Functional Capacity of Patients with Pacemaker Due to Isolated Congenital Atrioventricular Block

Background:Isolated congenital atrioventricular block (CAVB) is a rare condition with multiple clinical outcomes. Ventricular remodeling can occur in approximately 10% of the patients after pacemaker (PM) implantation.Objectives:To assess the functional capacity of children and young adults with isolated CAVB and chronic pacing of the right ventricle (RV) and evaluate its correlation with predictors of ventricular remodeling.Methods:This cross-sectional study used a cohort of patients with isolated CAVB and RV pacing for over a year. The subjects underwent clinical and echocardiographic evaluation. Functional capacity was assessed using the six-minute walk test. Chi-square test, Fisher's exact test, and Pearson correlation coefficient were used, considering a significance level of 5%.Results:A total of 61 individuals were evaluated between March 2010 and December 2013, of which 67.2% were women, aged between 7 and 41 years, who were using PMs for 13.5 ± 6.3 years. The percentage of ventricular pacing was 97.9 ± 4.1%, and the duration of the paced QRS complex was 153.7 ± 19.1 ms. Majority of the subjects (95.1%) were asymptomatic and did not use any medication. The mean distance walked was 546.9 ± 76.2 meters and was strongly correlated with the predicted distance (r = 0.907, p = 0.001) but not with risk factors for ventricular remodeling. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)Conclusions:The functional capacity of isolated CAVB patients with chronic RV pacing was satisfactory but did not correlate with risk factors for ventricular remodeling.

Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block

Abstract Background: Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB). Objective: To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. Methods: Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution’s ethics committee. Results: The patients’ mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001). Conclusion: The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB.

Optimal design in the presence of random or fixed block effects

Magdeburg, Univ., Fak. für Mathematik, Diss., 2014

A Bootstrap Neural Network Based Heterogeneous Panel Unit Root Test: Application to Exchange Rates

This paper proposes a bootstrap artificial neural network based panel unit root test in a dynamic heterogeneous panel context. An application to a panel of bilateral real exchange rate series with the US Dollar from the 20 major OECD countries is provided to investigate the Purchase Power Parity (PPP). The combination of neural network and bootstrapping significantly changes the findings of the economic study in favour of PPP.

A Consistent Nonparametric Bootstrap Test of Exogeneity

This paper proposes a novel way of testing exogeneity of an explanatory variable without any parametric assumptions in the presence of a "conditional" instrumental variable. A testable implication is derived that if an explanatory variable is endogenous, the conditional distribution of the outcome given the endogenous variable is not independent of its instrumental variable(s). The test rejects the null hypothesis with probability one if the explanatory variable is endogenous and it detects alternatives converging to the null at a rate n..1=2:We propose a consistent nonparametric bootstrap test to implement this testable implication. We show that the proposed bootstrap test can be asymptotically justi.ed in the sense that it produces asymptotically correct size under the null of exogeneity, and it has unit power asymptotically. Our nonparametric test can be applied to the cases in which the outcome is generated by an additively non-separable structural relation or in which the outcome is discrete, which has not been studied in the literature.

Juridical double taxation by cross border transactions: the Block Case (C-67/08)

Treaty Establishing the European Community, operative until December 1st 2009, had already established in its article 2 the mission of the up until then European Community and actual European Union is to promote an harmonious, equilibrated and sustainable development of the economic activities of the whole Community. This Mission must be achieved by establishing a Common Market, an Economic and Monetary Union and the realization of Common Policies. One of the instruments to obtain these objectives is the use of free circulation of people, services and capitals inside the Common and Interior Market of the European Union. The European Union is characterized by the confirmation of the total movement of capitals, services and individuals and legal peoples’ freedom; freedom that was already predicated by the Maastricht Treaty, through the suppression of whatever obstacles which are in the way of the objectives before exposed. The old TEC in its Title III, now Title IV of the Treaty on the Functioning of the European Union, covered the free circulation of people, services and capitals. Consequently, the inclusion of this mechanism inside one of the regulating texts of the European Union indicates the importance this freedom supposes for the European Union objectives’ development. Once stood up the relevance of the free movement of people, services and capitals, we must mention that in this paper we are going to centre our study in one of these freedoms of movement: the free movement of capital. In order to analyze in detail the free movement of capital within the European framework, we are going to depart from the analysis of the existent case law of the Court of Justice of the European Union. The use of jurisprudence is basic to know how Community legislation is interpreted. For this reason, we are going to develop this work through judgements dictated by the European Union Court. This way we can observe how Member States’ regulating laws and the European Common Law affect the free movement of capital. The starting point of this paper will be the Judgement C-67/08 European Court of Justice of February 12th 2009, known as Block case. So, following the argumentation the Luxemburg Court did about the mentioned case, we are going to develop how free movement of capital could be affected by the current disparity of Member States’ legislation. This disparity can produce double taxation cases due to the lack of tax harmonized legislation within the interior market and the lack of treaties to avoid double taxation within the European Union. Developing this idea we are going to see how double taxation, at least indirectly, can infringe free movement of capital.

Ultrasound-guided suprascapular nerve block, description of a novel supraclavicular approach.

BACKGROUND AND OBJECTIVES: The suprascapular nerve (SSN) block is frequently performed for different shoulder pain conditions and for perioperative and postoperative pain control after shoulder surgery. Blind and image-guided techniques have been described, all of which target the nerve within the supraspinous fossa or at the suprascapular notch. This classic target point is not always ideal when ultrasound (US) is used because it is located deep under the muscles, and hence the nerve is not always visible. Blocking the nerve in the supraclavicular region, where it passes underneath the omohyoid muscle, could be an attractive alternative. METHODS: In the first step, 60 volunteers were scanned with US, both in the supraclavicular and the classic target area. The visibility of the SSN in both regions was compared. In the second step, 20 needles were placed into or immediately next to the SSN in the supraclavicular region of 10 cadavers. The accuracy of needle placement was determined by injection of dye and following dissection. RESULTS: In the supraclavicular region of volunteers, the nerve was identified in 81% of examinations (95% confidence interval [CI], 74%-88%) and located at a median depth of 8 mm (interquartile range, 6-9 mm). Near the suprascapular notch (supraspinous fossa), the nerve was unambiguously identified in 36% of examinations (95% CI, 28%-44%) (P < 0.001) and located at a median depth of 35 mm (interquartile range, 31-38 mm; P < 0.001). In the cadaver investigation, the rate of correct needle placement of the supraclavicular approach was 95% (95% CI, 86%-100%). CONCLUSIONS: Visualization of the SSN with US is better in the supraclavicular region as compared with the supraspinous fossa. The anatomic dissections confirmed that our novel supraclavicular SSN block technique is accurate.

Use-dependent block of the voltage-gated Na+ channel by tetrodotoxin and saxitoxin: Effect of pore mutations that change ionic selectivity.

Voltage-gated Na(+) channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca(2+) permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca(2+) or Na(+) ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca(2+) permeability, suggesting that ion-toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation.

GLUT2 surface expression and intracellular transport via the constitutive pathway in pancreatic beta cells and insulinoma: evidence for a block in trans-Golgi network exit by brefeldin A.

The biosynthesis, intracellular transport, and surface expression of the beta cell glucose transporter GLUT2 was investigated in isolated islets and insulinoma cells. Using a trypsin sensitivity assay to measure cell surface expression, we determined that: (a) greater than 95% of GLUT2 was expressed on the plasma membrane; (b) GLUT2 did not recycle in intracellular vesicles; and (c) after trypsin treatment, reexpression of the intact transporter occurred with a t1/2 of approximately 7 h. Kinetics of intracellular transport of GLUT2 was investigated in pulse-labeling experiments combined with glycosidase treatment and the trypsin sensitivity assay. We determined that transport from the endoplasmic reticulum to the trans-Golgi network (TGN) occurred with a t1/2 of 15 min and that transport from the TGN to the plasma membrane required a similar half-time. When added at the start of a pulse-labeling experiment, brefeldin A prevented exit of GLUT2 from the endoplasmic reticulum. When the transporter was first accumulated in the TGN during a 15-min period of chase, but not following a low temperature (22 degrees C) incubation, addition of brefeldin A (BFA) prevented subsequent surface expression of the transporter. This indicated that brefeldin A prevented GLUT2 exit from the TGN by acting at a site proximal to the 22 degrees C block. Together, these data demonstrate that GLUT2 surface expression in beta cells is via the constitutive pathway, that transport can be blocked by BFA at two distinct steps and that once on the surface, GLUT2 does not recycle in intracellular vesicles.

Isolated congenital atrioventricular block diagnosed in utero: natural history and outcome.

BACKGROUND: Isolated congenital atrioventricular block (CAVB) diagnosed in utero is associated with a high morbidity and mortality. Prognosis is especially poor when heart rate drops below 55 beats per minute (bpm) and when fetal hydrops develops. We describe the natural history and outcome of 24 infants with isolated CAVB diagnosed in utero, review the literature, and assess the risk factors that could predict outcome. METHODS: This was a retrospective multicenter study of 24 patients with isolated CAVB diagnosed in utero. RESULTS: CAVB was detected at a mean gestational age (GA) of 24.7 +/- 5.1 weeks. Ten fetuses initially presented with complete heart block. Low heart rate or incomplete heart block was the first documentation of bradyarrhythmia in the other 14 fetuses. In 11 of them, CAVB developed during pregnancy after a median time of 3 (range 1-16) weeks. Fetal hydrops developed in 10 of 24 (42%) fetuses at a mean GA of 27.6 +/- 5.1 weeks. Hydropic fetuses showed lower heart rates during pregnancy (47 +/- 10 bpm) than non-hydropic fetuses (57 +/- 10 bpm). There were three intrauterine deaths; all were hydropic and female. Nine viable females and 12 males were born at a mean GA of 37.1 +/- 6.1 weeks with an average birth weight of 3097 +/- 852 g. Fifteen CAVB patients required pacemaker (PM) intervention, 10 of them immediately after birth. Dilated cardiomyopathy (DCM) developed in three infants of whom two died of congestive heart failure, shortly after the diagnosis was made; one is still alive. Mortality before or after birth was 21%, and was associated with heart rates below 50 bpm and development of fetal hydrops. Poor outcome, defined as death, PM implantation, or development of DCM, occurred in 83% of cases and was associated with heart rates below 60 bpm during pregnancy. CONCLUSIONS: Isolated CAVB diagnosed in utero is associated with high morbidity and mortality. Patients who develop fetal hydrops show lower heart rates during pregnancy than patients who do not. A fetal heart rate below 50 bpm and development of fetal hydrops is associated with increased mortality. Rates below 60 bpm are associated with PM requirement and/or DCM.