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.

Antacids have served us well for over a century. The attitude in the late 1950s to 1970s that antacids should be taken only on demand was unjustified and was based on what can be seen nowadays as misinterpretation of scientific data. Twelve recent endoscopic controlled studies have confirmed the efficacy of antacids in the healing of duodenal ulcer, achieving about 75% healing in 4 weeks. Like H2-receptor antagonists, the efficacy of antacids in the healing of gastric ulcers is controversial, most probably related to the even greater pathogenetic heterogeneity of this condition. Antacids should be given at least four times a day and at least 1 hour after meals, since their therapeutic success most likely depends on neutralization of postprandial acid secretion. In vivo, the newer tablet forms are indistinguishable from the liquid forms in terms of neutralizing efficiency and healing efficacy. The ideal dose is one that neutralizes 400 mmol of acid. Combination with an anticholinergic drug is effective and a recent report suggests that this may lead to longer remission than with H2-receptor antagonists. As a long-term therapy, antacids appear to work but need to be taken in multiple daily doses, a regimen which is unlikely to meet with long-term patient compliance. The success of antacids in duodenal ulcer healing should alert us to the importance of controlling the meal-stimulated acid secretion in ulcer therapy, and to the hard fact that acid is a non-permissive factor in ulcer healing.

The first histamine H2-receptor antagonists were developed in the early 1970s, and they have a dominant role in today's management of peptic ulceration. The original regimens using either cimetidine or ranitidine attempted to control acidity across the 24 hours, but more 'modern' regimens use a large single dose of the H2-blocker in the evening, which produces a pulse of decreased intragastric acidity during the night with a normal acidity in the daytime. High-dose regimens using a new generation of extremely potent histamine H2-receptor antagonists may improve ulcer healing rates at 4 weeks, and may be particularly useful for the management of either severe oesophagitis or intractable duodenal ulceration.

It has recently been shown that repeated large-volume paracentesis associated with intravenous albumin infusion is a rapid, effective, and safe therapy of ascites in cirrhosis. To investigate whether intravenous albumin infusion is necessary in the treatment of cirrhotics with large-volume paracentesis, 105 patients with tense ascites were randomly allocated into two groups. Fifty-two patients (group 1) were treated with paracentesis (4-6 L/day until disappearance of ascites) plus intravenous albumin infusion (40 g after each tap), and 53 (group 2) with paracentesis without albumin infusion. After disappearance of ascites, patients were discharged from the hospital with diuretics. Patients developing tense ascites during follow-up were treated according to their initial schedule. Paracentesis was effective in eliminating the ascites in 50 patients from group 1 and in 48 from group 2, with the duration of the hospital stay being approximately 11 days in both groups. Paracentesis plus intravenous albumin did not induce significant changes in standard renal function tests, plasma renin activity, and plasma aldosterone. In contrast, paracentesis without albumin was associated with a significant increase in blood urea nitrogen, a marked elevation in plasma renin activity and plasma aldosterone concentration, and a significant reduction in serum sodium concentration. One patient from group 1 and 11 from group 2 developed renal impairment or severe hyponatremia after treatment, or both (chi 2 = 9.19; p less than 0.01). The development of these complications could not be predicted by clinical and laboratory data before treatment. Although the probability of survival after entry into the study was similar in patients from both groups, a multivariate analysis identified the development of hyponatremia or renal impairment, or both, following the first paracentesis treatment and the occurrence of other complications during the first hospitalization (encephalopathy, gastrointestinal bleeding, and severe infection) as being the only independent predictors of mortality. These results indicate that intravenous albumin infusion is important in avoiding renal and electrolyte complications and activation of endogenous vasoactive systems in cirrhotics with ascites who are treated with repeated large-volume paracentesis. The development of such complications may impair survival in these patients.

To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.6% (95% confidence limits, 24%-54%) and mesalazine 37.5% (95% confidence limits, 24%-53%), chi 2 = 0.01, p greater than 0.90. Mean time to relapse, cumulative relapse rate, and relapse severity were similar in the two groups. Headaches and upper gastrointestinal symptoms--common at trial entry--improved to a greater extent in patients receiving mesalazine. Delayed-release mesalazine is an effective treatment for maintaining ulcerative colitis remission and is associated with fewer side effects than equivalent doses of enteric-coated sulfasalazine.

The effects of morphine and the opiate antagonist naloxone on human colonic transit were investigated. In a crossover, double-blind fashion, two groups of 6 normal volunteers were studied using colonic transit scintigraphy during the administration of a test drug or control. The test drugs were morphine (0.1 mg/kg every 6 h s.c.) or naloxone (0.8 mg every 6 h s.c.); control was saline (1 ml every 6 h s.c.). Morphine significantly delayed transit in the cecum and ascending colon (p less than 0.05), slowed the progression of the geometric center (p less than 0.01), and decreased the number of bowel movements per 48 h (p less than 0.005). Naloxone accelerated transit in the transverse colon and rectosigmoid colon (p less than 0.05) and accelerated the progression of the geometric center (p less than 0.05), but had no effect on the number of bowel movements per 48 h (p greater than 0.05). These results suggest that narcotic analgesics may cause constipation in part by slowing colonic transit in the proximal colon and by inhibiting defecation. Acceleration of transit by naloxone suggests that endogenous opiate peptides may play an inhibitory role in the regulation of human colonic transit.

In this study we investigated the site and nature of the signal responsible for the generation of the gastrocolonic response at the rectosigmoid region. Sixteen healthy subjects participated in this study. Motor activities were recorded with pressure transducers placed in the rectosigmoid colon. Balloon distention of the stomach with 100, 200, or 300 ml of water caused a volume-dependent increase in rectosigmoid motility that was abolished by atropine. To investigate the intestinal phase of the gastrocolonic response, we infused into the duodenum isocaloric (178 kcal) solutions of normal saline, lipid, glucose, or essential amino acids at 1.5 ml/min for 30 min in random order on separate days. Only lipid infusion caused an increase in rectosigmoid pressure and this was accompanied by an elevation of plasma cholecystokinin from 1.2 +/- 0.1 to 4.3 +/- 1.0 fmol/ml. The increase in motility associated with lipid infusion was antagonized (58% +/- 7%) by atropine. To further investigate the possible role of cholecystokinin as a mediator of the gastrocolonic response, we infused cholecystokinin-octapeptide intravenously at doses of 5, 10, and 20 ng/kg.h. A significant increase in rectosigmoid motility was observed only at 20 ng/kg.h and this was accompanied by an increase in plasma cholecystokinin levels to 12 +/- 2 fmol/ml, a value threefold greater than that produced by lipid infusion. These studies demonstrate that gastric distention and intestinal lipid are potent stimuli for the generation of the gastrocolonic response involving the rectosigmoid region. The gastric phase can be generated by mechanoreceptors utilizing the cholinergic pathways, whereas the intestinal phase is nutrient-specific, partially atropine-sensitive, and independent of cholecystokinin.

We conducted a double-blind, randomized, parallel group study in 169 patients with acute duodenal ulcers to compare omeprazole, 20 mg daily, with cimetidine, 600 mg twice daily. After 2 wk, 58% of the omeprazole-treated patients and 46% of the cimetidine-treated patients were completely healed (p = 0.056). After 4 and 6 wk 84% and 88% healed with omeprazole, and 80% and 89% healed with cimetidine (p = NS). After 2 wk, pain was completely gone in 62% of the omeprazole-treated patients versus 46% of the cimetidine-treated patients (p = 0.04). Clinical or laboratory adverse events were reported in 6 (7%) of the omeprazole-treated patients and 11 (13%) of the cimetidine-treated patients (p = NS). An adverse event caused withdrawal of 1 patient on omeprazole (anxiety and depression) and 2 patients on cimetidine (diarrhea and fall in hemoglobin). We conclude that omeprazole (20 mg daily) resulted in a trend toward more rapid ulcer healing compared with a relatively high dose of cimetidine (600 mg b.i.d.), and was preferred by patients for relief of ulcer pain.