Objective. There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (IV) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil and renal involvement. cytoplasmic antibody (ANCA)-associated vasculitis.significantly lower levels of follicle-stimulating hormone.Conclusion. This randomized study shows that lV CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis Methods. The efficacy and toxicity of IV pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvemen t.Results. The cumulative CYC dose was reduced by 57% in patients with IV pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups.However, the rate of leukopenia (P < 0.01) and severe infections ( P < 0.05 by 1-tailed test) was significantly reduced in the IV pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the IV pulse group, as indicated by

Three RNA features have been identified that elevate retroviral transgene expression: an intron in the 5 0 untranslated region (5 0 UTR), the absence of aberrant translational start codons and the presence of the post-transcriptional regulatory element (PRE) of the woodchuck hepatitis virus in the 3 0 UTR. To include such elements into self-inactivating (SIN) vectors with potentially improved safety, we excised the strong retroviral promoter from the U3 region of the 3 0 long terminal repeat (LTR) and inserted it either downstream or upstream of the retroviral RNA packaging signal (C). The latter concept is new and allows the use of an intron in the 5 0 UTR, taking advantage of retroviral splice sites surrounding C. Three LTR and four SIN vectors were compared to address the impact of RNA elements on titer, splice regulation and transgene expression. Although titers of SIN vectors were about 20-fold lower than those of their LTR counterparts, inclusion of the PRE allowed production of more than 10 6 infectious units per ml without further vector optimizations. In comparison with state-of-the-art LTR vectors, the intron-containing SIN vectors showed greatly improved splicing. With regard to transgene expression, the intron-containing SIN vectors largely matched or even exceeded the LTR counterparts in all cell types investigated (embryonic carcinoma cells, fibroblasts, primary T cells and hematopoietic progenitor cells).

Objective. There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (IV) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil and renal involvement. cytoplasmic antibody (ANCA)-associated vasculitis. significantly lower levels of follicle-stimulating hormone.Conclusion. This randomized study shows that lV CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis Methods. The efficacy and toxicity of IV pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvemen t.Results. The cumulative CYC dose was reduced by 57% in patients with IV pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups.However, the rate of leukopenia (P < 0.01) and severe infections ( P < 0.05 by 1-tailed test) was significantly reduced in the IV pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the IV pulse group, as indicated by

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