leucine was incorporated into protein by 100 mg wet weight of biopsies during an incubation of 2 hr. No [14C]leucine was incorporated by boiled biopsies. Homogenates of incubated biopsies were fractionated by ultracentrifugation: 43 +/- 2% of the incorporated 14C as found in the d less than 1.006 fraction; 3.2 +/- 0.6%, 8.1 +/- 1.0% and 48 +/- 2% were found to be associated with the d = 1.006 to 1.063, d = 1.063 to 1.25, and d greater than 1.25 fractions, respectively. The specific activity in the d less than 1.006 fraction was 5.6 times greater than that in the other fractions. Of the 14C incorporated into the d less than 1.006 fraction, 10.8, 7.2, and 7.1% were specifically precipitated by rabbit antihuman apoproteins A-I, A-II, and B, respectively. Of the 14C incorporated into the d = 1.006 to 1.063 fraction, 11.3 4.1, and 8.5% were specifically precipitated by rabbit antihuman apoprotein A-I, A-II, and B, respectively. Approximately 5% of the 14C incorporated by the d = 1.063 to 1.25 fractions were precipitated by rabbit antihuman apoprotein A-I or A-II. None of the d less than 1.25 fractions precipitated a significant amount of radioactivity with rabit antihuman apoprotein C-II, or antiarginine-rich apoprotein. None of the antibodies precipitated radioactivity from the d greater than 1.25 fraction. These experiments suggest that human duodenojejunal mucosa is able to synthesize in vitro apoproteins A-I, A-II, and B from amino acid precursors. The specificity of the immunoprecipitates was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis.

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.

Recent data seem to support a tubular defect as the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon has been proposed by some to be an important factor in this phenomenon. To examine the role of glucagon as this "tubular dysfunction factor", we investigated the effect of intravenously infused glucagon on the fractional excretion of amylase and the tubular handling of a low molecular weight protein, beta2 microglobulin, in normal, healthy volunteers. At glucagon levels far in excess of those seen in pancreatitis, the clearance ratio of beta2 microglobulin relative to creatinine increased, whereas the clearance ratio of amylase relative to creatinine did not increase above the normal range. The dissociation between beta2 microglobulin clearance and amylase clearance allows one to question the theory that tubular dysfunction is the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon does not appear to be the sole factor responsible for the elevation of renal clearance of amylase relative to creatinine in acute pancreatitis.

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.