Pitfalls in interpreting prostate specific antigen velocity.

PURPOSE: The concept of prostate specific antigen (PSA) velocity as an improved marker for prostate cancer detection is intriguing. However, before this concept is applied to individual patients several confounding parameters must be addressed. We determined the variability of serum PSA levels in men without prostate cancer. MATERIALS AND METHODS: We reviewed data from a prostate cancer screening program, and determined inter-assay and individual variability of the serum PSA values for a 2-year followup period in 265 men clinically free of prostate cancer. RESULTS: Our average inter-assay coefficient of variation was 7.5%. Therefore, we considered only PSA changes exceeding +/- 15% as significant. Fluctuations in serum PSA occurred in 78% of the men during the observation period, and 12.5% had at least a single PSA increase exceeding 0.75 ng/ml. per year. Fluctuations were noted throughout the entire range of serum PSA levels but became progressively larger with an increasing mean PSA. CONCLUSIONS: The inter-assay variability must be considered when interpreting PSA velocity. Individual fluctuations in serum PSA dictate an observation period of at least 2 years before PSA velocity is considered abnormal.

Temporal changes in the oxidation state in in vitro blood.

The rates at which the paramagnetic compounds deoxyhemoglobin (Hb) and methemoglobin (MHb) form in vivo within an area of hemorrhage are unknown. The present experiment establishes the baseline concentrations and rates of change in paramagnetic hemoglobin concentrations, as well as the pH in normal heparinized and clotted human blood maintained in vitro at 37 degrees C under anaerobic conditions over 30 hours. There was a moderate increase in Hb concentration in normal heparinized blood (average increase was 15.5%, rate = 0.50%/hour) and a slight increase in MHb concentration in the heparinized blood and clots (average increase was 1.4%, rate = 0.044%/hour). A second experiment was done to verify the activity of the RBC systems responsible for maintaining the hemoglobin molecule in the reduced state. Conversion of MHb to Hb in these samples proceeded at a rate of 5.6%/hour. In a third experiment, blood from 11 normal subjects maintained at 4 degrees C 25 degrees C was analyzed for MHb concentration over the course of 28 days. The level of MHb formation remained in the range of normal for at least 11 days in all subjects. The authors conclude that at basal conditions created in vitro, the blood levels of both Hb and MHb remain at relatively low levels. Therefore, if the accumulation of Hb and/or MHb occurs in acute in vivo hematomas it must be driven by intrinsic tissue factors.

Activation of the complement system by recombinant tissue plasminogen activator.

Recent trials have shown that recombinant tissue plasminogen activator (rt-PA) is an effective thrombolytic agent in patients with acute myocardial infarction. Because rt-PA converts plasminogen to plasmin, which is known to activate complement in vitro, we tested the hypothesis that rt-PA can induce in vivo activation of complement. Studies were performed in 12 patients with acute myocardial infarction. Six control patients had patent coronary arteries and did not receive rt-PA; these patients had normal values of the components of the complement system C4a (409 +/- 111 ng/ml) and C5a (8.8 +/- 1.8 ng/ml) with a slight elevation of C3a (204 +/- 6.6 ng/ml) in samples collected before coronary arteriography (253 +/- 25 minutes after onset of pain). After coronary arteriography, there was a slight decrease in the values of C4a (224 +/- 37 ng/ml), C5a (7.3 +/- 1.3 ng/ml) and C3a (164 +/- 35 ng/ml). The remaining six patients had complete coronary occlusion and received rt-PA (80 to 150 mg intravenously). In this treated group, before coronary arteriography the values of C4a (406 +/- 51.6 ng/ml) and C5a (8.1 +/- 1.9 ng/ml) were normal, and those of C3a were slightly elevated (250 +/- 76 ng/ml). All complement values obtained before rt-PA were similar to those in the untreated group. However, after administration of rt-PA (but before any angiographically detectable reperfusion), there was a striking increase in C4a (2,265 +/- 480 ng/ml; p less than 0.01), C3a (600 +/- 89 ng/ml; p less than 0.05) and C5a (30.0 +/- 4.5 ng/ml; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nifedipine on serum digoxin concentration and renal digoxin clearance.

Nifedipine has been reported either to decrease or not to affect digoxin elimination. We studied the effect of oral nifedipine on steady-state digoxin concentrations and renal clearance in 20 healthy male subjects. After 2 wk of digitalization, all received digoxin, 0.375 mg a day, with placebo for 2 wk, then digoxin and nifedipine, 18.5 +/- 4 mg every 8 hr, for 2 wk, and then digoxin with placebo for 2 wk. Mean (+/- SD) digoxin concentrations of 0.74 +/- 0.20 and 0.75 +/- 0.25 ng/ml on placebo were not altered by nifedipine (0.77 +/- 0.23 ng/ml). Digoxin clearance was 2.2 +/- 0.6 and 2.7 +/- 0.8 ml/kg/min on placebo and 2.5 +/- 0.6 ml/kg/min on nifedipine. No change in pharmacologic effect of digoxin by nifedipine was observed, but mean blood pressure was lower and heart rates were accelerated. These data indicate that oral nifedipine does not alter digoxin concentrations or decrease renal clearance in healthy subjects.