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Results 1-8 (8)

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author:(Liliane J dable)
1.  Vectorcardiography for Optimization of Stimulation Intervals in Cardiac Resynchronization Therapy 
Current optimization of atrioventricular (AV) and interventricular (VV) intervals in cardiac resynchronization therapy (CRT) is time consuming and subject to noise. We aimed to prove the principle that the best hemodynamic effect of CRT is achieved by cancelation of opposing electrical forces, detectable from the QRS morphology in the 3D vectorcardiogram (VCG). Different degrees of left (LV) and right ventricular (RV) pre-excitation were induced, using variation in AV intervals during LV pacing in 20 patients with left bundle branch block (LBBB) and variation in VV intervals during biventricular pacing in 18 patients with complete AV block or atrial fibrillation. The smallest QRS vector area identified stimulation intervals with minimal systolic stretch (median difference [IQR] 20 ms [−20, 20 ms] and maximal hemodynamic response (10 ms [−20, 40 ms]). Reliability of VCG measurements was superior to hemodynamic measurements. This study proves the principle that VCG analysis may allow easy and reliable optimization of stimulation intervals in CRT patients.
PMCID: PMC4382533  PMID: 25743446
Cardiac resynchronization therapy; Biventricular pacing; Vectorcardiography; Electrocardiography; Atrioventricular timing; Interventricular timing
2.  Changing the Concepts of Immune-Mediated Glomerular Diseases through Proteomics 
Standard classification of glomerular diseases is based on histopathologic abnormalities. The recent application of proteomic technologies has resulted in paradigm changes in the understanding and classification of idiopathic membranous nephropathy and membranoproliferative glomerulonephritis. Those examples provide evidence that proteomics will lead to advances in understanding of the molecular basis of other glomerular diseases, such as lupus nephritis. Proof of principle experiments show that proteomics can be applied to patient renal biopsy specimens. This viewpoint summarizes the advances in immune-mediated glomerular diseases that have relied on proteomics, and potential future applications are discussed.
PMCID: PMC4618780  PMID: 25907758
glomerulonephritis; autoimmunity; immune complex; antigen identification
3.  Comparison of the Rate of Renal Function Decline in Non-Proteinuric patients with and without Diabetes 
Patients with diabetes and chronic kidney disease (CKD) without proteinuria are often thought to have a cause of CKD other than diabetes. It was hypothesized that if this is true, the rate of renal function decline should be similar among non-proteinuric patients with and without diabetes.
Patients seen in the nephrology, endocrinology and general internal medicine clinics at the Medical University of South Carolina between 2008 and 2012 with hypertension and diabetes were identified by ICD9 diagnosis codes. Patients with less than 2 measures of serum creatinine, without urine studies over the study period and with proteinuria were excluded. 472 patients met the inclusion and exclusion criteria and had an initial eGFR between 35 and 80mL/min/1.73m2. The annual rate of decline in eGFR was estimated for each patient from the lowest eGFR in each year by fitting a regression model with random intercept and slope.
In unadjusted analyses the rate of eGFR decline was greater in patients with diabetes than without diabetes (−0.71 vs. −0.30mL/min/year, p=0.03). After adjusting for age, race, gender, baseline eGFR and use of renin-angiotensin aldosterone system blockade, the rate of decline was still greater among patients with diabetes than among those without diabetes (−0.68 vs. −0.36mL/min/year, p=0.03).
Patients with diabetes had more rapid decline in kidney function compared to individuals without diabetes, in spite of the absence of proteinuria. These results suggest that even in the absence of proteinuria, diabetes may be associated with CKD.
PMCID: PMC4667356  PMID: 26624901
diabetes; renal function decline; chronic kidney disease; proteinuria; hypertension
5.  Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma 
PLoS ONE  2015;10(9):e0138791.
Introduction and Aim
The role of B-lymphocytes in chemical-induced asthma is largely unknown. Recent work demonstrated that transferring B lymphocytes from toluene diisocyanate (TDI)-sensitized mice into naïve mice, B cell KO mice and SCID mice, triggered an asthma-like response in these mice after a subsequent TDI-challenge. We applied two-dimensional difference gel electrophoresis (2D-DIGE) to describe the “sensitized signature” of B lymphocytes comparing TDI-sensitized mice with control mice.
Sixteen proteins were identified that were significantly up- or down-regulated in B lymphocytes of sensitized mice. Particularly differences in the expression of cyclophilin A, cofilin 1 and zinc finger containing CCHC domain protein 11 could be correlated to the function of B lymphocytes as initiators of T lymphocyte independent asthma-like responses.
This study revealed important alterations in the proteome of sensitized B cells in a mouse model of chemical-induced asthma, which will have an important impact on the B cell function.
PMCID: PMC4580316  PMID: 26398101
6.  Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1low Monocytes 
Cell Reports  2015;12(11):1802-1815.
Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1low monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1low monocytes at the endothelial interface and a marked accumulation of CD68+ macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1low monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1low cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.
Graphical Abstract
•Hypertriglyceridemia promotes the extravasation of Gr1low monocytes•CD68+ tissue macrophages accumulate in the absence of overt inflammation•Hypertriglyceridemia is associated with increased CCL4 levels•CCL4 is involved in the migration of Gr1low monocytes
High levels of triglyceride-rich lipoproteins have been implicated in the pathogenesis of cardiovascular complications. Saja et al. demonstrate that hypertriglyceridemia promotes extravasation of Gr1low monocytes and accumulation of tissue macrophages. Hypertriglyceridemia was associated with increased levels of CCL4, which contributes to the migration of Gr1low monocytes.
PMCID: PMC4590546  PMID: 26344769
7.  Limitations of three-dimensional power Doppler angiography in preoperative evaluation of ovarian tumors 
This study describes the accuracy of three-dimensional power Doppler (3D-PD) angiography as secondary method for differential diagnosis of ovarian tumors.
Seventy-five women scheduled for surgical removal of adnexal masses were assessed by transvaginal ultrasound. Ovarian tumors were classified by IOTA simple rules and two three-dimensional blocks were recorded. In a second step analyses, a 4 cm3 spherical sample was obtained from the highest vascularized solid area of each stored block. Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) were calculated. The repeatability was assessed by concordance correlation coefficient (CCC) and limits of agreement (LoA), and diagnostic accuracy by area under ROC curve.
IOTA simple rules classified 26 cases as benign, nine as inconclusive and 40 as malignant. There were eight false positive and no false negative. Among the masses classified as inconclusive or malignant by IOTA simple rules, the CCCs were 0.91 for VI, 0.70 for FI, and 0.86 for VFI. The areas under ROC curve were 0.82 for VI, 0.67 for FI and 0.81 for VFI.
3D-PD angiography presented considerable intraobserver variability and low accuracy for identifying false positive results of IOTA simple rules.
PMCID: PMC4518533  PMID: 26219956
Ovarian neoplasms; Adnexal diseases; Ultrasonography; Doppler; Blood flow velocity
8.  Widespread presence of the pathogenic fungus Batrachochytrium dendrobatidis in wild amphibian communities in Madagascar 
Scientific Reports  2015;5:8633.
Amphibian chytridiomycosis, an emerging infectious disease caused by the fungus Batrachochytrium dendrobatidis (Bd), has been a significant driver of amphibian declines. While globally widespread, Bd had not yet been reported from within Madagascar. We document surveys conducted across the country between 2005 and 2014, showing Bd's first record in 2010. Subsequently, Bd was detected in multiple areas, with prevalence reaching up to 100%. Detection of Bd appears to be associated with mid to high elevation sites and to have a seasonal pattern, with greater detectability during the dry season. Lineage-based PCR was performed on a subset of samples. While some did not amplify with any lineage probe, when a positive signal was observed, samples were most similar to the Global Panzootic Lineage (BdGPL). These results may suggest that Bd arrived recently, but do not exclude the existence of a previously undetected endemic Bd genotype. Representatives of all native anuran families have tested Bd-positive, and exposure trials confirm infection by Bd is possible. Bd's presence could pose significant threats to Madagascar's unique “megadiverse” amphibians.
PMCID: PMC4341422  PMID: 25719857

Results 1-8 (8)