AimWe assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care.Methods and resultsWe conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (−0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups.ConclusionIn NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness.
Two RNA . protein complexes were isolated from duck erythroblast postribosomal supernatants. Their nominal sedimentation values on sucrose gradients are 12 S and 20 s, respectively. The 12-S particle contains a 4-6 S RNA, in the 20-S particle a 9-S RNA is found. This 9-S RNA is shown to direct the synthesis of all duck globin chains in a cell-free, messenger RNA-dependent protein-synthesizing system.The protein moiety of these ribosome-free particles is described and compared with the proteins found in the mRNA * protein complex liberated by EDTA from polyribosomes. We show that in the free-cytoplasmic particles no protein can be found which is identical to any of the polypeptides associated with polyribosomal mRNA. Some of these proteins are phosphorylated and contain phosphoserine. The electrophoretic patterns of phosphorylated proteins from the two globin mRNA-containing complexes differ, as do those of the unlabelled polypeptides. We conclude that the mRNA-associated protein population is exchanged when the mRNA enters the translation machinery.The possible role of the RNA-associated proteins in the post-transcriptional and translational control of eukaryotic protein synthesis is discussed.On the basis of experiments concerning the nucleic acid metabolism in duck immature red cells and in HeLa cells we postulated [I] that the regulation of gene expression in animal cells resides in a multistep process including the three principal phases of cellular information transfer : (a) the synthesis in the nucleus of giant precursor molecules (pre-mRNA) to messenger RNA (mRNA), (b) the processing of the pre-mRNA which gives rise ultimately to mRNA that is transported (and stored) in the cytoplasm, (c) the translation of the mRNA into protein. This regulational system governing the multiple steps involved in synthesis, processing and translation of mRNA was termed "Cascade Regulation" [l -31. Evidence that the giant nuclear RNA of molecular weight more than 5~1 0~is an informative precursor to mRNA was given recently by Imaizumi et al. [5] who showed conclusively by molecular hybridization that these RNA molecules, isolated from duck erythroblasts, contain sequences homologous to polyribosomal 9-S duck globin mRNA. However, the processing of pre-mRNA and the transfer of mRNA to the cytoplam are still obscure.Abbreviations. pre-mRNA, precursor molecule to mRNA; mRNA * protein, messenger ribonucleoprotein complex. strate that newly synthesized mRNA appears in the cytoplasm first free from ribosomes but associated with proteins in the form of ribonucleoprotein complexes. Some mRNA types then associate with ribosomes; others may be degraded without being translated.
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