Context.-The serotonin reuptake inhibitors are the treatment of choice for patients with obsessive-compulsive disorder; however, empirical support for this assertion has been weaker for children and adolescents than for adults.Objective.-To evaluate the safety and efficacy of the selective serotonin reuptake inhibitor sertraline hydrochloride in children and adolescents with obsessivecompulsive disorder.Design.-Randomized, double-blind, placebo-controlled trial.Patients.-One hundred eighty-seven patients: 107 children aged 6 to 12 years and 80 adolescents aged 13 to 17 years randomized to receive either sertraline (53 children, 39 adolescents) or placebo (54 children, 41 adolescents).Setting.-Twelve US academic and community clinics with experience conducting randomized controlled trials.Intervention.-Sertraline hydrochloride was titrated to a maximum of 200 mg/d during the first 4 weeks of double-blind therapy, after which patients continued to receive this dosage of medication for 8 more weeks. Control patients received placebo.Main Outcome Measures.-The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH GOCS), and the NIMH Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) rating scales.Results.-In intent-to-treat analyses, patients treated with sertraline showed significantly greater improvement than did placebo-treated patients on the CY-BOCS (adjusted mean, −6.8 vs −3.4, respectively; P = .005), the NIMH GOCS (−2.2 vs −1.3, respectively; P = .02), and the CGI-I (2.7 vs 3.3, respectively; P = .002) scales. Significant differences in efficacy between sertraline and placebo emerged at week 3 and persisted for the duration of the study. Based on CGI-I ratings at end point, 42% of patients receiving sertraline and 26% of patients receiving placebo were very much or much improved. Neither age nor sex predicted response to treatment. The incidence of insomnia, nausea, agitation, and tremor were significantly greater in patients receiving sertraline; 12 (13%) of 92 sertraline-treated patients and 3 (3.2%) of 95 placebo-treated patients discontinued prematurely because of adverse medical events (P = .02). No clinically meaningful abnormalities were apparent on vital sign determinations, laboratory findings, or electrocardiographic measurements.Conclusion.-Sertraline appears to be a safe and effective short-term treatment for children and adolescents with obsessive-compulsive disorder.
This paper reviews significant outcome studies regarding the hospitalization of latency-age children and examines pertinent admission criteria. Essential diagnostic and therapeutic components, including milieu therapy, individual therapy, family work, pharmacotherapy and school are discussed. The future role of psychiatric hospitalization of children is examined.
Vasodilatory prostaglandins (PG), contributing to the inflammatory reaction, have gained considerable attention. It is becoming apparent that PG have pharmacological effects traceable to biological activities distinct from smooth muscle relaxation. The data from pharmacological experiments presented here indicate the diverse action of vasodilatory PG analogues in the skin of laboratory animals. Nocloprost, a stable PGE2 analogue, induced erythema in intact skin of rats when applied topically and inhibited in the same dose range an irritant-induced inflammatory reaction in the ears of mice. Iloprost, a stable PGI2 analogue, showed proinflammatory activity after local application by enhancing the leukotriene B4 induced cell infiltration in the skin of mice. The attenuation of the spreading of ear necrosis in mice, on the other hand, indicates an anti-ischemic therapeutic potential of iloprost. Research in the past has elucidated the influence of PG on the vascular component of inflammation, but the role of PG on the cellular component of inflammation is less clear. The diverse effects of PG in skin indicate the need for a better understanding of their local actions.
This study was undertaken to evaluate the influence of the cyclooxygenase inhibitor indomethacin on the time course of the haemodynamic effects of lipopolysaccharide (LPS) intravenous infusion (10 mg.kg-1.h-1) in anaesthetized rats. LPS infusion produced a rapid (within 10 min) and prolonged (over the 90 min observation period) fall in mean arterial blood pressure (MABP) and a decrease in the pressor responses to noradrenaline (NA, 0.1, 0.3 and 1 microgram.kg-1, intravenously [i.v.]) elicited 60 and 90 min after the onset of LPS infusion. Indomethacin (7 mg.kg-1 i.v. 30 min prior to the onset of saline or LPS infusion), which by itself did not affect basal MABP nor reactivity to NA in control rats, significantly attenuated the fall in MABP observed within 20 min after the onset of LPS infusion (but did not significantly modify the hypotension observed between 30 and 90 min). Indomethacin also completely prevented the hyporeactivity to NA observed 60 min after the onset of LPS infusion, but it did so only partially at 90 min. Aortic rings removed from LPS or LPS + indomethacin-treated rats showed an identical profile of contractile reactivity (hyporesponsiveness to NA, relaxation to L-arginine, and restoration of the contractile response by methylene blue). These results suggest that in this model, cyclooxygenase products are involved in the early haemodynamic effects of LPS. However, they do not seem to play an obligatory role in the onset of longer term haemodynamic changes.
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