Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone.

The distribution of responses in study populations provides a novel method of comparing the benefit of two treatments. This 6-week, randomised, placebo-controlled, double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy, as measured by a clinical outcome (asthma control days). A total of 730 adult patients with asthma, age 15-65 yrs, with a forced expiratory volume in one second (FEV1) at baseline of 50-85% of predicted and > or = 15% improvement in FEV1 after inhaled beta-agonist were enrolled. After a 2-week placebo run-in period, patients were randomly allocated to receive montelukast (10 mg once daily), inhaled beclomethasone (200 microg twice daily) or placebo. The primary end-point (per cent of asthma control days) was compared between treatments as the overlap in the response distributions. The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89% for per cent asthma control days and 96% for change from baseline in FEV1. The mean (+/-SD) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group (placebo 40.0+/-35.8, montelukast 50.7+/-37.1, beclomethasone 57.9+/-36.1). The mean differences between montelukast and placebo, beclomethasone and placebo, and montelukast and beclomethasone were significant. The mean per cent change (+/-SD) from baseline in FEV1 was 12.1+/-18.7 and 13.9+/-20.8 in the montelukast and beclomethasone groups, respectively, and significantly greater than that in the placebo group (6.4+/-20.1); there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution. There was also no difference among treatment groups in the frequency of adverse experiences. A comparison of the response distribution is an important approach to comparing therapies; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6-week treatment period.

Use of oral montelukast in the treatment of asthma.

Montelukast, a new leukotriene modifier, has several benefits in the treatment of asthma in adults and children including improved relief of asthma symptoms, rapid onset, a safety profile comparable with placebo, and oral, once-daily dosing means excellent adherence.

Preferential destruction of cerebellar Purkinje cells by OX7-saporin.

Saporin, a plant toxin derived from Saponaria officinalis, disrupts protein synthesis by inactivating the 60S portion of the ribosomal complex. OX7 is a mouse monoclonal antibody directed against the Thy-1.1 receptor that is differentially expressed on subpopulations of central nervous system neurons. Disulfide conjugation of OX7 to saporin permits delivery of saporin to target neurons. OX7-saporin was used to study the behavioral and morphological consequences of selective destruction of cerebellar Purkinje cells which abundantly express the Thy-1.1 antigen. Male Sprague-Dawley rats received bilateral intraventricular injections of 1- or 2 microg OX7-saporin or 8 microl artificial CSF. Rats were tested for behavioral changes 1 week before and 1, 2, and 8 weeks post-treatment. OX7-saporin treatment resulted in dose- and time-dependent changes in motor performance, activity, and negative geotaxis, but did not affect foot splay. Following behavioral testing, cerebellar sections were prepared for microscopic examination and the pattern of Purkinje cell loss was determined in anatomically matched sections. OX7-saporin induced dose-dependent death of Purkinje cells, particularly in the anterior and superior portions of cerebellar folia 1-6 and folium 9. Other brain regions appeared largely unaffected. Data suggest that intraventricular injection of rats with OX7-saporin is an effective model with which to examine the consequences of Purkinje cell destruction.