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Background. Reliable predictors of the response of prostate cancer to androgen ablation therapy are lacking. The goals of this study were to determine whether nuclear androgen receptor (AR) concentrations in metastatic prostate cancer varied within and between specimens and to correlate this information with the response to therapy. Methods. AR concentration was evaluated by computer-assisted image analysis of immunohistochemical staining intensity in 200 malignant epithelial nuclei of each of 17 specimens of Stage D2 prostate cancer obtained before hormonal therapy. The data were correlated with the time to tumor progression (relapse) after hormonal therapy. Results. AR staining intensity varied within specimens, and the variance of staining intensity was significantly greater (P = 0.03) in the poor responders (n = 8; time to progression, < 20 months) than in the good responders (n = 9; time to progression, [is greater than or equal to] 20 months). The kurtosis was significantly lower in poor responders (P = 0.04). However, the mean AR staining intensity was not significantly different among patients. The frequency distribution plots of good responders were generally uniform and unimodal, but those of poor responders were flattened (more platykurtic), dispersed, and highly variable. Thus, the AR concentration per cell was significantly more heterogeneous in poor responders. Variance was a significant predictor of response. Five of 6 patients with a high variance (defined as variance greater than the mean) were poor responders, whereas 8 of 11 patients with a low variance were good responders (an overall classification accuracy of 13 of 17, 76%). Conclusions. The greater AR heterogeneity in poor responders may reflect a greater genetic instability in tumors that have progressed further toward androgen independence and may be a valuable predictor of progression. Cancer 1993; 71:2574-80.

An in vitro model was devised to evaluate the efficacy of the different irrigating solutions utilized for local dissolution of uric acid stones. Tris (hydroxymethyl) aminomethane proved to be several times faster than sodium bicarbonate in dissolving uric acid calculi. The maximal dissolution rate was obtained when the highest pH (10.5) of Tris buffer was used in concentrations at or above 0.2M. This makes the commercially available THAM-E an optimal choice. Stones averaging 1cm. in diameter were dissolved in less than 48 hours when this compound was used. Sodium bicarbonate should only be used in solutions with concentrations lower than 0.2M and pH below 9, if some dissolution is to be attempted. Concentrations and pH’s above these levels will coat the stones with hard shells of sodium urate, making it impossible to dissolve them. The in vitro findings were confirmed in vivo in a limited study in pigs with human uric acid calculi surgically placed in their kidneys. Our results indicate how to make the best use of the solutions clinically available in order to obtain total dissolution of uric acid stones in short periods of time. We recommend the use of a 0.3 molar concentration of this buffer (THAM-E) at flow rates of about 50cc per hour.