As pectin delays gastric emptying in normal subjects and satiety may be linked to the rate of gastric emptying, we designed this study to evaluate, in a group of obese subjects, the effect of adding pectin to a meal on gastric emptying, sensation of satiety, and postprandial plasma cholecystokinin and pancreatic polypeptide levels. We studied gastric emptying of solids in 9 adult obese subjects on 2 separate days in a randomized fashion. On day 1, 15 g of pectin was added to the meal, and on day 2 15 g of methylcellulose was added and served as control. Satiety was evaluated by an analogue rating scale. Pectin significantly delayed gastric emptying time [t1/2 = 116 +/- 23 min vs. 71 +/- 17 min observed with methylcellulose (p less than 0.001)]. Pectin also significantly increased subjects' sensation of satiety [98 +/- 7 vs. 74 +/- 17 (p less than 0.001)]. Postprandial release of cholecystokinin and pancreatic polypeptide was not modified by pectin. As pectin induces satiety and delays gastric emptying in obese patients, it may be a useful adjuvant in the treatment of disorders of overeating.

Endoscopic and microscopic appearances of antral and fundic mucosa were correlated with the presence or absence of Campylobacter pylori--and with plasma immunoglobulin G antibodies to that organism--in 23 healthy volunteers, 12 of whom had received indomethacin and 11 of whom had received no medication. Antral C. pylori, found in 9 of 23 biopsy specimens (3 of 11 controls, 6 of 12 indomethacin-treated patients; not significantly different), correlated strongly with histologic evidence of active superficial antral gastritis (p less than 0.005), but not with the endoscopic appearance of the antrum. In contrast to the antrum, fundic C. pylori, found in 14 of 23 biopsy specimens (61%), were frequently associated with histologically and endoscopically normal fundic mucosa. Campylobacter pylori-associated active antral gastritis occurred only in subjects whose fundus harbored this organism. Plasma immunoglobulin G antibody titers to C. pylori were highest in subjects with Campylobacter-associated antral gastritis and lowest in subjects without gastric Campylobacter. These studies suggest that healthy humans may harbor C. pylori in their proximal stomach without apparent ill effects. In some of these individuals, the organism also involves the antrum and is associated with active gastritis.

Forty-five patients with chronic hepatitis B were entered into a randomized controlled trial of recombinant human alpha-interferon therapy. All patients had hepatitis B surface antigen in serum for at least 1 yr and had stable serum levels of both hepatitis B virus deoxyribonucleic acid and hepatitis B e antigen. During the 4-mo period of therapy, 10 of 31 (32%) treated patients and only 1 of 14 (7%) control patients became negative for serum hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase. All 10 patients who became negative for serum hepatitis B virus deoxyribonucleic acid subsequently had a marked improvement in serum aminotransferase activities and lost hepatitis B e antigen from serum, and 9 of them had improvement in liver histology. Comparison of responders to nonresponders indicated that female sex and a high initial level of serum aspartate aminotransferase correlated best with response to interferon therapy. These findings indicate that a 4-mo course of recombinant alpha-interferon can induce a remission in disease in approximately one-third of patients with chronic hepatitis B.

We conducted a double-blind, placebo-controlled, randomized treatment study in Peruvian adults with antral gastritis associated with Campylobacter pylori. Patients received either 400 mg of furazolidone (n = 14), 400 mg of nitrofurantoin (n = 24), or a placebo (n = 31) for 14 days. Endoscopy was carried out at baseline, 1 day after ceasing therapy, and 6 wk after the end of treatment to verify colonization by C. pylori and determine the extent of gastric inflammation. Treatment with nitrofurantoin or furazolidone markedly reduced or, in some cases, cleared C. pylori from the antrum (p less than 0.0005 compared with placebo). Resolution of acute gastric inflammation, as evidenced by decreased polymorphonuclear leukocyte infiltration and regeneration of the mucus layer, paralleled the reduction in bacterial colonization (p less than 0.005 compared with placebo). A high percentage of patients experienced relapse (recolonization by C. pylori and return to pretreatment levels of gastritis) within 6 wk after cessation of treatment. Significant relief of dyspeptic symptoms was not evident during the study.

The indirect, noninvasive technique of breath hydrogen (H2) analysis was evaluated in 45 patients suspected of having bacterial overgrowth of the small intestine. Bacterial overgrowth, defined as a jejunal culture yielding at least 10(5) organisms/ml, was present in 27 patients. After dietary preparation and a 12-h fast, subjects received in random order and on separate days 50 g of glucose or 50 g of rice flour in the form of two pancakes. Normal values were established in 20 healthy controls. Twelve of 27 patients with proven bacterial overgrowth had an elevated (greater than 15 ppm) fasting breath H2 level on at least 1 test day. Fifteen of 18 patients with negative cultures had low fasting breath H2 levels. Based on values in controls, a positive breath test was defined as an increase in breath H2 of greater than or equal to 12 ppm after glucose or greater than or equal to 14 ppm after rice flour. A 2-h glucose breath H2 test had a sensitivity of 93% and a specificity of 78% in the diagnosis of overgrowth. The predictive value of a positive test was 86% and that of a negative test was 88%. The combination of both a high fasting breath H2 level and a diagnostic rise of breath H2 after glucose was present in 41% of patients with overgrowth and in none of the patients without overgrowth. Extending the test to 4 h did not increase sensitivity, but decreased specificity. Rice flour was a less satisfactory substrate in predicting the presence of bacterial overgrowth. In conclusion, a high fasting breath H2 level after dietary preparation suggests bacterial overgrowth but lacks sensitivity. The finding of a rise in breath H2 of at least 12 ppm within 2 h of a 50-g glucose challenge is a simple screen for bacterial overgrowth. The combined criteria of a high fasting breath H2 level and a significant rise after glucose are specific for bacterial overgrowth.

The effect of nifedipine on sphincter of Oddi (SO) motor activity was determined by endoscopic manometry. Sphincter of Oddi pressures and motor function were compared in 21 healthy volunteers and in 9 patients with SO dyskinesia. The effects of sublingual doses of 10 or 20 mg of nifedipine were compared with placebo. Neither placebo nor 10 mg of nifedipine produced any effect on SO motor activity. In healthy volunteers 20 mg of nifedipine produced a moderate but significant decrease in basal SO pressure from 12.0 to 6.7 mmHg as well as in the amplitude, duration, and frequency of phasic contractions. In patients with SO dyskinesia 20 mg of nifedipine also resulted in a significant but more profound decrease of the basal SO pressure from 47.1 to 17.3 mmHg as well as in a decrease of amplitude, duration, and frequency of the phasic contractions. Neither placebo nor 10 or 20 mg of nifedipine has any effect on the sequence of phasic contractions. In summary, nifedipine may have a possible therapeutic role in the treatment of SO dyskinesia.

We evaluated the therapeutic efficacy of penicillamine in primary sclerosing cholangitis. In a randomized, prospective, double-blind trial, 39 patients received penicillamine (250 mg t.i.d.) and 31 received a placebo. The two groups were highly comparable at entry with regard to clinical, biochemical, radiologic, and hepatic histologic features. Although a predictable cupruresis and a decrease in levels of hepatic copper were achieved in patients taking penicillamine, there was no beneficial effect on disease progression within 36 mo or on overall survival. Progressive symptoms, deterioration in serial hepatic laboratory values, or histologic progression on sequential liver biopsy specimens were similar in both groups, occurring in greater than 80% of the entire study population. The development of major side effects led to the permanent discontinuation of penicillamine in 21% of the patients taking the drug. We conclude that the use of penicillamine in primary sclerosing cholangitis is not associated with a beneficial effect on disease progression or survival, and has considerable toxicity. The study also suggests that primary sclerosing cholangitis is a progressive disease in many patients.

We have studied the response of erosive or ulcerative esophagitis to treatment with omeprazole and its subsequent relapse on cessation of therapy in 196 patients. In the first phase of the study omeprazole (20 or 40 mg daily) was compared with placebo in 64 patients. After 4 wk there was endoscopic healing in 81% (25 of 31) of omeprazole-treated patients and in only 6% (2 of 32) of placebo-treated patients. Endoscopic healing of esophagitis was accompanied by symptom relief and histologic healing of ulceration. In the second (dose finding) phase a further 132 patients were randomized to omeprazole (20 or 40 mg daily) and endoscopic healing was assessed. In patients with the mildest grade of ulcerative esophagitis (grade 2), healing occurred at 4 wk in 87% receiving 20 mg and in 97% receiving 40 mg. In patients with grade 3 esophagitis, 67% (20 mg) and 88% (40 mg) were healed. Less than half the patients with grade 4 esophagitis (Barrett's ulcers or confluent ulceration) healed with either 20 mg (48%) or 40 mg (44%). Regression analysis in the 164 omeprazole-treated patients showed no evidence that healing was influenced by factors other than severity of esophagitis at entry and omeprazole dose. In phase 3 of the study the rate of endoscopic relapse was determined in 107 endoscopically healed patients after stopping omeprazole. Erosive or ulcerative esophagitis recurred in 88 of 107 (82%) by 6 mo. Neither initial dose, grade of esophagitis, nor smoking was shown to influence relapse rate. Omeprazole is a highly effective treatment for peptic esophagitis. The 40-mg/day dosage produces endoscopic healing slightly more quickly than the 20-mg/day dosage, and the initial endoscopic gradings are of prognostic value. Relapse occurs rapidly when treatment is stopped.

Antral biopsy specimens from 89 consecutive patients with nonulcer dyspepsia and erosive prepyloric changes included in a prospective, randomized, double-blind 4-wk study of the effect of an aluminum-magnesium antacid (120 mmol/day) or pirenzepine (50 mg b.i.d.) vs. placebo were examined histologically. Campylobacter pylori (CP) was found by light microscopy of silver-stained sections in 25 patients (28%). Campylobacter pylori-positive patients were on average older than CP-negative patients (p = 0.02). There was a strong association between CP colonization and acute inflammation (p less than 0.001), both being rare in the absence of chronic inflammation. During treatment with antacids, the density of CP decreased (p less than 0.001) without any improvement of the inflammatory reaction. On the contrary, the number of patients with gastritis tended to increase after antacids as compared with placebo (p less than 0.10). A separate analysis showed no symptomatic effect of the drugs. Thus, neither nonulcer dyspepsia nor erosive prepyloric changes are strongly associated with antral CP colonization or acute inflammation. Aluminum-magnesium antacids may suppress antral CP infection without healing the gastritis or relieving symptoms.

In spite of the widespread use of the Garren-Edwards gastric bubble as an adjuvant device in weight reduction, its efficacy has not been established. Therefore, our purpose was to conduct a randomized, double-blind, crossover study of this device in the management of exogenous obesity. The study group consisted of 23 patients, 21 women and 2 men, ranging in age from 21 to 53 yr. Patients were 25%-111% above their ideal body weight. They were studied for 24 wk, consisting of two separate 12-wk evaluation periods. Patients were randomly assigned either to receive the gastric bubble or to have a sham procedure. After the first 12-wk evaluation period, the gastric bubble and sham were administered in crossover fashion, so that those who had received the gastric bubble initially received the sham later and vice versa. The study coordinator remained blind to the kind of treatment, weighed each patient biweekly, enforced dietary counseling, and provided behavior modification. Those who had passed or were found to have a deflated bubble at the end of the treatment period were excluded from the study. Mean weight reduction in the two evaluation periods did not differ significantly. Patients lost 5.4 +/- 1.7 kg (mean +/- SE) during the gastric bubble period and 5.20 +/- 0.8 kg during the sham period. The order of administration of the gastric bubble and sham did not significantly affect the result. The time-course of mean biweekly values, however, revealed that with the gastric bubble, weight loss was significantly greater only during first (p less than 0.005) and second (p less than 0.025) 2-wk evaluation periods. This difference, however, disappeared after the initial 4 wk of treatment. These observations suggest that although gastric bubble implantation reduced weight significantly more than the sham procedure initially, the mean weight loss during 12 wk of evaluation was not different between the two periods. In our opinion, the gastric bubble is of no value as an adjuvant device in weight reduction.

Since its approval by the Food and Drug Administration in September 1985, the Garren-Edwards gastric bubble has been extensively used as an adjunct to diet and behavioral modification in the treatment of exogenous obesity. In an attempt to evaluate the efficacy of the Garren-Edwards gastric bubble, a double-blind crossover study was undertaken. Ninety patients were randomized into three groups: bubble-sham, sham-bubble, and bubble-bubble in two successive 12-wk periods. Sixty-one patients completed the entire 24-wk study. All groups participated in ongoing diet and behavioral modification therapy in a free-standing obesity program, the members of which were blinded to randomization arms. All patient groups lost weight during this study. The mean cumulative weight loss in pounds at 12 wk was as follows: bubble-sham = 19, sham-bubble = 12, and bubble-bubble = 8; and at 24 wk: bubble-sham = 23, sham-bubble = 16, and bubble-bubble = 18. The mean cumulative change in body mass index (kg/m2) at 12 wk was as follows: bubble-sham = -3.1, sham-bubble = -2.3, and bubble-bubble = -2.9; and at 24 wk: bubble-sham = -3.1, sham-bubble = -3.0, and bubble-bubble = -3.3. Although weight loss occurred more consistently in patients with a Garren-Edwards gastric bubble, there were no significant differences between any of the three groups at 12 or 24 wk with respect to weight loss or change in body mass index. The major part of the weight loss noted during this study occurred during the first 12-wk period, irrespective of therapy (bubble or sham). Side effects observed during this study included gastric erosions (26%), gastric ulcers (14%), small bowel obstruction (2%), Mallory-Weiss tears (11%), and esophageal laceration (1%). We conclude that, in this study, the use of a Garren-Edwards gastric bubble did not result in significantly more weight loss than diet and behavioral modification alone in the management of exogenous obesity, and it may result in significant morbidity.

The use of sigmoidoscopy as a screening method for colorectal cancer is controversial. Evidence regarding its efficacy is reviewed critically, with special attention given to potential biases in screening studies. The vast majority of studies are uncontrolled and without follow-up information and thus shed little light on the actual benefits of sigmoidoscopy. Two uncontrolled studies with follow-up and one randomized trial suggest a colorectal cancer mortality reduction because of the use of sigmoidoscopy, but all three studies have major shortcomings. The authors conclude that the currently available data are insufficient to establish a national recommendation for screening with sigmoidoscopy. To establish such a recommendation, a properly conducted randomized trial with colorectal cancer mortality as an outcome is needed.

A total of 1192 consecutive patients with diffuse liver disease were randomized to have percutaneous liver biopsy specimens taken with the Menghini or the Tru-Cut needle, to compare tissue yield, safety, and accuracy of the two needles for diagnosing cirrhosis. The sites of puncture were determined by prebiopsy ultrasound scans. Adequate samples were obtained from 94% with the Tru-Cut needle and from 79.2% with the Menghini needle (p less than 0.001). Accuracy in diagnosing cirrhosis was 89.5% for the Tru-Cut needle and 65.5% for the Menghini needle (p less than 0.05). Complication rates were very low and similar for both needles. Under these conditions, the Tru-Cut needle is superior to the Menghini needle for diagnosing cirrhosis.

Ninety normal volunteers were entered into a double-blind, placebo-controlled study to compare the efficacy of misoprostol (200 micrograms q.i.d.) vs. cimetidine (300 mg q.i.d.) in protecting the gastric and duodenal mucosa from tolmetin-induced (400 mg q.i.d.) injury. After 6 days of treatment, the degree of mucosal injury between treatments was compared by endoscopy, using a predetermined rating scale of 0 (normal mucosa) to 4+ (greater than 25 hemorrhages or erosions or an invasive ulcer). Utilizing a score of less than or equal to 2+ (2-10 hemorrhages or erosions) as a therapeutic success, the overall success rates were 8/30 (26.7%) for placebo, 19/30 (63.3%) for cimetidine, and 27/29 (93.1%) for misoprostol (p less than 0.001). Pairwise comparisons were also significant: misoprostol vs. placebo (p less than 0.001), misoprostol vs. cimetidine (p = 0.006), and cimetidine vs. placebo (p = 0.004). A separate analysis of the gastric scores alone revealed success rates identical to those in the overall evaluation; however, success rates in the duodenum for both misoprostol (29/29) and cimetidine (29/30) were extremely high and did not differ. It is concluded that misoprostol is highly effective and significantly better than cimetidine in protecting the gastric mucosa from tolmetin-induced injury; however, both agents were highly protective in the duodenum.

The alpha-glucosidase inhibitor acarbose has been successfully used in diabetic patients to decrease the postprandial rise in blood glucose. The aim of the present experiments was to investigate the fate and effects of acarbose along the small intestine using a slow-marker perfusion technique. In 8 healthy volunteers, jejunal and ileal loads of acarbose, glucose, and total carbohydrates were determined following a liquid, 400-kcal formula meal containing either 200 mg of acarbose or placebo. Preprandial and postprandial plasma concentrations of glucose and several polypeptide hormones were determined. Recovery of acarbose during 4 h was 65% +/- 9% (mean +/- SEM) of ingested dose in the ileum but 94% +/- 9% in the jejunum, indicating that the compound was neither degraded nor absorbed by the intestine to a major degree. After acarbose administration, ileal loads of glucose and total carbohydrates were considerably higher, whereas postprandial plasma concentrations of glucose, insulin, and gastric inhibitory polypeptide were lower when compared with placebo. The retardation of carbohydrate digestion to be inferred from these findings is confirmed by significantly elevated plasma concentrations of enteroglucagon after acarbose administration compared with placebo administration.

The irritable bowel syndrome (IBS) is a common and poorly understood chronic condition that is treated with a great variety of drugs and other therapies without notable enduring success. As there are no objective markers of improvement, and because there may be a very large placebo response, potential treatments for IBS are difficult to assess. Probably the only method that can reliably evaluate IBS therapies is the randomized, double-blind, placebo-controlled treatment trial. The purpose of this review is to critically examine issues central to establishing the efficacy of treatments for IBS in such trials. These include the definition of IBS, measures of efficacy, the placebo response, trial length, maintaining blindedness, the crossover design, ability to generalize, and statistical considerations. With this background, all published IBS treatment trials are examined. It is concluded that not a single study offers convincing evidence that any therapy is effective in treating the IBS symptom complex. Well-designed and executed IBS treatment trials are urgently needed; suggestions are given for essential features of such trials.

We have conducted a double-blind controlled trial of colchicine in patients with primary biliary cirrhosis. Fifty-seven patients with biopsy-proven primary biliary cirrhosis were randomized to receive either 0.6 mg of colchicine twice daily or an identically appearing placebo. Patients underwent clinical and laboratory evaluation every 3 mo and liver biopsy annually. Differences in mean alkaline phosphatase and alanine aminotransferase values between the colchicine and placebo recipients were statistically significant at 4 yr. Differences in mean bilirubin and immunoglobulin M values, although lower in the colchicine group, did not reach statistical significance. In colchicine-treated patients, mean alkaline phosphatase values fell significantly compared with controls, from 281 to 112 IU/L (p less than 0.01). Similarly, mean alanine aminotransferase values fell significantly compared with controls, from 129 to 86 IU/L (p less than 0.05). Bilirubin values remained stable in drug-treated patients, even in those patients with initially elevated bilirubin values, whereas they nearly doubled in subjects receiving placebo. Although biochemical parameters of disease activity improved or stabilized in colchicine-treated subjects, no difference in histologic progression was detected between the two treatment groups. We conclude that colchicine is of clinical benefit to patients with primary biliary cirrhosis as judged by improvement in alkaline phosphatase and alanine aminotransferase activities as well as a tendency for stabilization of bilirubin values.