Moyamoya disease presenting as acute onset cortical blindness: A case report

We report a case where acute onset cortical blindness is the mode of presentation in Moyamoya disease. Cortical blindness is very rare presenting symptom of Moyamoya disease. Progressive visual loss and homonymous anopsia has been described previously, but this case had acute visual loss

Indexed Left Atrial Adipose Tissue Area Is Associated With Severity of Atrial Fibrillation and Atrial Fibrillation Recurrence Among Patients Undergoing Catheter Ablation

Background: Epicardial adipose tissue (EAT) has been associated with adverse left atrial (LA) remodeling and atrial fibrillation (AF) outcomes, possibly because of paracrine signaling. Objectives: We examined factors associated with a novel measure of EAT i.e., indexed LAEAT (iLAEAT) and its prognostic significance after catheter ablation (CA) of atrial fibrillation (AF). Methods: We performed a retrospective analysis of 274 participants with AF referred for CA. LAEAT area was measured from a single pre-ablation CT image and indexed to body surface area (BSA) to calculate iLAEAT. Clinical, echocardiographic data and 1-year AF recurrence rates after CA were compared across tertiles of iLAEAT. We performed logistic regression analysis adjusting for factors associated with AF to examine relations between iLAEAT and AF recurrence. Results: Mean age of participants was 61 +/- 10 years, 136 (49%) were women, mean BMI was 32 +/- 9 kg/m(2) and 85 (31%) had persistent AF. Mean iLAEAT was 0.82 +/- 0.53 cm(2)/m(2). Over 12-months, 109 (40%) had AF recurrence. Participants in the highest iLAEAT tertile were older, had higher CHA2DS2VASC scores, more likely to be male, have greater LA volume, and were more likely to have persistent (vs. paroxysmal) type AF than participants in the lowest iLAEAT tertile (p for all \u3c 0.05). In regression analyses, iLAEAT was associated with higher odds of AF recurrence (OR = 2.93; 95% CI 1.34-6.43). Conclusions: iLAEAT can quantify LA adipose tissue burden using standard CT images. It is strongly associated with AF risk factors and outcomes, supporting the hypothesis that EAT plays a role in the pathophysiology of AF

Beta-Blocker Use Is Associated With Impaired Left Atrial Function in Hypertension

BACKGROUND: Impaired left atrial (LA) mechanical function is present in hypertension and likely contributes to various complications, including atrial arrhythmias, stroke, and heart failure. Various antihypertensive drug classes exert differential effects on central hemodynamics and left ventricular function. However, little is known about their effects on LA function. METHODS AND RESULTS: We studied 212 subjects with hypertension and without heart failure or atrial fibrillation. LA strain was measured from cine steady-state free-precession cardiac MRI images using feature-tracking algorithms. In multivariable models adjusted for age, sex, race, body mass index, blood pressure, diabetes mellitus, LA volume, left ventricular mass, and left ventricular ejection fraction, beta-blocker use was associated with a lower total longitudinal strain (standardized beta=-0.21; P=0.008), and lower LA expansion index (standardized beta=-0.30; P \u3c 0.001), indicating impaired LA reservoir function. Beta-blocker use was also associated with a lower positive strain (standardized beta=-0.19; P=0.012) and early diastolic strain rate (standardized beta=0.15; P=0.039), indicating impaired LA conduit function. Finally, beta-blocker use was associated with a lower (less negative) late-diastolic strain (standardized beta=0.15; P=0.049), strain rate (standardized beta=0.18; P=0.019), and a lower active LA emptying fraction (standardized beta=-0.27; P\u3c 0.001), indicating impaired booster pump function. Use of other antihypertensive agents was not associated with LA function. CONCLUSIONS: Beta-blocker use is significantly associated with impaired LA function in hypertension. This association could underlie the increased risk of atrial fibrillation and stroke seen with the use of beta-blockers (as opposed to other antihypertensive agents) demonstrated in recent trials

Spondin-2 (SPON2), a More Prostate-Cancer-Specific Diagnostic Biomarker

BACKGROUND: Prostate-specific antigen (PSA) screening, although common, has recently been called into question. To find prostate cancer (PCa) diagnostic biomarkers that can make up for the defects of PSA, we compared the secretomes of several benign and PCa cell lines, selected candidate molecules, and then confirmed their clinical value. METHODOLOGY/PRINCIPAL FINDINGS: We first identified extracellular proteins by two-dimensional gel electrophoresis (2-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification. We then validated the secreted proteins on a cellular level, and finally determined whether they could be used as PCa diagnostic biomarkers using prostate tissue and serum specimens of Chinese volunteers by immunohistostaining and sandwich ELISA. We obtained credible extracellular protein 2-DE graphs of prostate cell lines. The 5 spots that showed superior repeatability were selected for LC-MS/MS analysis, which identified seven candidate molecules. One of the candidate molecules, spondin-2 (SPON2), was only expressed in the conditioned media (CM) of androgen receptor (AR) positive PCa cell lines. Using tissue microarray by immunohistostaining, we found SPON2 to be over-expressed in PCa. SPON2 staining was more intense in Gleason score sum 7-8 and in PCa patients with metastasis. By receiver operator characteristic (ROC) curve analysis, we found that the serum SPON2 level was elevated in PCa patients, showing sensitivity and specificity suitable for diagnostic use. We also found that SPON2 could be used to identify PCa patients with serum PSA levels no higher than 10 ng/ml from healthy elderly men. CONCLUSION/SIGNIFICANCE: SPON2 is a new serum and histological diagnostic biomarker for PCa. It can avoid some of the problems of PSA testing and was here found to offer relatively high sensitivity and specificity relative to PSA

Simvastatin ameliorates established pulmonary hypertension through a heme oxygenase-1 dependent pathway in rats

<p>Abstract</p> <p>Background</p> <p>Simvastatin has been shown to ameliorate pulmonary hypertension by several mechanisms in experimental animal models. In this study, we hypothesized that the major benefits of simvastatin in pulmonary hypertension occur via the heme oxygenase-1 pathway.</p> <p>Methods</p> <p>Simvastatin (10 mg/kgw/day) was tested in two rat models of pulmonary hypertension (PH): monocrotaline administration and chronic hypoxia. The hemodynamic changes, right heart hypertrophy, HO-1 protein expression, and heme oxygenase (HO) activity in lungs were measured in both models with and without simvastatin treatment. Tin-protoporphyrin (SnPP, 20 μmol/kg w/day), a potent inhibitor of HO activity, was used to confirm the role of HO-1.</p> <p>Results</p> <p>Simvastatin significantly ameliorated pulmonary arterial hypertension from 38.0 ± 2.2 mm Hg to 22.1 ± 1.9 mm Hg in monocrotaline-induced PH (MCT-PH) and from 33.3 ± 0.8 mm Hg to 17.5 ± 2.9 mm Hg in chronic hypoxia-induced PH (CH-PH) rats. The severity of right ventricular hypertrophy was significantly reduced by simvastatin in MCT-PH and CH-PH rats. Co-administration with SnPP abolished the benefits of simvastatin. Simvastatin significantly increased HO-1 protein expression and HO activity in the lungs of rats with PH; however co-administration of SnPP reduced HO-1 activity only. These observations indicate that the simvastatin-induced amelioration of pulmonary hypertension was directly related to the activity of HO-1, rather than its expression.</p> <p>Conclusion</p> <p>This study demonstrated that simvastatin treatment ameliorates established pulmonary hypertension primarily through an HO-1-dependent pathway.</p

Heme oxygenase-1 prevents smoke induced B-cell infiltrates: a role for regulatory T cells?

<p>Abstract</p> <p>Background</p> <p>Smoking is the most important cause for the development of COPD. Since not all smokers develop COPD, it is obvious that other factors must be involved in disease development. We hypothesize that heme oxygenase-1 (HO-1), a protective enzyme against oxidative stress and inflammation, is insufficiently upregulated in COPD.</p> <p>The effects of HO-1 modulation on cigarette smoke induced inflammation and emphysema were tested in a smoking mouse model.</p> <p>Methods</p> <p>Mice were either exposed or sham exposed to cigarette smoke exposure for 20 weeks. Cobalt protoporphyrin or tin protoporphyrin was injected during this period to induce or inhibit HO-1 activity, respectively. Afterwards, emphysema development, levels of inflammatory cells and cytokines, and the presence of B-cell infiltrates in lung tissue were analyzed.</p> <p>Results</p> <p>Smoke exposure induced emphysema and increased the numbers of inflammatory cells and numbers of B-cell infiltrates, as well as the levels of inflammatory cytokines in lung tissue. HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines. Interestingly, HO-1 induction prevented the development of smoke induced B-cell infiltrates and increased the levels of CD4⁺CD25⁺T cells and Foxp3 positive cells in the lungs. Additionally, the CD4⁺CD25⁺T cells correlated positively with the number of Foxp3 positive cells in lung tissue, indicating that these cells were regulatory T cells.</p> <p>Conclusion</p> <p>These results support the concept that HO-1 expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates. The translation of this interaction to human COPD should now be pursued.</p