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.

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.