Ablation of Atrial-Ventricular Junction Tissues via the Coronary Sinus Using Cryo Balloon Technology

Introduction: The coronary sinus (CS) can provide access to targets across and within the atrioventricular (AV) junction.Methods: In 12 dogs (32 ± 3 Kg), cryo balloons (10–19 mm) were applied to regions of the AV junction for 3 minutes at a temperature of –75.9 ± 9C (ranging –57 to –83). Electrical activity and pacing within the CS were assessed pre and post ablation and at least 3 months later in 9 dogs. In the 3 other dogs, hearts were examined immediately after cryo ablation. CS and circumflex angiography was performed pre and post ablation. The hearts, CS, and Cx were then examined for structural injury. The AV junction was sectioned and the hearts were immersed in Tetrazolium, and the lesions were inspected for transmurality across the AV groove.Results: In 3/12 dogs the distal CS cryo lesions resulted in inferior ST segment depression that resolved within 5 minutes. There was no arrhythmia or hemodynamic changes. No CS electrical activity was noted post ablation. The pacing threshold increased from 2 ± 2.3 mA to 7.4 ± 3.6 mA (p < 0.001). Pathological examination of 3 acute hearts revealed hematomas.There was no pericardial effusion. No evidence of stenosis or thrombosis was seen within the CS and the circumflex artery. After 3 months of recovery, transmural lesions across the AV groove were present in all of the targeted AV regions.Conclusion: Intra-CS cryo balloon ablation is safe and can potentially replace endocardial RF ablation targeting the AV junction and the CS muscular sleeve.This research was partially funded by: VA Merit grant, Boston Scientific Corporation/EP Technologies, Scimed.     

A comparison of conductive textile-based and silver/silver chloride gel electrodes in exercise electrocardiogram recordings

Background

The goal of this study was to compare disposable silver/silver chloride and reusable conductive textile-based electrodes in electrocardiogram (ECG) signal monitoring during physical activity.

Materials and Methods

The reusable electrodes were produced using thin silver-plated nylon 117/17 2-ply conductive thread (Statex Productions & Vertriebs GmbH, Bremen, Germany) sewed with a sewing machine on a chest belt. The disposable and reusable electrodes were compared in vivo according to ECG signal baseline drift, broadband electrode noise properties, and influence of electrode area to ECG signal morphology and frequency content. Twelve volunteers were included in this study.

Results

Electroconductive textile-based ECG electrodes produce significantly more noise in a very low frequency band (0-0.67 Hz) and not significantly less of broadband noise (0-250 Hz) than disposable silver/silver chloride electrodes. Decreasing area of textile electrodes decreases fidelity of registered ECG signals at low frequencies.

Conclusion

Textile electrodes having adequate area can be used in more applications than only R-R interval monitoring.     

Vaccination practices in pediatric transplantation: A survey among member centers of the European reference network TransplantChild

Background

There is considerable variation in vaccination practices between pediatric transplant centers. This study aims to evaluate active immunization attitudes and practices among ERN-TransplantChild centers and identify potential areas of improvement that could be addressed by shared evidence-based protocols.

Methods

A cross-sectional questionnaire of attitudes and practices toward immunization of pediatric SOT and HSCT candidates and recipients was sent to a representative member of multidisciplinary teams from 27 European centers belonging to the ERN-TransplantChild.

Results

A total of 28/62 SOT programs and 6/12 HSCT programs across 21 European centers participated. A quarter of centers did not have an on-site protocol for the immunizations. At the time of transplantation, pediatric candidates were fully immunized (80%–100%) in 57% and 33% of the SOT and HSCT programs. Variations in the time between vaccine administration and admission to the waiting list were reported between the centers, with 2 weeks for inactivated vaccines and variable time (2–4 weeks) for live-attenuated vaccines (LAVs). Almost all sites recommended immunization in the post-transplant period, with a time window of 4–8 months for the inactivated vaccines and 16–24 months for MMR and Varicella vaccines. Only five sites administer LAVs after transplantation, with seroconversion evaluated in 80% of cases.

Conclusions

The immunization coverage of European pediatric transplant recipients is still inconsistent and far from adequate. This survey is a starting point for developing shared evidence-based immunization protocols for safe vaccination among pediatric transplant centers and generating new research studies.     

Quantifying specific antibody concentrations by enzyme-linked immunosorbent assay using slope correction

Assessing the magnitude of an antibody response is important to many research and clinical endeavors; however, there are considerable differences in the experimental approaches used to achieve this end. Although the time-honored approach of end point titration has merit, the titer can often be misleading due to differences in how it is calculated or when samples contain high concentrations of low-avidity antibodies. One frequently employed alternative is to adapt commercially available enzyme-linked immunosorbent assay kits, designed to measure total antibody concentrations, to estimate antigen-specific antibody concentrations. This is accomplished by coating the specific antigen of interest in place of the capture antibody provided with the kit and then using the kit's standard curve to quantify the specific antibody concentration. This approach introduces considerable imprecision, due primarily to its reliance on a single sample dilution. This "single-point" approach fails to address differences in the slope of the sample titration curve compared to that of the standard curve. Here, we describe a general approach for estimating the effective concentration of specific antibodies, using antisera against foot-and-mouth disease virus VP1 peptide. This was accomplished by initially calculating the slope of the sample titration curve and then mathematically correcting the slope to that of a corresponding standard curve. A significantly higher degree of precision was attained using this approach rather than the single-point method.     

Linear lesions provide protection from atrial fibrillation induction with rapid atrial pacing

INTRODUCTION: In the animal model, segmentation of the atria with radiofrequency-generated linear lesions (LL) using the loop catheter has been shown to be highly effective in terminating chronic atrial fibrillation (AF). This study addresses the question whether the same lesion set also would prevent reinduction and sustainability of AF. METHODS AND RESULTS: We studied two groups of dogs. The AF group included eight dogs in which the atria were paced until chronic AF was present. After 6 months of sustained AF, the dogs were converted to normal sinus rhythm (NSR) by the creation of LL in both atria. Rapid atrial pacing was restarted 6 months later and continued for 4 weeks. In the NSR group, there were nine dogs in NSR without inducible AF at baseline. LL were created, and after 6 months rapid atrial pacing was applied for 4 weeks. Rhythm status was monitored weekly. Transthoracic echocardiography was performed at baseline, before linear lesion placement, and before pacing/repacing. At the conclusion of the study, the hearts were excised and examined. The lesions were stained, and their quality was assessed. AF was induced in a much shorter interval in the dogs in which AF had previously been present than in NSR dogs (8 +/- 5 days vs 25 +/- 13 days; P < 0.05). LL prevented sustainability of AF induced via rapid pacing once the pacing stimulus was stopped. Incomplete lesions were associated with increased inducibility of atrial tachycardia and AF. CONCLUSION: In this animal model of AF, LL are not only capable of terminating chronic AF, but also lead to self-termination of AF once the rapid pacing is stopped. Self-termination of AF after induction with rapid pacing was not observed in this AF model in the absence of LL. In the dogs with 6 months of AF, the presence of AF led to increased atrial susceptibility to AF induction by rapid pacing, even with LL and after 6 months of recovery. Incomplete LL allows induction of atrial tachycardia and AF.     

Effects of ploidy,growth conditions and the mitochondrial nucleoid-associated protein Ilv5p on the rate of mutation of mitochondrial DNA in<Emphasis Type="Italic"> Saccharomyces cerevisiae</Emphasis>

Microsatellites, or simple repetitive sequences, are abundant in eukaryotic genomes and in the mitochondrial genome of Saccharomyces cerevisiae. These sequences alter at rates significantly higher than non-repetitive sequences of comparable size. The stability of a mitochondrial microsatellite is nearly 100-fold greater in diploid yeast cells than in isogenic haploid cells. We were able to demonstrate that this effect is likely due to ploidy alone, rather than mating-type-specific gene expression. In addition, we demonstrated that amino acid starvation affects the organization of the mitochondrial DNA and its segregation into the bud. We also tested the effect of amino acid starvation on the copy number and the mutation rate of mitochondrial DNA in both haploid and diploid yeast cells. Yeast cells grown in rich medium have a lower mitochondrial DNA content than cells starved for amino acids and have a correspondingly higher mutation rate for both frameshift mutations and point mutations in mitochondrial DNA. These effects appear to be dependent on the mitochondrial nucleoid-associated protein Ilv5p.Communicated by M. Brunner     

KRAS,NRAS and BRAF mutations in colorectal cancer and melanoma

Cancers are the group of diseases, which arise because of the uncontrolled behavior of some of the genes in our cells. There are possibilities of gene amplifications, overexpressions, deletions and other anomalies which might lead to the development and spread of cancer. One of the most dangerous ways to the cancers is the mutations of the genes. The mutated genes can start unstoppable proliferation of cells, their uncontrolled motility, protection from apoptosis, the DNA mutation enhancement as well as other anomalies, leading to the cancer. This review focuses on the genes, which are frequently mutated in various cancers and are known to be important in the advance and progression of colorectal cancer and melanoma, namely KRAS, NRAS and BRAF.