SUMMARYThe mechanism of anti-tumour activity by BCG is not known clearly. However, many studies suggest that immunological response is related to effectiveness of intravesical instillation of BCG in the therapy for super®cial bladder carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with super®cial carcinoma at various times during the course of BCG instillation. Urine of patients showed increased levels of IL-1b, IL-2, IL-6, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-g) and macrophage colony-stimulating factor (M-CSF) after BCG instillation. Levels of IL-2 and IFN-g in the serum also increased after BCG instillation, but IL-1b, IL-6, TNF-a and M-CSF were not detectable. Maximal levels of IL-2 and IFN-g in the urine or serum were shown after the fourth instillation. BCG-induced killer cell activity in PBMC increased signi®cantly after the third BCG instillation. These results suggest that BCG instillation involved not only local immunological efforts but also systemic immune responses. Tumour-free patients produced higher BCG-induced killer cell activity than tumour recurrence patients. BCG-induced killer cell activity may be useful for monitoring the effectiveness of intravesical BCG instillation.

SummaryAn infl ammatory response is a key event for endothelial dysfunction. Pentraxin 3 (PTX3) is an infl ammatory protein produced at infl ammation sites such as leukocytes and vascular endothelial cells. Here, we compared the relationships between endothelial function assessed by fl ow-mediated dilation (FMD), and the levels of plasma PTX3 and highsensitive C-reactive protein (hsCRP), another infl ammatory protein of the pentraxin family.Levels of FMD, PTX3 and hsCRP were measured twice within 6 to 8 months and retrospectively analyzed in 36 patients with coronary artery disease. We examined the associations between the values of FMD and the levels of PTX3 and hsCRP at the fi rst measurement, and between the change ratios (second value/fi rst value) of these parameters.Univariate linear regression analysis showed signifi cantly negative correlations between FMD values and PTX3 and hsCRP levels at the fi rst measurement, and signifi cant associations with taking statins or calcium antagonists. Multivariate linear stepwise regression analysis identifi ed PTX3 levels and taking statins and calcium antagonists as independent factors for endothelial function. The change ratio of FMD correlated more closely with that of PTX3 than of hsCRP (r = -0.446, P = 0.006 versus r = -0.330, P = 0.050). Signifi cantly more patients with decreased FMD values had increased levels of PTX3 than those of hsCRP at the second measurement compared with the fi rst measurement. Furthermore, the ratio of patients with increased PTX3, but not increased hsCRP, was signifi cantly reduced among those with increased, rather than decreased, FMD values.Endothelial dysfunction might be more accurately predicted by plasma PTX3 levels than by serum hsCRP levels. (Int Heart J 2014; 55: 160-164)

Objective Previous studies have shown a possible role for obstructive sleep apnea syndrome (OSAS) in the development and/or progression of chronic kidney disease (CKD). However, the impact of treatment for OSAS on CKD has not been clarified. The aim of this study was to investigate the influence of OSAS and the short-term effects of nasal continuous positive airway pressure (CPAP) on the estimated glomerular filtration rate (eGFR). Methods We evaluated 38 men with OSAS diagnosed on polysomnography. The associations between the eGFR and patient characteristics, including polysomnographic parameters, were evaluated. A multivariate linear regression analysis was performed to determine the independent variables associated with eGFR. We reassessed the polysomnographic data and eGFR values after three months of CPAP treatment. Results The mean serum creatinine level was 0.83±0.10 mg/dL and the mean eGFR was 77.3±12.0 mL/ min/1.73 m 2 . A univariate analysis revealed that an older age (p<0.001), a longer mean apnea duration (p= 0.006) and BMI (p=0.022) were significantly associated with lower eGFRs. A multivariate linear regression analysis showed that the independent factors associated with lower eGFRs were older age (p<0.001) and a longer mean apnea duration (p=0.048). Three months after CPAP treatment, there were significant decreases in the serum creatinine levels (p=0.013) and increases in eGFR (p=0.014). Conclusion OSAS, especially that associated with an older age and a longer mean apnea duration, may contribute to lowering eGFR values, which can be reversed by CPAP treatment.

Higher levels of systemic PTX3 are associated with TCFA. Systemic PTX3 levels comprise a useful inflammatory marker that reflects coronary plaque vulnerability.

Aims: Echocardiography is widely used for screening of pulmonary hypertension (PH). More recently developed two-dimensional speckle-tracking echocardiography (2D-STE) can assess regional deformation of the myocardium and is useful for detecting left ventricular dysfunction. However, its usefulness to assess right ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was to investigate the ability of peak systolic strain (PSS) and post-systolic strain index (PSI) at the RV free wall determined by 2D-STE to detect PH.Main methods: Thirty-six images (27 images from PH patients, nine from patients with connective tissue disease without PH) obtained by 2D-STE were analysed. We investigated the relationship between RV hemodynamics measured by right heart catheterization and PSS, PSI and other echocardiographic parameters reflecting RV overload including RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure gradient (TRPG).Key findings: PSS, PSI, RVDd and TRPG were all correlated with mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Furthermore, when PSS and MPAP were measured twice, the change in PSS was correlated with the change in MPAP (r=0.633, p=0.037). Multivariate logistic regression analysis identified PSS as the only independent factor associated with MPAP≥35 mmHg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017-2.567; p=0.042] and PVR≥400 dyne·sec·cm -5 (OR, 1.804; 95% CI 1.131-2.877; p=0.013). Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was -20.75%, based on receiver operating characteristic curve analysis.Significance: PSS of the RV free wall might serve as a useful non-invasive 2 indicator of PH.

Objective Abnormal left ventricular (LV) geometry, especially concentric hypertrophy, is associated with cardiovascular morbidity and mortality. The aim of this study was to evaluate the impact of obstructive sleep apnea syndrome (OSAS) and the effects of nasal continuous positive airway pressure (CPAP) on the LV geometric patterns. Methods The LV morphological parameters, including the LV mass index (LVMI) and the relative wall thickness (RWT), were evaluated using echocardiography in 37 patients with OSAS diagnosed on polysomnography and 34 control subjects. Based on the values of LVMI and RWT, the LV geometry was classified as normal, concentric remodeling, concentric hypertrophy or eccentric hypertrophy. The echocardiographic parameters were reassessed after three months of CPAP treatment. Results Compared with the controls, the OSAS patients had a higher proportion of concentric hypertrophy patterns (54% vs. 0%, p<0.001) and a lower proportion of normal geometric patterns (5% vs. 62%, p<0.001). A univariate logistic regression analysis showed the apnea-hypopnea index, lowest oxygen saturation, hypoxemia index and body mass index to each be significantly associated with the presence of concentric hypertrophy. In a multivariate analysis of these factors, the apnea-hypopnea index was found to be a significant independent factor associated with the presence of concentric hypertrophy (odds ratio: 1.06, p=0.008). Three months of CPAP treatment resulted in significant decreases in LVMI and the proportion of cases with concentric hypertrophy (both p=0.025). Conclusion In our limited study population, OSAS patients were found to be associated with a high prevalence of concentric LV hypertrophy patterns that were able to be reversed with three months of CPAP treatment.

The influence of obstructive sleep apnea syndrome (OSAS) on left ventricular function remains controversial. We examined the influence of OSAS on global left ventricular function using the myocardial performance index (Tei-index) and plasma brain natriuretic peptide (BNP) level, and investigated the effect of nasal continuous positive airway pressure (nCPAP) on these parameters. We obtained echocardiographic indices including the Tei-index and BNP concentrations from 27 patients with OSAS whose mean apnea-hypopnea index (AHI) was 42.2 ± 21.5 events/hour and who were undergoing nCPAP, as well as from 22 control individuals. We defined global left ventricular dysfunction (GLVD) as a Tei-index of ≥ 0.50, and high BNP as ≥ 20 pg/ml. Compared with controls, the Tei-index of OSAS patients was significantly increased (P < 0.01) and the prevalence of GLVD was high (19%, P < 0.05). The correlation between the Tei-index and AHI was significant (r = 0.447, P < 0.05). Although BNP levels were higher in OSAS patients than in controls, the difference did not reach significance. The BNP level was high in 37% of OSAS patients and in only 9% of controls (P < 0.05). The Tei-index of OSAS patients was significantly decreased after 1 and 3 months of nCPAP (P < 0.01), and the prevalence of GLVD significantly decreased from 19% to 4% (P < 0.05). In contrast, BNP significantly decreased at 3 months after nCPAP (P < 0.05). In conclusion, patients with moderate to severe OSAS frequently have impaired global left ventricular myocardial performance, which can be reversed at the early stage after starting nCPAP.

The development and progression of atherosclerosis comprises various processes, such as endothelial dysfunction, chronic inflammation, thrombus formation and lipid profile modification.Statins are HMG-CoA reductase inhibitors that have pleiotropic effects in addition to cholesterol lowering properties. However, the mechanisms of these effects are not completely understood. Here, we investigated whether atorvastatin affects the levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, the proinflammatory cytokine interleukin-6 (IL-6), or platelet P-selectin, a marker of platelet activation, relative to that of LDL cholesterol (LDL-C). Forty-eight patients with coronary artery disease and hyperlipidemia were separated into 2 groups that were administered with weeks, whereas the IL-6 level was gradually, but not significantly, reduced at 12weeks. In contrast, none of these parameters significantly changed in the control group within these time frames. The reduction (%) in IL-6 between 4 and 12 weeks after atorvastatin administration significantly correlated with that of MDA-LDL and of platelet P-selectin (r = 0.65, p < 0.05 and r = 0.70, p < 0.05, respectively).These results suggested that the positive effects of atorvastatin on the LDL-C 3 oxidation, platelet activation and inflammation that are involved in atherosclerotic processes are exerted in concert after lowering LDL-C.