The incidence of prostate cancer in a screening population with a serum prostate specific antigen between 2.5 and 4.0 ng/ml: relation to biopsy strategy.

PURPOSE: It has recently been suggested that the diagnostic threshold for the prostate specific antigen (PSA) assay be lowered to enhance prostate cancer detection. A 22% incidence of prostate cancer has been reported in men with PSA between 2.5 and 4.0 ng/ml. We designed a study to confirm this observation. MATERIALS AND METHODS: Men who participated in our free early detection program and who had serum PSA between 2.5 and 4.0 ng/ml were asked to undergo prostate biopsy. Of 268 eligible men 151 (56%) agreed to participate in this free trial. All men underwent biopsy using an 11-core multisite directed biopsy scheme. All biopsy cores were color coded for location specificity and examined by 1 pathologist. RESULTS: Cancer was identified in 24.5% (37 of 151) of the men biopsied. The median age of men with cancer was 62 years (range 43 to 74). Conventional systematic sextant biopsies, which accounted for 6 of the 11 cores, detected 73.0% (27 of 37) of the cancers and the alternate site biopsies identified the remaining 10. Gleason score was 6 in 25 men, 3 + 4 in 5, 4 + 3 in 4 and 8 or greater in 3 (median Gleason score 6). There were 14 men who had 1 core positive for cancer, 9 had 2 and 14 had more than 2 (median number of positive cores 2). Of the 14 men with 1 positive core 11 had a less than 3 mm focus of cancer and 8 had only a positive alternate site biopsy. There were 11 cases of abnormal results on digital rectal examination, 5 of which were cancer, and 31 cases of abnormal results on ultrasonography, 13 of which were cancer. Median biological variability in PSA was +/-15% (range 0.4% to 440.0%). CONCLUSIONS: We found a significant incidence of cancer (24.5%, 37 of 51) in men with serum PSA between 2.5 and 4.0 ng/ml. In our study 67.6% of the detected cancers were significant based on the biopsy data. If the PSA threshold is lowered the conventional systematic sextant technique may be preferable to an extended strategy.

Effect of water deprivation for 48 hours on the pharmacokinetics and pharmacodynamics of azosemide in rats.

The effect of temporary water deprivation for 48 h on the pharmacokinetics and pharmacodynamics of azosemide was examined after intravenous (i.v., 10 mg/kg) and oral (20 mg/kg) administration of azosemide to the control and the water-deprived rats. After i.v. administration of azosemide, the area under the plasma concentration-time curve from time 0 to time infinity and the unbound fraction of azosemide to plasma proteins increased by 36 and 40%, respectively, and total body, renal (CLR), and nonrenal clearances, apparent volume of distribution at steady state, and total amount of azosemide excreted in urine (AeAZ0) decreased by 30, 44, 20, 25, and 33%, respectively, in the water-deprived rats (p < 0.05 vs controls). After oral administration of azosemide, the values of AeAZ0 (591 vs 318 micrograms) and CLR (2.22 vs 0.875 mL/min/kg) decreased significantly in the water-deprived rats. The 12-h urine output per g kidney was also reduced significantly in the water-deprived rats after both i.v. (70.3 vs 24.6 mL) and oral (70.7 and 20.7 mL) administration of azosemide. This could be due to the significantly reduced amount of azosemide excreted in 12 h urine, significantly higher plasma osmolarity, and increased blood vasopressin concentration in the water-deprived rats. The 12-h urinary excretion of sodium, potassium, and chloride per g kidney was also reduced significantly in the water-deprived rats after both i.v. and oral administration. The diuretic efficiency decreased significantly in the water-deprived rats after both i.v. and oral administration. The 12-h urine output per g kidney of i.v. and oral administration of azosemide in the control rats were similar (70.3 +/- 17.3 vs 70.7 +/- 13.8 mL), although the AeAZ0 after oral administration was significantly smaller than that after i.v. administration (473 +/- 98.5 vs 285 +/- 76.3 micrograms), and similar results were also obtained from the water-deprived rats. This could be rationalized by the concept of a single maximally efficient excretion rate of the drug in the pharmacodynamic model (sigmoid Emax), as shown for furosemide.