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Biomedical subjects

G Pledger

Publications and source records attributed to G Pledger.

25 records · Page 2Linked to original sources

Childhood deaths from intussusception in England and Wales, 1984-9.

OBJECTIVE: To assess the incidence of potentially avoidable factors contributing to death of children with intussusception. DESIGN: Review of children who died with intussusception in England and Wales between 1984 and 1989 from data of the Office of Population Censuses and Surveys, case notes, coroners' records, and necropsy reports. MAIN OUTCOME MEASURES: Unambiguous objective criteria such as failure to diagnose intussusception within 24 hours of admission. RESULTS: 33 children died of acute intussusception in England and Wales between 1984 and 1989 compared with 67 in the previous six years. Their median age was 7 months (range 2 months to 12 years), and two thirds were boys. Half of the deaths occurred at home or soon after arrival at hospital but 15 patients had surgery. Potentially avoidable factors contributing to death were identified in 20 (61%) children, all but three of whom had ileocolic intussusception. These factors were excessive delay in diagnosis, inadequate intravenous fluid and antibiotic therapy, delay in recognising recurrent or residual intussusception after hydrostatic reduction, and surgical complications. Of the 13 patients in whom no avoidable factors were identified, there were nine of 11 children with isolated small bowel intussusception, who tended to have atypical presentations. CONCLUSION: Although the mortality from intussusception has declined, there remains ample opportunity for improved management.

Child↗

The role of a placebo-treated control group in combination drug trials.

In order to satisfy regulatory requirements for fixed-dose combination drug products, clinical trials must demonstrate that each component contributes to the claimed effect of the combination. Thus, the comparisons of primary interest are usually of the combination versus combination minus one component, and do not involve placebo. However, a placebo-treated group can be useful for interpreting the primary comparisons and for clarifying the nature of effects in the presence of interactions. These points are illustrated by examples from various drug classes. Statistical analysis of combination drug trials, particularly the appropriateness of factorial analysis, is also discussed.

Clinical Trials as Topic↗

Planning roles.

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England↗

Determinants of resistance to the cardiotoxicity of isoproterenol in rats.

Induction of myocardial necrosis by isoproterenol produces resistance to the necrogenic effects of subsequent doses of the drug. A series of experiments were performed to further define the determinants of resistance. Myocardial necrosis was induced in male Sprague-Dawley rats by sc injection of isoproterenol at 50 micrograms/kg daily for 10 consecutive days or as a single dose at 50, 5, or 0.5 micrograms/kg. These preconditioning doses were followed, at various times, by a challenge dose of 50 micrograms/kg. The rats were killed 48 hr after the challenge dose, and their hearts were analyzed morphometrically to determine the amount of acute necrosis and scarring. The amount of scar tissue was a reflection of necrosis caused by the preconditioning dose whereas acute necrosis reflected response to the challenge dose. Resistance occurred and lasted longer than 19 to 20 weeks after both single or multiple isoproterenol injections of 50 micrograms/kg, but it was not observed 5 days after administration of a single preconditioning dose. Isoproterenol at 0.5 micrograms/kg produced only very minimal or no myocardial necrosis and did not produce resistance. The resistance was not dependent on the size of the area of necrosis produced during the preconditioning period, showing that it was not due to destruction of all vulnerable muscle by the preconditioning dose(s). The preexistence of lesions, however, was necessary for the development of resistance. It is concluded that development of resistance to the necrogenic effects of isoproterenol reflects an adaptive alteration in the myocardium which survives after a necrogenic dose.

Animals↗