Accuracy and reproducibility of quantitation of left ventricular function by real-time three-dimensional echocardiography versus cardiac magnetic resonance

The aim of this study was to investigate the accuracy and reproducibility of the quantification of left ventricular (LV) function by real-time 3-dimensional echocardiography (RT3DE) using current state-of-the-art hardware and software. Compared with cardiac magnetic resonance (CMR), previous generations of hardware and software for RT3DE significantly underestimated LV volumes partly because of inherent factors such as limited spatial and temporal resolution. Also, RT3DE volumes were compared with short-axis CMR data, whereas a combined short-axis and long-axis analysis is known to be superior. Twenty-four subjects (mean age 51 +/- 12 years, 17 men) in sinus rhythm and with good to excellent 2-dimensional image quality underwent RUDE and CMR within 1 day. The acquisition of RUDE data was done with current state-of-the-art hardware and software. Two blinded experts performed off-line LV volume analysis. Global LV volumes were determined from semiautomated border detection on the basis of endocardial speckle tracking with biplane projections using QLAB version 6.0. Volumes derived by magnetic resonance imaging were quantified from combined short-axis and long-axis series. The volume-rate on RT3DE was 33 +/- 8 Hz (range 19 to 42). Excellent correlations were found (R-2 >= 0.97) between CMR and RT3DE for global LV end-diastolic volume, LV end-systolic volume, the LV ejection fraction, and LV phase volumes (24 phases/cardiac cycle). Bland-Altman analyses showed mean differences of -7.1 ml, -4.2 ml, 0.2%, and -5.8 ml and 95% limits of agreement of +/- 19.7 ml, +/- 8.3 ml, +/- 6.2%, and +/- 15.4 ml for global LV end-diastolic volume, LV end-systolic volume, the LV ejection fraction, and LV phase volumes, respectively. Interobserver variability was 5.2% for global LV end-diastolic volume, 6.4% for LV end-systolic volume, and 7.6% for the LV ejection fraction. In conclusion, in patients with good acoustic windows, RUDE using state-of-the-art technology provides accurate and reproducible measurements of global LV volumes, LV volume changes over time, and the LV ejection fraction. (C) 2008 Elsevier Inc. All rights reserved

Leishmania proteophosphoglycans regurgitated from infected sand flies accelerate dermal wound repair and exacerbate leishmaniasis via insulin-like growth factor 1-dependent signalling

Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine sand flies as they bloodfeed by lacerating the upper capillaries of the dermis with their barbed mouthparts. In the sand fly midgut secreted proteophosphoglycans from Leishmania form a biological plug known as the promastigote secretory gel (PSG), which blocks the gut and facilitates the regurgitation of infective parasites. The interaction between the wound created by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly egested dose of PSG into BALB/c mouse skin that lead to the differential expression of 7,907 transcripts. These transcripts were transiently up-regulated during the first 6 hours post-wound and enriched for pathways involved in inflammation, cell proliferation, fibrosis, epithelial cell differentiation and wound remodelling. We found that PSG significantly accelerated wound healing in vitro and in mice; which was associated with an early up-regulation of transcripts involved in inflammation (IL-1β, IL-6, IL-10, TNFα) and inflammatory cell recruitment (CCL2, CCL3, CCL4, CXCL2), followed 6 days later by enhanced expression of transcripts associated with epithelial cell proliferation, fibroplasia and fibrosis (FGFR2, EGF, EGFR, IGF1). Dermal expression of IGF1 was enhanced following an infected sand fly bite and was acutely responsive to the deposition of PSG but not the inoculation of parasites or sand fly saliva. Antibody blockade of IGF1 ablated the gel's ability to promote wound closure in mouse ears and significantly reduced the virulence of Leishmania mexicana infection delivered by an individual sand fly bite. Dermal macrophages recruited to air-pouches on the backs of mice revealed that IGF1 was pivotal to the PSG's ability to promote macrophage alternative activation and Leishmania infection. Our data demonstrate that through the regurgitation of PSG Leishmania exploit the wound healing response of the host to the vector bite by promoting the action of IGF1 to drive the alternative activation of macrophages