In a prospective randomized study, selective intestinal decontamination with norfloxacin was performed during hospitalization in 32 cirrhotic patients with low ascitic fluid total protein levels. The incidence of infections was compared with that in a control group of 31 nontreated cirrhotic patients of similar characteristics. We found a significantly lower incidence of infections [1/32 (3.1%) vs. 13/31 (41.9%); P less than 0.005] and spontaneous bacterial peritonitis [0/32 (0%) vs. 7/31 (22.5%); P less than 0.05] in patients receiving norfloxacin. The lower incidence of extraperitoneal infections [1/32 (3.1%) vs. 7/31 (22.5%); P = 0.052] in the treated group did not reach statistical significance. The incidence of infections [1/28 (3.6%) vs. 9/22 (40.9%); P less than 0.01] and spontaneous bacterial peritonitis [0/28 (0%) vs. 5/22 (22.7%); P less than 0.05] in cirrhotic patients admitted because of ascites was also significantly lower in the treated group. The decrease in the rate of mortality observed in the group undergoing selective intestinal decontamination did not reach statistical significance. These data show that selective intestinal decontamination is useful to prevent spontaneous bacterial peritonitis and extraperitoneal infections in hospitalized cirrhotic patients with low ascitic fluid total protein levels.

One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy, relaxation, and standard medical treatment compared with standard medical treatment alone. Patients were only selected if their symptoms had not improved with standard medical treatment over the previous 6 months. At 3 months, the treatment group showed significantly greater improvement than the controls on both gastroenterologists' and patients' ratings of diarrhea and abdominal pain, but constipation changed little. Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress, whereas those with constant abdominal pain were helped little by this treatment. This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to standard medical treatment.

Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process.

Estrogen-replacement therapy is important for the prevention of postmenopausal osteoporosis. However, oral synthetic and conjugated estrogens increase biliary cholesterol saturation index and risk of gallstone disease. To examine whether transdermal estrogen administration could avoid these adverse effects, 17 postmenopausal women were treated with transdermal estradiol (Estraderm TTS; Ciba-Geigy, Arnhem, The Netherlands), 100 micrograms/day for 4 weeks, and after 1 month without therapy, with oral estradiol (Progynova; Schering, Weesp, The Netherlands), 2 mg/day for 4 weeks. The increase in the serum estradiol level was much higher during transdermal than oral estradiol administration. On the contrary, the increase in the serum estrone level was much more pronounced during oral treatment. Both modes of treatment led to a similar reduction of urinary calcium excretion. A highly significant decrease in serum phosphate levels was found during transdermal therapy. Biliary cholesterol saturation index did not change during transdermal therapy (mean +/- SEM, 1.25 +/- 0.06 before and 1.22 +/- 0.07 at the end of transdermal therapy; P = NS). A slight increase in cholesterol saturation index that did not reach statistical significance was found during oral therapy (1.28 +/- 0.09 before and 1.36 +/- 0.09 during oral treatment). However, the subgroup of women with strong increases in serum estrone levels during oral estradiol therapy (greater than 0.5 pmol/mL; n = 8) generally had increased biliary cholesterol saturation index, a decrease in relative percentage chenodeoxycholic acid in bile, and increased serum sex hormone-binding globulin levels during oral treatment. Cholesterol monohydrate crystals were never found in duodenal biles during either treatment. This study indicates that transdermal estradiol does not induce lithogenic bile. On the contrary, oral estradiol leads to lithogenic bile in a subgroup of women with strong increases in serum estrone levels during oral treatment.

A prospective randomized trial was performed to compare the efficacy of endoscopic epinephrine injection and heat probe treatment in actively bleeding peptic ulcers. Emergency endoscopy in 1758 patients over an 18-month period identified 132 patients with active ulcer bleeding. They were randomized to receive either endoscopic epinephrine injection or heat probe treatment. After endoscopy, the patients were transferred to the surgical gastroenterology ward and were managed by surgeons unaware of the treatment option. Bleeding was initially controlled in 96% by epinephrine injection and in 83% by heat probe (P less than 0.05). There was no significant difference in outcome as measured by transfusion requirement (4.5 units vs. 3.8 units), emergency surgery (20% vs. 22%), hospital stay (8 days vs. 7 days), and mortality (2 vs. 4) between the injection group and the heat probe group. Two patients in the heat probe group experienced perforation. We conclude that both endoscopic epinephrine injection and heat probe treatment are effective in stopping bleeding from actively bleeding ulcers. Epinephrine injection is technically easier to perform and has a higher initial success rate.

To determine if diets are associated with different rates of interdigestive and postprandial enzyme secretion and how quickly enzyme secretion is modulated by nutrients, 27 healthy humans were randomly selected to follow one of five diets. The calorie proportions of carbohydrate, fat, and protein in each diet was assigned by a mixture design. After the subjects followed a diet for 2 weeks, they were intubated with an oroduodenal tube, and enzyme outputs were measured during the interdigestive period and after eating a meal identical to meals eaten during the previous 2 weeks. For the next 24 hours subjects either followed the same diet or a diet that contained the same amount of fat, but the percent of carbohydrate and protein was changed by 30%. Then interdigestive and postprandial pancreatic enzyme outputs were remeasured. After 2 weeks, diets containing the most carbohydrate (50%-80%) were associated with the lowest interdigestive and postprandial amylase and lipase (P less than 0.05) and trypsin outputs (P less than or equal to 0.05). In contrast, diets containing the most fat (40%) were associated with the highest interdigestive and postprandial outputs of amylase (P less than 0.05) and trypsin (P less than 0.05). Maintaining or altering diets for 24 hours did not change interdigestive pancreatic enzyme outputs, but postprandial amylase output was significantly increased (P less than 0.05) by increasing protein and decreasing carbohydrate content of the diets by 30% for 24 hours. We conclude that diets containing a high proportion of calories as carbohydrate for 2 weeks are associated with lower interdigestive and postprandial pancreatic secretion than diets that have a high fat content. In response to diets, changes in postprandial pancreatic enzyme secretion occur within 24 hours whereas changes in interdigestive secretion (no nutrients in the lumen) occur after 24 hours.

The effects of a 7.5-day course of orally administered salsalate (3.0 g/day), aspirin (3.9 g/day), or placebo on gastroduodenal mucosal injury, mucosal prostaglandin content, and plasma prostaglandin concentrations in healthy, asymptomatic human volunteers were examined. Mean serum salicylate concentrations after these doses of salsalate and aspirin were nearly identical (approximately 15 mg/dL). When the gastroduodenal mucosa was assessed endoscopically 1 hour after the final dose of medication, there was minimal mucosal injury in placebo-treated or salsalate-treated subjects and considerable injury in the stomach and duodenum of aspirin-treated subjects (P less than 0.001, aspirin vs. salsalate or placebo). In both the stomach and duodenum, aspirin lowered mucosal prostaglandin F2a and E2 content by greater than 90% (P less than 0.001), whereas salsalate produced no significant change. Aspirin also lowered plasma prostaglandin F2a concentrations by 58% +/- 6%, whereas salsalate lowered them by only 11% +/- 9% (P less than 0.001). Thus, the nonacetylated salicylate, salsalate, produced much less gastroduodenal mucosal damage than aspirin at equivalent serum salicylate concentrations, possibly because salsalate did not inhibit mucosal prostaglandin synthesis.

To date, no satisfactory treatment has been developed for treatment of patients with advanced pancreatic carcinoma. The median survival of these patients is only three to six months. Of more than 30 agents evaluated over the past three decades, only 5-FU results in a response rate with 95% confidence intervals greater than 20%. Most responses are partial, of short duration, and of questionable clinical benefit. To date, efforts to improve response rates by biochemical modulation of 5-FU have been unsuccessful but additional studies are warranted and are ongoing. Although improved response rates have been reported with some drug combinations, such as streptozotocin, mitomycin and 5-FU (SMF), median survival for combination therapy is no better than that attained with single-agent therapy. Current therapeutic options for patients with advanced disease include 5-FU, supportive care, or investigational treatment in a clinical trial. In three out of four studies, patients with locally advanced pancreatic carcinoma who received combined modality therapy (radiation in combination with 5-FU) survived significantly longer than those treated with either radiation or chemotherapy alone. The brief survival advantage, however, must be considered in the context of the additional toxicity and treatment time required for the combined modality treatment. Radiotherapy in combination with 5-FU should be considered standard adjuvant therapy for patients with completely resected disease. The median survival of treated patients was 20 months and significantly longer than the surgery alone control group (11 months) (Kalser and Ellenberg, 1985; GITSG, 1987). Of greatest significance is the tail-end plateau on the survival curve suggesting that approximately 18% of patients who received combined modality therapy were cured. The results with currently available treatment for all stages of disease are poor; therefore, patients should be informed about ongoing clinical trials which may someday improve the prognosis for pancreatic cancer.

To investigate whether albumin can be substituted by less expensive plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis, 88 patients (16 with renal failure) submitted to this therapeutic procedure were randomly assigned to receive IV albumin (43 patients) or dextran-70. Both substances were given at a dose of 8 g/L of ascitic fluid removed. Patients were discharged from the hospital with diuretics, and cases developing tense ascites during follow-up were treated according to their initial schedule. Total paracentesis was effective in eliminating the ascites in all but two cases in each group. Neither paracentesis plus IV albumin infusion nor paracentesis plus IV dextran-70 infusion was associated with significant changes in renal and hepatic function or serum electrolytes. The incidence of renal impairment (one case in each group), hyponatremia (three and four cases, respectively), and other complications (hepatic encephalopathy, gastrointestinal hemorrhage, bacterial infections) after paracentesis, and the clinical course of the disease as estimated by the probability of readmission to hospital during follow-up, causes of readmission, probability of survival, and causes of death were similar in the two groups of patients. The effect of paracentesis on effective intravascular volume was indirectly assessed by measuring plasma renin activity and aldosterone concentration before and 2 and 6 days after treatment, the patients being without diuretics. In patients treated with albumin, no significant changes in renin and aldosterone were observed during the entire period of observation. In contrast, both parameters increased significantly on the 6th day of treatment in patients receiving dextran-70. A significant increase in plasma renin activity and aldosterone concentration (30% over baseline values) was observed in 51% of patients treated with dextran-70 and in only 15% of those treated with albumin (x2 = 10.4; P = 0.0012). These results indicate that although dextran-70 is less efficacious than albumin in protecting cirrhotic patients treated with total paracentesis from the decrease in effective intravascular volume, it appears to be capable of preventing the renal and electrolyte complications induced by this therapeutic procedure.

In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.

This study prospectively compares multipolar electrocoagulation and injection therapy in high-risk patients with bleeding ulcers. Patients were considered for entry if they had a bloody nasogastric aspirate, melena, or hematochezia and unstable vital signs, transfusion of greater than or equal to 2 U of blood in 12 hours, or a decrease in hematocrit of greater than or equal to 6% in 12 hours. Sixty patients with endoscopic evidence of an ulcer with active bleeding (n = 26) or a nonbleeding visible vessel (n = 34) were randomly assigned to receive multipolar electrocoagulation or injection with absolute ethanol. Hemostasis was achieved in 14 of 14 actively bleeding patients with multipolar electrocoagulation vs. 10 of 12 (83%) treated with injection. No significant differences were observed between electrocoagulation and injection therapy in any parameter assessed during the hospitalization: incidence of further bleeding (6% vs. 10%), units of blood transfused after treatment (1.8 +/- 0.6 vs. 1.3 +/- 0.4), incidence of surgery for bleeding (6% vs. 7%), length of hospital stay in days (5.8 +/- 0.9 vs. 7.2 +/- 2.5), cost of hospitalization (+7160 +/- +1630 vs. +8520 +/- +2960), or mortality rate (3% vs. 3%). Treatment induced bleeding in nonbleeding visible vessels in 35% of subjects in each group, but this was controlled with continued treatment in all patients. One delayed perforation occurred 9 days after multipolar electrocoagulation. Multipolar electrocoagulation and injection therapy are of comparable efficacy in the treatment of patients with clinical evidence of a major upper gastrointestinal bleed and endoscopic evidence of an ulcer with active bleeding or a nonbleeding visible vessel.

A randomized, double-blind, placebo-controlled trial of somatostatin was conducted among 120 patients admitted for bleeding esophageal varices (59 placebo, 61 somatostatin). An initial 250-micrograms bolus of somatostatin followed by a 5-day continuous infusion of 250 micrograms/h and an identical administration of placebo were evaluated for both the control of bleeding and prevention of early rebleeding from varices. Failure to control bleeding occurred in 22 (36%) somatostatin patients vs. 35 (59%) placebo patients, with time to failure occurring earlier with placebo (P = 0.036). blood and plasma transfused per hour during drug infusion of trial drug was reduced in the somatostatin group: median 0.033 vs. 0.105 unit/h (P = 0.025). Use of balloon tamponade was halved in somatostatin-treated patients. The average effect of somatostatin was a 41% reduction in the hazard of failure (95% confidence interval, -1% to 65%, P = 0.0545) after adjustment for the severity of liver disease, which was the only other variable having a significant influence on time to failure. There was no difference in 30-day mortality per admission (7 placebo, 9 somatostatin) or complications. It is concluded that somatostatin is safe and more effective than placebo for the control of variceal bleeding.

The therapeutic efficacy of Bioflorin (Streptococcus faecium SF68; Gipharmex, Milan, Italy) in acute watery diarrhea was evaluated in 183 Bangladeshi adults. Vibrio cholerae organisms were isolated from stool cultures in 114 patients, and enterotoxigenic Escherichia coli organisms were isolated in 41. In addition to IV rehydration, patients were randomly assigned to receive either capsules of Bioflorin containing 1 X 10(9) of live SF68 or capsules of placebo containing killed SF68 once every 8 hours for 3 days. No other drugs were allowed during this period. Bioflorin was well tolerated. It is concluded that Bioflorin has no demonstrable antidiarrheal property in adults with acute diarrhea due to V. cholerae or enterotoxigenic E. coli infection.

Although injection of cholecystokinin can reduce resting lower esophageal sphincter pressure, the physiological significance of this finding has not been established. The purpose of this double-blind crossover study was to determine the effect of physiological plasma levels of cholecystokinin on resting lower esophageal sphincter pressure. Eighteen normal male volunteers were studied on two separate days. Following a 20-minute baseline period, subjects received infusions of saline or synthetic cholecystokinin-8 at increasing rates. Basal plasma cholecystokinin levels averaged 1.3 +/- 0.2 pmol/L (mean +/- SE) and increased to levels of 7.4 +/- 0.9 pmol/L, 12.1 +/- 2.4 pmol/L, and 23.1 +/- 3.8 pmol/L during cholecystokinin infusion rates of 21, 42, and 84 pmol/min, respectively. Lower esophageal sphincter pressure was recorded continuously with a sleeved catheter. Basal lower esophageal sphincter pressure averaged 19.9 mm Hg and did not change with the first infusion, which produced physiological peak postprandial plasma levels of cholecystokinin. Lower esophageal sphincter pressure declined only during the infusions that produced plasma cholecystokinin levels two to four times greater than normal peak postprandial levels. Since infusion of cholecystokinin to levels that reproduce physiological blood levels does not significantly decrease lower esophageal sphincter pressure, it was concluded that cholecystokinin is not a major hormonal regulator of lower esophageal sphincter relaxation.