In 42 consecutive adult patients with benign gastric ulcers, endoscopic biopsy specimens were examined histologically for infiltration with Candida albicans before the patients entered a double-blind trial of either cimetidine or placebo. Fifteen cases of candidal infiltration were found, giving an overall incidence of 36%. Repeated endoscopy after 6 wk showed complete ulcer healing in 9 of 15 patients with Candida-infiltrated ulcers, compared with 20 of 27 patients with no infiltration. It is concluded that the occurrence of Candida in benign gastric ulcers has no influence on the healing process.

Previous studies have shown that approximately 50% and 70% of duodenal ulcers heal after 2 and 4 wk, respectively, of cimetidine, and at least one-third heal after 4 wk of placebo. In order to identify these groups of ulcers before treatment, a two-phase study was performed, including an initial double-blind trial of cimetidine vs. placebo in 120 patients, and a subsequent open study with identical protocol of cimetidine vs. no cimetidine in another 60 patients. Forty clinical, personal, physiologic, and endoscopic characteristics were prospectively obtained in each patient, and were analyzed by stepwise discriminant analysis at the end of phase 1. This identified the discriminants against healing after 2 wk of cimetidine as late onset disease, body weight, and ulcer diameter; those after 4 wk of cimetidine as analgesic consumption, neurosis, low fasting serum gastrin, low pentagastrin D50 and ulcer diameter; and those after 4 wk of placebo as back pain, bleeding, and alcohol consumption. Based on the discriminant scores derived, the sensitivity, specificity, and efficiency of prediction for complete healing as determined endoscopically were 74.4%, 90%, and 82.3% for 2-wk cimetidine, 100%, 87.5%, and 97.5% for 4-wk cimetidine, and 85.7%, 83.3%, and 84.2% for 4-wk placebo treatment. In phase 2, correct predictions were made in 36 of 40, 39 of 40, and 17 of 20 patients treated, respectively, for 2 and 4 wk with cimetidine, and 4 wk without cimetidine. Accurate prediction of duodenal-ulcer healing rate with and without cimetidine is thus possible by discriminant analysis. As many medical and surgical modalities of treatment are now available, this approach should have the potential of selecting the appropriate form of treatment for a given patient.

Sixty-six patients hospitalized for ulcerative colitis were treated in a prospective, double-blind, clinical trial. They received either 120 U/day of intravenous corticotropin or 300 mg/day of intravenous hydrocortisone. Patients were randomized within strata defined by whether they had received oral corticosteroids continuously for at least 30 days before the study (group A, 35 patients), or whether they had received no such prior treatment (group B, 31 patients). Twenty-eight of the 66 patients (42%) achieved remission. In group B, the proportion of patients entering remission was greater with corticotropin than with hydrocortisone (63% vs. 27%, 0.025 less than p less than 0.05). The opposite trend was observed within group A, for whom hydrocortisone appeared more effective (53% vs. 25%, 0.05 less than p less than 0.10). Impaired adrenal responsiveness, as measured by serum cortisol and dehydroepiandosterone-sulfate levels, did not explain the different responses to therapy within the two study groups. Twenty of 28 patients whose acute therapy was successful were still in remission 1 yr after study. These data suggest that, at the doses used, intravenous corticotropin therapy of severe ulcerative colitis is the more effective choice for those patients not previously treated with corticosteroids, while intravenous hydrocortisone seems preferable for patients already receiving steroid treatment.

The aim of the study was to determine the effectiveness of cimetidine in a dose of 400 mg twice daily in the prevention of gastric ulcer recurrence over a 2-yr period. The trial was double-blind and placebo-controlled; 24 patients received cimetidine and 25 received placebo. All had had a gastric ulcer within the prior 6 wk, and healing was demonstrated by endoscopy or by barium meal. The patients were contacted at monthly intervals, and if symptoms were present, investigations were performed. Annual barium meal examinations or endoscopy were also performed in all except 7 patients. In the placebo group, there was rapid recurrence within the first 12 mo; 12 of the 13 recurrences that occurred in this group over the 2-yr period took place within the first 12 mo. In the cimetidine-treated group, there were eight recurrences over the 2-yr period, five of which occurred in the first year. Log rank comparison showed a significant benefit due to cimetidine at 1 yr, but not over the 2-yr period.

The efficacy and safety of the new colonic lavage solution, Golytely (an electrolyte-polyethylene glycol solution), was compared with standard 2- and 3-day bowel preparations in a randomized blinded study of patients undergoing colonoscopy and barium enema examination. Side effects, patient preference, and quality of examinations were monitored. Colonoscopy was scored by colonic segment for type of residual stool and percentage of bowel wall visualized. Barium enema was graded by stool particle size in the least clean segment. For colonoscopy, preparation with Golytely allowed better visualization of colonic mucosa (p less than 0.002) due to less retained stool (p less than 0.002), produced more optimal exams (p less than 0.002), and required less time to reach the cecum (p less than 0.05). Furthermore, it was preferred by patients, required less than 5 preparation time, and caused no notable side effects. For barium enema, no significant difference existed between preparations. We conclude that Golytely is effective for barium enema examination and is the preparation of choice for colonoscopy.

Gastric emptying has been reported to be delayed in a significant percentage of patients with gastroesophageal reflux. The rationale for the use of metoclopramide and bethanechol in gastroesophageal reflux has been based on their ability to stimulate lower esophageal sphincter pressure and enhance acid clearance mechanisms. In this study, we investigated the comparative efficacies of metoclopramide and bethanchol in improving the rate of gastric emptying in gastroesophageal reflux patients in whom delayed emptying was present. Gastric emptying studies used an isotope-labeled mixed solid-liquid meal. Thirteen reflux patients with delayed gastric emptying received metoclopramide, 10 mg intramuscularly, and subcutaneous bethanechol, 0.07 mg/kg, in a randomized single-blind fashion. Eleven additional reflux patients with delayed gastric emptying received oral metoclopramide, 10 mg, in an open-labeled fashion. After parenteral metoclopramide, gastric emptying was significantly (p less than 0.05) faster compared with both the initial basal day and the bethanechol treatment day. Compared with the normal gastric emptying rate established in 26 control subjects, metoclopramide accelerated gastric emptying into the normal range. Bethanechol did not increase gastric emptying. Metoclopramide orally also significantly improved gastric emptying. Our study indicates that metoclopramide, both parenterally and orally, increased the rate of gastric emptying in those reflux esophagitis patients in whom it was delayed, while bethanechol did not improve the degree of gastric retention in the same patients. Our results extend the rationale for the therapeutic efficacy of metoclopramide in gastroesophageal reflux disease.

Loop and distal diuretics are the basic drugs for the treatment of ascites. Although pharmacologic studies indicate that the natriuretic potency of loop diuretics is much greater than that of distal diuretics, there are no studies comparing the efficacy of these drugs in cirrhosis. Forty nonazotemic cirrhotic patients with ascites and avid sodium retention were randomly allocated into two groups. Group 1 contained 21 patients treated with furosemide; group 2 contained 19 patients treated with spironolactone. The initial doses were 80 and 150 mg/day, respectively. These doses were increased to 160 and 300 mg/day, respectively, if there was no response. Cases not responding to furosemide and spironolactone were later treated with spironolactone and furosemide, respectively. In group 1, 11 of the 21 patients responded to furosemide, while in group 2, 18 of the 19 patients responded to spironolactone (p less than 0.01). Of the 10 patients in group 1 not responding to furosemide, 9 responded later to spironolactone. The diuretic response to furosemide and spironolactone was related to the activity of the renin-aldosterone system. Patients with higher renin and aldosterone did not respond to furosemide and required 300 mg/day of spironolactone to achieve a diuretic response. These results indicate that (a) at the dosages used in the study, spironolactone is more effective than furosemide in nonazotemic cirrhosis with ascites, and (b) the activity of the renin-aldosterone system influences the diuretic response to furosemide and spironolactone in these patients.

Eight patients with a short bowel resulting from intestinal resection and clinically stable for at least 6 mo were studied on two diets. Each diet was given for 5 days at a time and crossed over with the other. Both diets contained 20% of total calories as protein. The high-fat diet had 60% of calories as fat and 20% as carbohydrate. This ratio was reversed in the high-carbohydrate diet. Both diets were lactose free with low fiber. Fluid intake was kept constant. The results showed that there was no difference in the blood chemistry, stool, or ostomy volume, the zinc, calcium, and magnesium balances, urine volume, and electrolyte excretion between patients on the two diets. Bomb calorimetry showed that the total calories absorbed and excreted were comparable between the two diets. It was concluded that low-fat diets had no special benefit in the overall nutrition of the patient who has been in remission in regard to bowel disease for 6 mo or longer. Hence, dietary restriction is not recommended in these patients. However, this study did not resolve the question of the requirements and losses of fat-soluble vitamins in such patients when on a high-fat diet.

The purpose of this study was to determine whether or not nutrients in the colon influence pancreatic and biliary secretion in humans. In six healthy subjects, similar caloric loads (117 cals) of oleic acid, essential amino acids, and glucose in isomolar (280 mosmol/L), similar pH (7.4) solutions were infused into the right colon at 10 ml/min through a colonic tube passed by mouth. A background of submaximal pancreatic and biliary secretion was maintained by continuous intravenous infusion of the octapeptide of cholecystokinin. Biliary and pancreatic secretions were quantitated using the gastroduodenal intubation perfusion technique. Among the three nutrients tested, only oleic acid in the colon decreased pancreatic enzymes and bicarbonate outputs. The mean trypsin output decreased from 26.3 +/- 2.6 kU/h to 12.3 +/- 1.9 kU/h (46% +/- 6% of control), while the lipase output decreased from 62 +/- 6.6 kU/h to 36 +/- 5.6 kU/h (58% +/- 6% of control). Similarly, the output of bicarbonate in the duodenal aspirate decreased from 31 +/- 7.2 mEq/h to 16.3 +/- 3.1 mEq/h (61% +/- 5% of control). Intracolonic perfusion of essential amino acids or glucose had no effect on pancreatic enzymes and bicarbonate secretion. In contrast, all three nutrients in the colon inhibited biliary secretion. The mean output of bilirubin decreased from 56 +/- 6 mg/h to 19 +/- 2 mg/h (35% +/- 5% of control) during intracolonic perfusion of oleic acid. Essential amino acids lowered the output of bilirubin from 54 +/- 12 mg/h to 31 +/- 8.6 mg/h (65% +/- 6% of control), whereas glucose lowered it from 53 +/- 12 mg/h to 22 +/- 4 mg/h (45% +/- 5% of control). This differing response of pancreatic and biliary output to intracolonic perfusion of nutrients suggests differential sensitivity of the pancreas and gallbladder to these inhibitory influences. In malabsorption states, unabsorbed nutrients in the colon may inhibit pancreatic and biliary secretion, further contributing to the loss of nutrients from the gastrointestinal tract.

The therapeutic efficacy of a pH-sensitive enteric coated pancreatic enzyme preparation was compared with conventional pancreatic enzyme preparations in 6 adult patients with exocrine pancreatic insufficiency. Fecal fat excretion and postprandial duodenal recovery of orally ingested pancreatic enzymes were evaluated after ingestion of each preparation. Fecal fat excretion decreased significantly (p less than 0.005) on treatment with pH-sensitive and conventional pancreatic enzyme preparations. Postprandial concentration and delivery of trypsin and lipase in samples aspirated from duodenojejunal junction were higher after ingestion of conventional pancreatic enzyme preparation as compared to the pH-sensitive enteric coated preparation. The difference, however, did not reach statistical significance. Our observations suggest that the pH-sensitive enteric coated pancreatic enzyme preparation is only as effective as conventional pancreatic enzyme preparations in controlling fat malabsorption in patients with exocrine pancreatic insufficiency. Failure of pH-sensitive enteric coated preparation to deliver greater quantities of pancreatic enzymes at duodenojejunal junction is most likely related to the impaired release of enzymes from microspheres due to low intraluminal pH in the upper small intestine in pancreatic insufficiency.

A prospective blinded study comparing the indium 111 leukocyte scan to barium enema, colonoscopy, or surgery or a combination of these, was carried out in 15 patients (10 with active ulcerative colitis and 5 with active Crohn's colitis). Correlation of disease location to colonic regions between indium scan and other diagnostic studies was excellent in 11 instances, good in 2, and poor in 3. In 2 of the 3 studies where major disagreement occurred, the comparative barium enema was performed greater than 2 mo after the indium scan. Disease activity, estimated by the intensity of radionuclide uptake, was compared to clinical disease activity assessed by the Crohn's Disease Activity Index for both forms of colitis. The relative degree of inflammation estimated by the indium scan correlated well with the independent clinical assessment (correlation coefficient = 0.81). The indium 111 leukocyte scan appears to be an accurate, noninvasive method for assessing the extent and the severity of the inflammation in patients with acute ulcerative or Crohn's colitis.

We measured intestinal absorption of cholesterol by a plasma isotope ratio method and determined biliary bile acid and lipid composition of fasting gallbladder bile in 5 gallstone patients before therapy and during two randomized treatment periods with chenodeoxycholic or ursodeoxycholic acid (13 mg/kg . day). During chenodeoxycholic acid ingestion, biliary bile acids were composed predominantly (84%) of conjugates of chenodeoxycholic acid. During ursodeoxycholic acid administration, conjugates of ursodeoxycholic acid constituted half the bile acid pool (49%). Fasting gallbladder bile was supersaturated in cholesterol before treatment, but became unsaturated during administration of both chenodeoxycholic and ursodeoxycholic acids. In spite of these marked changes in biliary bile acid and lipid composition, cholesterol absorption was not significantly different before (45.4 +/- 4.3%, mean +/- SEM) or after chenodeoxycholic (42.7 +/- 5.1%) or ursodeoxycholic (46.8 +/- 3.7%) acid ingestion. We conclude that chenodeoxycholic and ursodeoxycholic acids unsaturate bile in cholesterol and dissolve gallstones by a mechanism other than the suppression of intestinal absorption of cholesterol.

A prospective, randomized double-blind trial of doxycycline prophylaxis for traveler's diarrhea was conducted on 145 volunteers during a 2.5-day visit to Mexico. Traveler's diarrhea occurred in 15 (21%) of the placebo group and in 3 (4%) of the doxycycline group (p = 0.002). There was no rebound increase in the incidence of acute diarrhea after departure from the high risk area in the doxycycline-treated group. A variety of bacterial pathogens were isolated from individuals symptomatic with traveler's diarrhea. Nausea alone (8%) or nausea with vomiting (4%) occurred in the doxycycline-treated group only and were the only side effects observed (p = 0.003). We conclude that doxycycline is safe and efficacious for the prophylaxis of traveler's diarrhea for short-term exposure in a high risk area.

Fructose is an increasingly important commercial sweetener. However, some patients report abdominal symptoms after ingesting fructose-containing foods. The completeness of fructose absorption by the small intestine was assessed by breath hydrogen analysis in 16 healthy volunteers and incomplete absorption was defined as a peak rise in breath hydrogen of greater than 20 parts per million. Fructose, 50 g as a 10% solution, was incompletely absorbed in 6 of 16 subjects (37.5%). Incomplete absorption was associated with symptoms of cramps or diarrhea, or both in 5 of these 6 individuals. Incomplete absorption was both concentration- and dose-related. Three subjects incompletely absorbed 37.5 g of fructose. In comparison, all 15 subjects who were studied after ingestion of sucrose, 50 g and a 10% solution, completely absorbed this sugar load. Incomplete absorption of fructose should be considered as a possible case of gastrointestinal symptoms.