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Background: There are considerable variations in estimates of the number of emergency upper gastrointestinal admissions per annum which are attributable to nonsteroidal anti-inflammatory drug (NSAID) use., Aim: To obtain a more accurate estimate of the number of these emergency admissions per annum in UK., Methods: A retrospective survey of the case notes of all emergency admissions for upper gastrointestinal disease ('Cases') to two English District General Hospitals with a combined catchment population of 550,000. Records of all community deaths attributed to upper gastrointestinal diagnoses (with the same ICD codes) were also surveyed. Matched controls were identified from emergency admissions not caused by upper gastrointestinal diagnoses. The proportions of patients taking NSAIDs on admission to hospital (or at the time of death at home) and the outcome following admission to hospital were analysed., Results: 620 emergency upper gastrointestinal admissions were identified and matched with 460 controls. Cases were more likely to be NSAID users than Controls (31% vs. 16%, OR 2.4, 95% CI: 1.8, 3.3: P < 0.001). Case NSAID use was higher in females and with increasing age. As severity of mode of presentation worsened, the probability of NSAID use increased (e.g. OR relative to controls for peptic pain 1.9, for perforation 5.9). Blood transfusion requirements were significantly higher (P < 0.0001) in Cases taking NSAIDs, although NSAID use did not influence mortality. Extrapolation from these data indicate that there are 65,000 emergency upper gastrointestinal admissions per annum in UK; 12,000 of these admissions (including 2230 deaths) are attributable to NSAID use. A further 330 attributable deaths occur in the community., Conclusions: There is a strong association between NSAID use and propensity for upper gastrointestinal emergency admission; NSAID use is associated with significant morbidity and mortality each year in UK.

Background: This article reviews various issues surrounding NSAID-induced gastroduodenal ulceration, about which there appear to be conflicting views and data in the literature. These issues include the size, clinical relevance and main site of the problem; when complications occur (early or late?); the relevance of non-ulcer lesions and whether adaptation is a clinically relevant phenomenon., Method: A comprehensive literature search was carried out to identify relevant new data published since 1987., Results: NSAIDs are causally associated with more gastric than duodenal ulcers but their use may be associated with duodenal ulcers or complications. Erosive lesions may progress to more severe damage. The theories of early or late onset of complications during a course of NSAID therapy may not be mutually exclusive., Conclusions: Available data indicate that NSAID ulcers are at least as dangerous as classic peptic ulcers, and result in significant morbidity and mortality which in the patient population does not appear to be significantly reduced by processes such as adaptation.

Twelve healthy volunteers took part in a randomised, double-blind, balanced, cross-over study to investigate the effect of misoprostol on the pharmacokinetics of propranolol. The subjects took propranolol 80 mg twice daily by mouth plus either misoprostol 400 micrograms twice daily or placebo by mouth for 14.5 days, followed by a 2-week washout period, followed by the alternate treatment for 14.5 days. Misoprostol had no significant effect on the t/2, Cmax or AUC of propranolol either after a single dose or at steady state.

First, the pharmacokinetics of antipyrine were studied in 12 healthy male and female volunteers (i) before misoprostol, (ii) after they had received misoprostol 400 micrograms twice daily for 28 days and (iii) after a further 28 days during which no misoprostol was taken. The plasma half-life and area under the plasma concentration-time curve of antipyrine were unchanged. The findings suggest that misoprostol is not an hepatic enzyme inducer. Second, 12 healthy male and female volunteers took propranolol 80 mg twice daily for four weeks; during the second and third of these weeks the volunteers also took misoprostol 400 micrograms twice daily. The plasma concentrations of propranolol under these steady state dosing conditions increased when misoprostol was added to propranolol. The mechanism underlying this finding should be clarified.

Nineteen boys, mean age 14.4 years (range 12.9-16.3), with constitutional delay of growth and puberty were randomised into two groups in a double blind fashion for a three month period. Ten boys received oxandrolone, 2.5 mg per day (mean dose 0.072 mg/kg/day), and nine boys were treated with placebo. Mean growth velocity increased from 4.5 cm/year in the oxandrolone treated group to 9.6 cm/year in three months, and this was sustained at 8.6 cm/year after cessation of treatment. In the placebo treated group, growth rate showed no alteration from 5.1 cm/year to 5.2 cm/year; boys in this group were then treated with oxandrolone, 2.5 mg a day (mean dose 0.073 mg/kg/day) for three months and growth velocity accelerated to 8.6 cm/year. Serum concentrations of insulin-like growth factor -1/somatomedin-C (IGF-1) increased during oxandrolone treatment and continued to rise after treatment had ceased. There was no change in serum IGF-1 concentration during treatment with placebo. Oxandrolone, when used in an appropriate regimen, is an effective, safe treatment for boys with constitutional delay of growth and puberty.