Comparison of prognostic value of echographic [corrected] risk score with the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry in Acute Coronary Events (GRACE) risk scores in acute coronary syndrome

Risk stratification in patients with acute coronary syndromes (ACS) is achieved today by clinical models, "blind" to the prognostic support of imaging methods. To assess the value of simple at rest cardiac chest sonography in predicting the intra- and extrahospital risk of death or myocardial infarction, we enrolled 470 consecutive in-patients (312 men, age 71 ± 12 years) who had been admitted for ACS. On admission, all had received a clinical score using the Global Registry in Acute Coronary Events and Thrombolysis in Myocardial Infarction systems and, within 1 to 12 hours, a comprehensive cardiac-chest ultrasound scan. Each of the 16 echocardiographic parameters evaluating left and right, systolic and diastolic, ventricular function and structure, was scored from 0 (normal) to 3 (severely abnormal). The median follow-up was 5 months (interquartile range 1 to 10). Patients with hard events (n = 102) could be separated from patients without events (n = 368) using the Global Registry in Acute Coronary Events score, Thrombolysis in Myocardial Infarction score, and several echocardiographic parameters. On multivariate Cox analysis, ejection fraction (hazard ratio 1.45, 95% confidence interval 1.02 to 2.08, p = 0.040), tricuspid annular plane systolic excursion (hazard ratio 1.66, 95% confidence interval 1.13 to 2.45, p = 0.010) and ultrasound lung comets (hazard ratio 1.69, 95% confidence interval 1.25 to 2.27, p = 0.001) were independent predictors of cardiac events. The 3-variable echocardiographic score (from 0, normal to 9, severe abnormalities in ejection fraction, ultrasound lung comets, and tricuspid annular plane systolic excursion) effectively stratified patients and added value (hazard ratio 2.52, 95% confidence interval 1.89 to 3.37, p <0.0001) to the Global Registry in Acute Coronary Events score (hazard ratio 1.60, 95% confidence interval 1.07 to 2.39, p = 0.003). In conclusion, for patients with ACS, effective risk stratification can be achieved with cardiac and chest ultrasound imaging parameters, adding prognostic value to the clinical risk scores.     

Congenital muscular dystrophy with muscle inflammation alpha dystroglycan glycosylation defect and no mutation in FKRP gene

Congenital muscular dystrophies (CMD) are autosomal recessive infantile disorders characterized by dystrophic changes at muscle biopsy and contractures. Central nervous system (CNS) abnormalities associated with mental retardation are often present. We describe a patient affected with muscle weakness, psychomotor developmental delay and normal brain MRI. Muscle biopsy showed complete absence of the alpha-dystroglycan (DG) glycosylated epitope and preservation of alpha-dystroglycan (alpha-DG) protein core. The analysis of FKRP, LARGE, POMT1 and POMGnT1 genes did not show any pathogenic mutations, suggesting that at least another gene may account for CMD with secondary glycosylated alpha-DG deficiency.     

Soluble E-cadherin and IL-6 serum levels in patients affected by prostate cancer before and after prostatectomy

Prostate specific antigen (PSA) is still the best available tumour marker in prostate cancer (PCa), but presents some limits. Therefore, there is a need for novel markers in the detection and management of PCa. The 80-kDa soluble form of E-cadherin (sE-cad) and the cytokine IL-6 are being discussed as supplemental serum markers for PCa. In this study, sE-cad and IL-6 serum levels were determined in patients with pathological localized or locally advanced PCa without any previous treatment. These patients underwent radical retropubic prostatectomy (RRP) in accordance with the EAU Guidelines on Prostate Cancer. The molecules were determined via immunoenzymatic assays in samples collected before and after surgery. Statistical analysis was performed by Student's t-test and Pearson's correlation test. sE-cad levels were 6.0 ± 2.7 and 4.6 ± 2.3 μg/ml, before and after RRP, respectively. A highly statistically significant decrease in sE-cad concentrations after RRP was observed (p<0.0001), in 50/61 patients (82%). sE-cad levels before and after surgery were correlated (Pearson's correlation coefficient, r=0.6993, p<0.0001). sE-cad values detected after surgery were higher in patients with PSA levels >10 ng/ml (p<0.05). sE-cad levels before RRP were significantly higher in patients with G3 tumours compared to those with G2 tumours (p<0.02). Finally, sE-cad concentrations both before and after surgery were higher in tumours with Gleason score =7 compared to those with Gleason score <7 (p<0.002 and p<0.05, respectively). Preliminary data from 20 patients indicated a statistically significant increase in IL-6 levels after RRP (11.2 vs. 7.2 pg/ml, p<0.001). This is the first study on the reduction in sE-cad levels after RRP in PCa patients. Moreover, it shows that preoperative sE-cad concentrations are higher in patients with less differentiated PCa. Promising findings of this pilot study may lead to investigation of sE-cad in a larger study with follow-up.     

Fos protein expression following acute administration of diethyldithiocarbamate in rats

Dithiocarbamates are compounds commonly used in medicine and in agriculture and their prolonged use is known to result in neurotoxicity. Whether this response may be related to early gene expression has not been investigated. We have addressed this issue by mapping Fos expression in rats acutely injected with diethyldithiocarbamate (DDTC) and correlating these data to neural damage in the hippocampus as determined by pyknotic nuclei count. In comparison to saline injected rats, DDTC treatment induced a marked Fos expression in most brain regions at 1 and 3 h. In the hippocampus, a high Fos expression was followed by a variable number of pyknotic nuclei at 6 h, depending on the subregion. The data suggest that, in this model of neurotoxicity, c-fos induction does not reflect a cell commitment to die or survive, but rather a cell response to the DDTC-induced oxidative disorder.     

The beneficial effect of insulin, glucose, and dipyridamole on regional left ventricular function early after acute myocardial infarction

BACKGROUND: High-dose glucose-insulin-potassium (GIK) solution has beneficial effects on reducing mortality in acute myocardial infarction. Dipyridamole (DIP) is a powerful antioxidant and increases adenosine concentration. Experimentally, GIK and DIP have additive protective effects in ischemia-reperfusion injury. AIM: This work aims to assess the acute effects of DIP alone, GIK alone, and GIK+DIP on left ventricular function in patients evaluated early after an acute myocardial infarction. METHODS: Ten male patients (age 63+/-11 years) with uncomplicated acute myocardial infarction were evaluated within 3 days after admission. All had been treated with systemic thrombolysis and were on full therapy (including beta-blockers) at the time of testing. They underwent stress echocardiography [2D echo, with wall motion score index (WMSI) evaluated in a 16-segment model of the left ventricle, with each segment scored from 1=normal to 4=dyskinetic] during low-dose DIP alone (0.28 mg/kg in 4 min); GIK alone (4-h infusion of glucose 30%, 25 insulin units, and 40 mEq of KCl, at an infusion rate of 1.5 ml/kg/h); and GIK+DIP. RESULTS: Regional systolic function (baseline WMSI=1.69+/-0.2) improved after DIP (1.54+/-0.1), GIK (1.54+/-0.1), and, to a greater extent, after GIK+DIP (1.33+/-0.2; p<0.001 vs. baseline; p<0.05 vs. DIP; p<0.05 vs. GIK). CONCLUSION: High-dose GIK has an acute beneficial effect on regional left ventricular function in patients with acute myocardial infarction. This beneficial effect is potentiated by low-dose DIP coadministration.     

Structural defects and variations in the HIV-1 nef gene from rapid,slow and non-progressor children

OBJECTIVES: Evaluation of sequence evolution as well as structural defects and mutations of the human immunodeficiency virus-type 1 (HIV-1) nef gene in relation to disease progression in infected children. DESIGN: We examined a large number of nef alleles sequentially derived from perinatally HIV-1-infected children with different rates of disease progression: six non-progressors (NPs), four rapid progressors (RPs), and three slow progressors (SPs). METHODS: Nef alleles (182 total) were isolated from patients' peripheral blood mononuclear cells (PBMCs), sequenced and analysed for their evolutionary pattern, frequency of mutations and occurrence of amino acid variations associated with different stages of disease. RESULTS: The evolution rate of the nef gene apparently correlated with CD4+ decline in all progression groups. Evidence for rapid viral turnover and positive selection for changes were found only in two SPs and two RPs respectively. In NPs, a higher proportion of disrupted sequences and mutations at various functional motifs were observed. Furthermore, NP-derived Nef proteins were often changed at residues localized in the folded core domain at cytotoxic T lymphocytes (CTL) epitopes (E(105), K(106), E(110), Y(132), K(164), and R(200)), while other residues outside the core domain are more often changed in RPs (A(43)) and SPs (N(173) and Y(214)). CONCLUSIONS: Our results suggest a link between nef gene functions and the progression rate in HIV-1-infected children. Moreover, non-progressor-associated variations in the core domain of Nef, together with the genetic analysis, suggest that nef gene evolution is shaped by an effective immune system in these patients.