Intervention for arch obstruction after the Norwood procedure: Prevalence,associated factors,and practice variability

Objective

Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.

Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system

BACKGROUND: Plasma uric acid has been associated with hypertension in a variety of disorders, and has been shown to be predictive of hypertension. The mechanistic role of uric acid in the development of hypertension is not known however. METHOD: We tested the hypothesis that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation and oxidative stress by stimulating the vascular renin-angiotensin system (RAS). Rat VSMC were exposed to 0-300 micromol uric acid for 48 h. RESULTS: Uric acid (200 and 300 micromol) stimulated the proliferation of VSMC as measured by thymidine uptake. This effect was prevented by 10(-6) mol losartan or by 10(-6) mol captopril. Incubation of VSMC with uric acid for 48 h also increased angiotensinogen messenger RNA expression and intracellular concentrations of angiotensin II. These responses were also inhibited by losartan and captopril. Increased expression of angiotensinogen mRNA was also inhibited by co-incubation with PD 98059, a mitogen-activated protein (MAP) kinase inhibitor. Uric acid stimulated the production of hydrogen peroxide and 8-isoprostane in VSMC. These increases in oxidative stress indicators were significantly reduced by co-incubating the cells with captopril or losartan. Uric acid also decreased nitrite and nitrate concentrations in the culture medium, an effect that was prevented by losartan and captopril. CONCLUSION: These results demonstrate that uric acid stimulates proliferation, angiotensin II production, and oxidative stress in VSMC through tissue RAS. This suggests that uric acid causes cardiovascular disorders by stimulating the vascular RAS, and this stimulation may be mediated by the MAP kinase pathway.     

Adenoviral gene transfer into dendritic cells efficiently amplifies the immune response to LMP2A antigen: a potential treatment strategy for Epstein-Barr virus--positive Hodgkin's lymphoma

The EBV-encoded LMP2A protein is consistently expressed in EBV(+) Hodgkin's lymphoma and can be targeted by CTLs. CTLs stimulated conventionally by LCLs have little activity against LMP2A(+) target cells. Here, we describe an alternative approach, based on the in vitro stimulation of CTLs with DCs genetically modified with 2 E1/E3-deleted recombinant adenoviruses, AdGFPLMP2A, encoding a fusion gene of GFP and LMP2A, and AdLMP2A, encoding LMP2A only. Transduction of DCs with AdGFPLMP2A at MOI 1,000 resulted in LMP2A expression in up to 88% of DCs. LMP2A protein was expressed in 40% of DCs transduced with AdLMP2A at an MOI of 100. Higher MOI resulted in DC death. CTL lines activated by transduced DCs had a higher frequency of LMP2A tetramer-specific CTLs than CTL lines activated by LCLs. CTLs stimulated with transduced DCs lysed both autologous fibroblasts infected with vaccinia virus LMP2A (FBvaccLMP2A) and autologous LCLs, which express LMP2A at lower levels. In contrast, CTLs generated from the same donors by stimulation with autologous LCLs showed minimal lysis of FBvaccLMP2A. Moreover, 1 donor who did not respond to LMP2A when CTLs were stimulated with LCLs became a responder when LMP2A was expressed by transduced DCs. Hence, recombinant adenoviruses encoding LMP2A effectively transduce DCs and direct the generation of LMP2A-specific CTLs. This approach will be a potent strategy in Hodgkin's lymphoma immunotherapy.     

Characterization of human coronary sinus valves by direct visualization during biventricular pacemaker implantation

BACKGROUND: The precise reasons for failure to cannulate the coronary sinus during biventricular device implantation are unknown. Visualization of the coronary sinus ostium during electrophysiology procedures may enhance understanding of how unusual anatomy can affect successful cannulation of the coronary sinus. OBJECTIVES: The aim of this study was to describe the morphology of valves at the coronary sinus ostium (CSO) visualized directly with an illuminated fiberoptic endoscope during implantation of biventricular devices. METHODS: The coronary sinus anatomy of one hundred consecutive patients undergoing implantation of biventricular devices was investigated using a fiberoptic endocardial visualization catheter (EVC). RESULTS: The CSO was clearly visualized in 98 patients using the EVC. A Thebesian valve was seen in 54% of these. Almost all Thebesian valves were positioned at the inferior (61%) or posterior (33%) aspect of the CSO. Only six patients had Thebesian valves that covered more than 70% of the CSO, but all were successfully implanted with a transvenous left ventricular pacing lead after cannulating the coronary sinus under direct visualization. CONCLUSIONS: Over half of patients undergoing biventricular device implantation have identifiable Thebesian valves. Even valves covering the majority of the ostial area may be traversed using direct visualization and modern catheterization techniques.