Immediate reproducibility of electrically induced sustained monomorphic ventricular tachycardia before and during antiarrhythmic therapy

AbstractThe immediate reproducibility of sustained ventricular tachycardia induction was evaluated prospectively during 106 studies performed in 53 patients with clinical sustained monomorphic ventricular tachycardia. Programmed electrical stimulation was performed twice, using the same protocol during 53 drug-free studies and 53 subsequent studies on antiarrhythmic therapy.Sustained monomorphic ventricular tachycardia was reproduced in 104 (98%) of the 106 studies. There was no significant difference in the incidence of reproducible tachycardia in the drug-free state compared with that observed during treatment with different classes of antiarrhythmic drugs. An increase in the number of extrastimuli was required to reinitiate the tachycardia in 9 (11%) of 83 studies in which single or double extrastimuli were initially required to induce the tachycardia. In 39 (37%) of 104 studies with reproducible tachycardia induction, the two tachycardias significantly differed in electrocardiographic (ECG) configuration and cycle length.These observations suggest that the overall reproducibility of ventricular tachycardia induction is sufficiently high to provide a reliable marker for evaluating the efficacy of therapeutic interventions. However, specific tachycardia characteristics such as cycle length and ECG configuration are more variable even within the same study and may be less useful in assessing the effects of subsequent interventions

Electrophysiological effects of prazosin during acute myocardial ischemia

Prazosin, 100 [mu]g/kg, had no effect on baseline refractoriness or intraventricular conduction in anesthetized dogs. During 1 h of coronary artery occlusion followed by reperfusion, prazosin significantly blunted the shortening of the ventricular effective refractory periods within ischemic myocardial region relative to vehicle-treated animals. Prazosin treatment also prevented the delayed conduction of paced ventricular complexes entering and exiting the ischemic zone. These effects may be associated with the blockade of [alpha]1-adrenoceptor activation during the acute phase of myocardial ischemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26081/1/0000157.pd

Use of the Pill Electrode for Transesophageal Atrial Pacing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72094/1/j.1540-8159.1985.tb05853.x.pd

Postinfarction sudden death: Significance of inducible ventricular tachycardia and infarct size in a conscious canine model

The relationship between inducible ventricular tachycardia in the convalescent phase of myocardial infarction and subsequent spontaneous ventricular fibrillation is uncertain. Thirty conscious instrumented dogs underwent programmed ventricular stimulation 5 days after anterior infarction; 15 had inducible ventricular tachycardia and 15 were noninducible. Following programmed ventricular stimulation, the application of a 150 uA current to the intima of the proximal circumflex artery initiated intimal damage, thrombosis, and acute ischemia of the posterolateral wall. After 20 minutes of ischemia, 73% inducible and 15% noninducible anlmals developed ventricular fibrillation (p p p < 0.001) animals. Inducible ventricular tachycardia following infarction was highly predictive of spontaneous ventricular fibrillation during a later ischemic episode in this model. The mass of previously injured myocardium was a critical determinant of both.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25787/1/0000349.pd

Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon

BACKGROUND: Insertional mutagenesis techniques with transposable elements have been popular among geneticists studying model organisms from E. coli to Drosophila and, more recently, the mouse. One such element is the Sleeping Beauty (SB) transposon that has been shown in several studies to be an effective insertional mutagen in the mouse germline. SB transposon vector studies have employed different functional elements and reporter molecules to disrupt and report the expression of endogenous mouse genes. We sought to generate a transposon system that would be capable of reporting the expression pattern of a mouse gene while allowing for conditional expression of a gene of interest in a tissue- or temporal-specific pattern. RESULTS: Here we report the systematic development and testing of a transposon-based gene-trap system incorporating the doxycycline-repressible Tet-Off (tTA) system that is capable of activating the expression of genes under control of a Tet response element (TRE) promoter. We demonstrate that the gene trap system is fully functional in vitro by introducing the "gene-trap tTA" vector into human cells by transposition and identifying clones that activate expression of a TRE-luciferase transgene in a doxycycline-dependent manner. In transgenic mice, we mobilize gene-trap tTA vectors, discover parameters that can affect germline mobilization rates, and identify candidate gene insertions to demonstrate the in vivo functionality of the vector system. We further demonstrate that the gene-trap can act as a reporter of endogenous gene expression and it can be coupled with bioluminescent imaging to identify genes with tissue-specific expression patterns. CONCLUSION: Akin to the GAL4/UAS system used in the fly, we have made progress developing a tool for mutating and revealing the expression of mouse genes by generating the tTA transactivator in the presence of a secondary TRE-regulated reporter molecule. A vector like the gene-trap tTA could provide a means for both annotating mouse genes and creating a resource of mice that express a regulable transcription factor in temporally- and tissue-specific patterns for conditional gene expression studies. These mice would be a valuable resource to the mouse genetics community for purpose of dissecting mammalian gene function

Validation of a clinical-grade assay to measure donor-derived cell-free DNA in solid organ transplant recipients

[Abstract] The use of circulating cell-free DNA (cfDNA) as a biomarker in transplant recipients offers advantages over invasive tissue biopsy as a quantitative measure for detection of transplant rejection and immunosuppression optimization. However, the fraction of donor-derived cfDNA (dd-cfDNA) in transplant recipient plasma is low and challenging to quantify. Previously reported methods to measure dd-cfDNA require donor and recipient genotyping, which is impractical in clinical settings and adds cost. We developed a targeted next-generation sequencing assay that uses 266 single-nucleotide polymorphisms to accurately quantify dd-cfDNA in transplant recipients without separate genotyping. Analytical performance of the assay was characterized and validated using 1117 samples comprising the National Institute for Standards and Technology Genome in a Bottle human reference genome, independently validated reference materials, and clinical samples. The assay quantifies the fraction of dd-cfDNA in both unrelated and related donor-recipient pairs. The dd-cfDNA assay can reliably measure dd-cfDNA (limit of blank, 0.10%; limit of detection, 0.16%; limit of quantification, 0.20%) across the linear quantifiable range (0.2% to 16%) with across-run CVs of 6.8%. Precision was also evaluated for independently processed clinical sample replicates and is similar to across-run precision. Application of the assay to clinical samples from heart transplant recipients demonstrated increased levels of dd-cfDNA in patients with biopsy-confirmed rejection and decreased levels of dd-cfDNA after successful rejection treatment. This noninvasive clinical-grade sequencing assay can be completed within 3 days, providing the practical turnaround time preferred for transplanted organ surveillance

Soccer-based promotion of voluntary medical male circumcision: A mixed-methods feasibility study with secondary students in Uganda.

The Ugandan government is committed to scaling-up proven HIV prevention strategies including safe male circumcision, and innovative strategies are needed to increase circumcision uptake. The aim of this study was to assess the acceptability and feasibility of implementing a soccer-based intervention ("Make The Cut") among schoolboys in a peri-urban district of Uganda. The intervention was led by trained, recently circumcised "coaches" who facilitated a 60-minute session delivered in schools, including an interactive penalty shoot-out game using metaphors for HIV prevention, sharing of the coaches' circumcision story, group discussion and ongoing engagement from the coach to facilitate linkage to male circumcision. The study took place in four secondary schools in Entebbe sub-district, Uganda. Acceptability of safe male circumcision was assessed through a cross-sectional quantitative survey. The feasibility of implementing the intervention was assessed by piloting the intervention in one school, modifying it, and implementing the modified version in a second school. Perceptions of the intervention were assessed with in-depth interviews with participants. Of the 210 boys in the cross-sectional survey, 59% reported being circumcised. Findings showed high levels of knowledge and generally favourable perceptions of circumcision. The initial implementation of Make The Cut resulted in 6/58 uncircumcised boys (10.3%) becoming circumcised. Changes made included increasing engagement with parents and improved liaison with schools regarding the timing of the intervention. Following this, uptake improved to 18/69 (26.1%) in the second school. In-depth interviews highlighted the important role of family and peer support and the coach in facilitating the decision to circumcise. This study showed that the modified Make The Cut intervention may be effective to increase uptake of safe male circumcision in this population. However, the intervention is time-intensive, and further work is needed to assess the cost-effectiveness of the intervention conducted at scale

LOFAR discovery of a double radio halo system in Abell 1758 and radio/X-ray study of the cluster pair

Radio halos and radio relics are diffuse synchrotron sources that extend over Mpc-scales and are found in a number of merger galaxy clusters. They are believed to form as a consequence of the energy that is dissipated by turbulence and shocks in the intra-cluster medium (ICM). However, the precise physical processes that generate these steep synchrotron spectrum sources are still poorly constrained. We present a new LOFAR observation of the double galaxy cluster Abell 1758. This system is composed of A1758N, a massive cluster hosting a known giant radio halo, and A1758S, which is a less massive cluster whose diffuse radio emission is confirmed here for the first time. Our observations have revealed a radio halo and a candidate radio relic in A1758S, and a suggestion of emission along the bridge connecting the two systems which deserves confirmation. We combined the LOFAR data with archival VLA and GMRT observations to constrain the spectral properties of the diffuse emission. We also analyzed a deep archival Chandra observation and used this to provide evidence that A1758N and A1758S are in a pre-merger phase. The ICM temperature across the bridge that connects the two systems shows a jump which might indicate the presence of a transversal shock generated in the initial stage of the merger

The Nature Drawings of Peter Karklins

https://via.library.depaul.edu/museum-publications/1010/thumbnail.jp