Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.
INTRODUCTION Cardiac resynchronization therapy (CRT) is relatively new tool in treatment of chronic heart failure (HF), especially in dilated cardiomyopathy (DCM) with the left bundle branch block (LBBB). OBJECTIVE The objective of our study was to assess the success of CRT in treatment of severe HF and the role of echocardiography in the evaluation of results of such therapy. METHOD The group consisted of 19 patients, 13 males and 6 females, mean age 58.0 +/- 8.22 years (47-65 years) with CRT applied for DCM, severe HF (NYHA III-IV), LBBB and ejection fraction (EF) <35%. The mean follow up was 17 months (6.5-30). Standard color Doppler echocardiography examination was performed in all patients before and after CRT. The parameters of systolic and diastolic left ventricular function, mitral insufficiency and the right ventricular pressure were evaluated. RESULTS Following the CRT, statistically significant improvement of the end-systolic LV dimension, cardiac output, cardiac index, myocardial performance index (p < 0.01) and stroke index (p < 0.05) was recorded. The mean value of EFLV was increased by 10% and LV fractional shortening improved by 6% in 10/16 (62%) patients. CRT resulted in decreased MR (p < 0.01), prolonged LV diastolic filling time (p < 0.02) and reduced RV pressure (p < 0.05). Interventricular mechanical delay was shortened by 28% (18 msec) CONCLUSION CRT has an important role in improvement of LV function and correction of ventricular asynchrony. The echocardiography is a useful tool for evaluation of HF treatment with CRT.
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