Age-related white matter changes are common in the elderly and are considered as manifestation of arteriolosclerotic small vessel disease. Most recent studies have shown that the white matter changes are associated with cognitive impairment and dementia, urinary incontinence, gait disturbances, depression and increased risk of stroke and death. Although the clinical phenotypes of the white matter changes have been extensively studied, to date, only few clinical trials have been conducted in this area. In this review, we discussed the current understanding in the epidemiology, pathogenesis, imaging features, chemical biomarkers, clinical importance, and management of age-related white matter changes, with special emphasis in studies that were conducted among Asians.

OBJECTIVE: To evaluated whether clusterin over-expression is significantly correlated with paclitaxel resistance in ovarian cancer cell lines. METHODS: Clusterin was validated by performing expression profiling analysis and subsequently, the correlation between clusterin mRNA expression levels and the IC50 of paclitaxel was tested. Transfection of clusterin was performed on SKOV3, which expressed paclitaxel-sensitivity and low level of clusterin, and transfection of clusterin siRNA on PEOH, which expressed paclitaxel-resistance and high level of clusterin, to evaluate their effect on chemo-sensitivity, apoptosis, and cell cycle by XTT assay, cell death ELISA, and flow cytometry, respectively. RESULTS: Clusterin mRNA and protein expression levels were significantly correlated with paclitaxel resistance (P<0.001). Transfection of cluterin on SKOV3 significantly decreased apoptosis and increased paclitaxel resistance. And transfection of clusterin siRNA on PEOH significantly increased paclitaxel-sensitivity (P<0.05), and shifted cells from S to G2/M phase of the cell cycle after paclitaxel treatment. CONCLUSION: These findings suggested that clusterin overexpression confers paclitaxel-resistance by the modulation of the apoptotic pathway and cell cycle progression in ovarian cancer cells.
Apoptosis ; Cell Cycle ; Cell Death ; Cell Line ; Clusterin* ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Inhibitory Concentration 50 ; Ovarian Neoplasms* ; Paclitaxel* ; RNA, Messenger ; RNA, Small Interfering ; Transfection

Lacunar infarcts/lacunes, white matter hyperintensities (WMH), and cerebral microbleeds (CMBs) are considered various manifestations of cerebral small vessel disease (SVD). Since the exact mechanisms of these manifestations differ, their associated risk factors differ. High blood pressure is the most consistent risk factor for all of these manifestations. However, a "J curve" phenomenon in terms of blood pressure probably exists for WMH. The association between cholesterol levels and lacunar infarcts/lacunes or WMH was less consistent and sometimes conflicting; a low cholesterol level probably increases the risk of CMBs. Homocysteinemia appears to be associated with WMH. It is noteworthy that the risk factors profile may also differ between different lacunar patterns and CMBs located at different parts of the brain. Thrombolysis, antihypertensives, and statins are used to treat patients with symptomatic lacunar infarction, just as in those with other stroke subtypes. However, it should be remembered that bleeding risks increase in patients with extensive WMH and CMBs after thrombolysis therapy. According to the Secondary Prevention of Small Subcortical Strokes trial results, a blood pressure reduction to <130 mmHg is recommended in patients with symptomatic lacunar infarction. However, an excessive blood pressure decrease may induce cognitive decline in older patients with extensive WMH. Dual antiplatelet therapy (aspirin plus clopidogrel) should be avoided because of the excessive risk of intracerebral hemorrhage. Although no particular antiplatelet is recommended, drugs such as cilostazol or triflusal may have advantages for patients with SVD since they are associated with less frequent bleeding complications than aspirin.
Antihypertensive Agents ; Aspirin ; Blood Pressure ; Brain ; Cerebral Hemorrhage ; Cerebral Small Vessel Diseases* ; Cholesterol ; Hemorrhage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypertension ; Risk Factors ; Secondary Prevention ; Stroke ; Stroke, Lacunar

Objectives: Intracranial atherosclerosis, especially the middle cerebral artery (MCA), is the commonestvascular lesion for ischemic stroke the Chinese population. We explored the association of geneticpolymorphism and environmental factors in MCA atherosclerosis in the Chinese population. Methods:One hundred fifty-six ischemic stroke patients with MCA stenosis and 181 well-matched ischemicstroke patients without MCA stenosis were examined by polymerase chain reaction (PCR). ThePCR products were analyzed for lipoprotein lipase (LPL) S447X and paraoxonase1 (PON1) Q192Rpolymorphisms by restriction enzyme digestion. Medical history documentation and investigationof biochemical markers were performed for each subject. Results: Univariate analysis showed thatthe levels of systolic blood pressure (SBP) were higher in the MCA stenosis group. There were nosignificant differences in the genotype and allele frequencies of the LPL S447X and PON1 Q192Rpolymorphism observed between the two groups. But, in the patients above 60 years of age with andwithout MCA stenosis, LPL X carriers have higher level of SBP than the LPL SS genotype carriers.Multivariate logistic regression found that SBP was the significant, independent predictor of thepresence of MCA stenosis patients above 60 years of age (P < 0.001, OR=1.206, 95% confidenceintervals: 1.014-1.032).Conclusions: SBP appears to contribute to the pathogenesis of MCA stenosis among Chinese. Thegene polymorphism of LPL S447X may be associated with atherosclerotic MCA stenosis in Chinesepopulation.

Background: and Purpose Paroxysmal atrial fibrillation (PAF) underlying acute stroke frequently evades detection by standard practice, considered to be a combination of routine electrocardiogram (ECG) monitoring, and 24-hour Holter recordings. We hypothesized that nurse-led in-hospital intermittent monitoring approach would increase PAF detection rate. Methods: We recruited patients hospitalised for stroke/transient ischemic attack, without history of atrial fibrillation (AF), in a prospective multi-centre observational study. Patients were monitored using a smartphone-enabled handheld ECG (iECG) during routine nursing observations, and underwent 24-hour Holter monitoring according to local practice. The primary outcome was comparison of AF detection by nurse-led iECG versus Holter monitoring in patients who received both tests: secondary outcome was oral anticoagulant commencement at 3-month following PAF detection. Results: One thousand and seventy-nine patients underwent iECG monitoring: 294 had iECG and Holter monitoring. AF was detected in 25/294 (8.5%) by iECG, and 8/294 (2.8%) by 24-hour Holter recordings (P<0.001). Median duration from stroke onset to AF detection for iECG was 3 days (interquartile range [IQR], 2 to 6) compared with 7 days (IQR, 6 to 10) for Holter recordings (P=0.02). Of 25 patients with AF detected by iECG, 11 were commenced on oral anticoagulant, compared to 5/8 for Holter. AF was detected in 8.8% (69/785 patients) who underwent iECG recordings only (P=0.8 vs. those who had both iECG and 24-hour Holter). Conclusions Nurse-led in-hospital iECG surveillance after stroke is feasible and effective and detects more PAF earlier and more frequently than routine 24-hour Holter recordings. Screening with iECG could be incorporated into routine post-stroke nursing observations to increase diagnosis of PAF, and facilitate institution of guideline-recommended anticoagulation.

No abstract available.
Hong Kong* ; Rehabilitation* ; Stroke*