Genetic testing in congenital heart disease:A clinical approach

Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.

Electrophysiological Evidence against the Magnocellular Deficit Theory in Developmental Dyslexia

Over the last two decades, the hypothesis of a magnocellular deficit in dyslexia has raised considerable interest and controversy. Using an electrophysiological procedure (visual evoked potentials, VEP), we compared magnocellular and parvocellular contrast and spatial frequency-response functions between phonological dyslexics (n = 16) and a typical reading group (n = 12) matched for age and socioeconomic background. No significant differences were found between the two groups in the amplitude of the VEP components associated with either magnocellular or parvocellular responses. However, topographic analyses revealed a group difference in the distribution of amplitude in the right frontal and left temporal regions, which appeared to be underactivated in dyslexics. These results suggest a deficit in the higher-level cortical regions involved in phonological and/or linguistic processing, and calls into question the notion of a magnocellular involvement in dyslexia.

Pandemic influenza 2009: Impact of vaccination coverage on critical illness in children, a Canada and France observational study

AIM To study the impact of vaccination critical illness due to H1N1pdm09, we compared the incidence and severity of H1N1pdm09 infection in Canada and France.METHODS We studied two national cohorts that included children with documented H1N1pdm09 infection, admitted to a pediatric intensive care unit(PICU) in Canada and in France between October 1, 2009 and January 31, 2010.RESULTS Vaccination coverage prior to admission to PICUs was higher in Canada than in France(21% vs 2% of children respectively, P < 0.001), and in both countries, vaccination coverage prior to admission of these critically ill patients was substantially lower than in the general pediatric population(P < 0.001). In Canada, 160 children(incidence = 2.6/100000 children) were hospitalized in PICU compared to 125 children(incidence = 1.1/100000) in France(P < 0.001). Mortality rates were similar in Canada and France(4.4% vs 6.5%, P = 0.45, respectively), median invasive mechanical ventilation duration and mean PICU length of stay were shorter in Canada(4 d vs 6 d, P = 0.02 and 5.7 d vs 8.2 d, P = 0.03, respectively). H1N1pdm09 vaccination prior to PICU admission was associated with a decreased risk of requiring invasive mechanical ventilation(OR = 0.30, 95%CI: 0.11-0.83, P = 0.02).CONCLUSION The critical illness due to H1N1pdm09 had a higher incidence in Canada than in France. Critically ill children were less likely to have received vaccination prior to hospitalization in comparison to general population and children vaccinated had lower risk of ventilation.

Normalized intervertebral disc MRI signal as a biomarker of pain

The drop in the MRI signal intensity, analysed without any normalisation, was found related to the intervertebral disc degeneration, but its association with low back pain remains controversial. The authors developed the analysis of MR signal intensity distribution (AMRSID) method that analyzes the 3D distribution of the normalized T2-weighted MR signal intensity within the intervertebral disc using descriptive statistics of histograms and weighted centers. In this study, we hypothesized that the distribution of the normalized MRI signal intensity within T2- weighted images of the intervertebral disc is a bio-marker of low back pain (LBP) independently of age and disc degenerescence. The aims were to: 1) characterize intervertebral disc degeneration in vertebral fracture from MR T1-weighted and T2-weighted images;2) evaluate the sensitivity of the normalized MRI signal distribution to the presence of LBP, discs height loss and aging. We prospectively studied 22 patients who underwent an MRI acquisition within 48h after an accidental lumbar vertebral fracture. The presence of prefracture low back pain, spinal stenosis, annular disruption, intervertebral disc height loss was noted from each patient’s medical record. The presence of Modic changes, High-Intensity Zones (HIZs) and vertebral endplate perforations was recorded from MRI. The descriptive statistics of the normalized T2-weighted signal were compared using one-way ANOVAs and a principal component analysis was proposed. MRI, associated to normalisation of the signal intensity and principal component analysis, offers a remarkable potential for in-vivo imaging and analysis of vertebral fractures and adjacent tissues for the patient’s follow-up. The mean normalized MRI signal intensity of the adjacent intervertebral disc to the vertebral fracture was found to be a bio-marker of pain, independently of age and disc degeneration. However, the parameters describing the distribution of the normalized signal intensity were found to be not sensitive to the presence of low back pain, discs height loss and aging. Further studies need to be performed to detect small abnormalities that may explain the presence of LBP.

Assessment of Mechanical Properties of Muscles from Multi-Parametric Magnetic Resonance Imaging

We hypothesized that a relationship existed between the mechanical properties and the magnetic resonance imaging (MRI) parameters of muscles, as already demonstrated in cartilaginous tissues. The aim was to develop an indirect evaluation tool of the mechanical properties of degenerated muscles. Leg and arm muscles of adult rabbits were dissected, and tested 12 hours post mortem, in a state of rigor mortis, or 72 hours post mortem, in a state of post-rigor mortis. The tests consisted of a multi-parametric MRI acquisition followed by a uniaxial tensile test until failure. The statistical analysis consisted of multiple linear regressions and principal component analysis. Significant differences existed between the rigor mortis and post-rigor mortis groups for E but not for the MRI parameters. 78%, 60% or 33% of the Young’s modulus could be explained by the MRI parameters in the post-rigor mortis group, rigor mortis group or both groups respectively. These relationships were confirmed by the principal component analysis. The proposed multi-parametric MRI protocol associated to principal component analysis is a promising tool for the indirect evaluation of muscle mechanical properties and should be useful to find biomarkers and predictive factors of the evolution of the pathologies.

早期大剂量左旋甲状腺素治疗先天性甲状腺功能减退患儿入学时的认知能力和行为

目的:为了评价经大剂量左旋甲状腺素早期治疗的先天性甲状腺功能减退(CH)患儿入学时的认知能力和行为。试验设计:18例先天性甲状腺功能减退的患儿(CH:9例重度和9例中度,重、中度的诊断是依据膝盖骨的骨骺分别【或≥0.05cm2),从中位年龄14d起,接受中位剂量12.0μg/(kg·d)的左旋甲状腺素治疗。

新生儿胆汁淤积症与胎儿期心律不齐相关

We evaluated the consequence of different types of fetal arrhythmia in the development of neonatal cholestasis.The charts of 38 children born at St.Justine Hospital between 1993 and 2001 with sustained and hemodynamically significant fetal arrhythmias were studied: 19 with supraventricular tachycardia, 14 with atrial flutter, and 5 with atrio-ventricular (AV) block.Six of these 38 children presented with cholestasis.The average duration of arrhythmia was 15.7 days in the noncholestatic group, compared with 40.3 days in the cholestatic group (P<.05).The three infants with supraventricular tachycardia who developed cholestasis survived and resolved their cholestasis, whereas 2 of 3 infants with AV block died.No infant with atrial flutter developed cholestasis.We conclude that newborns who developed tachyarrhythmia during their fetal life can show transient neonatal cholestasis.In patients with AV block, severe and irreversible liver failure could be observed.In addition, extensive collapse of the stroma and the absence of hepatocytes (foie vide) also were observed in a patient with anti-Ro antibodies.

大肠埃希菌O157:H7相关的溶血性尿毒综合征患儿中降钙素原的作用

Shiga toxin producing Escherichia coli (STEC) are noninvasive enteric pathogens that may cause hemorrhagic colitis (HC) and diarrhea-associated hemolytic uremic syndrome (D+HUS). We hypothesized that development of D+HUS is associated with increased serum procalcitonin (PCT) levels. PCT was measured by an immunoluminometric assay in 113 patients. Concentrations of PCT were different in normal controls,disease control groups (rotavirus enteritis,HC due to non-STEC pathogens,chronic renal failure),and children with uncomplicated O157:H7HC or D+HUS. Children with D+HUS showed higher PCT levels than those with uncomplicated O157:H7 HC,and increased concentrations were noted in cases requiring peritoneal dialysis. Severely increased concentrations were observed in children with D+HUS on d 5 or 6 after the onset of enteritis,whereas serial measurements in those with uncomplicated O157:H7 HC remained within the normal range throughout the first week of illness. PCT was correlated with serum concentrations of lipopolysaccharide (LPS)-binding protein and serum levels of alanine aminotransferase. Using two separate sets of real-time PCR primers,we were unable to detect elevated PCT mRNA transcripts in nonadherent undifferentiated (monocytic) or differentiated (macrophage-like) THP-1 cells stimulated with purified Shiga toxin-1 and/or LPS. Our data show that serum levels of PCT are associated with the severity of illness in children with D+HUS. Further studies are needed to determine the role of PCT in the pathogenesis of thrombotic microangiopathy associated to childhood D+HUS.

Chronic Immune Activation and Sexual Exposure among HIV Serodiscordant Couples in Senegal

Purpose: In Sub-Saharan Africa, an important proportion of incident HIV cases occur among heterosexual serodiscordant couples (HSDC) but the majority of HIV negative partners can remain seronegative. These are called HIV-exposed seronegative (HESN). We aimed to compare immune activation (IA) levels between HESN, their HIV infected counterparts (HIV+ partners) and HIV unexposed uninfected individuals (HIV-neg Controls) and to evaluate the association between sexual exposure to HIV (SEHIV) and IA. Methods: We conducted a cross-sectional study in Dakar, Senegal on 148 participants recruited between November 2013 and February 2014: 40 HIV-neg Controls, 54 HESN and 54 HIV+ Partners. SEHIV was evaluated individually using questionnaires. IA level was measured by plasma level of β2-microglobulin (β2m). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the different associations. Results: The median levels of β2m were 1.57 mg/l (IQR: 1.37 - 1.77), 2.14 mg/l (IQR: 1.76 - 2.43) and 2.24 mg/l (IQR: 1.80 - 3.17) for HIV-neg Controls, HESN and HIV+ partners, respectively. After adjustment, HESN had similar levels of IA with HIV+ partners but significantly higher than that of HIV-neg Controls (adjusted OR = 6.28;95% CI: [2.19 - 18.00]). The association between IA and SEHIV was evaluated in the HIV negative individuals. High frequency of SEHIV was associated with a β2m > 2.2 mg/l (OR = 6.56;95% CI: [1.71 - 25.21]);significantly more than median cut off value of >1.81 mg/l. Conclusions: Our study shows that, despite being uninfected with HIV, HESN individuals show a high level of IA, which was depended on the level of SEHIV.

儿童功能性胃肠病罗马Ⅳ标准

罗马标准是目前关于功能性胃肠病（ FGID）分类最全面且不断更新的标准。罗马Ⅰ、Ⅱ标准分别于1994年、1999年发布。罗马Ⅱ标准开始单列儿童FGID分类。2006年，根据年龄不同，婴幼儿（0-36个月）和儿童（〉36个月） FGID的罗马Ⅲ诊断标准发布，但相关的流行病学、病理生理学、诊断检查、治疗策略以及预后等资料都很少。