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 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.

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.

This study was undertaken to test the hypothesis that external stimuli acting through the central nervous system perturb the normal gastrointestinal response to meals. Thus, in 4 healthy volunteers we used a multilumen gastroduodenal tube system that allowed simultaneous measurements of gastroduodenal motility, gastric emptying rate, gastric acid secretion, and pancreatic trypsin output. Blood pressure, pulse rate, and skin temperature were also monitored for autonomic response. All subjects were studied on 2 days, receiving on each day two identical test meals. After one of the meals on each day, vertigo was induced by labyrinthine stimulation (ear irrigation with ice water) while the other meal was followed by one of two controls, ear irrigation at 37 degrees C (control stimulation) on 1 day and no stimulation on the other, the order of the tests being randomized. Labyrinthine stimulation at subnauseant levels resulted in a consistent and reproducible delay in gastric emptying of the meal. Further, in 2 of the 4 subjects a marked and reproducible alteration of the postprandial duodenal motility pattern occurred, with a change to one resembling the fasted state, even though nutrients continued to be present in the stomach. Duodenogastric reflux and gastric acid output remained unchanged. Trypsin output decreased initially but later returned to control values. These studies emphasize the role of the central nervous system in the control of gut function after feeding. Labyrinthine stimulation nay be a useful method for investigating inhibitory and disruptive effects of centrally acting stimuli on the human upper gut.

Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded favorably in the first period. The plasma concentration of orosomucoid increased significantly among the patients in the sulfasalazine group but not in the metronidazole group. It is therefore concluded that metronidazole is slightly more effective than sulfasalazine in the treatment of crohn's disease. It is worthwhile switching the drug regimen from sulfasalazine, when it fails, to metronidazole, but not from metronidazole to sulfasalazine.

The design and execution of the Cooperative Crohn's Disease Study in Sweden are described in this paper. A double-blind, double-dummy, crossover (2 X 4 mo) technique was used to compare the suppressive efficacy of metronidazole (0.4 g b.i.d.) and sulfasalazine (1.5 g b.i.d.). The number of randomized patients (78) presented approximately one-third of the available population. The Crohn's Disease Activity Index and the plasma level of orosomucoid were the main variables for clinical evaluation. Results were analyzed primarily in the first treatment period by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. The cross-over data only served as additional information. Thirty-six patients had had earlier and mostly positive experience with sulfasalazine. Repeated plasma drug analysis indicated good compliance. The blindness of the trial was tested and appeared satisfactory. The coordination of the trial proceeded as planned. A lack of full conformity in the electroimmunoassay of orosomucoid was taken care of satisfactorily.

A trial of neodymium-yttrium-aluminum-garnet laser treatment was conducted in 152 patients with upper gastrointestinal hemorrhage. Laser photocoagulation was applied in 0.5- to 1-s pulses of 55-80 W power. A first part of the trial studying patients with arterial bleeding was uncontrolled. Spurting arterial bleedings could be stopped in 87% of the 23 patients with acute arterial hemorrhage. The recurrence rate after endoscopic treatment of this type of bleeding was high (55%). The operation rate of 61% was, however, lower than the operative indications amounting to 95% in patients with arterial spurters admitted previously to our department. One hundred twenty-nine patients were included in a controlled randomized trial of laser photocoagulation. In 86 patients with active, nonspurting bleeding, the laser was significantly better (p less than 0.001) at stopping the bleeding than conservative treatment in randomized controls, and there was a numerical although not significant reduction of the rate of bleeding recurrence and the necessity for surgery (both p less than 0.1). In 43 patients with fresh stigmata of bleeding (i.e., fresh clot or visible vessel) laser treatment resulted in a numerical reduction in the rate of rebleeding and in the operative indications, but the difference did not reach statistical significance. The mortality rates were not influenced in any of the groups.

A multicenter study was conducted on 173 patients with active, endoscopically proven duodenal ulcers (158 men, 15 women). They were randomly assigned, in a double-blind manner, to two groups: those receiving placebo capsules (91 patients) and those receiving capsules containing 100 microgram of 15(R)-15-methyl prostaglandin E2 (arbaprostil) (82 patients). Each drug was ingested four times a day (1 h before meals and at bedtime) for 28 days. Endoscopy was performed on days 0, 14, and 28 after the trial began. At each examination, the ulcer size was measured and whether the ulcer had healed was recorded. Arbaprostil increased the incidence of ulcer healing to approximately the same degree as reported in most extensive studies with cimetidine. At 14 days, three times as many patients were totally healed in the arbaprostil-treated as in the placebo-treated group (37% vs. 12%, p less than 0.001). At 28 days, 67% of patients receiving arbaprostil were healed compared with 39% in the group receiving placebo (p less than 0.001). Similarly, the ulcer size, measured endoscopically, was much smaller after arbaprostil administration than in the group receiving placebo after both 14 and 28 days (p less than 0.001). Side effects attributable to treatment consisted primarily of loose stools and diarrhea (34%). Smoking retarded healing in the placebo-treated group (p less than 0.05), but did not significantly retard healing in patients treated with arbaprostil. We conclude that arbaprostil markedly accelerates the healing rate of active duodenal ulcers. This effect may be due to inhibition of acid secretion as well as gastric cytoprotection.

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.