Predictors of duodenal ulcer healing and relapse were examined in a population known to have a high healing incidence. Two double-blind prospective studies were performed in 134 patients over 4 wk and in 66 patients over 1 yr, respectively. Short-term treatment consisted either of cimetidine 1 g/day, pirenzepine 75 mg/day, or placebo. In a multiple stepwise linear regression analysis the following factors proved to increase healing incidence in decreasing order of importance: female sex, moderate alcohol consumption, abstinence from smoking, young age, and cimetidine treatment. The following factors had no influence on duodenal ulcer healing: number and total area of peptic lesions, concomitant disease, relatives with duodenal ulcer, duration of duodenal ulcer disease, and status as a migrant worker. In the long-term study, treatment consisted either of cimetidine 400 mg at bedtime, pirenzepine 30 mg at bedtime, or placebo. Cimetidine prevented ulcer relapse. Smoking favored duodenal ulcer relapse in the placebo group, but not in the cimetidine and pirenzepine group. For all the other factors no statistically significant effect was found. It is concluded that in a population with high spontaneous healing incidence (a) factors other than drug treatment such as sex, alcohol intake, smoking, and age are at least as important predictors of the outcome of short-term treatment as the drug treatment itself; (b) moderate alcohol intake might favor ulcer healing; (c) the unfavorable effect of smoking on ulcer relapse is overcome by low-dose, long-term, antisecretory treatment.

The natural history of gastrointestinal bleeding in cirrhosis has been studied using prospectively collected data of 532 patients included in a randomized clinical trial with a regular follow-up of up to 12 yr. Of the total 199 patients who experienced gastrointestinal bleeding, 95 (48%) bled from esophageal or gastric varices, 67 (34%) bled from peptic ulcer or gastritis, and 37 (18%) had either insufficient evidence of the source (33) or mixed sources (4). In the total group of patients the cumulative percentage of patients in whom varices had been demonstrated of patients in whom varices had been demonstrated by radiography increased from 12 to 90 in 10 yr, while that of bleeding from varices increased from 7 to 40. In 104 patients who bled for the first time during the trial period (trial bleeding patients) the median number of bleeding episodes was one (range 1-8). In these patients the fatality from bleeding from varices was 82%. The risk of rebleeding from varices was 81%, and 4 yr after the first bleeding the cumulative survival had decreased to less than 10%. Rebleeding was significantly less frequent and survival significantly higher in patients bleeding from sources other than varices. Prednisone reduced the occurrence rate of varices, bleeding from varices, and death from bleeding varices in nonalcoholic females without ascites, 40% of whom fulfilled the histologic criteria of chronic active hepatitis. Prednisone significantly increased the occurrence rate of varices inpatient with ascites and of bleeding from varices in alcoholic patients. Prednisone significantly increased the occurrence rate of peptic ulcer in males and in patients without chronic active hepatitis.

Duodenogastric reflux may have pathophysiologic importance, but its mechanism is poorly understood. We propose that duodenogastric reflux and periodic changes in motor and secretory activity of the upper gut during fasting may be related. Therefore we determined the relationships between duodenogastric reflux and interdigestive motor-secretory cycles in a group of 6 healthy individuals, on each of whom we performed three 7-h studies in random order on separate days. In all studies gastric intubation and antral pressure recordings were performed. However, in design 1 we used a slow duodenal perfusion rate of [14C]PEG in saline (0.25 ml/min) while in design 3 we used a fast perfusion rate (3.0 ml/min). Duodenal pressures were also recorded during these designs. In design 2 no transpyloric tubes were present. Our study shows that, in humans, fasting duodenogastric reflux of bile and pancreatic juice is cyclic and closely related to the interdigestive migrating motor complex. Reflux is highest during late phase II (when secretory activity is also on the rise) and lowest after phase III. One of the important functions of the migrating motor complex in humans may be to clear the stomach of refluxed duodenal secretions.

Serum amino acid levels were determined in 29 patients with severe chronic active liver disease before, during, and after administration of prednisone or placebo and in 22 healthy controls. The pretreatment molar ratio of amino acids was less in patients than in controls (p less than 0.001) and was lower in those with cirrhosis (p less than 0.02). Branched-chain amino acid levels were elevated in patients without cirrhosis (p less than 0.02) but not in those with cirrhosis; aromatic amino acid concentrations were increased in all (p less than 0.01). The ratio improved with remission and predicted behavior after discontinuation of treatment. Patients who deteriorated failed to improve the ratio and those whose ratio improved incompletely relapsed. The ratio correlated with histologic severity and serum concentrations of albumin, bilirubin, and gamma-globulin and not with clinical manifestations of encephalopathy. We conclude that amino acid abnormalities reflect liver dysfunction and that normalization of the molar ratio may have therapeutic and prognostic significance.

The administration of insulin of hypercatabolic patients with burns or multiple fractures has been shown to be associated with increased nitrogen retention during intravenous nutrition (IVN) with solutions of amino acids and hypertonic dextrose. It is not known if gastroenterologic patients in whom the degree of stress is much less, show a similar response. In a controlled study of two comparable groups of 16 gastroenterologic patients on a surgical service who received IVN for 2 wk the changes in body weight, fat, water, protein, and potassium that occurred were measured. The control group received a nutrient solution of hypertonic glucose and amino acids (44.7 +/- 9.0 kcal/kg/day) and the comparative group (45.9 +/- 6.6 kcal/kg/day) in addition had 30 IU of soluble insulin added to each 1006 kcal of nutrient solution. Both groups of patients gained similar amounts of weight, fat, and water, and body protein was maintained to the same extent. Those patients receiving insulin demonstrated a gain of total body potassium (p less than 0.001). The results show that the routine administration of insulin is not indicated in this type of patient, provided that glucose intolerance is absent.

A randomized, double-blind comparison of lactose enemas plus placebo tablets vs. starch enemas plus neomycin tablets was performed on 18 patients with acute portal systemic encephalopathy. Ten patients received starch enemas (10%; 1000 ml t.i.d.) plus neomycin tablets and 8 patients received lactose enemas (20%; 1000 ml t.i.d.) plus placebo tablets. A significant mental state improvement was demonstrated in the group of patients treated with starch enemas-neomycin tablets (p less than 0.05) and in the group of patients treated with lactose enemas-placebo tablets (p less than 0.025). Both treatments significantly improved the frequency of asterixis, ammonia blood levels, and electroencephalograms. In addition, patients treated with lactose enemas showed significant improvement in number-connection test times (p less than 0.02), and their stools showed a more acid pH (p less than 0.05). No side effects were evident with either treatment. Lactose enemas are a safe and effective treatment for acute portal systemic encephalopathy.

Fifty consecutive patients with symptomatic endoscopically proven duodenal ulcer were randomized double-blind to Mylanta II or cimetidine treatment schedules. Smoking habits were noted, but patients were not advised to alter these. Healing was determined by reendoscopy at 6 wk. Eighty percent of patients on active cimetidine and 52% on active Mylanta II had healed at 6 wk (not significantly); 85% of nonsmokers healed compared to 44% of smokers (p less than 0.03). In smokers, cimetidine achieved healing in 50%, Mylanta II in 39% (not significantly); while in nonsmokers, cimetidine achieved healing in 100%, Mylanta II in 67% (not significantly). These results indicate a significant and equally adverse effect of smoking on the healing rate of duodenal ulcer achieved by either cimetidine or Mylanta II.

A randomized, double-blind, controlled trial of insulin and glucagon infusion was conducted in 50 patients with acute alcoholic hepatitis. Twenty-five treatment patients received 24 U regular insulin and 2.4 mg glucagon over 12 h daily for 3 wk. Twenty-five control patients received 200 ml dextrose solution in identical bottles over the same time period. Six control and 2 treatment patients died from liver failure during study, and another treatment patient died from hypoglycemia. In the 34 patients with prothrombin times greater than 3 s prolonged, fewer deaths occurred among the insulin- and glucagon-infused patients (p less than 0.10). Clinical features of liver disease on entry into the study were similar in the two groups, and total serum bilirubin and prothrombin time improved more rapidly in the treatment group (p less than 0.05). Insulin and glucagon infusion is a promising treatment of alcoholic hepatitis and merits further study in the most severely ill patients.

One hundred and forty-one attempts at percutaneous transhepatic variceal obliteration were made in 116 patients with portal hypertension complicated by variceal hemorrhage. Varices were successfully obliterated in 80% of procedures and included 37 patients with continuous, acute variceal hemorrhage. Hemorrhage ceased immediately in these patients. Sixty-five percent of patients rebled a mean of 4.6 mo after successful transhepatic variceal obliteration. A randomized controlled trial against conventional medical therapy (29 treatment, 25 control) failed to show a significant reduction in death rate after transhepatic sclerotherapy, although the onset of further variceal hemorrhage was delayed. Follow-up portography in 50 patients demonstrated new vessel formation in 38 patients and recanalization of previously occluded varices in 5 patients. Complications arose in 29 of 141 procedures. There was one death but all the other complications responded to conservative management. Transhepatic variceal obliteration is an excellent, safe emergency treatment for variceal hemorrhage, especially in patients with decompensated liver disease. A high incidence of rebleeding is a long-term disadvantage and means that transhepatic variceal obliteration should not be used for the prophylaxis of variceal hemorrhage. Successful emergency treatment of variceal hemorrhage should be followed by elective portal decompression in suitable patients.

A controlled trial has been undertaken to evaluate adenine arabinoside in the treatment of hepatitis B surface antigen-positive chronic liver disease. Thirteen patients (7 hepatitis B virus DNA polymerase and hepatitis B e antigen-positive, 6 DNA polymerase negative and hepatitis B e antibody-positive) were treated with adenine arabinoside. Eleven comparable patients served as controls, and follow-up was for 6 mo. In the 7 hepatitis B e antigen-positive patients, adenine arabinoside produced a fall in DNA polymerase activity during treatment. When this effect was sustained, it was followed by a loss of e antigen (3 patients). Hepatitis B surface antigen concentrations and aspartate transaminase levels fell significantly at 6 mo (p less than 0.05) in the treated group compared with controls. In the hepatitis B e antibody-positive patients, adenine arabinoside treatment produced no significant change in hepatitis B surface antigen concentrations or aspartate transaminase levels at 6 mo as compared with controls. Adenine arabinoside would appear to reduce either transiently or permanently, hepatitis B virus replication, and it may therefore be useful in reducing the infectivity of some carriers of this virus. In the dose used, adenine arabinoside was ineffective in clearing hepatitis B surface antigen from the serum and eradicating hepatitis B virus from the liver, but combination with other antiviral or immunostimulant agents may enhance its therapeutic effectiveness.

During a 7-yr period (1967-1974), 89 patients with alcoholic liver disease and at least one severe upper gastrointestinal hemorrhage thought to be from esophageal varices entered a randomized, controlled trial of medical therapy vs. end-to-side portacaval shunt. Follow-up continued to September, 1979, so that all surviving patients had at least 5 yr observation after randomization. Among 45 patients randomized to surgical therapy, 4 did not receive portacaval shunt, for various reasons. Among shunted patients there were 11 episodes of upper gastrointestinal bleeding, none fatal and none thought to be from esophageal varices. Thirty-seven percent of eligible patients have had moderate or severe hepatic encephalopathy ascribed to the shunt. Of 44 patients randomized to medical therapy, 7 eventually received portacaval shunt after multiple bleeding episodes. Since randomization there have been 190 episodes of bleeding requiring 589 transfusions and resulting in 23 deaths from bleeding or hepatic failure precipitated by bleeding. THere are 12 survivors in the surgically treated group and 8 in the group treated medically. Life-table analysis shows a small increase in survival in the surgically treated group throughout the study, which is not statistically significant. From our data, we could not identify risk factors that would improve the selection of patients for medical or surgical therapy.

A prospective and randomized study was performed comparing pneumatic forceful dilatation and surgical esophagomyotomy as primary treatment of patients with achalasia of the esophagus. Eighteen dilated and 20 operated patients were studied before and after treatment with 1 patient lost. Clinical, radiologic, and manometric evaluations were performed before and after treatment and acid reflux test in the late follow-up period. Immediately after treatment, a significant improvement was seen clinically, by radiologic studies and after manometric evaluation. In the late follow-up period, operated patients showed a permanent improvement in all of them, but dilated patients remained a symptomatic in about 50% of the cases. The rest had to be redilated or reoperated on due to a failure of primary dilatation leading to final good or excellent results in 60% and failure in 40% of patients. Acid reflux test showed a positive test in 31% of the operated patients and in 7% of the dilated patients. This controlled study suggests that surgical treatment of achalasia, used as primary treatment, is accompanied by significantly better long-term results compared with pneumatic dilatation according to the technique utilized by us.

The effect of natural motilin on the rate of gastric emptying of 200 ml 25% glucose was studied in seven subjects using a 99mtechnetium tin colloid marker. On the control day the subjects received intravenous saline while on the test day they received a motilin infusion of 0.2 pmol/kg/min. Infusions were blind and given in random order. Thirty minutes after glucose ingestion, 25.5 +/- 2% of the isotope had emptied during motilin infusion, compared with 11.0 +/- 1.5% with saline (p < 0.005). Plasma motilin concentrations rose from a basal value of 23 +/- 5 pM to 57 +/- 9 pM during the motilin infusion. The faster emptying rates after motilin were reflected in a faster rise of plasma glucose and insulin. The rate of emptying of 99mtechnetium-labeled double cream (200 ml, 24 g fat) was measured in 5 subjects. The rate of gastric emptying of the cream was unaffected by exogenous motilin. Gel chromatographic analysis of basal plasmas revealed two immunoreactive motilin peaks. After ingestion of cream during motilin infusion, there was an increase of the second peak but a reduction of the first peak whereas both peaks rose on the control day. Thus low-dose exogenous motilin stimulates the gastric emptying of glucose but not of fat.

A prospective, double-blinded, randomized trial of corticosteroid therapy in patients with severe acute viral hepatitis has been conducted. At the same time, we have examined the prognostic significance of the presence of bridging necrosis in liver biopsies obtained from such patients as well as the predictive value of certain serologic markers. Forty-two of the 77 patients admitted to the trial were shown to have bridging necrosis on their initial biopsies. Two patients progressed to death with massive hepatic necrosis, while 5 patients developed chronic liver disease. A complicated course could not be predicted by the initial biopsy findings nor by any of the serologic markers assessed. We could not identify any clinical or epidemiologic features with prognostic impact. No advantage was demonstrated to be associated with the use of corticosteroids early in the course of severe viral hepatitis.

The effects of tiotidine, a new histamine H2-receptor antagonist, and cimetidine on food-stimulated gastric acid secretion were evaluated in duodenal ulcer patients. Homogenized steak meals were infused immediately after, 1 h after, 5 h after, and 10 h after an oral dose of medication, and food-stimulated acid secretion was measured by in vivo intragastric titration. Tiotidine and cimetidine had a similar onset of action; however, tiotidine was more potent and had a longer duration of effect. Increased potency was demonstrated by the fact that from 1 to 2 h after medication 150 mg tiotidine inhibited acid secretion to approximately the same extent as did 300 mg cimetidine, and by the fact that for a given percent inhibition of acid secretion, plasma tiotidine concentration was eight to nine times lower than plasma cimetidine concentration. Longer duration of effect was demonstrated by the fact that from 5 to 7 h after medication, acid secretion was inhibited by 80% and 97% with 150 and 300 mg tiotidine, respectively, whereas 300 mg cimetidine inhibited acid secretion by only 22%. Also, 10-12 h after medication, 150 and 300 mg tiotidine inhibited acid secretion by 22% and 53%, respectively, while 300 mg cimetidine had no inhibitory effect. The long duration of effect was due in part to increased potency and in part to a plateau in plasma concentration of tiotidine, which was maintained from 2 to 6 h after medication. Neither tiotidine nor cimetidine had a significant effect on food-stimulated gastrin release or gastric emptying of a nonabsorbable marker.