To determine the value of bethanechol in the treatment of erosive esophagitis, a double-blind study was undertaken in which 28 patients were randomized to either bethanechol and antacid, or placebo and antacid. Patients were evaluated clinically, endoscopically, and by esophageal manometry before and after 8 wk of therapy. After treatment both groups showed significant improvement in heartburn and in healing of esophageal lesions. Patients who received bethanechol plus antacids did not show a greater improvement than patients who received placebo plus antacids in any category, nor did patients in the bethanechol-treated group have a greater incidence of complete healing. In addition, pretreatment mean lower esophageal sphincter pressure was normal in approximately 30% of patients with erosive esophagitis and this finding was associated with a greater chance for complete healing of esophageal lesions. These results fail to show that the addition of bethanechol to an intensive antacid regimen is more effective than the antacid regimen alone in the treatment of erosive esophagitis and that patients with esophagitis and normal lower esophageal sphincter pressures respond more favorably to medical treatment.

Four hundred and ten patients with severe watery diarrhea; including 316 patients with cholera, were studied in a double-blind, randomized, placebo controlled trial to determine if chlorpromazine (1 mg/kg) would be useful in the management of such patients. All patients were at least 7.5% dehydrated on admission into the study; all received intravenous fluids followed by oral rehydration solution and all received tetracycline. In addition, one-half of the patients received chlorpromazine, 1 mg/kg, orally as a single dose 2 h after admission. Effectiveness of the chlorpromazine was determined by comparing oral therapy failure rates, purging rates, vomiting rates, i.v. fluid requirements and hospitalization time in groups of the patients receiving and not receiving the drug. In children with severe cholera, e.g., with shock on admission or with very high purging rates, chlorpromazine lowered the oral therapy failure rate by about 50%. However, children with less severe cholera, adults with cholera, and patients of all ages with noncholera diarrhea could not be demonstrated to benefit significantly from the drug. In these groups of patients, oral therapy failures were rare irrespective of whether or not chlorpromazine had been given. We, therefore, do not recommend chlorpromazine in the routine management of patients with watery diarrhea, however, it may be useful in treatment of children with severe cholera when added to standard treatment of hydration and tetracycline.

The most promising endoscopic hemostatic techniques all depend upon heat to coagulate. Four thermally active techniques under similar controlled conditions in this endoscopic study were compared. The study was undertaken to compare the efficacy and histologic damage of monopolar electrocoagulation (MPEC), bipolar electrocoagulation (BPEC), argon laser photocoagulation (ALP) and neodymium-yytrium-aluminum-garnet (YAG) laser photocoagulation applied endoscopically to control bleeding from standard canine gastric ulcers. An open-closed model utilizing a nontraumatic intestinal clamp in heparinized adult mongrel dogs was used. Bleeding ulcers were randomly assigned to an endoscopic treatment modality or control. The endoscopic techniques and parameters of treatment for this study were established from a previous experience with each modality and from endoscopic treatment in pilot studies. Quantitative efficacy and subjective ease of endoscopic treatment were evaluated acutely; gross and histologic injury were determined after 7 days. Our conclusions were that more energy or greater power was required with each method to treat bleeding standard ulcers efficiently through the endoscope than at laparotomy. It was also concluded that each method was 93% or more effective in halting bleeding in this canine ulcer model but there were differences in ease of endoscopic use. Both lasers were much easier to apply than electrocoagulation. The order of decreasing ease of application was YAG, ALP, MPEC, BPEC. Argon laser and BPEC caused significantly less tissue injury than either MPEC or YAG. The order of increasing injury or decreasing margin of safety was ALP, BPEC, YAG and MPEC. In contrast to electrocoagulation, especially monopolar, laser related tissue injury was generally predictable and correlated with total treatment energy, animal weight or gastric overdistension, or both. The limitations, advantages, and disadvantages of each hemostatic technique are discussed and compared.

Sixty-seven patients entered a double-blind, controlled trial to evaluate the efficacy of propylthiouracil treatment in severe alcoholic hepatitis. Twenty-three percent (7 of 31) given propylthiouracil and 19% (7 of 36) given placebo died during the 6-wk study. Propylthiouracil treatment did not reduce the frequency and incidence of complications in alcoholic hepatitis, but induced hypothyroidism in 4 patients. Treatment produced no beneficial effect on any of the hepatic biochemical tests. We were unable to show any beneficial effect of propylthiouracil treatment on morbidity and mortality in patients with severe acute alcoholic hepatitis.

Subjects in the National Cooperative Gallstone Study undergoing 12 mo of therapy with chenodeoxycholic acid for the dissolution of gallstones (low-dose, 375 mg/day, n =252; high-dose, 750 mg/day, n = 253) had a mean increase in serum cholesterol of 20 mg/dl as compared with a 5 mg/dl increase in the placebo group (n = 258). The effect of chenodeoxycholic acid on lipoproteins was determined in a random subset of the high-dose (n = 136) and placebo (n = 143) groups. For men, the mean baseline adjusted estimated low-density lipoprotein cholesterol level at 12 mo was significantly higher in the high-dose group than in the placebo group (159 vs. 148 mg/dl, p less than 0.01), whereas among women this difference was not demonstrated. Change in low-density lipoprotein cholesterol level was inversely related to baseline cholesterol to an equivalent degree in each group among men and women. Women in the high-dose group had significantly lower very-low-density lipoprotein cholesterol levels than did the corresponding placebo group (27 vs. 32 mg/dl, p less than 0.003). Very-low-density lipoprotein cholesterol levels did not differ significantly between the high-dose and placebo group in men. Treatment did not significantly affect the levels of high-density lipoprotein cholesterol or apoproteins A-I, A-II, or B. Chenodeoxycholic acid therapy produces an increase in total cholesterol and low-density lipoprotein cholesterol but does not alter high-density lipoprotein cholesterol levels.

An oral electrolyte solution containing 125 mM/L sodium, 10 mM/L potassium, 80 mM/L sulfate, 20 mM/L bicarbonate, and 80 mM/L of polyethylene glycol, and associated with little water or electrolyte absorption from the gut was recently described in this journal. To determine the efficacy of this solution (Golytely) for colonoscopy, 20 consecutive patients were randomized to either a standard colonoscopy prep or Golytely. Both preps resulted in a feces-free colon, allowing colonoscopy to the cecum in most cases. Although Golytely produced mild cramps (3 of 12) and transient fullness (6 of 12 vs. 0 of 8 with standard prep, p less than 0.02), 11 of 12 were willing to repeat Golytely vs. 3 of 8 with the standard prep (p less than 0.02). It is concluded that Golytely is an effective prep for colonoscopy and well tolerated by patients. It is especially useful for those requiring repeated examinations because of patient acceptance and efficacy.

Fifty-nine outpatients with endoscopically proven duodenal ulcer were evaluated for 4-8 wk in a randomized, double-blind trial comparing sucralfate, a sulfated disaccharide, (1 g, 0.5 h before each meal and at bedtime) with cimetidine (300 mg, 0.5 h before each meal and at bedtime). Ulcer symptoms and their relief were recorded by patients in a diary, along with data on cigarette, alcohol, coffee, and drug intake. Duodenoscopy was performed after 4 wk to assess healing, and was repeated after 8 wk if healing had not occurred by the 4-wk evaluation. Twenty-four of 30 patients taking sucralfate (80.0%) and 22 of 29 patients taking cimetidine (75.9%) had their ulcer completely healed after 4 wk. The overall healing rates after 8 wk for the sucralfate and cimetidine groups were 90.0% (27 of 30 patients) and 86.2% (25 of 29 patients), respectively. There were no significant differences between the two treatment groups in ulcer healing, symptom relief, and side effects. Symptoms were relieved equally with respect to time and efficacy. Minor adverse experiences were reported in each treatment group. None of these experiences were serious enough to warrant discontinuation of treatment. These results suggest tha sucralfate is as effective as cimetidine in the short-term treatment of duodenal ulcer.

The most comfortable gas for peritoneoscopy has been the subject of debate. We subjected 46 patients to double-blind comparison of carbon dioxide and nitrous oxide during initial pneumoperitoneum. The discomfort from local anesthesia was similar in both patient groups. The patient's and the physician's assessment of discomfort during gas insufflation showed that carbon dioxide was more uncomfortable as perceived by the patient (p = 0.02), the physician (p = 0.0006), and objectively assessed by degree of abdominal splinting (p = 0.006). The presence of intraabdominal adhesions had no relationship to discomfort. We conclude that nitrous oxide is more comfortable for institution of pneumoperitoneum during peritoneoscopy under local anesthesia.

The effect of estrogen treatment on risk for cholecystectomy, cholelithiasis, peptic ulcer, and other disorders was investigated using autopsy data from a study of patients randomized to hormonal therapy for prostatic cancer. Treatment with diethylstilbestrol, a nonsteroidal estrogen, was associated with an increased number of cholecystectomies but was unrelated to the presence of cholelithiasis at autopsy. These findings support previous reports of an association between steroidal estrogen use and cholecystectomy, but the risk estimate was more than three times that previously reported. Despite this risk and ample experimental evidence demonstrating that estrogen increases bile lithogenicity, no relationship between estrogen use and cholelithiasis was observed. The absence of such a relationship could not be readily explained by the study size, dose, or duration of estrogen treatment, treatment after leaving the study, or the frequency of preexisting stones. Given these findings the increases cholecystectomy risk may have resulted from estrogen related symptomatology mimicking gallbladder disease or an actual pathophysiologic effect of estrogen on the gallbladder, perhaps involving impaired emptying. In addition, estrogens, orchiectomy, or both were associated with a decreased frequency of peptic ulcer, supporting reports of the efficacy of estrogen in the treatment of peptic ulcer.

The effect of wine on gastric emptying of meals was studied in 10 healthy male subjects. A dual radioisotopic method was employed utilizing isotope tracers added to the liquid (111In-diethyltriamine pentaacetic acid) and solid phases (99mT-tagged chicken liver) of the meal. In a random design subjects were fed two standardized 900-g meals containing 450 g of solid food ingredients and 450 g of either Cabernet Sauvignon (mean ethanol concentration = 9500 mg/dl) or low-alcohol Cabernet Sauvignon (mean ethanol concentration = 1312 mg/dl). In addition, 7 of the 10 subjects were fed wine and low-alcohol wine without solid food. Wine, when compared with low-alcohol wine, did not significantly alter gastric emptying of either liquid or solid food components.

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.

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.