Early detection of tuberculosis (TB) is essential for infection control. The geneCube (Toyobo) is a novel fully automated gene analyzer that can amplify target DNAs within 60 min. In this study, we evaluated the ability of the geneCube to directly detect Mycobacterium tuberculosis complex (MTBC) and Mycobacterium avium complex (MAC) in clinical specimens. The results were then compared with those obtained using conventional culture, microscopy, and the Cobas Amplicor assay (Roche). We examined a total of 516 frozen samples from 69 patients who showed culture-positive infection (73 samples; 39 MTBC, 32 MAC, and 2 mixed infections) and from 354 patients who were culture negative (443 samples). Assays using the geneCube had a sensitivity of 85.4% and a specificity of 99.8% for detection of MTBC and a sensitivity of 85.3% and a specificity of 99.8% for detection of MAC. These results are similar to those obtained using the Amplicor system but were obtained much more rapidly (1 h with the geneCube versus 5.5 h with the Amplicor system). The geneCube thus enables a significant shortening of the assay time with no loss of sensitivity or specificity.T uberculosis (TB) is a major public health problem worldwide. According to a recent World Health Organization (WHO) report, 1.1 million people around the world died of TB in 2010 (29). In Japan, the number of TB patients has been declining yearly; nonetheless, 24,170 new cases were reported in 2009 (28). The prevalence of TB is higher in Japan than in Western countries, and it remains a serious public health problem, even now. Reducing the incidence of TB will require optimal control of infection and early diagnosis. However, members of the Mycobacterium tuberculosis complex (MTBC) grow slower than other bacteria and so require a long incubation time for diagnosis in culture. To overcome that situation, more rapid diagnosis with genetic testing using PCR is now widespread in hospital laboratories (1-3, 6-15, 17-21, 24, 26, 31).The Cobas Amplicor MTB (Roche Diagnostics, Basel, Switzerland) PCR assay for direct detection of MTBC is popular in many countries, and numerous studies have been conducted to evaluate the system (2, 6-9, 11-13, 19-21, 24). This assay was approved by the FDA for testing of respiratory samples but requires about 6 h and cannot be applied to screening of nonrespiratory samples due to the presence of a PCR inhibitor in those tissues. Recently, the geneCube system (Toyobo, Osaka, Japan), a fully automated gene analyzer, was developed as a new detection method that can detect and distinguish between DNA from MTBC and Mycobacterium avium complex (MAC) within 60 min. This assay technique is based on real-time PCR technology targeting the dnaJ genes of MTBC and MAC and uses quenching probes (Qprobes) to confirm the presence of MTBC or MAC (25,27,30). In the present study, we compared the ability of the geneCube system to directly detect MTBC and MAC with that of the Cobas Amplicor system, using the standard culture method as the reference. MATERIALS AND METH...
BackgroundStatins decrease cholesteryl ester transfer protein (CETP) levels, which have been positively associated with hepatic lipid content as well as serum low density lipoproteins-cholesterol (LDL-C) levels. However, the relationship between the CETP status and statin-induced reductions in LDL-C levels has not yet been elucidated in detail. We herein examined the influence of the CETP status on the lipid-reducing effects of pitavastatin in hypercholesterolemic patients with type 2 diabetes mellitus as well as the molecular mechanism underlying pitavastatin-induced modifications in CETP levels.MethodsFifty-three patients were treated with 2 mg of pitavastatin for 3 months. Serum levels of LDL-C, small dense (sd) LDL-C, and CETP were measured before and after the pitavastatin treatment. The effects of pitavastatin, T0901317, a specific agonist for liver X receptor (LXR) that reflects hepatic cholesterol contents, and LXR silencing on CETP mRNA expression in HepG2 cells were also examined by a real-time PCR assay.ResultsThe pitavastatin treatment decreased LDL-C, sdLDL-C, and CETP levels by 39, 42, and 23 %, respectively. Despite the absence of a significant association between CETP and LDL-C levels at baseline, baseline CETP levels and its percentage change were an independent positive determinant for the changes observed in LDL-C and sdLDL-C levels. The LXR activation with T0901317 (0.5 μM), an in vitro condition analogous to hepatic cholesterol accumulation, increased CETP mRNA levels in HepG2 cells by approximately 220 %, while LXR silencing markedly diminished the increased expression of CETP. Pitavastatin (5 μM) decreased basal CETP mRNA levels by 21 %, and this was completely reversed by T0901317.ConclusionBaseline CETP levels may predict the lipid-reducing effects of pitavastatin. Pitavastatin-induced CETP reductions may be partially attributed to decreased LXR activity, predictable by the ensuing decline in hepatic cholesterol synthesis.Trial registrationUMIN Clinical Trials Registry ID UMIN000019020
Myelolipoma of the adrenal gland is a rare, benign, nonfunctioning lesion consisting of fat and bone marrowelements in varying proportions. This tumor is commonlyasymptomatic and usually discovered during various diagnostic imaging examinations performed for unrelated diseases. If a primary malignant or metastatic adrenal tumor cannot be excluded, ultrasoundor computedtomography-guided needle biopsy of the tumor is necessary. Wereport a case of adrenal myelolipoma associated with advanced gastric carcinoma and compare the diagnostic imaging findings with the pathological findings of the adrenal myelolipoma.
These suggest that a smaller LDL size, which is associated with higher levels of TG and CETP and the HL/CC genotype, may serve as a risk factor for CAD in HD patients.
Background Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) as a treatment for advanced non‐small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD‐(L)1] inhibitor failure. Methods Nab‐paclitaxel (100 mg/m2) was administered on Days 1, 8, and 15 of a 28‐day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD‐(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. Results Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%–79.6%) and the DCR was 86.2% (95% CI: 65.9%–97.0%). The median PFS was 5.6 months (95% CI: 4.4–6.7 months), and PFS rates at 1‐ and 2‐year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8–23.0 months). Good performance status and responder of previous PD‐(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%). Conclusions Nab‐paclitaxel therapy improved ORR after PD‐(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC.
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