The Endurant Stent Graft System: 15-month follow-up report in patients with challenging abdominal aortic anatomies

Objective  

The objective of this study is to report a 15-month follow-up with the Endurant Stent Graft System in patients with challenging aortic anatomies.     

Regulatory cells, cytokine pattern and clinical risk factors for asthma in infants and young children with recurrent wheeze

Background Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms. Objectives This study was designed to assess and compare the immunological status during the first 2 years in steroid‐naïve young children with three episodes of physician‐confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age‐matched healthy controls (n=30). Methods Peripheral blood CD4⁺CD25⁺ and CD4⁺CD25^high T cells and their cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN‐γ, TGF‐β and IL‐10), CTLA‐4 and Foxp3 mRNA expression were evaluated (real‐time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12‐myristate 13‐acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day). Results Flow cytometry results showed a significant reduction in the absolute number of CD4⁺CD25^high and the absolute and percentage numbers of CD4⁺CD25⁺CTLA‐4⁺ in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4⁺CD25⁺ (P=0.01) and CD4⁺CD25^high (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA‐4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA‐4 (P=0.03) and IFN‐γ (P=0.04) expression was diminished in wheezy children compared with healthy children. High‐risk children had lower expression of IFN‐γ (P=0.03) compared with low‐risk and healthy children and lower expression of CTLA‐4 (P=0.01) compared with healthy children. Conclusions Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life.     

Limitations of dual x-ray absorptiometry in children with chronic kidney disease

Dual x-ray absorptiometry (DXA) is the most widely used densitometric method for diagnosing osteoporosis in adults. It has also been widely adopted as a diagnostic tool in the pediatric population. The most significant limitation of DXA is its reliance on areal rather than volumetric bone mineral density (BMD), which results in an artificial underestimation of bone density in short people. Poor longitudinal growth, however, is an eminent problem in children with chronic kidney disease (CKD). There is also no evidence in children that areal BMD is predictive of future fracture risk, which is the traditional rationale for measuring BMD in children with CKD. Therefore, the Kidney Disease Outcomes Quality Initiative guidelines and the current position of the International Society for Clinical Densitometry (ISCD) on pediatric patients, both of which are presented in this issue of Pediatric Nephrology, do not recommend the use of DXA in children with CKD. To date, there is no consensus on the best method to assess the degree of renal osteodystrophy in this patient population, and further collaborative efforts to correlate densitometric findings with clinical outcomes are warranted.     

Left Ventricular Diastolic Function and Exercise Capacity in Patients with Chagas Cardiomyopathy

Parameters of diastolic function have been shown to correlate with exercise capacity (EC) in individuals with impaired left ventricular (LV) systolic function. However, the role of LV diastolic function in predicting EC in Chagas cardiomyopathy has not been reported. Objectives: This study aimed to determine the relationship between LV diastolic parameters assessed by echocardiography and EC in patients with Chagas cardiomyopathy. Methods: We studied 40 patients (23 men; 49 ± 8 years), with diagnosis of Chagas disease and dilated cardiomyopathy. Medical therapy was individually adjusted according to standardized guidelines. Methods of acquiring two‐dimensional Doppler, tissue Doppler imaging (TDI), and their measurements were described. Exercise testing was performed by a Bruce protocol. Brain natriuretic peptide (BNP) levels were also determined. Results: Most patients (63%) were in NYHA functional class I. Mean peak oxygen consumption estimated (peakVO₂) was 31.7 ± 10.2 mL/kg per minute, and mean left ventricular ejection fraction (LVEF) was 36.3 ± 7.8%. Univariate analysis showed that various echocardiographic parameters of diastolic function were correlated with peakVO₂. There was no correlation between BNP levels or LVEF and EC. Multivariate analysis, after adjustment for age and gender, revealed that E/E′ ratio and left atrial volume (LAV), emerged as independent predictors of EC, as demonstrated in the model: peakVO₂= 60.825 + (0.439 × LAV) ? (1.620 × E/E′ ratio) ? (0.483 × age) ? (4.821 × female gender). The R² of this model was 0.52. Conclusions: Functional capacity assessed by peakVO₂ was related to increase LV filling pressures, independently on systolic function in patients with Chagas cardiomyopathy. (Echocardiography 2010;27:519‐524)     

Rippling muscle disease: Variable phenotype in a family with five afflicted members

We report a family with rippling muscle disease (RMD) who had an autosomal dominant mode of inheritance. The father, mother, and one daughter proved to be heterozygous, and two sons were homozygous for the A92T mutation of the caveolin‐3 gene. The cardinal features of RMD, particularly percussion‐induced rapid contractions, muscle mounding, and muscle rippling, varied considerably among these subjects. Moreover, all examined individuals showed muscle weakness; however, the patterns were inconsistent. Muscle Nerve, 2010     

Comparative study of NMP‐preloaded and dip‐loaded membranes for guided bone regeneration of rabbit cranial defects

Guided bone regeneration (GBR) has been utilized for several decades for the healing of cranio‐maxillofacial bone defects and, particularly in the dental field, by creating space with a barrier membrane to exclude soft tissue and encourage bone growth in the membrane‐protected volume. Although the first membranes were non‐resorbable, a new generation of GBR membranes aims to biodegrade and provide bioactivity for better overall results. The Inion GTR? poly(lactide‐co‐glycolide) (PLGA) membrane is not only resorbable but also bioactive, since it includes N‐methylpyrrolidone (NMP), which has been shown to promote bone regeneration. In this study, the effects of loading different amounts of NMP onto the membrane through chemical vapour deposition or dipping have been explored. In vitro release demonstrated that lower levels of NMP led to lower NMP concentrations and slower release, based on total NMP loaded in the membrane. The dipped membrane released almost all of the NMP within 15 min, leading to a high NMP concentration. For the in vivo studies in rabbits, 6 mm calvarial defects were created and left untreated or covered with an ePTFE membrane or PLGA membranes dipped in, or preloaded with, NMP. Evaluation of the bony regeneration revealed that the barrier membranes improved bony healing and that a decrease in NMP content improved the performance. Overall, we have demonstrated the potential of these PLGA membranes with a more favourable NMP release profile and the significance of exploring the effect of NMP on these PLGA membranes with regard to bone ingrowth. Copyright © 2014 John Wiley & Sons, Ltd.     

The impact of citrate concentration on adhesion of platelets and leukocytes to adsorbents in whole blood lipoprotein apheresis

Lipoprotein apheresis is applied to deplete low density lipoprotein and other apolipoprotein B containing lipoproteins in patients with severe familial hypercholesterolemia, hypertriglyceridemia associated pancreatitis, or lipoprotein (a)‐hyperlipoproteinemia. Anticoagulation of the extracorporeal circuit may influence cellular activation, as evidenced by a reduction of inflammatory parameters during regional citrate anticoagulation with acid citrate dextrose A (ACD‐A) commonly used in whole blood lipid apheresis. While the citrate concentration in the extracorporeal circuit has to ensure efficient anticoagulation, citrate infusion into the patient should be limited to avoid citrate overload. We assessed the influence of citrate concentration on cellular activation during in vitro circulation of whole blood containing 2.8 mM citrate (ACD‐A 1:40), 5.6 mM citrate (ACD‐A 1:20), or 13 mM citrate over polyacrylate‐based adsorbents for lipoprotein apheresis. We found increased platelet adhesion for anticoagulation with 2.8 mM citrate as compared to 5.6 or 13 mM citrate, as shown by cell counting and confirmed by scanning electron microscopy of adsorbent beads as well as by elevated levels of platelet activation markers and of platelet‐derived microvesicles. Leukocytes showed an equivalent adhesion pattern, while red blood cells remained unaffected at all citrate concentrations. Passage of blood over two consecutive columns resulted in enhanced platelet adhesion to the second column, presumably due to upstream preactivation. In conclusion, citrate influences activation and adhesion of platelets and leukocytes in a concentration‐dependent manner, and ACD‐A 1:20, equivalent to a citrate concentration of 5.6 mM in whole blood, ensures minimal cellular activation during passage of whole blood over polyacrylate‐based adsorbents.     

Cloning and characterization of DNA polymerase η from Trypanosoma cruzi: Roles for translesion bypass of oxidative damage

We report the cloning and characterization of the DNA polymerase η gene from Trypanosoma cruzi (TcPolη), the causative agent of Chagas disease. This protein, which can bypass cyclobutane pyrimidine dimers, contains motifs that are conserved between Y family polymerases. In vitro assays showed that the recombinant protein is capable of synthesizing DNA in undamaged primer‐templates. Intriguingly, T. cruzi overexpressing TcPolη does not increase its resistance to UV‐light (with or without caffeine) or cisplatin, despite the ability of the protein to enhance UV resistance in a RAD30 mutant of Saccharomyces cerevisiae. Parasites overexpressing TcPolη are also unable to restore growth after treatment with zeocin or gamma irradiation. T. cruzi overexpressing TcPolη are more resistant to treatment with hydrogen peroxide (H₂O₂) compared to nontransfected cells. The observed H₂O₂ resistance could be associated with its ability to bypass 8‐oxoguanine lesions in vitro. The results presented here suggest that TcPolη is able to bypass UV and oxidative lesions. However the overexpression of the gene only interferes in response to oxidative lesions, possibly due to the presence of these lesions during the S phase. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.