Since myocardial perfusion by MDCT is based on the myocardial signal density (SD), it is pivotal to determine the normal values of myocardial SD and to identify potential mechanisms of misinterpretation of perfusion defects. In routine MDCT acquisitions, we commonly visualize a considerable SD drop at the posterobasal wall resembling perfusion defects, being attributed to beam hardening artifacts. Consecutive asymptomatic patients without history of coronary artery disease (CAD) and low probability of CAD who were referred for MDCT evaluation at our institution due to inconclusive or discordant functional tests constituted the study population. Perfusion defects were defined as a myocardial segment having a SD two standard deviations below the average myocardial SD for the 16 left ventricular American Heart Association (AHA) segments. Thirty six asymptomatic patients constituted the study population. Myocardial SD was evaluated in 576 American Heart Association (AHA) segments and 36 posterobasal segments. The mean myocardial SD at the posterobasal segment was 53.5 +/- 35.1 HU, whereas the mean myocardial SD at the basal, mid and apical myocardium was 97.4 +/- 17.3, with significant differences (p < 0.001) between posterobasal and all AHA segments. Posterobasal "perfusion defects" were identified in 26 (72%) patients. The only variable associated to the presence of posterobasal SD deficit was the heart rate (61.8 +/- 6.2 bpm vs. 56.3 +/- 8.1 bpm, p = 0.04), whereas body mass index, blood SD of the left and right ventricles, contrast-to-noise ratio, and the extent of atherosclerosis were not related to the presence of "perfusion defects". In an asymptomatic population with no history of coronary artery disease, a myocardial signal density deficit mimicking a perfusion defect is a common finding in the posterobasal wall and is not related to body mass index or scan quality.
Progesterone, an agonist for the progesterone receptor (PR), can be an efficacious and well-tolerated treatment in endometrial cancer. The clinical use of progesterone is limited due to the lack of biomarkers that predict hormone sensitivity. Despite its efficacy in cancer therapy, mechanisms and site of action for progesterone remain unknown. Using an in vivo endometrial cancer mouse model driven by clinically relevant genetic changes but dichotomous responses to hormonal therapy, we demonstrate that signaling through stromal PR is necessary and sufficient for progesterone anti-tumor effects. Endometrial cancers resulting from epithelial loss of PTEN (PTENKO) were hormone sensitive and had abundant expression of stromal PR. Stromal deletion of PR as a single genetic change in these tumors induced progesterone resistance indicating that paracrine signaling through the stroma is essential for the progesterone therapeutic effects. A hormone refractory endometrial tumor with low levels of stromal PR developed when activation of KRAS was coupled with PTEN-loss (PTENKO/Kras). The innate progesterone resistance in PTENKO/Kras tumors stemmed from methylation of PR in the tumor microenvironment. Add-back of stromal PR expressed from a constitutively active promoter sensitized these tumors to progesterone therapy. Results demonstrate that signaling through stromal PR is sufficient for inducing hormone responsiveness. Our findings suggest that epigenetic de-repression of stromal PR could be a potential therapeutic target for sensitizing hormone refractory endometrial tumors to progesterone therapy. Based on these results, stromal expression of PR may emerge as a reliable biomarker in predicting response to hormonal therapy.
The aim of the study was to explore the differences in plaque burden at different segments of the left main bifurcation and its relationship with the bifurcation angle using high-resolution multislice CT coronary angiography (MSCT). Patients were evaluated using a 40-row MSCT scanner. One observer assessed the localization, severity and distribution of plaques within the left main (LMCA) bifurcation, whereas another observer defined the angle. Fifty patients were included. The mean heart rate was 59.8 +/- 7.1. Seventeen (34%) patients presented at least wall irregularities in the LMCA and in the ostial LCx, whereas the ostial LAD was affected in 32 (64%) patients. More than 90% of plaques were located opposite to the flow divider. The median bifurcation angle was 88.5 degrees (IQR 68.8 degrees, 101.4 degrees). Of the 18 patients with a normal ostial LAD, 13 (72%) had a bifurcation angle < 88.5 degrees , whereas the 63% of the patients with any LAD disease had an angle >or= 88.5 degrees (P = 0.018). In conclusion, at the left main bifurcation, atherosclerotic plaques are commonly located at the ostial LAD and opposite to the flow divider. The angle of the left main bifurcation and the presence of plaques within the bifurcation are closely related.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.