Epirubicin and medroxyprogesterone acetate versus estramustine phosphate in hormone-resistant prostatic cancer: a prospective randomized study.

The effect of a medroxyprogesterone acetate (MPA) plus epirubicin combination versus estramustine phosphate was evaluated in 149 prospectively randomized patients with hormone-resistant prostatic cancer. The estimated probability of being free from progression after 1 year was 17% for the patients treated with estramustine and 29% for the MPA-epirubicin group. There is a significant difference between the two groups regarding risk of progression (p = 0.013). However, no difference in survival was recorded (p > 0.30) with about 60% of the patients dead during the first year in both groups. Progression was highly correlated to sedimentation rate (p < 0.001) and to performance index (p = 0.002). Heart failure occurred in a substantial number of patients in both groups which must be considered before starting therapy.

Effects of oxygen free radical scavengers, xanthine oxidase inhibition and calcium entry-blockers on leakage of albumin after ischaemia. An experimental study in rabbit kidneys.

The effect of pretreatment with various substances protecting against oxygen free radicals on the leakage of proteins across the vessel walls of rabbit kidneys induced by ischaemia has been studied. The leakage of proteins was estimated from the difference between the 120-min distribution space of [131I]albumin and the 5-min distribution space of [125I]albumin, the latter mainly measuring the intravascular volume. Neither SOD (superoxide dismutase), catalase, allopurinol or two different Ca2+ channel blockers (nifedipine, felodipine) could alone reduce the leakage induced by ischaemia. A combined pretreatment with SOD, catalase and nifedipine reduced the leakage in the cortex, and pretreatment with mannitol alone reduced the leakage in the cortex and outer stripe of the medulla. The results indicate that oxygen free radicals are involved in the leakage of proteins across the vessel walls induced by ischaemia, but that other mechanisms are involved as well.

Effects of ischaemia on leakage of albumin in rabbit kidneys.

The effect of ischaemia on the leakage of proteins across the vessel walls in rabbit kidneys was studied. The leakage of proteins was estimated from the distribution space of labelled albumin. Various methods to calculate the vascular volume yielding the true extravascular leakage were tested. The most reliable method appeared to be to use the same tracer (131I-albumin, 125I-albumin) for both estimating the leakage and the intravascular volume. One hour of ischaemia induced a drastic increase in the extravasation of proteins in the cortex and outer zone of the medulla but not in the inner zone.

Effect of oxygen free radicals on rabbit and human erythrocytes. Studies on cellular deformability.

Changes in deformability of rabbit and human erythrocytes caused by exposure in vitro to the oxygen free radical generator hypoxanthine and xanthine oxidase were studied. The deformability reduction observed after 30 min of exposure to hypoxanthine-xanthine oxidase could be prevented by pretreatment with SOD, while after only 5 min of such exposure allopurinol and catalase also appeared to have a protective effect. Exposure of human erythrocytes to hypoxanthine and xanthine oxidase in Krebs solution prevented an otherwise occurring hemolysis. Exposure to both substances or to xanthine oxidase alone in Dulbeccos phosphate solution produced a reduction in deformability. The results indicate that exposure of erythrocytes to free oxygen radicals reduces deformability and that this effect may contribute to the myocardial dysfunction and the epicardial erythrostasis observed during open-heart surgery.