Probability of prostate cancer detection based on results of a multicenter study using the AxSYM free PSA and total PSA assays.

OBJECTIVES: The determination of the percentage of free prostate-specific antigen (%fPSA) enhances the specificity of prostate cancer (CaP) detection. This study was undertaken to assess the performance of %fPSA in differentiating benign prostate disease from CaP and to determine the CaP probability estimates using the AxSYM Free PSA and AxSYM Total PSA assays. METHODS: In this prospective study, 297 men, 50 years old or older, with a total PSA level between 4 and 10 ng/mL and a nonsuspicious digital rectal examination were enrolled at 10 clinical sites. All subjects underwent at least sextant prostate biopsies to establish the diagnosis. fPSA and total PSA (tPSA) levels were determined using the AxSYM Free PSA and AxSYM Total PSA assays. Percent fPSA values were compared with tPSA values to determine the appropriate cutoffs for prostate biopsy and to calculate the CaP probability estimates. RESULTS: The strongest predictor of CaP in a logistic regression model was %fPSA (odds ratio 2.29), which contributed significantly more than age or tPSA to the predictive model. In this study population, a %fPSA cutoff of 26.4% would have detected 96% of subjects with CaP (sensitivity) and would have eliminated 27.4% of unnecessary biopsies (specificity). CaP probability estimates ranged from 9% to 69% and increased as the %fPSA value decreased. Men with a %fPSA level of 10% or lower had a 69% probability of CaP, and men with a %fPSA level of greater than 26% had a 9% probability of CaP. CONCLUSIONS: Percent fPSA values can help differentiate CaP from benign prostate disease and reduce unnecessary biopsies in 27% of men 50 years old or older whose digital rectal examination was normal and whose tPSA level was between 4 and 10 ng/mL. A %fPSA result can assist the physician and patient in determining the probability of CaP and assessing the need for prostate biopsy.

Elevated salivary cortisol in the evening in healthy elderly men and women: correlation with bone mineral density.

BACKGROUND: Aging is associated with a loss of bone mineral density (BMD) in men and women. Loss of BMD can also be caused by hypercortisolemia in men or women at any age. This study measured salivary cortisol at 2300 h and 0700 h as indices of cortisol secretory activity in 228 elderly, community-dwelling subjects. Salivary cortisol results were correlated with BMD. We hypothesized that salivary cortisol is elevated at 2300 h in elderly people, and that salivary cortisol will correlate negatively with BMD. METHODS: Saliva was sampled at 2300 h (nadir in circadian rhythm) and 0700 h (peak in circadian rhythm) in 130 men (70.7 +/- 0.4 years old) and 98 women (70.0 +/- 0.4 years old); approximately half of the women were receiving hormone replacement therapy (HRT). BMD was measured by dual energy x-ray absorptiometry. RESULTS: Salivary cortisol at 2300 h was significantly elevated in men (2.3 +/- 0.1 nmol/L) and women (2.1 +/- 0.1 nmol/L) as compared to 73 younger controls (1.2 +/- 0.1 nmol/L; 37 +/- 1 year old). Salivary cortisol at 0700 h was not different between older subjects and younger controls. There was a significant negative correlation of lumbar (L2-4) BMD and 2300 h salivary cortisol in older women (r = -0.20, p = .05; n = 98); this correlation was significant only in women not on HRT. There was a highly significant negative correlation of lumbar (L2-4) BMD and 0700 h salivary cortisol in older men (r = -0.31, p = .0003). CONCLUSIONS: Salivary cortisol is a simple, nonstressful method for assessing activity of the hypothalamic-pituitary-adrenal (HPA) axis in the elderly population. A major finding was an elevation in the late night nadir in cortisol secretion. We also suggest that elevated cortisol secretion in elderly people may contribute to the age-related loss in bone mineral density and that this effect is prevented by HRT.

Totally automated analysis by robotized PrepStation and liquid chromatography: direct-sample analysis of felbamate.

A totally automated analysis of felbamate was developed by using a robotized PrepStation for extraction, followed by automated liquid chromatographic (LC) analysis and data reduction. This is one of the newer direct-sample analysis approaches by LC. Felbamate was a previously approved antiepileptic agent used to treat partial seizures with and without generalization and to treat Lennox-Gastaut syndrome in pediatric patients. However, due to the reported incidences of aplastic anemia, its clinical application was recently restricted to the treatment of the latter syndrome. The automated assay using Bench Supervisor, PrepStation, and LC, based on a previously developed manual method, used 200 microliters of serum standards, quality control, or patients' plasma. These were mixed with 600 microliters of internal standard (IS) W509 dissolved in acetonitrile for protein precipitation. After axial centrifugation and standing, aliquots of the clear supernatant were transferred and washed with hexane. Aliquots of the supernatant were transferred and injected into a high-performance liquid chromatograph (HPLC). HPLC parameters included an mu Bondapak C-18 column, phosphate/acetonitrile (8:2) as mobile phase, and detection at 214 nm. Retention times were 2.9 and 4.2 min for felbamate and IS, respectively. Calibration was linear for concentrations from 10 to 200 mg/L with r > 0.994. Precision studies showed coefficients of variation ranging from 2.7% to 8.8%. Correlation with the manual method showed that r = 0.934, slope = 1.048, intercept = -2.642, and n = 21. Phenobarbital coeluted with the IS. This study demonstrated the feasibility of using a robotized, automated method for monitoring felbamate, readily extended to monitoring other antiepileptic drugs with minimal modification.

Variability in cholesterol measurements: comparison of calculated and direct LDL cholesterol determinations.

Calculated low-density lipoprotein cholesterol (LDL-C) concentrations determined from the Friedewald equation have a large intraindividual CV, in part because the calculation incorporates the variability of cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride measurements. We studied whether a new assay that measures LDL-C directly will reduce this variability and reduce the need for averaging serial specimens. Four blood samples were obtained 1 week apart from 35 mildly hypercholesterolemic subjects and analyzed for total cholesterol, triglycerides, and HDL-C. LDL-C was calculated by the Friedewald equation, and was also measured directly with a commercially available direct LDL-C assay. The intraindividual CV for the direct and calculated LDL-C assays were similar [CV of direct LDL-C assay (mean +/- SE): 6.8 +/- 0.5% vs calculated LDL-C: 7.3 +/- 0.6%; difference 0.44%, 95% confidence interval: -0.7-1.5%]. For both assays, at least two blood tests were required from each subject to reduce total variability of LDL-C to less than or equal to 5%. We conclude that the direct LDL-C assay did not reduce the variability in LDL-C compared with the conventional LDL-C calculation. However, it may have a specific role in lipid disorder evaluation and (or) monitoring when triglycerides are increased or the LDL-C value alone is needed.

Pharmacokinetic evaluation of a new oral cyclosporine formulation.

STUDY OBJECTIVE: To compare the pharmacokinetics of a new oral cyclosporine preparation with those of cyclosporine solution diluted in Isocal and the intravenous formulation. DESIGN: Randomized, crossover trial. SETTING: Tertiary care referral center. PATIENTS: Seven pediatric liver transplant recipients who were receiving oral cyclosporine as part of their immunosuppressive regimen. All patients completed the study. INTERVENTIONS: Pharmacokinetic studies were performed with the intravenous and oral dosage forms. Patients received one dose of intravenous cyclosporine, and then were randomized to receive their usual oral cyclosporine dose incorporated into a chocolate wafer or mixed with Isocal. After a minimum of 3 days, the alternative preparation was administered. Serial cyclosporine blood samples were collected at predetermined intervals for 12 hours after the third dose for each regimen. Concentrations were determined by high-performance liquid chromatography. The data for the three dosage forms were fit simultaneously with a two-compartment model. MEASUREMENTS AND MAIN RESULTS: No difference was seen in F, ka, Cmax, and tmax between the two oral cyclosporine preparations (p > 0.05). No new rejection episodes occurred during the study period. CONCLUSIONS: We conclude there is no difference in the bioavailability of the oral solution and the chocolate formulation. We believe the new preparation may increase patient compliance and ensure administration of a complete dose compared with the currently marketed solution.

Determination of reference intervals in the clinical laboratory using the proposed guideline National Committee for Clinical Laboratory Standards C28-P.

The Subcommittee on Reference Intervals of the National Committee for Clinical Laboratory Standards (NCCLS) has recently completed a proposed guideline, NCCLS Document C28-P, entitled "How to Define, Determine, and Utilize Reference Intervals in the Clinical Laboratory." This guideline document is an attempt to combine a concise set of procedures and recommendations, largely taken from the original literature, to form a standard, uniform, and reasonable protocol for determining population-based reference intervals. The intent of the guideline is to set forth the minimum requirements for the determination of a reliable and clinically useful reference interval. The subcommittee hopes the document will set a standard that upgrades the quality of reference intervals to a level worthy of their use in clinical medicine.

Sustained coronary-risk-factor reduction after gastric bypass for morbid obesity.

Lipids and clinical changes including diabetes and hypertension were monitored in morbidly obese patients after Roux-Y gastric bypass. Total cholesterol (Chol), high-density-lipoprotein (HDL) cholesterol, and triglycerides at 1 and at 5-7 y postoperatively in 33 patients and at 1 y in 23 patients (including apolipoproteins A-I and B) were compared with preoperative concentrations. Mean concentrations of Chol and both apolipoproteins were unchanged. Elevated serum triglycerides became normal, and reduced concentrations persisted at 5-7 y in men (p less than 0.025). HDL-cholesterol concentrations increased at 1 y (p less than 0.01) and remained higher at 5-7 y in women. Ratios of Chol to HDL cholesterol were lower at 1 y (p less than 0.01) in both men and women. Diabetes (9 patients) and hypertension (22 patients) also were reduced at 1 y (p less than 0.01) and remained lower at 5-7 y. A mean 61% of excess weight was lost in 1 y whereas a 12% weight gain occurred by 5-7 y. The beneficial changes in most coronary risk factors lasted 5-7 y after surgery.

Body fat distribution and male/female differences in lipids and lipoproteins.

The role of body fat distribution, as assessed by the ratio of waist-to-hip circumferences (WHR), in statistically explaining differences in levels of lipoproteins between men and women was studied using data collected in 1985-1986 from employed adults (mean age, 40 years). As compared with the 415 women, the 709 men had higher mean levels of triglycerides (+38 mg/dl) and apolipoprotein B (+11 mg/dl) as well as lower mean levels of high density lipoprotein (HDL) cholesterol (-15 mg/dl) and apolipoprotein A-I (-19 mg/dl). Additionally, men were more overweight, consumed more alcohol, and exercised more frequently than women but were less likely to smoke cigarettes. Controlling for these characteristics, however, did not alter the differences in lipoprotein levels between men and women. In contrast, adjustment for WHR (which was greater among men) reduced the sex differences in levels of apolipoprotein B (by 98%), triglycerides (by 94%), HDL cholesterol (by 33%), and apolipoprotein A-I (by 21%). Similar results were obtained using analysis of covariance, stratification, or matching; at comparable levels of WHR, differences in lipid and lipoprotein levels between men and women were greatly reduced. Although these results are based on cross-sectional analyses of employed adults and need to be replicated in other populations, the findings emphasize the relative importance of body fat distribution. Whereas generalized obesity and body fat distribution are associated with lipid levels, fat distribution (or a characteristic influencing fat patterning) can be an important determinant of sex differences in levels of triglycerides, HDL cholesterol, and apolipoproteins B and A-I.

Hierarchical information system for the cost analysis of clinical laboratory tests.

A microcomputer-based information system that integrates the concepts of text processing, data base processing, and data base analysis has been designed for cost evaluation in our laboratories. This forms a flexible package that is directed by the needs of the user. The package, which has been used to calculate various cost parameters and productivity on the basis of comprehensive data and user-defined rules, serves as a tool for good financial management at various organizational levels in the clinical laboratory.

Correlation of the extent of coronary occlusion with Apo B levels. Application of a new enzyme immunoassay technique for Apo B.

A new rapid and sensitive method for measurement of apolipoprotein B (Apo B) in plasma has been developed. This method, based on a Competitive Enzyme-Linked Immunoassay (CELIA), has been used to study the association between the extent of coronary artery occlusion as measured by coronary arteriography and the levels of plasma Apo B. The correlation between Apo B levels and some other plasma lipids was also determined. Significant relationship was found between the extent of coronary artery occlusion and Apo B, as well as between Apo B and plasma total cholesterol and plasma triglyceride levels.

Factor VIII competitive enzyme assay: observations in von Willebrand's variants and hemophiliacs.

The competitive enzyme-linked immunoassay (CELIA) was used to quantitate factor VIII antigen in plasma from 24 patients with von Willebrand's disease (VWD), VWD variant or hemophilia A. This demonstration of CELIA's clinical usefulness is significant because the simplicity and efficiency of the technique make it suitable for use in many health-related institutions regardless of size or sophistication.

Examination of a competitive enzyme-linked immunoassay (CELIA) technique and a laser nephelometric immunoassay technique for the measurement of apolipoprotein B.

A competitive enzyme-linked immunoassay (CELIA) technique for quantitative measurement of apolipoprotein B (Apo B) was developed. The method is a non-isotopic immunoassay that utilizes a soluble enzyme/antibody complex as a universal labeling reagent. The method was characterized according to precision, sensitivity, recovery and parallelism. The CELIA Apo B method was compared to a commercially available laser nephelometric immunoassay. We found that the nephelometric results were highly correlated with triglyceride levels and the nephelometric assay was susceptible to interference from lipemia or turbidity. The range of values obtained on 56 apparently healthy, fasting young adults was 0.35-1.25 g/l by the CELIA method and 0.40-1.00 g/l by the nephelometric immunoassay. The nephelometric method was more precise (coefficient of variation 5%) than the CELIA technique (CV 10%); however, the CELIA method seems to be less sensitive to interferences.

Excretion of aqueous myelographic contrast media in animals undergoing a repeat myelogram.

The rate of elimination of contrast media may be a factor in side effects and complications of aqueous myelography. The authors studied the effect of a previous myelogram and arachnoiditis on the elimination of aqueous contrast media from the subarachnoid space. Serum and cisternal CSF iodine concentrations were measured after experimental myelography in subhuman primates. The transfer of the aqueous contrast media from CSF to serum was slowed and the circulation with the cerebrospinal fluid into the intracranial cisterns was increased by a previous myelogram or arachnoiditis.