Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial.

OBJECTIVE: Erythropoietin (EPO) is neuroprotective after asphyxia in animal studies. The efficacy and safety of EPO monotherapy in term neonates with hypoxic ischemic encephalopathy (HIE) is uncertain. STUDY DESIGN: Hundred term neonates with moderate or severe HIE were randomized by random permuted block algorithm to receive either EPO 500 U kg-1 per dose in 2 ml saline intravenously (50 neonates) on alternate days for a total of five doses with the first dose given by 6 h of age (treatment group) or 2 ml of normal saline (50 neonates) similarly for a total of five doses (placebo group) in a double-blind study. No hypothermia was given. The primary outcome was combined end point of death or moderate or severe disability at mean age of 19 months (s.d., 0.61). RESULTS: Death or moderate or severe disability occurred in 40% of neonates in the treatment group vs 70% in the placebo group (risk ratio, 0.57; 95% confidence interval (CI) 0.38 to 0.85; P=0.003). Death occurred in 16% of patients in both the groups (risk ratio, 1.0; 95% CI 0.33 to 2.9; P=0.61). The risk of cerebral palsy was lower among survivors in the treatment group (risk ratio, 0.52; 95% CI 0.25 to 1.03; P=0.04) and lesser number of babies were on anticonvulsants at assessment (risk ratio, 0.47; 95% CI 0.20 to 1.01; P=0.03). Neonatal brain magnetic resonance imaging showed more abnormalities in the placebo group (relative risk, 0.66; 95% CI 0.42 to 1.03; P=0.04)). Improvement in other neurological outcomes was not significant. CONCLUSION: EPO monotherapy reduces the risk of death or disability in term neonates with moderate or severe encephalopathy.

Cathepsin B and uPAR knockdown inhibits tumor-induced angiogenesis by modulating VEGF expression in glioma.

Angiogenesis, which is the process of sprouting of new blood vessels from pre-existing vessels, is vital for tumor progression. Proteolytic remodeling of extracellular matrix is a key event in vessel sprouting during angiogenesis. Urokinase type plasminogen activator receptor (uPAR) and cathepsin B are both known to be overexpressed and implicated in tumor angiogenesis. In the present study, we observed that knockdown of uPAR and cathepsin B using puPAR (pU), pCathepsin B (pC), and a bicistronic construct of uPAR and cathepsin B (pCU) caused significant inhibition of angiogenesis by disrupting the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway-dependent expression of vascular endothelial growth factor (VEGF). Further, transcriptional suppression of uPAR and cathepsin B inhibited tumor-induced migration, proliferation of endothelial cells and decreased tumor-promoted expression of VEGF receptor-2, Rac1, gp91phox, cyclin D1, cyclin dependent kinase 4 and p-Rb in human dermal microvascular endothelial cell. Furthermore, U251 and SNB19 xenograft tissue sections from nude mice treated with pCU showed reduced expression of VEGF and CD31, which is a blood vessel visualization marker. Overall, results revealed that knockdown of uPAR and cathepsin B inhibited tumor-induced angiogenesis by disrupting the JAK/STAT pathway-dependent expression of VEGF. These data provide new insight in characterizing the pathways involved in the angiogenic cascade and for the identification of novel target proteins for use in therapeutic intervention for gliomas.

In hospital complications and mortality of patients of inferior wall myocardial infarction with right ventricular infarction.

This is a cross-sectional study of patients with inferior wall Myocardial Infarction (MI), who attended emergency and got admitted in ICU/CCU of TU Teaching Hospital, Maharajgunj and Bir Hospital, Kathmandu, Nepal during November 1999 to October 2000. This study was undertaken to compare the in-hospital complications and mortality of patients of inferior wall myocardial infarction with or without associated right ventricular infarction. Total 53 consecutive patients with acute inferior wall myocardial infarction were enrolled in the study. Right ventricular infarction was determined by the presence of ST elevation of more than 0.1 mv in V4R. All the patients of inferior wall myocardial infarction were divided into two groups. Group A consisted of patients of inferior wall MI with right ventricular infarction and group B consisted of patients of inferior wall MI without right ventricular infarction. In-hospital complications and mortality of group A were compared with group B. Among 20 patients of group A and 33 patients of group B, incidence of cardiogenic shock was significantly higher in patients of group A compared to group B (p=0.05). Ten patients of group A developed third degree AV Block compared to only one in group B; the incidence of which was significantly higher (p<0.001). Sinus nodal dysfunction, manifested by junctional rhythm was found in six patients of group A compared to only two patients of group B (p<0.05). Mortality was found higher in patients of group A, but it was not statistically significant. Two patients of group A expired on first day whereas only one patient of group B expired on the eighth day of admission. In hospital complications especially cardiogenic shock, complete A-V block and junctional rhythm are significantly higher in inferior wall MI when associated with RV infarction.