Carol M. Preissner

Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt–Jakob disease

CSF 14-3-3 and neuron-specific enolase (NSE) proteins were quantitated from patients who had Creutzfeldt–Jakob disease (CJD) or other rapidly dementing disorders initially considered to be CJD. Thirty-one patients were diagnosed as having CJD among 152 studied. CSF 14-3-3 values more than 8 ng/mL correlated with CJD. CSF NSE values less than 30 ng/mL and 14-3-3 values less than 8 ng/mL made a diagnosis of CJD unlikely, but did not exclude it.

Procalcitonin: A Marker for the Diagnosis and Follow-Up of Patients with Medullary Thyroid Carcinoma

CONTEXT Calcitonin (CT) is the main medullary thyroid carcinoma (MTC) tumor marker. However, it has several limitations, including a concentration-dependent biphasic half-life, sensitivity to rapid in vitro degradation, and the presence of different isoforms/fragments. Procalcitonin (PCT), the prohormone of calcitonin, is free of these limitations but is currently used only as a sepsis marker. OBJECTIVES The objective of the study was to determine whether PCT is suited as a MTC tumor marker by comparing the diagnostic performance of PCT with that of CT in MTC. DESIGN PCT and CT were measured in a total of 835 subjects, including normal volunteers (n = 197) and patients with active-MTC (n = 91), cured-MTC (n = 42), neuroendocrine tumors (n = 225), mastocytosis (n = 48), follicular cell-derived thyroid carcinoma (cured = 120, persistent/recurrent = 55), and benign thyroid disease (n = 57). RESULTS PCT levels were significantly higher in the active-MTC patients (mean 126.4 ng/ml) than the cured-MTC patients (mean <0.1 ng/ml). The overall concordance between the two markers was 95.7% (kappa = 0.81). Receiver-operating characteristic curve analysis showed no significant difference in diagnostic performance between CT and PCT. PCTs diagnostic sensitivity and specificity were 91 and 96%, respectively. The corresponding values for CT were 99 and 98%. Analyte stability studies showed that CT is very unstable in vitro with a decrease of 35-50% from the original value 24 h after the blood draw, whereas PCT levels did not significantly change during this time. CONCLUSIONS A strong correlation was observed between PCT and CT levels in patients with MCT. Given PCTs greater analytical stability, we conclude that it represents a promising complementary MTC tumor marker.

Heterophilic Serum Antibodies: A Cause for Falsely Elevated Serum Thyrotropin Levels

We report two cases of euthyroid patients with inappropriately elevated serum levels of thyrotropin (TSH) in whom investigation led to the detection of heterophilic antibodies. In addition, we compare the performance of two TSH immunometric assay systems in this setting. Even when monoclonal assay systems are used, TSH results must be critically interpreted when they are at variance with clinical and other biochemical findings.

Development of a highly sensitiveimmunochemiluminometric assay for prostate-specific antigen

Abstract Objectives. An assay is described for measuring very low concentrations of prostate-specific antigen (PSA) which could be used to reliably monitor patients with radical prostatectornies potentially to detect early recurrence of prostate cancer. Methods. A combination of immobilized and acridinium ester-labeled monoclonal antibodies was used to develop a two-step, 90-minute chemiluminometric assay. The reference standards for the serum assays were prepared by adding patient sera with a high concentration of PSA to base pools of female sera, which were selected because of low background counts and good recovery of added PSA. The assay was standardized to match the Abbott IMx PSA Assay. Results. The serum-based analytic detection limit (calculated as response 2.5 standard deviations [SD] above the zero standard) is 0.004 ng/mL, whereas the “biologic detection limit” (calculated as 2.0 SD above the analytic detection limit) is 0.008 ng/mL. The assay is highly reproducible with interassay coefficients of variation (CV) under 12% down to 0.02 ng/mL, qualifying this as a “second generation” assay (eg, CV Conclusions. This assay can measure very low concentrations of PSA in plasma and a wide range of PSA concentrations in urine. This assay will provide a valuable analytic tool for the future evaluation of the clinical utility of “ultrasensitive” PSA measurements for the management of prostate cancer.

Comparison of Thyrotropin-Receptor Antibodies Measured by Four Commercially Available Methods with a Bioassay That Uses Fisher Rat Thyroid Cells

Quantification of thyrotropin-receptor antibodies is important in the diagnosis and management of patients with Graves disease (1). Antibodies with stimulating activity (TSI) have traditionally been detected in bioassays that measure their effect on cloned rat thyroid cells (FRTL-5) or on Chinese hamster ovary (CHO) cells transfected with recombinant human thyrotropin-stimulating hormone (TSH) receptor (2)(3). These assays can detect antibodies in up to 95% of untreated hyperthyroid Graves patients, but, with few exceptions (4), they require cell culture facilities and are labor intensive and time consuming. As an alternative to bioassays, several manufacturers have developed competitive immunoassays that measure the inhibition of the binding of labeled TSH by antibodies in patients’ sera. These methods use porcine TSH receptors and claim clinical sensitivities of ∼90%. They cannot, however, distinguish whether the autoantibodies have blocking or stimulating capabilities, which can be important in a subset of patients. The more recent LUMItest® TRAK (TRAK) human assay (BRAHMS AG) uses human recombinant TSH receptors and luminescence-labeled bovine TSH. The manufacturer’s literature cites a clinical trial that achieved a diagnostic sensitivity of almost 99% with the research version of the DYNOtest® TRAK human assay (5). We have been performing the TSI bioassay with FRTL-5 cells routinely for more than 15 years. The TSI test volumes have increased steadily over that time, requiring an ever-increasing number of assays each week. In 1998, we added the Kronus® TRAb radioreceptor assay (TRAb) to our test menu to reduce the number of requests for TSI. During the preimplementation evaluation of the Kronus reagents, we found equivalent results in 80 of 89 random patient samples. Of the remaining nine samples, five were positive by TSI and not by TRAb, and four were positive by TRAb and not by TSI. The availability of the BRAHMS reagents as well as …