Assessment of Left Ventricular Volumes and Function by Real Time Three‐Dimensional Echocardiography in a Pediatric Population: A TomTec versus QLAB Comparison

Background: Three‐dimensional echocardiography (3DE) allows accurate calculation of ventricular volumes despite a remaining geometric assumption on the ventricular shape. Few studies involving full volume reconstruction software have been performed on children. Our aim was to compare the left ventricular (LV) volume measurements obtained with the most used 3D analysis software in a pediatric population. Methods: Fifty patients (median age: 9.5 years) without cardiac disease were included in the study. 3DE was performed with the X4–2 or X7–2 matrix probe (ie33, Philips). The LV volume analysis was performed with QLAB 6.0 (semiautomated border detection) and TomTec 4D LV (primary manual tracking with semiautomated border detection). Results: TomTec analysis feasibility amounted to 94% whereas QLAB analysis feasibility only reached 80% (P = 0.037). The analysis time was shorter with QLAB than TomTec (5 ± 2 versus 6 ± 3 minutes, P < 0.05). The stroke volume, end diastolic and end systolic LV volume measurements performed on the 40 patients were strongly correlated (r > 0.97; P < 0.0001) with minimal bias. The LV ejection fraction was well correlated (r = 0.79; P < 0.0001). Conclusion: 3D LV volume quantification is feasible either by using manual or automated reconstruction software in a normal pediatric population. LV Measurements are well correlated. Differences in volume reconstruction algorithms provide specific software performance characteristics. TomTec is a more feasible method but requires a longer analysis time. Further studies are needed to validate the accuracy of the method to calculate enlarged LV volumes in patients with congenital heart diseases. (Echocardiography 2010;27:1263‐1273)     

A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis

Leber congenital amaurosis (LCA) is a genetically heterogeneous autosomal recessive condition responsible for congenital blindness or greatly impaired vision since birth. Eight LCA loci have been mapped, but only six out of eight genes have been hitherto identified. A genome-wide screen for homozygosity was conducted in a large consanguineous family originating from Palestine, for which no mutation was found in any of the six known LCA genes and that excluded the LCA3 and LCA5 loci. Evidence for homozygosity, however, was found in all affected patients of the family on chromosome 1q31, a region in which the human homologue of the Drosophila melanogaster crumbs gene (CRB1) has been mapped. Consequently, we proposed a hypothesis that the disease-causing mutation in this family might lie in an unexplored region of this LCA gene. As a matter of fact, while no mutation was found in any of the 11 CRB1 exons originally reported, we identified a 10-bp (del 4121-4130) deletion segregating with the disease in a later reported 12th exon lying in the 3' end of the gene. Interestingly, this deletion disrupts an amino acid sequence that was shown to be crucial for the function of the protein in the Drosophila counterpart (CRB).     

Quinacrine increases endothelial nitric oxide release: role of superoxide anion

The effect of acute quinacrine treatment on agonist-induced nitric oxide (NO) release was investigated in cultured human endothelial cells using electrochemical monitoring of the in situ NO concentration. Quinacrine dose-dependently increased NO release with an apparent EC50 of 0.2 microM and a maximal effect at 1 microM. Quinacrine did not modify the dependence of NO release on extracellular L-arginine. Acceleration or deceleration of O2- dismutation, which altered NO release in control cells, did not modify it in quinacrine-treated cells. Quinacrine did not modify NO amperometric signal or reaction with O2- produced by xanthine oxidation. In the presence of quinacrine, agonist-induced NO release became Mg2+ -independent and could not be attributed to an inhibition of phospholipase A2 activity. Quinacrine made NO release insensitive to Cu2+ chelation. The present study demonstrates that acute treatment by low quinacrine concentrations increases endothelial NO release, possibly through an inhibition of O2- production.     

Personality pathology and cognitive-behavioral treatment of fear of flying

Studies have been inconclusive about the influence of personality pathology on treatment outcome in anxiety disorders. In general, it has been presumed that treatment outcome is negatively influenced by the presence of personality pathology. This is a study of the prevalence of personality pathology among persons who were seeking help for fear of flying. Moreover, the effects of personality pathology on the results of a multimodal, standardized, cognitive-behavioral fear of flying treatment program employed by an agency that specializes in treating people with fear of flying were studied. Personality pathology was determined with a self-report questionnaire, which provides ICD-10 diagnoses of personality disorders and dimensional severity scores for personality pathology. Treatment outcome was assessed with three different fear of flying questionnaires. Based on clinical judgment after individual-case conceptualization, participants (N=922) were assigned to a particular treatment for fear of flying. Self-report data for fear of flying were collected at pretreatment and at 3, 6 and 12-month follow-ups in 659 participants who followed the 2-day treatment program. Moreover, the number of flights made in the year following treatment was determined.The results of this study showed that participants with personality pathology, mainly from cluster C (anxiety), report greater fear of flying before treatment than participants without personality pathology. After treatment fear of flying was significantly reduced. Presence of personality pathology was not predictive of the number of flights after treatment and scores on the VAFAS scale at short or long term. Only on two questionnaires for fear of flying collected at short-term participants with personality pathology obtained significantly higher scores, although the size of the differences was relatively small. It was concluded that participants with personality pathology also benefited from fear of flying treatment and that the presence of personality pathology although cannot be regarded as a contra indication for a standardized, cognitive-behavioral group treatment.     

Urticaria pigmentosa localized on radiation field

A woman previously treated by radiotherapy for a breast cancer developed urticaria pigmentosa mainly restricted to the irradiation field, without any systemic symptoms. Localized forms of urticaria pigmentosa are exceptional, and their triggering factors are poorly understood. Several hypotheses can be discussed in this peculiar observation, among which a direct role of radiotherapy in the occurrence of cutaneous lesions cannot be ruled out.     

How does the Hospital and Anxiety and Depression Scale measure anxiety and depression in healthy subjects?

Many anxiety and depression scales are commonly used, although the assumption that they all measure the same construct may be questioned. Thus, researchers have to pay attention to the nature of the scales they use. The Hospital Anxiety and Depression Scale (HADS) was constructed in 1983 to allow a rapid and separate measure of depression and generalised anxiety. Surprisingly, since its introduction, there has been no comprehensive documentation of its psychometric properties. Therefore, as a contribution to assessing the construct validity of the HADS, we conducted a set of confirmatory factor analyses in a sample of 195 healthy students. None of the formerly proposed models fit our data. We were able to split the original Anxiety subscale into two components that we have labelled 'Anxiety' and 'Restlessness', while the original Depression subscale is slightly modified. The results are discussed from both clinical and theoretical points of view.     

Instrumental activation of bid by caspase-1 in a transgenic mouse model of ALS

Transgenic expression of mutant superoxide dismutase-1 (SOD1) produces an animal model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We have previously shown that the mitochondrial-dependent programmed cell death (PCD) pathway, including the redistribution of Bax, the cytosolic release of cytochrome c, and the activation of caspase-9, is recruited during neurodegeneration in spinal cords of transgenic mutant SOD1 mice. Herein, we show that the pro-PCD protein Bid is highly expressed in spinal cords of both wild-type and transgenic mutant SOD1 mice. While full-length Bid is found in the spinal cord of the two groups of mice, its cleaved form is only seen in transgenic mutant SOD1 mice, as early as the beginning of symptoms. In contrast, activated caspase-8, which is known to cleave Bid, is detected only at the end-stage of the disease. We also found that the expression of a dominant negative mutant of caspase-1 attenuates Bid cleavage as well as the mitochondrial release of cytochrome c, and the ensuing activation of caspase-9 and -3 in spinal cords of transgenic mutant SOD1 mice. These findings suggest that Bid cleavage may occur in this model by a pathway other than caspase-8 and shed light onto the molecular correlates of the previously reported beneficial effect of caspase-1 inhibition in transgenic mutant SOD1 mice.