Potential effects of age-specific reference ranges for serum prostate-specific antigen.

Age-specific reference ranges for serum prostate-specific antigen (PSA) may improve this test for detecting prostate cancer. We have analyzed PSA levels from 10,024 men to determine the potential effects of these reference ranges. PSA levels (ng/ml) were grouped by patient age for comparison between standard (all ages: PSA < or = 4.0) and age-specific (< or = 49 years: PSA < or = 2.5; 50-59 years: PSA < or = 3.5; 60-69 years: PSA < or = 4.5; > or = 70 years: PSA < or = 6.5) reference ranges. Serum PSA correlated significantly with age (r = 0.33; p < 0.001). Fewer men > or = 60 years had elevated levels when age-specific reference ranges were applied (1,373 vs. 1,967; p < 0.001). Prostate biopsies and prebiopsy PSA levels from 865 men were reviewed. Sensitivities and specificities were calculated using both reference ranges. A significant increase in specificity with the age-specific reference ranges was seen for men > or = 70 years (58.6 vs. 34.2%; p < 0.001). There was, however, a concomitant decrease in sensitivity (77.6 vs. 91.7%; p < 0.001). We conclude serum PSA increases with age and we support the concept of age-specific reference ranges. However, the specificity of this test remains low, illustrating its limitations for prostate cancer detection.

Chemical control of reaction time in an enzyme assay and feasibility of enzyme spot tests.

There are many circumstances in which the understanding of a patient's status would be improved by knowing one or more enzyme activities. Such data are routinely produced in clinical laboratories, but simple, noninstrumental tests for enzymes are a rarity, so their extralaboratory determination is also rare. The essential problem is that effective clinical determinations of enzyme activities are typically carried out by measuring reaction rates, so the reaction time needs to be controlled. The reaction time of a sample can be controlled by using a passive, ion exchange-based titration. In this work, OH-, H+, and quinidine have been used to stop the enzymes LDH (EC 1.1.1.27) (with H+ and OH-) and cholinesterase (EC 3.1.1.8) (with quinidine). The ion exchange material containing the enzyme-stopping ion is separated from the sample by a filter. The sample contains ions that can exchange with the enzyme-stopping ion in the ion exchange material, and it may contain species that buffer the enzyme-stopping ion. The reaction time is governed by the exchanging ion's concentration in the sample, the quantity of buffer in the sample, the thickness of the filter between the ion exchange material and the sample, and the temperature. A test for LDH requiring 50 microL of serum and no instrumentation can be made so that results from sera with elevated levels appear different than those with normal levels.

Comparison of particle-enhanced turbidimetric inhibition immunoassay and fluorescence polarization immunoassay using monoclonal antibodies for theophylline.

The DuPont theophylline assay reagent kit, a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) method adapted for use on a centrifugal fast analyzer, was evaluated. It was compared with fluorescence polarization immunoassay (FPIA). Day-to-day precision was 4.7% at 6.8 micrograms/ml, and 3.3% at 26.6 micrograms/ml. The assay is linear to a concentration of 40 micrograms/ml. Good correlation was found between the two methods (PETINIA/FPIA: y = 1.04x + 0.15, r = 0.988, Syx = 1.19) in the evaluation of 176 patients receiving theophylline. This method offers a precise and accurate alternative to FPIA.

Influence of gestational age on prediction of fetal lung maturity by fluorescence polarization of amniotic fluid.

Compared are the amniotic fluid fluorescence polarization values and the neonatal outcomes of 201 pregnant women who delivered from 28 through 37 weeks of gestation within 48 hours of the fluorescence polarization determinations. Thirty-five neonates developed hyaline membrane disease. The corresponding fluorescence polarization values ranged from 0.275 to 0.391. Eight of those 35 tests results were less than 0.325. The predictiveness of the method was studied using different threshold fluorescence polarization values. At the authors' own threshold of less than or equal to 0.325, the overall predictive value was as follows: false mature predictions: 6.2%, false immature predictions: 62.5%, sensitivity: 77.1%, and specificity: 72.8%. However, the false mature prediction rate was 21 to 40% from week 28 through week 33 versus 3.4 to 5.8% from week 34 through week 37, depending on the selected cutoff fluorescence polarization value. The sensitivity and specificity before, at, or after week 34 were significantly different at all tested fluorescence polarization values (P less than .05 to P less than .01) with the exception of the sensitivity at 0.310 and at 0.316 (P = .057). Caution is advised against relying on the fluorescence polarization method to predict fetal lung maturity at least before 34 weeks of gestation.

Indophenol method for acetaminophen in serum examined.

We show that an indophenol-based colorimetric method for acetaminophen (Clin Toxicol 15: 67-73, 1979) has less than maximal sensitivity because of (a) incomplete hydrolysis, related to suboptimal acid concentration; (b) suboptimal hydrolysis time; and (c) possible deterioration of the ammonium hydroxide reagent after 2.5 months. We have modified the method by optimizing duration of hydrolysis and color development. Results by the method correlate linearly with acetaminophen concentrations to 250 mg/L (1.66 mmol/L). Moreover, the modified method is free from interference by compounds in serum from uremic patients.

A flexible and versatile program for blood-gas quality control.

A quality control program which related quality control data to maintenance procedures has been developed. Whole blood tonometered at three levels of pCO2 and pO2 is used as the quality control material. A key feature of the program is that control values are independent of barometric pressure. The recording format consolidates results at all levels for each constituent, and permits direct comparison with maintenance procedures or electrode changes. The tonometry system consists of a precision gas mixer, Corning Model 192, and a two-channel syringe tonometer, Corning Model 184. This system provides several advantages for quality control, including: (1) use of Levy-Jenning charts with constant "mean values" for tonometered blood; (2) evaluation of electrode linearity over a wide range of partial pressures; and (3) multiple values for each parameter tested. Recovery of theoretical values over a broad range of partial pressure allows more accurate assessment of proportional response for assignment of pO2 "correction factors." Differences between instruments may also be investigated in closer detail.

Fetal lung maturity in complicated pregnancy, as predicted from microviscosity of amniotic fluid.

We measured the microviscosity of amniotic fluid between 28 and 40 weeks of gestation in 252 normal pregnancies and in 172 pregnancies complicated by factors known to influence fetal lung maturation, including chronic high blood pressure, pregnancy-induced hypertension, diabetes mellitus, and therapy with betamethasone. Comparison of the microviscosity value distributions and regression analysis indicated significantly lower microviscosity values in hypertensive disorders, in Class D and Classes F or R diabetes, and after 48 h of treatment with betamethasone. Few changes were observed in Classes A, B, or C diabetes. These observations are consistent with the accelerated maturation of surfactant observed in chronic intrauterine stress and the lower incidence of hyaline membrane disease reported after glucocorticoids.

Effect of centrifugation on fluorescence polarization of amniotic fluid.

Fluorescence polarization was measured on amniotic fluids of different gestational ages before and after centrifugation at relative centrifugal forces of 34 to 4955 x g. Centrifugation significantly increased the fluorescence polarization values over those of uncentrifuged amniotic fluids. The greatest increase was observed in the most "mature" fluids centrifuged at 34 to 230 x g. Almost without exception, use of centrifugal forces greater than 1239 x g did not further increase fluorescence polarization values.

Prediction of fetal lung maturity by amniotic fluid fluorescence polarization, L:S ratio, and phosphatidyl glycerol.

The relation of amniotic fluid fluorescence polarization (FP) to fetal lung maturity was examined in 186 pregnancies terminating within 48 hours of the fluid collection. Among the 9 babies who developed hyaline membrane disease (HMD), 8 were associated with FP values of 0.340 or more, and 1 had an FP value of 0.329. In 95 of these patients, the lecithin:sphingomyelin (L:S) ratio and the presence or absence of phosphatidyl glycerol (PG) were also determined. All 9 infants with HMD had L:S ratios less than 2.00 and no PG detectable in the amniotic fluid. Using an FP value of 0.325 or less, an L:S ratio of 2.00 or more, and the presence of PG as criteria for lung maturity, FP, L:S ratio, and PG did not differ significantly in the number of false predictions of HMD. Each test detected some mature infants who would have been incorrectly classified by at least 1 of the other tests. The status of all infants born at 33 weeks' gestation or later who did not develop HMD would have been correctly predicted by FP, L:S ratio, or both. These 3 tests, therefore, are complementary and can be used in combination to reduce the number of false predictions of HMD.

Evaluation of the operating characteristics of a bichromatic analyzer, the ABA-200.

We investigated certain operating characteristics of a new bichromatic analyzer, the ABA-200. The reliability of filter factor assignments was found to be within 3% for NADH and p-nitroaniline, 6% for p-nitrophenol. The accuracy and precision of the dilutor is a function of dilution ratio and sample size. Accuracy of dilution ratio was within 3% at all ratios tested except 1:201 at a sample volume of 1.25 microL. Coefficients of variation were less than 1.3% at all ratios. Photometric linearity was observed to 3.2 Ad for all filter sets. Photometric precision measurements showed a CV of 0.27% at an absorbance difference of 1.0.

Creatine kinase B-subunit activity in human sera: temporal aspects of its sensitivity after myocardial infarction.

We assessed the changes in sensitivity and specificity of creatine kinase (CK) isoenzymes at various times after acute myocardial infarction. CK-B was measured by an immunoinhibition technique. CK-MB was measured both by column chromatography on Sephadex DEAE A-50 and by electrophoresis on agarose gel. For CK-B, the sensitivity in detecting infarct varied from 11% in the first 8 h after onset of symptoms to 80% at 32 h after the infarct. Sensitivities for CK-MB by column and by electrophoresis were 25 and 45% for the first 8-h period and 80 and 89% at the 32nd hour, respectively. Comparison of values for CK-B with values for CK-MB by column and by electrophoresis gave correlation coefficients of 0.935 and 0.896, respectively. Patients having macro CK-BB exhibit anomalously high values for CK-B with respect to total CK. Patients having a mild infarct may show no increase in CK-isoenzymes.