Objective. To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG).Methods. Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/ day) and a 0.7-gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first-line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued.Results. Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P C 0.05). The incidence of Pneumocystis curinii pneumonia was higher in oral CYC-treated patients (30.4%) than in pulse CYC-treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) ( P = 0.02).Conclusion. Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.Wegener's granulomatosis (WG) was described in 1936 by Friedriech Wegener (1) and is characterized by involvement of lung (nodules and infiltrates), ear, nose, and throat (ENT), and kidneys (rapidly progressive glomerulonephritis [ RPGN]); the necrotizing vasculitis involves medium-and small-sized arteries, veins, and capillaries, and extravascular granulomas are
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Reversed-phase high-performance liquid chromatography/mass spectrometry (LC/MS), with an atmospheric-pressure chemical ionization (APCI) interface, has been applied to the identification of metabolites and derivatives of paclitaxel (taxol) in plasma and urine of patients treated with this new anticancer drug. Protonated molecules with substantial fragmentation were obtained using this ionization technique. The three ion series observed are characteristic of the intact molecule, the taxane ring, and the side chain at C13. Their analysis gives information about chemical modifications of the taxane structure at different positions of the molecule. Urine and plasma extracts were evaluated using the capacity to perform MS analysis directly on the entire effluent from conventional LC columns. Excellent spectra were obtained with 50 pmol of separated compounds in full scan mode. This technique allowed highly sensitive identification of 6 alpha-hydroxytaxol, the major human biliary metabolite, and of 7-epitaxol in extracts of plasma and urine from patients. Taxol hydrolysis derivatives were observed for the first time in urine 24 hours after the end of the infusion period. Sensitivity could be increased further using single ion monitoring (SIM) mode, once a target derivative was identified. These results demonstrate that LC/MS with an APCI interface is useful for the characterization and pharmacokinetic analysis of taxoids in biological matrices.
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