Clinical variables associated with indeterminate QuantiFERON®-TB Gold assay results: role of pre-incubation delay.

SETTING: The QuantiFERON®-TB Gold (QFT) assay is an interferon-gamma release assay used for the clinical diagnosis of latent tuberculous infection. Relatively high rates of indeterminate results are a significant downside of the test. OBJECTIVE: To evaluate clinical variables associated with lower QFT-indeterminate rates after reducing pre-incubation delay. DESIGN: In 2016, a new protocol of on-site incubation of QFT samples, followed by analysis at the outside laboratory, was implemented, resulting in much shorter pre-incubation delay of the samples. We retrospectively identified 3583 patients who underwent QFT before and after implementation of the new protocol. Patient records were scrutinized and QFT results were evaluated with respect to associated clinical conditions. RESULTS: The patients were analyzed by dividing them into two cohorts based on maximum pre-incubation time (standard vs. immediate). Monthly indeterminate results dropped from 12.7% ± 0.02 in the standard cohort to 5.5% ± 0.03 in the immediate cohort (P < 0.001). A significant reduction in relative indeterminate rates was found in the immediate cohort patients with immunocompromised state, autoimmune conditions, liver disease and hypoalbuminemia. No difference was identified in patients with malignancies and renal failure. CONCLUSION: Limiting the pre-incubation time to 1 h maximum significantly improved QFT performance, especially in patients from certain clinical categories.

Calpain activation by ROS mediates human ether-a-go-go-related gene protein degradation by intermittent hypoxia.

Human ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K(+) current. However, little information is available on physiological situations affecting hERG channel protein and function. In the present study we examined the effects of intermittent hypoxia (IH), which is a hallmark manifestation of sleep apnea, on hERG channel protein and function. Experiments were performed on SH-SY5Y neuroblastoma cells, which express hERG protein. Cells were exposed to IH consisting of alternating cycles of 30 s of hypoxia (1.5% O2) and 5 min of 20% O2. IH decreased hERG protein expression in a stimulus-dependent manner. A similar reduction in hERG protein was also seen in adrenal medullary chromaffin cells from IH-exposed neonatal rats. The decreased hERG protein was associated with attenuated hERG K(+) current. IH-evoked hERG protein degradation was not due to reduced transcription or increased proteosome/lysomal degradation. Rather it was mediated by calcium-activated calpain proteases. Both COOH- and NH2-terminal sequences of the hERG protein were the targets of calpain-dependent degradation. IH increased reactive oxygen species (ROS) levels, intracellular Ca(2+) concentration ([Ca(2+)]i), calpain enzyme activity, and hERG protein degradation, and all these effects were prevented by manganese-(111)-tetrakis-(1-methyl-4-pyridyl)-porphyrin pentachloride, a membrane-permeable ROS scavenger. These results demonstrate that activation of calpains by ROS-dependent elevation of [Ca(2+)]i mediates hERG protein degradation by IH.

[Determination of capillary plasma C-reactive protein during therapy for acute infectious lung diseases].

Changes in the concentration of C-reactive protein (CRP), leukocytes, erythrocyte sedimentation rate, and differential blood count were comparatively estimated in the treatment of 66 infants (aged 1.12 +/- 0.95 years) with acute infectious lung diseases. There was a high correlation between capillary plasma and venous serum CRP concentrations. On the first day of effective antibiotic therapy, there was a significant decrease in CRP levels; the sensitivity and specificity were 96 and 94%, respectively. Thus, measurement of capillary blood CRP is an accessible and informative tool to monitor therapy for infectious lung diseases in infants.

[Endothelial injury markers as a possible criterion for the efficiency of treatment for arterial hypertension].

Endothelial injury markers, including endothelial microparticles (CD31+ particles, 1.5-4.0 microm in diameter), von Willebrand factor, endothelin-big 1-38, and plasma concentrations of thiobarbituric acid reactive substances in patients with essential hypertension (EH), were evaluated. The endothelial injury markers and the concentrations of thiobarbituric acid reactive substances were significantly elevated in patients with EH, as compared to healthy subjects and decreased, so was blood pressure in response to antihypertensive pharmacotherapy. However, the patients and the healthy subjects had differences in these parameters. It is suggested that all the studied parameters of endothelial injury are suitable for laboratory monitoring of treatment in patients with EH in different periods of the disease, including a stable blood pressure period.

[Effect of moderately low temperatures (-30 C to -70 C) on the permeability of erythrocyte membranes]. / Vliianie umerenno nizkikh temperatur (-30 C do -70 C) na pronitsaemost' membran éritrotsitov.

The barrier properties of reconstituted and native erythrocyte membranes frozen to -30, -40 or -70 degrees C and stored for a month were studied. The release of markers, namely haemoglobin molecules, [14C] sucrose and K+ ions from cells and membrane structures was measured. The main changes in the barrier function of ghosts and cells have been found to be due to freeze-thawing rather than to storage conditions. Glycerol, a cryoprotectant, appeared to stabilize the barrier properties of erythrocyte membranes for haemoglobin molecules, [14C] sucrose and to a lesser extent for K+ ions. The cryoprotective effect of glycerol has been shown to be considerably greater towards erythrocytes ghosts than to native erythrocytes.