Effect of omeprazole on the outcome of endoscopically treated bleeding peptic ulcers. Randomized double-blind placebo-controlled multicentre study.

BACKGROUND: Haemostasis is highly pH-dependent and severely impaired at low pH. However, there is no clear evidence that acid-suppressing drugs have beneficial effects in peptic ulcer haemorrhage. Endoscopic haemostatic treatment provides important reduction in morbidity and may be more efficient when a neutral intragastric pH is maintained. METHODS: We conducted a double-blind, placebo-controlled multicentre study of intravenous infusion of omeprazole (80 mg as bolus, followed by 8 mg/h) or placebo for 72 h. All patients received 20 mg omeprazole orally from day 3 until follow-up on day 21. Only patients with ulcer haemorrhage, endoscoped within 12 h after admission, and with a history or signs of circulatory failure and spurting bleeding, oozing bleeding, visible vessel, or clot, were included. Endoscopic intervention was aimed at when spurting bleeding, oozing bleeding, or a visible vessel was observed. The primary efficacy measure was the worst ranking on an overall outcome scale (5 = death, 4 = surgery, 3 = additional endoscopic treatment, 2 = more than 3 units of blood, and 1 = no more than 3 units of blood transfused). Base-line prognostic factors of treatment success by day 3 and of other binary outcomes were considered in a logistic regression model. RESULTS: Two hundred and seventy-four patients were randomly assigned to omeprazole (134 patients) or placebo (140 patients). The number of patients included in the 'intention-to-treat' analysis was 130 in the omeprazole group and 135 in the placebo group. The primary variable, the overall outcome at 72 h, showed a difference (P = 0.004) between the two treatments in favour of omeprazole. Treatment success by 72 h defined as no death, no operation, or no additional endoscopic treatment was 91.0% in the omeprazole group and 79.7% in the placebo group (therapeutic gain, 11.3 percentage units; 95% confidence interval, 2.3 to 20.4 percentage units). Significant differences in favour of omeprazole were also found for secondary variables such as number of blood transfusions, duration and degree of bleeding, and the need for surgery and additional endoscopic treatments on day 3 and day 21. However, the numbers of deaths by day 3, 21, or 35 were very similar. CONCLUSIONS: We found a beneficial effect of intravenous omeprazole in severe ulcer haemorrhage, with a reduction in the number of operations, in endoscopic treatments, and in the duration and severity of bleeding.

Continuous intravenous infusion of omeprazole in elderly patients with peptic ulcer bleeding. Results of a placebo-controlled multicenter study.

BACKGROUND: Does profound acid inhibition by continuous infusion of omeprazole for 72 h reduce further bleeding in elderly patients with peptic ulcer bleeding (PUB)? METHODS: Three hundred and thirty-three patients > or = 60 years old with PUB were randomized to omeprazole (80 mg + mg/h) or placebo as continuous infusion for 72 h. From day 4 to 21 all patients received 20 mg omeprazole orally once daily. RESULTS: When evaluated on day 3, the primary variable 'overall outcome' (based on an ordinal ranking scale; see Study variables) (P = 0.017) and the secondary variables, surgery (P = 0.003), degree (P = 0.004) and duration of bleeding (P = 0.003) all favored the omeprazole group. Blood transfusions, need for endoscopic treatment, and mortality were not statistically different. On follow-up, by day 21, the mortality in the group initially receiving intravenous omeprazole was 6.9%, while the intravenous placebo group showed an extremely low mortality, 0.6%. CONCLUSION: Three days' infusion of omeprazole improved overall outcome and reduced need for intervention in PUB patients.

Experience with the murine local lymph node assay: inability to discriminate between allergens and irritants.

The murine local lymph node assay is a new predictive test for identifying contact sensitizers. It measures the proliferative response in the lymph nodes during the sensitization phase. In the present study, moderate-to-extreme allergens (from human and guinea pig experience) gave clearly positive results in this assay. However, irritants tested, i.e. sodium dodecyl sulphate (SDS), chloroform/methanol, oxalic acid, triton X-100 and methylsalicylate, also gave positive results, not distinguishable from the results with low-grade/moderate allergens. Two allergens were also tested in the presence of 10% SDS. The effect on proliferation was additive in the first case and synergistic in the second. The local lymph node assay in its present design and with the criteria used for a positive response requires further validation studies and perhaps further development before it can be accepted as an alternative to guinea pig tests for allergenicity. Substances with exclusively irritating properties could falsely be classified as allergens by the method or, alternatively, the allergenicity of chemicals with both allergenic and irritating properties could be overestimated.

Percutaneous uptake and kinetics of methyl isobutyl ketone (MIBK) in the guinea-pig.

Continuous intravenous infusion of 0.478 mumol/min methyl isobutyl ketone (MIBK) was performed for 30 min in pentobarbital-anesthetized guinea-pigs. Epicutaneous exposure for 150 min was carried out 2.5 h later after administration of MIBK to a sealed glass ring on the clipped back of the animals. Arterial blood was analyzed for MIBK by gas chromatography. Blood clearance averaged 201 ml.min-1.kg-1 body wt. A maximum percutaneous uptake of 1.1 mumol.min-1.cm-2 was reached 10-45 min after the onset of exposure and decreased to 0.56 mumol.min-1.cm-2 during the latter part of exposure.

Prereferral intervention: a prescriptive approach.

This investigation assessed effects of three increasingly inclusive versions of the Behavioral Consultation (BC) model on problem behavior of students in mainstream classrooms in an effort to develop an effective and efficient approach to prereferral intervention. Subjects were 43 general educators, their 43 most difficult-to-teach students (without disabilities), and 12 school consultants, representing seven inner-city middle schools. Teachers and students were assigned to three BC groups, representing least (BC 1), more (BC 2), and most (BC 3) inclusive variants of BC, and one control group. Preintervention, postintervention, and follow-up observations of student behavior indicated that more inclusive BC versions exerted stronger effects than the least inclusive variant in reducing problem behavior. Theoretical and practical implications for consultation-related activity are discussed.

Percutaneous absorption of 4 organic solvents in the guinea pig (II). Effect of surfactants.

Percutaneous absorption of 4 organic solvents (1,1,1-trichloroethane, 1,1,2-trichloroethane, toluene and butanol) from various colloidal preparations in a surfactant-water-organic solvent system was studied in vivo in guinea pigs. The preparations examined were binary solutions of organic solvents and surfactants, o/w emulsions and microemulsions. Phase diagram, birefringence microscopy and droplet size distribution analysis were used for characterization of the preparations. It was found that skin absorption of the solvents depends on the type of surfactant, type of preparation and also on phase equilibria in the systems studied. The presence of nonionic surfactants in the solvents and in a microemulsion with butanol caused skin absorption to decrease. A reduced uptake of solvents from o/w emulsions was observed. The absorption of butanol from a microemulsion with anionic surfactant was greater than from the pure solvent.

Influence of water on the percutaneous absorption of 2-butoxyethanol in guinea pigs.

Anesthetized guinea pigs were exposed for 2 h to aqueous solutions (5-100%, corresponding to 0.38-7.6 mol/l) of 2-butoxyethanol (ethylene glycol monobutyl ether, BE) by epicutaneous administration in a sealed glass ring on the clipped back of the animal. After a recovery period of 2 h, the animals were exposed to undiluted BE in a second glass ring for an additional period of 2 h. Blood samples were obtained via the carotid artery and analyzed for BE by gas chromatography. To reduce the influence of interindividual variation in the kinetics, the dermal uptake rate of BE from the water solutions was expressed relative to that of the undiluted solvent obtained from the second exposure period of the same animal. The relative percutaneous uptake rates were approximately equal from the 5, 10, 20, and 100% solutions of BE, while they were approximately twice as high from the 40 and 80% solutions. The results suggest that water facilitates the percutaneous absorption of BE.

Percutaneous uptake rate of 2-butoxyethanol in the guinea pig.

The percutaneous absorption rate and elimination kinetics of 2-butoxyethanol (ethylene glycol monobutyl ether) were estimated in the guinea pig. An intravenous bolus dose of 42 or 92 mumol/kg of body weight was administered into the jugular vein of 10 pentobarbital-anesthetized animals. Epicutaneous administration of 2-butoxyethanol followed 2.5 h later in one or two sealed glass rings on the clipped back of the animal. Arterial blood samples were obtained and then analyzed for 2-butoxyethanol by gas chromatography. Following the intravenous dose, the apparent total clearance and mean residence time of 2-butoxyethanol were calculated to be 128 ml X min-1 X kg-1 (SD 30%) and 4.7 min (SD 30%), respectively. During the latter part of the 2-h skin exposure, the concentration of 2-butoxyethanol in the blood appeared to level off at an average concentration of 21 mumol/l (SD 45%). The absorption rate through the skin was estimated to be 0.25 (range 0.05-0.46) mumol X min-1 X cm-2 (SD 49%). The skin uptake rate in the guinea pig was extrapolated to man for a comparison of the percutaneous absorption of liquid solvent with respiratory uptake of solvent vapor. The extrapolation indicated a risk of acute adverse effects when large areas of the skin are exposed to 2-butoxyethanol.