Chylothorax as a complication of coronary artery bypass grafting operation

The authors present the case of a 72-year-old woman who underwent coronary bypass grafting. Left sided chylothorax due to accidental dissection of a thoracic duct branch developed 2 months after sternotomy. As conservative therapy has failed, surgical pleurodesis was performed successfully. Chylothorax is a rare and underestimated complication of coronary bypass grafting. The worldwide increasing number of coronary artery bypass grafting surgeries makes it important to pay attention to this condition. Thus diagnosis of the chyle is relatively easy by its high chylomicron and triglyceride content, but identification of the etiology and its treatment is sometimes challenging for the physician. The treatment of chylothorax is usually conservative. The main goal is to keep the volume of the chyle under control. The number of surgical interventions because of chylothorax is increasing due to an increase of iatrogenic etiology.     

Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model

A simple and efficient synthetic method for the preparation of quinazoline type phosphodiesterase 7 (PDE7) inhibitors, based on microwave irradiation, has been developed. The use of this methodology improved yields and reaction times, providing a scalable procedure. These compounds are pharmacologically interesting because of their in?vivo efficacy both in spinal cord injury and Parkinson's disease models, as shown in previous studies from our group. Herein we describe for the first time that administration of one of the PDE7 inhibitors here optimized, 3-phenyl-2,4-dithioxo-1,2,3,4-tetrahydroquinazoline (compound 5), ameliorated brain damage and improved behavioral outcome in a permanent middle cerebral artery occlusion (pMCAO) stroke model. Furthermore, we demonstrate that these PDE7 inhibitors are potent anti-inflammatory as well as neuroprotective agents in primary cultures of neural cells. These results led us to propose PDE7 inhibitors as a new class of therapeutic agents for neuroprotection.     

Selenium supplementation in the critically ill

Selenium (Se) is an essential trace element with antioxidant, immunological, and anti-inflammatory properties, which are attributed to its presence in selenoproteins, as the 21st amino acid selenocysteine. These selenoenzymes are involved in redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses. Dietary intakes differ considerably between geographical regions, due to variability of the Se food content, leading to differences in dietary reference intakes and toxicity cautions. Critical illness with systemic inflammatory response syndrome (SIRS) is characterized by Se depletion with high morbidity and mortality. Se status correlates well with clinical outcome in SIRS and may be useful as an early predictor of survival. Several investigators have evaluated the benefits of Se supplementation for the critically ill, either as monotherapy or in an antioxidant micronutrient combination. Pharmaconutrition, with high-dose Se (from 500-1600 μg/d) involving an initial loading bolus, followed by continuous infusion, appears to be safe and efficacious, with evidence that it can improve clinical outcome by reducing illness severity, infectious complications, and decreasing mortality in the intensive care unit (ICU). We now have a clearer understanding of the pharmacokinetics of the initial and transient pro-oxidant effect of an intravenous bolus of selenite and the antioxidant effect of continuous infusion. Better biomarkers to ascertain optimum Se requirements for individual patients are now needed, and clinical practice guidelines need improvement. Nevertheless, sufficient evidence is available to consider initiating high-dose intravenous Se therapy routinely in critically ill SIRS patients, immediately on admission to the ICU.     

Accuracy of anthropometric measurements in estimating fat mass in individuals with 21-hydroxylase deficiency

ObjectiveThe use of anthropometric measurements to estimate the percentage of body fat (%BF) is easy and inexpensive. However, the accuracy of these methods in patients with 21-hydroxylase deficiency (21OHD) has not been explored. The objective of this study was to evaluate the accuracy of skinfold-based models, body mass index (BMI), and waist circumference (WC) in estimations of %BF using dual-energy X-ray absorptiometry (DXA) as the reference method in individuals with 21OHD.MethodsFifty-four 21OHD patients (32 women and 22 men), aged 7 to 20 y, were recruited for the study. DXA was used to determine %BF; four predictive skinfold equations, BMI, and WC were assessed for accuracy in determining %BF.ResultsAll predictive skinfold equations were highly associated (R, range: 0.82-0.89) with DXA %BF values. In women, BMI and WC showed moderate correlations (R = 0.69 for both BMI and WC) with DXA values. In contrast, among men there was a low explanatory power for BMI (13%) and WC (4%) and high errors (BMI, 6.9%; WC, 7.4%). All predictive equations significantly underestimated %BF (range of differences, ?4.1 to ?8.9) compared with DXA (women, 31.3 ± 6.1; men, 24.4 ± 7.3), and large limits of agreement were observed (range, ?15.3 to 1.7 and ?15.5 to 4.2 for women and men, respectively).ConclusionIn children and adolescents with 21OHD, %BF as estimated by skinfold measurements was associated more strongly with DXA-assessed %BF than both BMI and WC. However, still, the skinfold-based assessment underestimated DXA %BF and showed moderate agreement.     

Dynamic arterial elastance as a predictor of arterial pressure response to fluid administration: a validation study

Introduction

Functional assessment of arterial load by dynamic arterial elastance (Ea_dyn), defined as the ratio between pulse pressure variation (PPV) and stroke volume variation (SVV), has recently been shown to predict the arterial pressure response to volume expansion (VE) in hypotensive, preload-dependent patients. However, because both SVV and PPV were obtained from pulse pressure analysis, a mathematical coupling factor could not be excluded. We therefore designed this study to confirm whether Ea_dyn, obtained from two independent signals, allows the prediction of arterial pressure response to VE in fluid-responsive patients.

Methods

We analyzed the response of arterial pressure to an intravenous infusion of 500 ml of normal saline in 53 mechanically ventilated patients with acute circulatory failure and preserved preload dependence. Ea_dyn was calculated as the simultaneous ratio between PPV (obtained from an arterial line) and SVV (obtained by esophageal Doppler imaging). A total of 80 fluid challenges were performed (median, 1.5 per patient; interquartile range, 1 to 2). Patients were classified according to the increase in mean arterial pressure (MAP) after fluid administration in pressure responders (≥10%) and non-responders.

Results

Thirty-three fluid challenges (41.2%) significantly increased MAP. At baseline, Ea_dyn was higher in pressure responders (1.04 ± 0.28 versus 0.60 ± 0.14; P <0.0001). Preinfusion Ea_dyn was related to changes in MAP after fluid administration (R² = 0.60; P <0.0001). At baseline, Ea_dyn predicted the arterial pressure increase to volume expansion (area under the receiver operating characteristic curve, 0.94; 95% confidence interval (CI): 0.86 to 0.98; P <0.0001). A preinfusion Ea_dyn value ≥0.73 (gray zone: 0.72 to 0.88) discriminated pressure responder patients with a sensitivity of 90.9% (95% CI: 75.6 to 98.1%) and a specificity of 91.5% (95% CI: 79.6 to 97.6%).

Conclusions

Functional assessment of arterial load by Ea_dyn, obtained from two independent signals, enabled the prediction of arterial pressure response to fluid administration in mechanically ventilated, preload-dependent patients with acute circulatory failure.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0626-6) contains supplementary material, which is available to authorized users.     

Surface characterization and in vivo evaluation of laser sintered and machined implants followed by resorbable-blasting media process: A study in sheep

Background

This study aimed to compare the histomorphometric and histological bone response to laser-sintered implants followed by resorbable-blasting media (RBM) process relative to standard machined/RBM surface treated implants.

Material and Methods

Six male sheep (n=6) received 2 Ti-6Al-4V implants (1 per surface) in each side of the mandible for 6 weeks in vivo. The histomorphometric parameters bone-implant contact (BIC) and bone area fraction occupancy (BAFO) were evaluated.

Results

Optical interferometry revealed higher Sa and Sq values for the laser-sintered/RBM surface in relation to standard/RBM implants. No significant differences in BIC were observed between the two groups (p>0.2), but significantly higher BAFO was observed for standard/RBM implants (p<0.01).

Conclusions

The present study demonstrated that both surfaces were biocompatible and osseoconductive, and the combination of laser sintering and RBM has no advantage over the standard machined implants with subsequent RBM. Key words:Dental implants, osseointegration, resorbable- blasting media, sheep, in vivo.     

A novel glucokinase activator modulates pancreatic islet and hepatocyte function

The glucose-sensing enzyme glucokinase (GK) plays a key role in glucose metabolism. We report here the effects of a novel glucokinase activator, LY2121260. The activator enhanced GK activity via binding to the allosteric site located in the hinge region of the enzyme. LY2121260 stimulated insulin secretion in a glucose-dependent manner in pancreatic beta-cells and increased glucose use in rat hepatocytes. In addition, incubation of beta-cells with the GK activator resulted in increased GK protein levels, suggesting that enhanced insulin secretion on chronic treatment with a GK activator may be due to not only changed enzyme kinetics but also elevated enzyme levels. Animals treated with LY2121260 showed an improved glucose tolerance after oral glucose challenge. These results support the concept that GK activators represent a new class of compounds that increase both insulin secretion and hepatic glucose use and in doing so may prove to be effective agents for the control of blood glucose levels in patients with type 2 diabetes.     

The Tie receptor tyrosine kinase is expressed by human hematopoietic progenitor cells and by a subset of megakaryocytic cells

Growth factor receptors in human hematopoietic progenitor cells have become the focus of intense interest, because they may provide tools for the monitoring, enrichment, and expansion of stem cells. We have shown earlier that the Tie receptor tyrosine kinase is expressed in erythroid and megakaryoblastic human leukemia cell lines, in the blood islands of the yolk sac, and in endothelial cells starting from day 8.0 of mouse development. Here, the expression of Tie was studied in human hematopoietic cells of various sources. Peripheral blood mononuclear cells were Tie-. However, a large fraction of CD34+ cells from umbilical cord blood (UCB) and bone marrow (BM) expressed tie protein and mRNA. On average, 64% of the fluorescence-activated cell sorting- gated UCB CD34+ cells including CD38- cells and a fraction of cells expressing low levels of c-Kit were Tie+. Also, 30% to 60% of BM CD34+ cells were Tie+, including most of the BM CD34+CD38-, CD34+Thy-1+, and CD34+HLA-DR- cells. Under culture conditions allowing myeloid, erythroid, and/or megakaryocytic differentiation, purified UCB CD34+ cells lost Tie mRNA and protein expression concomitantly with that of CD34; however, a significant fraction of cells expressed Tie during megakaryocytic differentiation. These data suggest that, in humans, the Tie receptor and presumably its ligand may function at an early stage of hematopoietic cell differentiation.