A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin as treatment for children with autism.

OBJECTIVE: To determine whether a single injection of intravenous secretin results in measurable improvements in socialization and/or communication skills in children with autism. STUDY DESIGN: Sixty subjects with autism were randomly selected and assigned to either treatment or placebo group. Subjects in the treatment group received 2.0 clinical units of secretin per kilogram of body weight as a single intravenous dose. Subjects in the placebo group received normal saline solution. Neurodevelopmental and behavioral assessments were performed for all subjects before injection and at 3 and 6 weeks after injection. RESULTS: Assessment of language skills and parents' behavioral assessments revealed no significant differences between the treatment and placebo groups. Raters' assessments of severity of autistic symptoms did not differ for the 2 groups at 6 weeks after injection. A marginally statistically significant improvement in autistic behaviors was seen in the treatment group at 3 weeks after injection (P =.051). CONCLUSIONS: A single dose of intravenous secretin does not appear to have significant effects on either parents' perception of autistic behaviors or language skills at 6 weeks after injection. Transient, marginally significant improvements in autistic behaviors may occur in some children.

Differences in clearance and sensitivity to Triazolam in American blacks as compared with whites

BACKGROUND: Inter-ethnic differences exist in both pharmocodynamics and pharmocokinetics. CYP3A is the most abundant cytochrome P450 enzyme in human liver and is responsible for the metabolism of a large number of drugs and xenobiotics. AIM OF STUDY: The purpose of the present study was to determine whether there are differences in the metabolism and drug responsiveness to triazolam, a substrate of CYP3A, in American blacks and whites. METHODS: Eight American blacks and eight age - and body weight- matched whites receved orally a triazolam 0.375 mg tablet in a double-blind placebo-controlled randomized study. Plasma concentrations and effects of triazolam were measured at multiple time points over 24 hours. The pharmacodynamics of triazolam were examined by measurement of postural sway, digital symbol substitution testing (DSST), and a visual analog scale (VAS) of drowiness. Sensitivity, or the drug effect at a given concentration, was determined. RESULTS: Following oral administration of triazolam, the AUC was significantly lower in blacks (625 +- 160 ng/ml/min) (P<0.05). The systemic clearance of triazolam was three and a half fold higher in blacks (6.6 +- 2.0 vs 1.8 +- 0.2 ml/min/kg in whites, P<0.05) resulting in a shorter elimination t 1/2 (98 +- 24 vs 199 +- 29 min, P<0.05). Triazolam significantly increased postural sway and drowsiness and impaired DSST in both groups. However, there was no significant differences between the two groups in drug effects such that a similar effect of triazolam was observed in blacks with lower plasma concentration. When compared to whites, the sensitivity to triazolam was significantly higher in blacks (P<0.05). CONCLUSIONS: This study demonstrates increased clearance and increased sensitivity to triazlam in American blacks. These findings may have major therapeutic implications in a racially diverse population. (AU)

Studies of the coagulation system and blood pressure during experimental Bolivian hemorrhagic fever in rhesus monkeys.

Experimental infection of rhesus monkeys (Macaca mulatta) with Machupo virus produced a hemorrhagic disease similar to that of Bolivian hemorrhagic fever in humans. The disease in infected animals was also characterized by the development of hypotension and coagulation abnormalities as indicated by severe thrombocytopenia and prolongation of the activated partial thromboplastin time. Evidence for disseminated intravascular coagulation was inconclusive due to the presence of normal to elevated fibrinogen levels, relatively low levels of circulating fibrin split products, and the lack of widespread fibrin thrombus deposition. The most likely causes of the hemorrhagic tendencies of this disease in infected monkeys were thrombocytopenia and decreased synthesis of coagulation and other plasma proteins due to severe hepatocellular necrosis. Hypotension may also have been due to decreased plasma protein synthesis.