High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma

Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27), 13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27), 17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 <89.58–96.81> MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96–61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 <60.43–60.53> that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies

Second diastolic pulmonary venous flow and isolated late diastolic mitral valve regurgitation in first-degree atrioventricular block

The authors report the case of a 77-year-old male patient with sinus rhythm and a first-degree atrioventricular (AV) block who was referred for echocardiographic follow-up 18 years after aortic valve replacement. Left ventricular systolic function as well as the function of the aortic prosthesis was normal. Systolic mitral regurgitation (MR) was virtually absent, but isolated late diastolic MR was detected by colour Doppler imaging. Coincidental to the occurrence of diastolic MR, a second late diastolic forward flow in the pulmonary veins was observed. Therefore, during the prolonged left atrial relaxation caused by first-degree AV block, the left atrial pressure drops below the pressure in both adjacent chambers in late diastole, resulting in both late diastolic MR and a second diastolic pulmonary venous forward flow

Left ventricular dyssynchrony in patients with normal ventricular systolic function referred for exercise echocardiography

Exercise testing is often normal despite the presence of exertional symptoms. We hypothesized that left ventricular (LV) dyssynchrony might occur in some patients in the absence of ischemia, LV dysfunction, or wide QRS, and might contribute to exertional symptoms and diminished exercise capacity

Efficacy and safety of transcatheter closure in adults with large or small atrial septal defects

BACKGROUND: In most patients with secundum atrial septal defects (ASD), transcatheter closure is the preferred treatment strategy, but whether device size affects clinical outcomes is unknown. We sought to study the efficacy and safety of large closure devices compared to the use of smaller devices. METHODS: Using a single-center, prospective registry of adult patients undergoing transcatheter ASD closure, patients receiving a large closure device (waist diameter ≥25 mm, n = 41) were compared to patients receiving smaller devices (waist diameter ≤24 mm, n = 66). We analyzed pre-interventional clinical, hemodynamic and echocardiographic data, interventional success and complication rates, and 6-month clinical and echocardiographic outcomes. The primary efficacy outcome was successful ASD closure achieved by a single procedure and confirmed by lack of a significant residual shunt at 6 months. The primary safety outcome was a composite of device embolization, major bleeding, and new-onset atrial arrhythmia occurring within 6 months. RESULTS: Transcatheter ASD closure using large devices was successful in 90 % compared to 97 % of patients receiving smaller devices as defined by the primary efficacy outcome (p = 0.20). The primary safety outcome occurred in 4 patients of the large and 6 patients of the small device group, resulting in an event-free rate of 90 and 91 %, respectively (p = 0.89). Similar significant symptomatic improvement was observed in both treatment groups after 6 months, indicated by a 50 % increase in the fraction of patients in NYHA class I (p < 0.0001 vs. baseline). CONCLUSIONS: Transcatheter closure in this cohort of patients with large or small ASD was effective with similar complication rates during short-term follow-up irrespective of the size of the implanted device

Is the standard weight-based dosing of dobutamine for stress testing appropriate for patients of widely varying body mass index?

Although a gradual increase in heart rate (HR) during dobutamine stress testing (DST) is desired, few data exists regarding whether this is similarly achieved in patients of widely varying body mass index (BMI). Whether difference in BMI contributes to variation in the hemodynamic and symptomatic response to dobutamine is also unknown

Diastolic stress echocardiography in the young: a study in nonathletic and endurance-trained healthy subjects

BACKGROUND: The response of diastolic Doppler indices to exercise is not well defined for young subjects. The aims of this study were to evaluate this in nonathletic and endurance-trained probands and to correlate echocardiographic data with maximal oxygen consumption. METHODS: In this prospective study, Doppler echocardiography was performed at rest and after exercise in 40 nonathletes (NAs) and 20 endurance-trained athletes (ETs) aged > 40 years, matched for age and gender. Diastolic function was assessed by mitral inflow and early diastolic velocities of the septal (e' septal) and lateral (e' lateral) mitral annulus. Maximal oxygen consumption quantification was performed simultaneously. RESULTS: All cardiac chambers were larger in ETs than NAs. ETs had higher e' lateral at rest (18.1 +/- 2.7 vs 16.3 +/- 3.3 cm/sec, P = .02) and higher mitral E (141 +/- 15 vs 132 +/- 15 cm/sec, P = .02) and e' lateral (23.5 +/- 2.5 vs 21.4 +/- 3.0 cm/sec, P = .01) with exercise than NAs. There was a slight increase in E/e' septal (overall, from 6.8 +/- 1.3 to 7.2 +/- 1.2; P = .02) and E/e' lateral (overall, from 5.0 +/- 0.8 to 6.2 +/- 0.9; P > .0001) with exercise. Changes in diastolic parameters with exercise were similar in ETs and NAs. Percentage of predicted maximal oxygen consumption was correlated with exertional E (r = 0.28, P = .03) and e' lateral (r = 0.32, P = .01), but the strongest predictor was indexed left ventricular end-diastolic volume (r = 0.66, P > .0001). CONCLUSIONS: During exercise, E/e' increases but remains within normal ranges in healthy young subjects, and the response to exercise does not differ between ETs and NAs. These data help define the normal diastolic stress echocardiographic response in the young. Exercise capacity shows a correlation with enhanced exertional early diastolic velocities but is more closely related to cardiac structural adaption to endurance training

Does the prognostic value of dobutamine stress echocardiography differ among different age groups?

Age is associated with reduced exercise capacity and greater prevalence of coronary artery disease. Whether the prognostic information obtained from dobutamine stress echocardiography (DSE), a stress test commonly used for patients unable to perform an exercise test, provides differential information based on age is not well known