Accuracy of Xpert(®) MTB/RIF assay compared with AdvanSure™ TB/NTM real-time PCR using bronchoscopy specimens.

BACKGROUND: The performance of Xpert(®) MTB/RIF assay, an automated nucleic acid amplification test (NAAT) that was developed for the detection of tuberculosis (TB), has been evaluated in various clinical settings. However, few studies have compared Xpert with other NAATs, especially its performance using lower respiratory tract specimens (LRTS). OBJECTIVE: To compare the practical diagnostic performance of the Xpert assay with that of the AdvanSure™ TB/NTM RT-PCR kit in the detection of pulmonary TB (PTB), using LRTS obtained through bronchoscopy. RESULTS: Of 249 patients included, 105 had culture-confirmed PTB. Using culture as reference, the overall sensitivity of Xpert and AdvanSure was respectively 92.4% and 83.8%. When acid-fast bacilli smear results were taken into consideration, the sensitivity of Xpert for smear-positive and smear-negative LRTS was respectively 100% and 88.9%, while that of the AdvanSure was 100% and 76.4%. Xpert showed better results than AdvanSure in terms of sensitivity in smear-negative LRTS (P = 0.012), but no difference in smear-positive LRTS. CONCLUSIONS: Xpert may be advantageous in the detection of PTB using LRTS, particularly in low microbiological burden settings.

Changes in lung function according to disease extent before and after pulmonary tuberculosis.

OBJECTIVE: To evaluate changes in lung function in individuals before and after treatment for pulmonary tuberculosis (PTB) in relation to extent of disease. DESIGN: Using a retrospective cohort design, changes in and predictors of lung function were evaluated. RESULTS: A total of 41 patients were included in the final analysis. The median decline in annualised forced expiratory volume in 1 sec (FEV1) was 180.0 ml/year (95%CI 118.9-356.1) in advanced PTB and 94.7 ml/year (95%CI 33.4-147.3) in localised PTB (ΔFEV1% predicted/year 9.4%, 95%CI 4.4-14.0 vs. 3.8%, 95%CI 1.8-6.2). The median decline in annualised forced vital capacity (FVC) was 309.6 ml/year (95%CI 137.0-359.0) in advanced PTB and 101.1 ml/year (95%CI 30.3-219.6) in localised PTB (ΔFVC % predicted/year 7.3%, 95%CI 5.3-12.3 vs. 2.9%, 95%CI 0.9-6.5). CONCLUSIONS: As the sample size of our study was small, the conclusions could be biased. Nevertheless, our findings show that PTB causes a significant decline in lung function even in localised PTB, whereas advanced PTB was associated with excessive or even higher decline. This study suggests that early diagnosis and treatment of PTB is needed to preserve lung function.

Pharmacokinetics and bioequivalence evaluation of leflunomide tablets in Korean healthy volunteers.

Leflunomide is a disease-modifying antirheumatic drug. The purpose of this study was to evaluate the bioequivalence of a test drug (CJ leflunomide) and a commercially available reference drug (Arava®) at 2 doses (10 and 20 mg) in healthy Korean volunteers. This was a single-dose (28 individuals enrolled at each dose group), randomized, open-label, 2-way crossover study. The 2 treatment periods were separated by a 56-day wash-out interval. Blood sampling was conducted until 672 h after drug administration. Plasma teriflunomide (active metabolite of leflunomide) concentrations were determined, and pharmacokinetic parameters were calculated. Bioequivalence was evaluated using an ANOVA model, based on the AUCt and the Cmax after administration of leflunomide tablets. Bioequivalence was defined as the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUCt and Cmax for the test and reference drugs being within the range of 0.80-1.25. The GMRs (90% CI) for AUCt and Cmax were 0.9506 (0.9091-0.9941) and 0.9861 (0.9360-1.0389), respectively, in the 10 mg study, and 0.9524 (0.9101-0.9968) and 0.9740 (0.9314-1.0186), respectively, in the 20 mg study. The 90% CIs of AUCt and Cmax at each dose were within the accepted range for bioequivalence. Based on the results, the test drug (CJ leflunomide) was bioequivalent to the commercially available reference drug (Arava®) at both doses.

The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma.

BACKGROUND: High-mobility group box 1 protein (HMGB1) belonging to endogenous danger signals prolongs eosinophil survival and acts as a chemoattractant. OBJECTIVE: The authors evaluated the role of HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. METHODS: Firstly, HMGB1 expressions in induced sputum obtained from human asthmatics were determined. This was followed by an evaluation of the role of HMGB1 in a murine model of asthma using anti-HMGB1 antibodies. Then the effect of HMGB1 on the receptor of advanced glycation end products (RAGE) expressions on CD11b-CD11c(+) cells isolated from a murine model of asthma were measured to elucidate the mechanisms involved. RESULTS: Sputum HMGB1 expressions were markedly higher in asthmatics than in normal controls, and were positively correlated with sputum eosinophilia and sputum TNF-α, IL-5 and IL-13 expressions. In a murine model of asthma, HMGB1 expressions in lung tissue and HMGB1 levels in bronchoalveolar lavage fluid were significantly elevated and eosinophilic airway inflammation, non-specific airway hyperresponsiveness, and pathological changes were attenuated by blocking HMGB1 activity. Furthermore, we found that enhanced RAGE expressions on CD11b-CD11c(+) also significantly decreased when HMGB1 activity was blocked. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest that HMGB1 plays a key role in the pathogenesis of clinical and experimental asthma characterized by eosinophilic airway inflammation.

Anxiety, helplessness/hopelessness and 'desire for hastened death' in Korean cancer patients.

Despite a relatively high rate of suicide associated with cancer, this issue has not been explored in Korean patients. This study investigates the prevalence and factors related to 'the desire for hastened death' (DHD) in Korean cancer patients. A cross-sectional survey using standardised measures, including the Schedule of Attitudes toward Hastened Death and the Hospital Anxiety and Depression Scale, was performed with 131 patients with different types of cancer. 13.7% of the participants experienced moderate DHD (Schedule of Attitudes toward Hastened Death scores 5-9) and 1.7% experienced high DHD (≥10). Socio-demographic and disease-associated factors of the DHD included age, overall health and shortness of breath. The majority of psychosocial variables such as sadness, distress, 'helplessness/hopelessness' and 'anxious preoccupation' had a moderate association with DHD. Patients with a clinically significant level of anxiety or depression reported higher levels of DHD. Other significant correlates included 'meaning/peace', a sense of burdening family, dignity impairment and suicidal thoughts after diagnosis. Helplessness/hopelessness and anxiety were the strongest predictors of DHD in multivariate analysis. In view of significant role of helplessness/hopelessness and anxiety in the DHD of cancer patients, careful monitoring and management of these factors should be an integral part of cancer care to reduce the occurrence of DHD.

Genetic variants of the organic cation transporter 2 influence the disposition of metformin.

Genetic variants of the organic cation transporter 2 (protein, OCT2; gene, SLC22A2) were evaluated for their contribution to the variations in the pharmacokinetics of metformin, especially to its renal elimination. Genetic variants of SLC22A2 (c.596C>T, c.602C>T, and c.808G>T) showed significant differences in metformin pharmacokinetics when compared with the reference genotype, with higher peak plasma concentration (C(max)) and area under the curve (AUC) and lower renal clearance (Cl(renal)), thereby suggesting that a decrease in transport function associated with the SLC22A2 variants results in reduced Cl(renal) of metformin and consequently leads to increased plasma concentrations.

Depression and the vision-related quality of life in patients with retinitis pigmentosa.

AIMS: To assess the relationship between depression and the vision-related quality of life in patients with retinitis pigmentosa (RP). METHODS: The study included 144 patients diagnosed as having RP. The mean age of the patients was 38.5 (SD 13.3) years, and 42% of the subjects were women. They answered the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to assess the vision-related quality of life and the Beck Depression Inventory (BDI) to assess depressive symptoms. Patients were classified into groups with and without depression according to the BDI score. The NEI-VFQ composite and subscale scores were compared between groups. The correlations between the BDI and the NEI-VFQ, weighted visual acuity (WVA) and functional vision score (FVS) were investigated. RESULTS: The depressed group had significantly less subjective visual function compared with the non-depressed group. A negative correlation was observed between the BDI and the NEI-VFQ scores, while no correlation was found between the BDI score and WVA or FVS. CONCLUSION: The RP patients with depression had poorer vision-related functions compared with those patients without depression, which cannot be explained by the visual acuity. Interventions to diagnose and treat depression are necessary to enhance the overall quality of life in RP patients.

The effect of single or repeated restraint stress on several signal molecules in paraventricular nucleus, arcuate nucleus and locus coeruleus.

The effect of single or repeated restraint stress on several signal molecules in the hypothalamus was studied in ICR mice. Single restraint stress was induced for 30, 60, and 120 min. A repeated restraint stress was induced for 2 h daily during four consecutive days, and then induced in the same time course on the fifth day. In the immunoblot assay, we observed that the signal molecules c-Fos, phosphorylated extracellular cell-regulated protein kinase (pERK), phosphorylated calcium/calmodulin dependent protein kinase II (pCaMKII) and phosphorylated cyclic-AMP response element binding protein (pCREB) in the hypothalamus were increased by single restraint, and the increased c-Fos and pERK levels were attenuated by repeated restraint stress. However, pCaMKII and pCREB levels were increased by both single and repeated restraint stress. We also observed in the immunohistochemistry study that immunoreactivities (IR) of these signal molecules were changed in paraventricular (PVN) and arcuate nuclei (ArcN) of the hypothalamus in accordance with immunoblot results. Furthermore, in confocal immunofluorescence, the pCaMKII and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of PVN and ArcN. In addition, we found that c-Fos and pCaMKII IR in locus coeruleus (LC) were increased by single restraint, and were attenuated by repeated restraint stress. However, the pERK and pCREB IR were increased by both single and repeated restraint stress. The confocal study revealed that pERK and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of LC. Our results suggest that single and repeated restraint stress differentially triggers the induction and phosphorylation of several signal molecules in the PVN, ArcN, and LC. In addition, single and repeated stress stimuli elicited the brain-region specific changes of signal molecules examined. Furthermore, the upstream signal molecule activating CREB may be also brain-region specific, especially in repeated stress stimuli.