Assessment of the antihypertensive efficacy of various doses of delapril by office and ambulatory blood pressure measurement: the DEFIND study.

This study was undertaken to compare and verify the antihypertensive effects of various delapril doses versus placebo on office and ambulatory blood pressure (BP). After a 2-wk placebo period, 303 patients with mild to moderate essential hypertension were randomized in a double-blind study to 8 wk of treatment with placebo, or delapril 7.5 mg twice daily, delapril 15 mg twice daily, delapril 30 mg twice daily, or delapril 30 mg once daily. BP changes versus baseline and rates of normalized office systolic blood pressure (SBP) <140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg, as well as responder office SBP <140 mm Hg or reduction > or = 20 mm Hg and office DBP <90 mm Hg or reduction > or = 10 mm Hg, were calculated. In the intention-to-treat population (n=296), office SBP and DBP reductions were more notable with 30 mg twice daily (15.6/11.5 mm Hg) and 15 mg twice daily (14.8/12.5 mm Hg) than with other delapril regimens (30 mg once daily: 11.8/10.5 mm Hg; 7.5 mg twice daily: 12.9/10.1 mm Hg) and placebo (P<.05 for DBP; P<.01 for SBP). The same was true for frequency of responders (63.8% and 60.3%; P< or =.05 vs placebo) and normalized patients (58.6% and 53.4%; P<.05 vs placebo). Analysis of ambulatory BPs confirmed the accuracy of office BPs. Drug-related adverse events occurred in 3.4% to 6.7% of patients given delapril and in 6.5% of those given placebo. The lowest effective dose of delapril, 15 mg twice daily, may be recommended as the initial dose for patients who begin treatment with this agent.

Reduced circulating natural killer T cells and gamma/delta T cells in patients with systemic sclerosis.

OBJECTIVE: To evaluate peripheral blood mononuclear cells (PBMC) expressing natural killer (NK) cell surface markers (CD16 and CD56, in both CD3- and CD3+ cells) and g/d T cell receptors (TCR) involved in non-MHC-restricted cytotoxicity, assessing their possible relationship with clinical and laboratory variables in patients with systemic sclerosis (SSc). METHODS: We submitted 50 patients with SSc to detailed clinical and laboratory assessment, and also performed PBMC subset analyses by direct dual immunofluorescence and flow cytometry. RESULTS: No statistically significant differences were found in the percentages or the absolute numbers of total lymphocytes, of B cells, and of CD4+ T cells. The absolute number of CD8+ cells was lower (p < 0.03), while HLA-DR+ elements were higher in frequency (p < 0.03) in SSc patients than in healthy controls. SSc patients had lower values (both percentage and absolute number) of NK-T cells (p < 0.01 and p < 0.003, respectively) and of T cells expressing g/d TCR (p < 0.01 and p < 0.005, respectively); whereas NK cells were marginally but not significantly decreased. The absolute number of NK-T cells showed an inverse correlation to erythrocyte sedimentation rate values (p < 0.03; rs = -0.306), percentage of g-globulins (p < 0.01; rs = -0.353), and serum concentrations of IgG (p < 0.02; rs = -0.334). CONCLUSION: Impairment of NK-T cells and of T cells expressing g/d TCR may lead to downregulation of normal immune response, and seems to be important for immunological and inflammatory aspects of SSc.