The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial.

AIMS: No antithrombotic therapy has been shown to reduce mortality when used with thrombolytics in acute myocardial infarction (AMI). In the OASIS-6 trial, fondaparinux significantly reduced mortality and reinfarction without increasing bleeding in 12 092 patients with acute ST elevation MI. METHODS AND RESULTS: We report the results of a subgroup analysis in the 5436 patients (45%) receiving thrombolytics. According to local practice, 4415 patients did not have an indication for unfractionated heparin (stratum 1) and 1021 did (stratum 2). Fondaparinux reduced the primary study outcome of death or MI at 30 days [Hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.68-0.92] with consistent reductions in both mortality (HR and CI) and reinfarction (HR and CI). There was a non-significantly lower rate of stroke (HR 0.77, CI 0.48-1.25). The risk of severe bleeding was significantly reduced (HR 0.62, CI 0.40-0.94), and thus the balance of benefit and risk (death, MI and severe haemorrhage) was clearly reduced by fondaparinux (HR 0.77, 95% CI 0.67-0.90). Results were consistent in the two strata, by the different types of thrombolytics and across various time intervals from symptom onset to treatment. CONCLUSION: In STEMI patients treated with thrombolytic agents (predominantly streptokinase), fondaparinux significantly reduced the risk of death, re-MI and severe bleeds.     

Should angiotensin-converting enzyme-inhibitors be used to improve outcome in patients with coronary artery disease and 'preserved' left ventricular function?

Early clinical studies investigating the role of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure unexpectedly demonstrated a possible reduction in coronary heart disease endpoints. Two large scale clinical trials, HOPE and EUROPA, both studies in patients with coronary artery disease (CAD) but without clinical evidence of heart failure, showed a highly significant improvement in coronary heart disease outcomes on treatment with ramipril and perindopril, respectively, in contrast, in a similar population, PEACE was unable to demonstrate such benefit with trandolapril. Meta-analyses of all trials involving ACE-inhibitors showed a highly significant improvement in coronary heart disease endpoints. Current ESC guidelines recommend ACE-inhibitor therapy in CAD patients with co-existing indications for ACE-inhibitors, such as hypertension, heart failure, left ventricular dysfunction, prior MI was left ventricular dysfunction, or diabetes (class I, level of evidence A). These guidelines also recommend ACE-inhibitor therapy in all patients with angina and proven coronary disease (class IIa, level of evidence B). However, in angina patients without independent indication for ACE-inhibitor treatment, the anticipated benefit should be weighted against the costs and risks of side effects; in these patients, only agents and doses of proven efficacy for secondary prevention should be employed.     

PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide

Plasmatic levels of PDGF-AB, TGFbeta1, and bFGF are increased in patients with essential thrombocythemia (ET) while intraplatelet levels are low for PDGF, normal for TGFbeta, and elevated for bFGF. To evaluate the contribution of gene expression to the dysregulated cytokine levels, we studied platelet PDGF-A, PDGF-B, TGFbeta1, and bFGF mRNA in ET patients before and during anagrelide treatment. We found decreased PDGF-A and PDGF-B, increased TGFbeta1, and normal bFGF mRNA levels. During treatment, mRNA levels remained decreased for PDGF-A, were increased for PDGF-B and normal for TGFbeta1. In untreated patients, protein expression of PDGF paralleled its mRNA levels while different patterns of RNA and protein were found for TGFbeta1 and bFGF.     

Effect of color of the cement and the composite resin foundation on the resultant color of resin-matrix ceramics

Statement of problemAn improper restoration color match to the adjacent natural teeth can jeopardize esthetic success. The type of resin-matrix ceramic (RMC), the shade of the underlying foundation, and the shade of cement may affect the optical behavior of RMC materials, but studies on this issue are lacking.PurposeThe purpose of this in vitro study was to assess the cumulative effect of different shades of composite resin foundation (CRF) and cement on the optical behaviors of 3 different RMCs.Material and methodsForty-five rectangular RMC specimens (14×12×1 mm, shade A2) were prepared from 3 different blocks, including a polymer-infiltrated ceramic network (Vita Enamic [VE]), a resin nanoceramic (Lava Ultimate [LU]), and a flexible nanoparticle-filled resin (GC Cerasmart [GC]) (n=15 per RMC block). CRFs (14×12×4 mm) were fabricated in white and dentin shades (n=1 per composite resin shade). Cement specimens (G-CEM LinkForce) were prepared from 3 shades (A2, opaque [OP], and translucent [TR]) (n=15 per shade). For control groups, 3 rectangular RMC foundations (14×12×4 mm) were also milled from RMC blocks (n=1 per block). Color coordinates were recorded by using a digital spectrophotometer. The coordinates of 4-mm-thick RMC foundations served as the control groups. The coordinates of RMC specimens on each combination of CRF and cement served as test groups. The CIEDE2000 (ΔE₀₀) formula was used to assess color differences. Data were subjected to 3-way ANOVA and Tukey honestly significant difference (HSD) tests (α=.05).ResultsΔE₀₀ values of specimens were influenced by the CRF shade, cement shade, RMC type, as well as the interaction terms of the 3 variables (P<.001). Color differences in groups VE-A2-dentin, VE-OP-dentin, LU-OP-dentin, and GC-OP-dentin showed perceptible but clinically acceptable values (0.8<ΔE₀₀≤1.8). The highest and lowest ΔE₀₀ values were observed in the white-OP-LU (5.32 ±0.34) and dentin-OP-VE (0.94 ±0.31) groups.ConclusionsOpaque cement on the white foundation led to the highest ΔE₀₀ values in the resultant colors of all RMC groups. When used with the same shade on the dentin foundation, this cement produced clinically acceptable results.     

The mechanism of vagotomy-induced acute gastric mucosal injury in the rat

The present study investigated the integrity of the rat gastric mucosa after 6 hours of vagotomy without drainage. Transection vagotomy was employed to ensure complete gastric vagal denervation. Vagotomy without drainage produced gastric distension and mucosal injury confined to the glandular part. Anterior truncal vagotomy produced injury in 70% of rats, whereas truncal or transection vagotomy produced injury in all rats. The injury score with transection vagotomy was significantly higher than that with anterior truncal (21.2 mm2 +/- 1.6 vs. 8 mm2 +/- 2.7, mean +/- SEM, n = 10, p less than .01) or truncal vagotomy (21.2 mm2 +/- 1.6 vs. 15.6 mm2 +/- 1.4, mean +/- SEM, n = 10, p less than .05). Histologic examination of the mucosal injury revealed necrosis involving the epithelium and lamina propria. Cholestyramine, pyloroplasty, or gastric diversion protected the stomach against the vagotomy-induced mucosal injury. The results demonstrate in the rat that vagotomy without drainage produces within 6 hours injury of the gastric mucosa, which increases as vagal denervation is rendered more complete. Because cholestyramine protects the rat stomach against vagotomy-induced acute gastric mucosal injury, reflux of duodenal contents appears to be the principal factor behind this injury. Pyloroplasty prevents gastric distension but probably not duodenal contents refluxing, suggesting that this distention also may have a role in the mechanism of the said injury.     

Association of NT-ProBNP,Blood Pressure,and Cardiovascular Events: The ARIC Study

BackgroundAlthough intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.ObjectivesThis study examined whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.MethodsParticipants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.ResultsThere were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.ConclusionsElevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.