Genotype-phenotype correlations to aid in the prognosis of individuals with uncommon 20q13.33 subtelomere deletions: a collaborative study on behalf of the 'association des Cytogénéticiens de langue Française'

The identification of subtelomeric rearrangements as a cause of mental retardation has made a considerable contribution to diagnosing patients with mental retardation. It is remarkable that for certain subtelomeric regions, deletions have hardly ever been reported so far. All the laboratories from the 'Association des Cytogénéticiens de Langue Fran?aise' were surveyed for cases where an abnormality of the subtelomere FISH analysis had been ascertained. Among 1511 cases referred owing to unexplained mental retardation, 115 (7.6%) patients showed a clinically significant subtelomeric abnormality. We report the clinical features and the molecular cytogenetic delineation of isolated de novo deletions on 20q13.33 in two cases. Detailed mapping was performed by micro-array CGH in one patient and confirmed by FISH in the two patients. We compare our data with the only three patients reported in the literature. Both patients shared a deleted region of approximately 1.33 Mb including 40 genes, with a 324 kb difference between the two patients. Haploinsufficiency for CHRNA4 and ARFGAP1 may have contributed towards a severe phenotype. In addition, the data in all patients suggest that haploinsufficiency for SOX18 may not cause the hypotrichosis-lymphedema-telangiectasia syndrome, or causes milder disease. Our study gives important information by defining the size of imbalance and better predicting the phenotype. Two clinically distinct phenotypes may be drawn, a mild mental retardation or a more complex and severe phenotype, according to the presence or absence of the CHRNA4 and ARFGAP1 genes respectively.     

The effect of vestibular nerve section on the expression of the hyaluronan in the frog, Rana esculenta

Following postganglionic lesion of the eighth cranial nerve, the changes in the expression of hyaluronan (HA), one of the extracellular matrix macromolecules, were examined in the medial (MVN) and lateral (LVN) vestibular nuclei and in the entry or transitional zone (TZ) of the nerve in the frog. HA was detected in different survival times by using a specific biotinylated hyaluronan-binding probe. HA expression was defined by the area-integrated optical density (AIOD), calculated from pixel intensities of digitally captured images. During the first postoperative days the perineuronal net (PN), a HA-rich area around the neurons, was not distinguishable from the surrounding neuropil in the MVN and LVN, characterized by a bilateral drop of AIOD specifically on the operated side. From postoperative day 14 onwards AIOD increased whilst the PN reorganized. In contrast, the AIOD wobbled up and down bilaterally without any trend in the TZ. Statistical analysis indicated that AIOD changes in the structures studied ran parallel bilaterally presumably because of the operation. Our results demonstrated for the first time that (1) the lesion of the eighth cranial nerve is accompanied by the modification of AIOD reflected HA expression in the MVN, LVN and TZ, (2) different tendencies exist in the time course of AIOD in the structures studied and (3) these tendencies are similar on the intact and operated sides. Our findings may suggest an area dependent molecular mechanism of HA in the restoration of vestibular function.     

Heme, heme oxygenase, and ferritin: how the vascular endothelium survives (and dies) in an iron-rich environment

Iron-derived reactive oxygen species are involved in the pathogenesis of numerous vascular disorders. One abundant source of redox active iron is heme, which is inherently dangerous when it escapes from its physiologic sites. Here, we present a review of the nature of heme-mediated cytotoxicity and of the strategies by which endothelium manages to protect itself from this clear and present danger. Of all sites in the body, the endothelium may be at greatest risk of exposure to heme. Heme greatly potentiates endothelial cell killing mediated by leukocytes and other sources of reactive oxygen. Heme also promotes the conversion of low-density lipoprotein to cytotoxic oxidized products. Hemoglobin in plasma, when oxidized, transfers heme to endothelium and lipoprotein, thereby enhancing susceptibility to oxidant-mediated injury. As a defense against such stress, endothelial cells upregulate heme oxygenase-1 and ferritin. Heme oxygenase opens the porphyrin ring, producing biliverdin, carbon monoxide, and a most dangerous product-redox active iron. The latter can be effectively controlled by ferritin via sequestration and ferroxidase activity. These homeostatic adjustments have been shown to be effective in the protection of endothelium against the damaging effects of heme and oxidants; lack of adaptation in an iron-rich environment led to extensive endothelial damage in humans.     

Comparing the young asthmatics running fitness

INTRODUCTION: Nowadays, doctors strongly recommend physical activity for asthmatic children, since the resulting improved physical fitness and psychological change also raise the quality of life. AIMS: The aim of this study was to compare the physical fitness of asthmatic children who regularly participate in therapeutic swimming, with asthmatic children who do not participate in this training and with non-swimming, healthy children using the 12 minute free running, Cooper test. METHOD: The children from the swimmer asthmatic group (n= 51, age = 9-22 yrs) took part in a special, long term, swimming exercise program (Gyene method). Whereas, the non-swimmer asthmatics (n = 28, age = 8-22 yrs) and the healthy children (n: 179, age: 9-22 yrs) only took part in the normal school physical education classes. Fitness was measured using the Cooper test. RESULTS: Data was collected from 258 subjects and showed that the fitness of swimmer asthmatics is significantly better than that of the non-swimmer asthmatics and even better than that of the healthy subjects (swimmer/ non swimmer asthmatic p = 0.01; swimmer asthmatic/ healthy p < 0.0001 Chi(2) test). The difference in the fitness acquired from swimming was the most pronounced for the 8-11 years old asthmatics, presumably because of greater motivational factors. No differences were found between genders for the two asthmatic groups, whereas healthy boys were found to have significantly greater levels of fitness than healthy girls. CONCLUSIONS: Fitness is substantially increased with regular swimming. The favourable effects of swimming are expressed not only in comparison with the non-swimmer asthmatics but with the healthy subjects too. The regular therapeutic swimming program helps the formation of running fitness too.     

"Turnaround time": a new parameter for the characterization of the overall efficacy of laboratory diagnostic processes

INTRODUCTION: The authors developed a special computer-aided routine in their laboratory for the calculation of "turnaround time" which parameter is suitable for the characterization of the overall efficacy of laboratory diagnostic processes. The turnaround time is defined as the interval between the arrival time of a sample in the laboratory and the time of clinical validation. It characterizes the efficacy of the result generation process very well, and therefore, is considered as an important parameter of laboratory quality control. METHODS: In their present study the authors analyzed the data of the urgent (stat), routine and special laboratory tests of 6 months and presented the median, 5- and 95-percentile values of turnaround time. Beside this, they calculated the rate of "outliers": the number of tests having a longer turnaround time value, than the defined maximal turnaround time (stat 1 hour, routine 4 hours, special 2-14 days). RESULTS: The median turnaround time values were 9-70 minutes for the stat tests and 33-190 minutes for the routine analytes. In case of special tests, the results were much more heterogeneous, in general non-automated hemostasis and immunochemistry assays, with low sample numbers had longer turnaround time values and higher number of outliers. Longitudinal analysis of routine tests showed clearly that turnaround time values became shorter in every unit during the 1st 6 months of 2006. Clinical validation is an important component altering turnaround time that can be shortened substantially with the installation of an autovalidation program. Based on the data of the authors the median turnaround time values of routine assays were shortened by 1-2 hours after introduction of autovalidation. The applied program for turnaround time analysis is suitable for evaluation of sample transfer times, too, that was presented by comparison of two "emergency units" having different sample transfer facilities. CONCLUSIONS: The described turnaround time analysis is part of the general routine processes in laboratories of the developed countries but is the first such trial in Hungary.     

Thromboembolic splenic infarction

Splenic infarction occurs as a consequence of systemic thromboembolization in association with several cardiovascular disorders. We describe a case of splenic infarction in a patient who had paroxysmal atrial fibrillation after aortic valve replacement. In an autopsy series of 96 consecutive cases of splenic infarction, only 10% had been suspected clinically even though the splenic infarctions had contributed substantially to morbidity and mortality in 44% of the cases. Thromboembolic causes were responsible for the splenic infarcts in 67% of the cases, and concomitant infarcts in other organ systems were found in 62%. Embolization of atheromatous debris from the aorta, thrombotic elements from the left ventricle (in dilated cardiomyopathy and acute myocardial infarction), and vegetations from infected valves are the most common settings in which thromboembolic splenic infarcts are noted. The clinical picture associated with splenic infarction is typically nonspecific; manifestations may include fever, tachycardia, and left-upper-quadrant tenderness. Computed tomographic scanning and, to a lesser degree, ultrasonography are the imaging techniques of choice for diagnosing splenic infarction.     

Septal Myectomy in Hypertrophic Cardiomyopathy: National Outcomes of Concomitant Mitral Surgery

Objectives

To assess the frequency and implications of mitral valve (MV) surgery at the time of septal myectomy (SM) for hypertrophic cardiomyopathy (HCM) in a national cohort.