Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis.

Four different cimetidine dosage regimens--800 mg u.i.d. HS or nocte, 800 mg u.i.d. dinnertime, 400 mg q.i.d., and 800 mg b.i.d.--were investigated for the treatment of reflux esophagitis in three independent large-scale, double-blind, controlled multicenter trials in which more than 1100 patients participated. Analysis of the data shows that the percentage of endoscopic healing after 6 and 12 weeks of treatment was fairly constant in patients with the same endoscopic grade of severity of reflux esophagitis at the start of treatment, whether they were treated with 800 mg u.i.d. (HS or dinnertime), 800 mg b.i.d., or 400 mg q.i.d. Healing percentages after 12 weeks of therapy ranged from 79%-92% for grade I, from 65%-70% for grade II, and from 41%-54% for grade III. Differences within the three grades for the various treatment regimens did not reach statistical significance. Symptomatic improvement was evaluated with the Standardized Total Heartburn Index, which is based on frequency and severity of heartburn as well as on the number of patients in the study population experiencing heartburn at a given time in relation to the total heartburn load at the start of the study. All three treatment schedules resulted in a substantial reduction of the Standardized Total Heartburn Index. Treatment with cimetidine, 800 mg u.i.d., for 6-12 weeks was efficacious in the majority of patients with reflux esophagitis grade I-III. Symptom relief was superior with dosing after dinner time compared with dosing HS. A single dose of 800 mg administered after the evening meal approached the efficacy achieved with 400 mg q.i.d. Based on these objectives and symptomatic results, a u.i.d. cimetidine regimen appears to be the treatment of choice for the initial approach of a patient with reflux esophagitis. A u.i.d. regimen may enhance patient compliance, comfort, and safety as well as ease of prescription while also being less expensive.

Twenty-nine nongastrectomized and three partially gastrectomized patients with chronic reflux esophagitis resistant to 12 weeks' treatment with histamine H2-receptor antagonists were treated with a daily oral dose of 20-40 mg of omeprazole for 12-30 months. Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals. Serum gastrin levels significantly (P less than 0.01) increased threefold to fourfold during the first 1-2 months of the study when all patients ingested 40 mg of omeprazole daily. Dose reduction to 20 mg did not significantly decrease gastrin levels. Serum gastrin levels showed a trend to further increase after the first 3 months of treatment, reaching statistically significant differences for values from the 3-12-month period (P less than 0.05) and from the 3-24-month period (P less than 0.005). Women and patients with high basal serum gastrin levels before omeprazole treatment were more likely to achieve higher serum gastrin levels during omeprazole treatment. Serum pepsinogen A and C levels were significantly (P less than 0.01) increased at all time intervals during long-term treatment with omeprazole. No significant tendency toward higher serum pepsinogen C levels in time was observed. However, serum pepsinogen A levels and the ratio of pepsinogen A to pepsinogen C further increased significantly (P less than or equal to 0.05) during the initial 3-12-month period. However, this trend was not observed anymore afterward. Antrectomized patients did not show increases in serum gastrin and serum pepsinogen A and C levels, suggesting that hypergastrinemia may be involved in the observed hyperpepsinogenemia.

Known properties of hepatitis A virus are described in this article. HAV is a small non-enveloped picornavirus, grouped in the Enterovirus family, with unique biological features. The genome structure resembles that of other picornaviruses. Replication in cell cultures takes much longer than that of other picornaviruses and the yield is much lower. HAV is extremely heat- and pH-stable. Variants may induce cytopathogenic effects in vitro. Normally, however, the virus is non-cytopathogenic. The elimination of virus in vivo is assumed to be caused by action of HAV antigen specific CD8+ lymphocytes. In industrialized countries there is a declining incidence of reported hepatitis A cases, and the prevalence of antibodies in younger populations is low. Vaccines have been developed and in studies using human volunteers, good immunogenicity has been demonstrated. In the very near future a cell cultured derived, highly purified, inactivated vaccine will be available.

A historical cohort was used to assess the ability of clinical features and laboratory values recorded at the time of initial diagnostic investigations to predict nondiagnostic hospital admissions in the first 3 months following the diagnosis of Crohn's disease. Data were abstracted from the medical records of 225 eligible patients at primary and secondary care level whose disease was diagnosed between 1977 and 1985. The total study group was randomly divided into two groups (group 1, n = 112; group 2, n = 113). Discriminant analysis was performed on data of patients in group 1. The resulting predictive model was then cross-validated on data of patients in group 2. The variables entered into the predictive model were identified using bivariate analysis. Results show that presence of abdominal mass, body temperature, absolute basophil and lymphocyte counts, aspartate aminotransferase and blood urea nitrogen serum levels, and place of residence (urban, rural, or out of province) were the most useful variables for predicting hospitalization in the first 3 months (P for model = 0.0010; accuracy = 88%). Cross-validation on group 2 showed an accuracy of 80%, a positive predictive value of 62%, and a negative predictive value of 84%. This predictive model could be useful for counseling purposes on the primary or secondary care levels.

A prolonged randomized, prospective, double-blind, crossover study, including a sham-sham-treated group, was undertaken to evaluate the efficacy and safety of a 500-mL gastric bubble (Ballobes; DOT ApS, Rödovre, Denmark) as an adjunct to diet, physical training, and behavioral modification. Only supermorbidly obese patients who fulfilled the usual criteria for surgery were admitted. A weight loss of 38 kg in the first 17 weeks and another 12 kg in the second 18 weeks could be achieved. The body mass index, the percentage of overweight and the loss in percentage of initial weight, paralleled this impressive weight loss. In the second period, a plateau effect occurred after the massive changes in the first period, and only one third of the changes in all parameters was seen. Stratification into a sham-sham, sham-balloon, balloon-sham, and balloon-balloon group did not show any statistical difference for all parameters between the four groups. The double-blind nature of the study was affirmed by the patient's correct judgment of the presence or absence of a balloon in only 21% of the balloon and 44% of the sham procedures. Gastrointestinal complications were infrequent and consisted of erosions (three patients), asymptomatic reflux oesophagitis (one patient), and asymptomatic gastric ulcer (one patient). Only the latter patient had elevated gastrin levels. One patient could not tolerate the balloon. All balloons remained airtight during both parts of the study for a mean of 123 days. This study confirmed the safety of the balloon, but no additional benefit could be ascribed to the balloon compared with a very low-calorie diet and medical and dietary support.

It was hypothesized that low-molecular-weight products of carbohydrate fermentation would contribute only a small percentage to the total fecal excretion of nonfat, nonnitrogenous energy (carbohydrate energy) in premature infants. Infants born at 28-32 weeks' gestation who were 2-4 weeks of age were randomized to receive a formula with lactose as the sole carbohydrate (n = 7) or the same formula with 50% of the carbohydrate as glucose polymer (n = 8). The percent contribution (X +/- SD) to total carbohydrate energy of sugars (glucose, galactose, lactose, glucose polymer), short-chain fatty acids (acetate, propionate, butyrate, isobutyrate, valerate, and isovalerate), and D- and L-lactate was 9.4% +/- 2.9% for the 15 subjects and was not significantly different between groups. The percent contribution of all four sugars was 5.8% +/- 1.7% and did not differ between the two groups. Doubling the lactose intake resulted in significant increases in fecal excretion (kilocalories per kilogram per day) of acetate (77% increase; P = 0.03), total short-chain fatty acids (54%; P = 0.04), and galactose (188%; P = 0.03). These data suggest that as much as 90% of fecal carbohydrate energy may be in the form of large-molecular-weight compounds, presumably bacterial in origin.

Parenteral S-adenosylmethionine proved to be effective in reversing intrahepatic cholestasis in pregnant women. Based on these findings, a prospective multicenter, double-blind, placebo-controlled trial was planned to assess whether oral S-adenosylmethionine is effective in cholestatic patients with chronic liver disease. Accordingly, 220 inpatients (26% chronic active hepatitis, 68% cirrhosis, 6% primary biliary cirrhosis) with stable (1 month or more) at least twofold increases in serum total and conjugated bilirubin and alkaline phosphatase volunteered for the trial. Serum markers of cholestasis significantly (P less than 0.01) decreased after oral S-adenosylmethionine administration (1600 mg/day), and their values were significantly (P less than 0.01) lower than the corresponding values in the placebo group. S-adenosylmethionine significantly (P less than 0.01) improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell, whereas placebo was ineffective. Two patients in the S-adenosylmethionine group and 9 controls (P less than 0.05) withdrew from the trial for reduced compliance because of inefficacy of treatment. Oral S-adenosylmethionine was tolerated to the same extent as placebo. In conclusion, short-term administration of oral S-adenosylmethionine is more effective than placebo in improving clinical and laboratory measures of intrahepatic cholestasis and offers a new therapeutic modality for the symptomatic management of this syndrome.

Enprostil, a synthetic analogue of prostaglandin E2, has been shown to protect the human gastroduodenal mucosa from aspirin injury. This study was designed to determine if enprostil protected against alcohol damage. A double-blind, randomized, cross-over study was performed on eight healthy adult men. After an overnight fast, a gastroscope was inserted and the antral mucosa was sprayed with a 10-mL test solution containing either enprostil (70 micrograms) or its vehicle (control). After 15 minutes, mucosal injury was scored (0-5), and the mucosa was sprayed with 100 mL 80% ethanol. Mucosal injury was scored after a further 15, 20, 25, and 30 minutes. The entire experiment was recorded on video film, which a second endoscopist used to score the damage independently. The two experiments were separated by an interval of 1 week. There was close agreement between the two endoscopists (r = 0.9385), and their scores were averaged. Using Friedman's two-way analysis of variance, a highly significant (P less than 0.00004) increase in injury was demonstrated following enprostil pretreatment. The Wilcoxin signed rank test showed the differences to be significant (P less than 0.05) at every time point. We conclude that enprostil, rather than protecting the human antral mucosa from alcohol injury, appears to potentiate this injury and may itself be damaging in therapeutic concentrations. This unexpected result cannot yet be explained but demands caution in the clinical use of enprostil.

The effects of cimetidine maintenance therapy on the socioeconomic life of patients with peptic ulcers in the 3 years after healing and the extent to which treatment was cost-effective were studied. Three hundred eleven patients with healed ulcers (184 gastric, 127 duodenal) were studied for periods of up to 3 years; 261 patients (152 gastric ulcer, 109 duodenal ulcer) completed the 3-year follow-up. Cimetidine (400 mg at night) was compared with placebo in a double-blind, randomized prospective study. Intention-to-treat analysis was used. In the placebo group, the major costs of ulcer disease in gastric ulcer patients were attributable to endoscopic procedures and absenteeism; in duodenal ulcer patients, the major costs were endoscopic procedures, absenteeism, and surgery. Cimetidine was cost-effective in both gastric ulcer and duodenal ulcer patients in the first 2 years after healing. Over the 3-year period it was also cost-effective, but no benefit was seen in the third year.

The effects of lovastatin and ursodeoxycholic acid on cholesterol saturation of gallbladder bile were examined, alone and in combination. Nine volunteers were studied before any treatment and after each of three treatment periods: lovastatin, 40 mg, twice a day; ursodeoxycholic acid, 10 mg/kg per day; and the combination of both drugs. Treatment periods were randomly ordered, lasted 4-5 wk, and each was preceded by a 3-wk washout period. Mean cholesterol saturation index decreased from a baseline value of 1.40-0.92 on lovastatin (p less than 0.008). Mean cholesterol saturation index on ursodeoxycholic acid was 0.87 and decreased to 0.70 with the addition of lovastatin (p less than 0.030). There was a strong correlation (r = 0.87, p less than 0.003) between saturation index on ursodeoxycholic acid and the further incremental reduction in saturation index with addition of lovastatin. These findings raise the possibility that addition of lovastatin to ursodeoxycholic acid treatment might improve the efficacy of this bile salt for dissolution of cholesterol gallstones, especially in patients with a suboptimal response to ursodeoxycholic acid.

Three randomized, placebo-controlled multiclinic trials involving arbaprostil dosages of (a) 10 micrograms; (b) 25 micrograms; and (c) 10, 25, or 50 micrograms orally for 4 wk in patients older than 18 yr with rheumatoid arthritis or osteoarthritis who had endoscopically documented nonsteroidal antiinflammatory drug-associated gastric mucosal damage were conducted in the United States. All patients continued taking the nonsteroidal antiinflammatory drugs and were reendoscoped after 4 wk of therapy. Success at that time was defined as complete resolution of all gastric mucosal damage. Six hundred fifty-eight patients were enrolled in the three trials. Significantly more patients experienced healing in the arbaprostil treatment groups in all trials compared with those who received placebo. The healing rates in the various trials were 68% and 32% (10 micrograms vs. placebo; p = 0.007); 77% and 23% (25 micrograms vs. placebo; p less than 0.001); and 52%, 46%, 35%, and 16% (50, 25, and 10 micrograms vs. placebo; p less than 0.001, less than 0.001, and 0.002, respectively). Diarrhea, mostly of a mild nature, was the only arbaprostil-associated side effect and was found with the 25- and 50-microgram dosages (33% and 59%, respectively). No exacerbation of arthritis signs or symptoms was found. Arbaprostil at doses with varying effects on gastric acid secretion (25 and 50 micrograms) was documented in these trials to be an effective and safe agent for healing gastric mucosal damage associated with aspirin or other nonsteroidal antiinflammatory drugs in patients with either rheumatoid arthritis or osteoarthritis without adversely affecting joint symptomatology.

Of 550 patients admitted with acute upper gastrointestinal hemorrhage, 143 with peptic ulcers containing stigmata of recent hemorrhage accessible to endoscopic therapy were included in a randomized comparison of neodymium yttrium aluminum garnet laser, heater probe, and no endoscopic therapy. The rebleeding rate in laser-treated patients (20%) was significantly less than in controls (42%; p less than 0.05), but in heater probe-treated patients (28%) it was not significantly different from either of the other two groups. The mortality rate in the laser group (2%) was not significantly different from either the heater probe (10%) or the control (9%) group. This trial has confirmed the efficacy of the Nd YAG laser but not that of the heater probe in the prevention of rebleeding from recently bleeding peptic ulcers.

One hundred forty-two patients with active colonic or ileocolonic Crohn's disease were included in a multicenter prospective study. Data collection included 28 clinical, biological, and endoscopic items; the latter were recorded according to a standardized colonoscopic protocol; a previously validated endoscopic index of severity was calculated. Oral prednisolone (1 mg/kg body wt per day) was started and maintained until clinical remission and for at least 3 and at most 7 wk. A second clinical biological and endoscopic evaluation was then performed. At initial colonoscopy, mucosal lesions were, by decreasing order of frequency, superficial ulcerations, deep ulcerations, mucosal edema, erythema, pseudopolyps, aphthoid ulcers, ulcerated stenosis, and nonulcerated stenosis (93%, 74%, 48%, 44%, 41%, 35%, 10%, 8%, and 2% of cases, respectively). No correlation was found between the clinical activity index and any of the endoscopical data (lesion frequency and surface, endoscopic severity index). Ninety-two percent of patients underwent clinical remission within 7 wk of treatment. None of the 28 clinical biological and endoscopical items collected just before treatment could predict clinical response to steroids. Only 38 of the 131 patients in clinical remission were also in endoscopic remission. In conclusion, (a) the description and severity of colonoscopic lesions in active Crohn's disease have been quantified; (b) no correlation exists between clinical severity and nature, surface, or severity of endoscopic lesions; (c) Oral prednisolone (1 mg/kg body wt per day) induces a clinical remission in 92% of patients within 7 wk; (d) resistance to steroids cannot be predicted from the data collected before treatment onset; and (e) only 29% of patients in clinical remission also achieve endoscopic remission.

Chronic cholestatic liver disease in children frequently results in severe intractable pruritus. Current forms of therapy, including cholestyramine, are usually ineffective. Therefore, a 6-wk, double-blind, crossover study was designed to test the ability of rifampin to relieve pruritus in children with chronic cholestasis. Rifampin proved effective in alleviating pruritus in all five children tested compared with a placebo-treated group. After the 6-wk study period, rifampin was continued for 6 mo, and its effectiveness was maintained. No complications resulted from rifampin use. This study and a similar study in older patients with primary biliary cirrhosis suggest that a highly effective form of therapy is available for treatment of severe pruritus in patients with chronic cholestasis. These patients must be carefully selected and frequently monitored.

A randomized, controlled trial was performed to compare the diagnostic yields and cost-effectiveness of two strategies for the evaluation of nonemergent lower gastrointestinal bleeding. Three hundred eighty patients aged greater than or equal to 40 yr were randomized to undergo initial flexible sigmoidoscopy plus air contrast barium enema or colonoscopy; 332 completed the initial studies. Initial colonoscopy detected more cases of polyps less than 9 mm in size, adenomas, and arteriovenous malformations but fewer cases of diverticulosis. No significant difference was found between strategies in the number of patients detected with cancers or polyps greater than or equal to 9 mm in size. In both strategies, cancers were more common in subjects aged greater than or equal to 55 yr (8% overall) than in those aged less than 55 yr (1%). Among patients aged less than 55 yr with suspected lower gastrointestinal bleeding, initial flexible sigmoidoscopy plus air contrast barium enema is a more cost-effective strategy for the detection of colonic neoplasms than initial colonoscopy. However, initial colonoscopy is more cost effective for those aged greater than or equal to 55 yr.