Megadose heparin and streptokinase produce similar TIMI 3 flow at discharge in patients of acute myocardial infarction presenting between 7-12 hours

The present study was undertaken to assess the impact of megadose heparin bolus on angiographic patency of infarct-related artery in patients of acute myocardial infarction presenting between 7-12 hours and to compare it with streptokinase. Forty-seven patients (27 males, mean age 58.1 +/- 9.6 years) of acute myocardial infarction between 7-12 hours of onset of chest pain were randomised to receive either megadose heparin bolus (300 IU/kg body weight, group 1, n = 24; or streptokinase 1.5 million units over one hour, group 2, n = 23). Parameters noted were: relief of pain at 90 minutes, 50 percent or more resolution of ST segment at 90 minutes, TIMI grade flow and left ventricular ejection fraction at discharge. Mean age (59.0 +/- 12.9 years in group 1; 57.2 +/- 8.1 years in group 2), mean time to drug (7.5 +/- 1.3 hours in group 1; 7.8 +/- 1.6 hours in group 2), site of anterior wall infarction (12 in group 1, 10 in group 2), relief of pain at 90 minutes (15 in group 1, 14 in group 2) and more than 50 percent resolution of ST segment elevation at 90 minutes (12 patients in each group) were similar. On coronary angiography performed in 42 patients (21 in each group) at a mean interval of 7.2 +/- 1.3 days after acute myocardial infarction, TIMI grade 3 flow was seen in 7 (33.3%) patients in each group and TIMI grade 2/3 flow was also similar in both the groups (p = NS). No major bleed occurred in either group. We conclude that heparin given as a megadose bolus produces similar TIMI 3 flow in infarct-related artery as compared to streptokinase in acute myocardial infarction patients presenting between 7-12 hours.     

Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease

Huntington's disease (HD), spinocerebellar ataxias types 1 and 3 (SCA1, SCA3), and spinobulbar muscular atrophy (SBMA) are caused by CAG/polyglutamine expansion mutations. A feature of these diseases is ubiquitinated intraneuronal inclusions derived from the mutant proteins, which colocalize with heat shock proteins (HSPs) in SCA1 and SBMA and proteasomal components in SCA1, SCA3, and SBMA. Previous studies suggested that HSPs might protect against inclusion formation, because overexpression of HDJ-2/HSDJ (a human HSP40 homologue) reduced ataxin-1 (SCA1) and androgen receptor (SBMA) aggregate formation in HeLa cells. We investigated these phenomena by transiently transfecting part of huntingtin exon 1 in COS-7, PC12, and SH-SY5Y cells. Inclusion formation was not seen with constructs expressing 23 glutamines but was repeat length and time dependent for mutant constructs with 43-74 repeats. HSP70, HSP40, the 20S proteasome and ubiquitin colocalized with inclusions. Treatment with heat shock and lactacystin, a proteasome inhibitor, increased the proportion of mutant huntingtin exon 1-expressing cells with inclusions. Thus, inclusion formation may be enhanced in polyglutamine diseases, if the pathological process results in proteasome inhibition or a heat-shock response. Overexpression of HDJ-2/HSDJ did not modify inclusion formation in PC12 and SH-SY5Y cells but increased inclusion formation in COS-7 cells. To our knowledge, this is the first report of an HSP increasing aggregation of an abnormally folded protein in mammalian cells and expands the current understanding of the roles of HDJ-2/HSDJ in protein folding.     

High sensitivity C-reactive protein in systemic lupus erythematosus: relation to disease activity, clinical presentation and implications for cardiovascular risk

Measurement of high sensitivity C-reactive protein (hs-CRP), has been used in the assessment of disease activity in numerous rheumatic conditions including systemic lupus erythematosus (SLE). However, the utility of hs-CRP measurement in patients with lupus is uncertain. This study examined if hs-CRP can be used to assess disease activity, severity and cardiovascular risk in SLE. Serum samples from 601 visits of 213 SLE patients and 134 controls were analysed for hs-CRP by nephelometry. Detailed demographic data were obtained from all subjects and medication history and key laboratory parameters were collected. Disease activity was assessed using the SLEDAI. High sensitivity CRP was not associated with disease activity (SLEDAI), number of ACR SLE criteria or presence of any particular organ involvement. hs-CRP levels were significantly correlated with standard cardiovascular risk factors including body weight (P = 0.0002), hypertension (P = 0.001), and apolipoprotein A-I (P < 0.0001). Interestingly an inverse correlation was seen between hs-CRP levels and antimalarial use (P = 0.0018). Our results suggest that measurement of hs-CRP, though not valuable as marker of disease activity in SLE may be of some use in the assessment of cardiovascular risk. We speculate that antimalarials may help to reduce cardiovascular risk in patients with SLE.     

Right ventricular blood cyst causing outflow tract obstruction in an adult

Blood cysts are benign intracardiac masses that are well described in infants. We present a rare adult presentation of a blood cyst tethered to the right ventricular wall and the tricuspid valve causing right ventricular outflow obstruction. Multimodality imaging approach was found to be of great importance in the diagnosis and treatment of this patient.