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Biomedical subjects

Leonor Parreira

Publications and source records attributed to Leonor Parreira.

7 recordsLinked to original sources

The spatial organization of centromeric heterochromatin during normal human lymphopoiesis: evidence for ontogenically determined spatial patterns.

It is believed that pericentromeric heterochromatin may play a major role in the epigenetic regulation of gene expression. We have previously shown that centromeres in human peripheral blood cells aggregate into distinct "myeloid" and "lymphoid" spatial patterns, suggesting that the three-dimensional organization of centromeric heterochromatin in interphase may be ontogenically determined during hematopoietic differentiation. To investigate this possibility, the spatial patterns of association of different centromeres were analyzed in hematopoietic progenitors and compared with those in early-B and early-T cells, mature B and T lymphocytes, and, additionally, mature granulocytes and monocytes. We show that those patterns change during lymphoid differentiation, with major spatial arrangements taking place at different stages during T and B cell differentiation. Heritable patterns of centromere association are observed, which can occur either at the level of the common lymphoid progenitor, or in early-T or early-B committed cells. A correlation of the observed patterns of centromere association with the gene content of the respective chromosomes further suggests that the variation in the composition of these heterochromatic structures may contribute to the dynamic relocation of genes in different nuclear compartments during cell differentiation, which might have functional implications for cell-stage-specific gene expression.

Antigens, CD34↗

Notch and lymphopoiesis: a view from the microenvironment.

The differentiation of B- and T-cells in primary lymphoid organs depends on, or is strongly influenced by, signals provided by stromal cells, extracellular matrix components as well as by direct contacts between differentiating lymphocytes and distinct environmental cells. Notch receptors and their ligands mediate intercellular contacts and are crucially important for the development of T- and B-cell lineages. Here we start by reviewing current knowledge on the expression patterns of Notch receptors and their ligands in primary lymphoid organs and the effects induced by their functional interactions. Then we shall attempt to discuss how those interactions may regulate not only lymphopoiesis per se but also morphogenesis and the functional compartmentalization of lymphopoietic organs during development.

Animals↗

Ablation of atrial fibrillation in mitral valve disease patients: five year follow-up after percutaneous pulmonary vein isolation and mitral balloon valvuloplasty.

BACKGROUND: The association between atrial fibrillation (AF) and mitral valve disease is frequent. Isolation of the pulmonary veins by radiofrequency energy applications performed intraoperatively has been proposed for patients with AF in whom mitral valve surgery has been indicated. Balloon mitral valvuloplasty is currently the preferred procedure for patients with mitral stenosis and a favorable valve anatomy. AIM: To evaluate the short- and long-term results of percutaneous pulmonary vein isolation for the treatment of AF in patients with mitral stenosis undergoing balloon mitral valvuloplasty. METHODS: Five patients (four male and one female, age 43 +/- 4 years) underwent balloon mitral valvuloplasty concomitant with pulmonary vein isolation between August 1996 and February 1997. These patients had permanent AF, diagnosed 31 +/- 12 months previously; their mitral valve area was 1.0 +/- 0.25 cm2 and their left atria measured 54 +/- 5 mm. Balloon mitral valvuloplasty was performed via a transseptal approach, and then four ablation lines were created in the left atrial posterior wall to encircle all four pulmonary veins. Radiofrequency applications lasted 45 seconds each, and aimed at a maximum preset temperature of 65 degrees C. Electrical cardioversion was performed at the end of the procedure. RESULTS: Mitral valve area increased 1.0 +/- 0.3 cm2 after valvuloplasty. The number of radiofrequency applications per patient was 37 +/- 3, and the average duration of the entire treatment was 131 +/- 28 minutes. Fluoroscopy time averaged 32 +/- 12 minutes. All patients were discharged in sinus rhythm, and mitral flow Doppler evaluation at one month showed a biphasic pattern in all cases, with the A wave measuring 70 +/- 15 cm/sec. Three patients maintained sinus rhythm at five-year follow-up. Of these patients, one had developed a left atrial flutter at four-year follow-up and underwent ablation. The remaining two patients presented AF at five year follow-up. CONCLUSIONS: Percutaneous isolation of the pulmonary veins concomitant with balloon mitral valvuloplasty had suppressed AF in 60% of patients by five-year follow-up.

Adult↗

Non invasive hemodynamic monitorization for AV interval optimization in patients with ventricular resynchronization therapy.

INTRODUCTION AND OBJECTIVE: In patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances, resynchronization therapy improves cardiac function and functional capacity. Determination of the optimal AV interval is essential to optimize the therapy results and various methods have been used in daily practice to obtain such an interval. The aim of this work is to assess optimal AV determined by impedance cardiography and compare it to the interval previously obtained by transmitral flow Doppler echocardiography. PATIENTS: Seven pts were evaluated, five men, mean age of 61 +/- 10 years, with dilated cardiomyopathy, intra-ventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Four pts had ischemic cardiomyopathy and three idiopathic. All pts had an implanted cardioverter-defibrillator with cardiac resynchronization. METHODS: The optimal AV delay was estimated by transmitral flow pulsed Doppler using the method previously described by Ritter. Subsequently, cardiac output (CO) was determined by impedance cardiography. CO was estimated for different AV delays, beginning with 80 ms until occurrence of fusion QRS. The optimal AV delay was defined as the value corresponding to the highest measured CO. The ideal AV interval was compared between the two methods used. RESULTS: The AV delay determined by echocardiography varied between 120 and 170 ms (134 +/- 17 ms). The optimum AV delay based on CO estimation varied between 110 and 190 ms (137 +/- 26 ms). There was a correlation between the delays determined by the two methods (r = 0.844; p = 0.017). CONCLUSIONS: In pts undergoing ventricular resynchronization therapy, AV delay optimization based on CO determined by impedance cardiography is comparable to that measured by transmitral flow pulsed Doppler. However, impedance cardiography seems a more objective and simpler technique.

Aged↗

Effects of cardiac resynchronization therapy on right ventricular function--evaluation with tissue Doppler echocardiography.

INTRODUCTION AND OBJECTIVE: Ventricular resynchronization therapy improves cardiac function in patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances. The effects of ventricular resynchronization on right ventricular function have been poorly studied. Tricuspid annular motion can be studied with tissue Doppler echocardiography, which enables quantitative assessment of right ventricular function. The aim of this study was to evaluate the effects of ventricular resynchronization on right ventricular function with pulsed tissue Doppler. PATIENTS: We studied ten pts, eight male, mean age 65 +/- 10 years, with dilated cardiomyopathy, intraventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Five pts had coronary artery disease and the others idiopathic dilated cardiomyopathy. All pts had an implanted cardioverter-defibrillator with ventricular resynchronization. METHODS: Before and one month after device implantation right ventricular function was evaluated with pulsed wave tissue Doppler study of tricuspid annular motion. The maximum velocity of the S wave (MV-S), E wave (MV-E), and A wave (MV-A), E/A ratio, isovolumetric contraction time (IVCT) and ejection time (ET) were determined. Right ventricular size and left ventricular ejection fraction (EF) were measured. Functional class before and after implantation was assessed. RESULTS: MV-S, MV-E and MV-A did not change significantly. The E/A ratio decreased significantly (p = 0.017). There were no differences in IVCT and ET, nor in right ventricular size before and after resynchronization. EF improved in all but one patient (p = 0.003). All pts had an improvement in functional class, except the one without increased EF. CONCLUSIONS: Ventricular resynchronization therapy does not appear to have a deleterious effect on right ventricular function in pts with dilated cardiomyopathy and intraventricular conduction disturbances. The main beneficial effect of this type of therapy appears to be improvement in left ventricular function.

Aged↗

Tissue Doppler echocardiography for evaluation of patients with ventricular resynchronization therapy.

INTRODUCTION AND OBJECTIVE: Ventricular resynchronization therapy optimizes cardiac function and induces reverse remodeling of the left ventricle (LV) in patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances. Improvement of LV mechanical synchrony seems to be the predominant mechanism. There is a growing interest in objective quantification of desynchronization. This study aims to evaluate the effect of ventricular resynchronization therapy on LV remodeling and on LV desynchronization, assessed by tissue Doppler echocardiography. PATIENTS: We studied ten pts, eight male, mean age 65 +/- 10 years, with dilated cardiomyopathy, intraventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Five pts had coronary artery disease and the others idiopathic dilated cardiomyopathy. All pts had an implanted cardioverter, defibrillator with cardiac resynchronization therapy. The LV pacing electrode was placed in the lateral or posterolateral vein. METHODS: Before and one month after resynchronization therapy the following parameters were measured with conventional Doppler echocardiography: LV end-diastolic (LVd) and end-systolic (LVs) size, ejection fraction (EF) and mitral regurgitation (MR) area. For diastolic function the maximum velocity of the E wave (MV-E) and A wave (MV-A), E/A ratio, LV filling time (LV-FT) and isovolumetric relaxation time (IVRT) were meadured. Mitral longitudinal motion was studied with pulsed tissue Doppler. Maximum velocity of the systolic S wave (MV-S) and isovolumetric contraction time (IVCT) were measured in the tissue Doppler curve of the septum and lateral, inferior and anterior walls. To evaluate the degree of desynchronization the RV index was calculated for each patient, based on the difference between the maximum and minimum IVCT, normalized for the maximum IVCT. RESULTS: There was a significant reduction in LVd and MR. EF increased significantly (p = 0.003). There were no differences in diastolic function parameters. MV-S did not increase significantly. IVCT increased significantly at the lateral wall (p = 0.037). The RV index demonstrated a significant reduction in ventricular desynchronization (p = 0.001). CONCLUSIONS: Ventricular resynchronization therapy induces reverse remodeling and improves LV function in selected pts. Improvement of mechanical LV synchrony seems to be the predominant mechanism. Ventricular desynchronization can be measured by tissue Doppler echocardiography.

Aged↗

The rationale behind ventricular resynchronization.

Biventricular pacing or cardiac resynchronization therapy was first proposed in 1994 as a form of non-pharmacological therapy in patients with heart failure and intraventricular and atrioventricular conduction delay, refractory to medical therapy. In this group of patients the presence of ventricular dyssynchrony is associated with progressive adverse remodeling and worsening of systolic and diastolic performance and carries independent prognostic significance. Acute clinical studies have demonstrated hemodynamic benefit as well as improved systolic and diastolic ventricular performance. Also, most clinical short- and medium-term studies have shown clinical and hemodynamic improvement associated with reverse ventricular remodeling. It has recently been demonstrated that cardiac resynchronization therapy reduces morbidity and mortality. This paper analyzes the pathophysiology of abnormal electrical conduction and the acute and chronic response to cardiac resynchronization, and reviews the most relevant aspects of the various trials.

Arrhythmias, Cardiac↗