http://repub.eur.nl/res/aut/8399/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39460/ 2013-03-20T00:00:00Z Patients with deficiency in the interferon gamma receptor (IFN-γR) are unable to respond properly to IFN-γ and develop severe infections with nontuberculous mycobacteria (NTM). IFN-γ and IFN-α are known to signal through STAT1 and activate many downstream effector genes in common. Therefore, we added IFN-α for treatment of patients with disseminated mycobacterial disease in an effort to complement their IFN-γ signaling defect. We treated four patients with IFN-γR deficiency with adjunctive IFN-α therapy in addition to best available antimicrobial therapy, with or without IFN-γ, depending on the defect. During IFN-α treatment, ex vivo induction of IFN target genes was detected. In addition, IFN-α driven gene expression in patients' cells and mycobacteria induced cytokine response were observed in vitro. Clinical responses varied in these patients. IFN-α therapy was associated with either improvement or stabilization of disease. In no case was disease exacerbated. In patients with profoundly impaired IFN-γ signaling who have refractory infections, IFN-α may have adjunctive anti-mycobacterial effects. http://repub.eur.nl/res/pub/4548/ 1993-01-01T00:00:00Z BACKGROUND. Ketanserin is a serotonin S2-receptor antagonist that inhibits the platelet activation and vasoconstriction induced by serotonin and also inhibits the mitogenic effect of serotonin on vascular smooth muscle cells. METHODS AND RESULTS. We conducted a randomized, double blind, placebo-controlled trial to assess the effect of ketanserin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either ketanserin (loading dose, 40 mg 1 hour before PTCA; maintenance dose, 40 mg bid for 6 months) or matched placebo. In addition, all patients received aspirin for 6 months. Coronary angiograms before PTCA, after PTCA, and at 6 months were quantitatively analyzed. Six hundred fifty-eight patients were entered into the intention-to-treat analysis. The primary clinical end point of the study was the occurrence between PTCA and 6 months of any one of the following: cardiac death, myocardial infarction, the need for repeat angioplasty, or bypass surgery. It also included the need for revascularization actuated by findings at 6-month follow-up angiography. The primary clinical end point was reached by 92 (28%) patients in the ketanserin group and 104 (32%) in the placebo group (RR, 0.89; 95% CI, 0.70, 1.13; P = .38). Quantitative angiography after PTCA and at follow-up was available in 592 patients (ketanserin, 287; control, 305). The mean difference in minimal lumen diameter between post-PTCA and follow-up angiogram (primary angiographic end point) was 0.27 +/- 0.49 mm in the ketanserin group and 0.24 +/- 0.52 mm in the control group (difference, 0.03 mm; 95% CI, -0.05, 0.11; P = .50). CONCLUSIONS. Ketanserin at the dose administered in this trial failed to reduce the loss in minimal lumen diameter during follow-up after PTCA and did not significantly improve the clinical outcome.