Mesure de la pression artérielle et dépistage de l'hypertension chez l'enfant. [Blood pressure measurement and screening of hypertension in children].

Children with elevated blood pressure are at risk of being hypertensive in adulthood and of developing complications such as ventricular hypertrophy. Obesity is a cause of hypertension. Because the prevalence of obesity is increasing, some authors argue that the systematic screening for hypertension in children and adolescents is justified for early prevention and treatment. Sex, age and height all influence children's blood pressure. When elevated blood pressure is identified, complementary investigations and treatment might be necessary. However, due to the difficulties of obtaining a valid estimate of blood pressure, to the moderate tracking of blood pressure from childhood to adulthood, and the rarity of hypertension cases in childhood, the usefulness of systematic screening of hypertension during childhood is still controversial. Un enfant dont la pression artérielle est élevée a un risque accru d'être hypertendu à l'âge adulte et de présenter des complications telles que l'hypertrophie ventriculaire gauche. L'augmentation de la prévalence de l'obésité justifierait selon certains auteurs le dépistage systématique de l'hypertension dès le plus jeune âge afin d'instaurer des mesures préventives ou curatives précoces. Les normes de pression dépendent du sexe, de l'âge et de la taille de l'enfant. En cas de pression élevée, des investigations complémentaires, voire un traitement, peuvent être indiqués. Au vu des difficultés pour obtenir une mesure fiable, des incertitudes entachant la valeur pronostique d'une pression artérielle élevée et de la rareté des cas d'hypertension, il n'y a pas de consensus sur l'utilité du dépistage systématique de l'hypertension durant l'enfance.

Improved coronary artery definition with T2-weighted, free-breathing, three-dimensional coronary MRA.

BACKGROUND: Three-dimensional (3D) navigator-gated and prospectively corrected free-breathing coronary magnetic resonance angiography (MRA) allows for submillimeter image resolution but suffers from poor contrast between coronary blood and myocardium. Data collected over >100 ms/heart beat are also susceptible to bulk cardiac and respiratory motion. To address these problems, we examined the effect of a T2 preparation prepulse (T2prep) for myocardial suppression and a shortened acquisition window on coronary definition. METHODS AND RESULTS: Eight healthy adult subjects and 5 patients with confirmed coronary artery disease (CAD) underwent free-breathing 3D MRA with and without T2prep and with 120- and 60-ms data-acquisition windows. The T2prep resulted in a 123% (P<0. 001) increase in contrast-to-noise ratio (CNR). Coronary edge definition was improved by 33% (P<0.001). Acquisition window shortening from 120 to 60 ms resulted in better vessel definition (11%; P<0.001). Among patients with CAD, there was a good correspondence with disease. CONCLUSIONS: Free-breathing, T2prep, 3D coronary MRA with a shorter acquisition window resulted in improved CNR and better coronary artery definition, allowing the assessment of coronary disease. This approach offers the potential for free-breathing, noninvasive assessment of the major coronary arteries.

Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia.

Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10(-8)) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10(-4)) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.

Comparison of C-reactive protein and white blood cell count with differential in neonates at risk for septicaemia.

We prospectively compared the diagnostic value of C-reactive protein (CRP) and white blood cell counts for detection of neonatal septicaemia. Sensitivity and specifity in receiver operating characteristics, and positive and negative predictive value of CRP and white blood cell count were compared in 195 critically ill preterm and term newborns clinically suspected of infection. Blood cultures were positive in 33 cases. During the first 3 days after birth CRP elevation (sensitivity 75%, specifity 86%), leukopenia (67%/90%), neutropenia (78%/80%) and immature to total neutrophil count (I/T) ratio (78%/73%) were good diagnostic parameters, as opposed to band forms with absolute count (84%/66%) or percentage (79%/71%), thrombocytopenia (65%/57%) and toxic granulations (44%/94%). Beyond 3 days of age elevated CRP (88%/87%) was the best parameter. Increased total (84%/66%) or percentage band count (79%/71%) were also useful. Leukocytosis (74%/56%), increased neutrophils (67%/65%), I/T ratio (79%/47%), thrombocytopenia (65%/57%) and toxic granulations had a low specifity. The positive predictive value of CRP was 32% before and 37% after 3 days of age, that of leukopenia was 37% in the first 3 days. CONCLUSION: During the first 3 days of life CRP, leukopenia and neutropenia were comparably good tests while after 3 days of life CRP was the best single test in early detection of neonatal septicaemia. Serial CRP estimations confirm the diagnosis, monitor the course of infection and the efficacy of antibiotic treatment.

A pilot assessment of alpha-stat vs pH-stat arterial blood gas analysis after cardiac arrest.

PURPOSE: Resuscitated cardiac arrest (CA) patients typically receive therapeutic hypothermia, but arterial blood gases (ABGs) are often assessed after adjustment to 37°C (alpha-stat) instead of actual body temperature (pH-stat). We sought to compare alpha-stat and pH-stat assessment of Pao2 and Paco2 in such patients. MATERIALS AND METHODS: Using ABG data obtained during the first 24 hours of intensive care unit admission, we determined the impact of measured alpha vs calculated pH-stat on Pao2 and Paco2 on patient classification and outcomes for CA patients. RESULTS: We assessed 1013 ABGs from 120 CA patients with a median age of patients 66 years (interquartile range, 50-76). Median alpha-stat Pao2 changed from 122 (95-156) to 107 (82-143) mm Hg with pH-stat and median Paco2 from 39 (34-46) to 35 (30-41) mm Hg (both P < .001). Using the categories of hyperoxemia, normoxemia, and hypoxemia, pH-stat estimation of Pao2 reclassified approximately 20% of patients. Using the categories of hypercapnia, normocapnia, and hypocapnia, pH stat estimation of Paco2 reclassified approximately 40% of patients. The mortality of patients in different Pao2 and Paco2 categories was similar for pH-stat and alpha-stat. CONCLUSIONS: Using the pH-stat method, fewer resuscitated CA patients admitted to intensive care unit were classified as hyperoxemic or hypercapnic compared with alpha-stat. These findings suggest an impact of ABG assessment methodology on Pao2, Paco2, and patient classification but not on associated outcomes.

Obese and fit adolescents have lower blood pressure levels than obese and unfit counterparts.

The aim of the study was to assess the effects of physical fitness on the relationships between body mass index (BMI) and body fat (BF) on blood pressure (BP) levels. Cross-sectional study conducted in 25 schools of Lisbon (Portugal), including 2041 boys and 1995 girls aged 10-18. BF was assessed by bioimpedance. Cardiovascular fitness was assessed by the 20-meter shuttle run and classified as fit/unfit. Obesity (BMI or BF defined) was defined according to international criteria. In both sexes, BMI was positively related with systolic and diastolic BP, while BF was only positively related with diastolic BP z-scores. No interaction was found between fitness and BMI categories regarding BP levels, while for BF a significant interaction was found. Being fit reduced the BF-induced increase in the Odds ratio (OR) of presenting with high BP: OR (95% confidence interval) 1.01 (0.73-1.40) and 0.99 (0.70-1.38) for overweight and obese fit boys, respectively, the corresponding values for unfit overweight and obese boys being 1.33 (0.94-1.90) and 1.75 (1.34-2.28), respectively. The values were 0.88 (0.57-1.35) and 1.66 (0.98-2.80) for overweight and obese fit girls, respectively, the corresponding values for unfit overweight and obese being 1.63 (1.12-2.37) and 1.90 (1.32-2.73) respectively. No interaction was found between fitness and BMI-defined overweight and obesity. Being fit reduces the negative impact of BF on BP levels and high BP status in adolescents. This protective effect was not found with BMI.

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

Architectural and Functional Similarities between Trimeric ATP-Gated P2X Receptors and Acid-Sensing Ion Channels

ATP-gated P2X receptors and acid-sensing ion channels are two distinct ligand-gated ion channels that assemble into trimers. They are involved in many important physiological functions such as pain sensation and are recognized as important therapeutic targets. They have unrelated primary structures and respond to different ligands (ATP and protons) and are thus considered as two different ion channels. As a consequence, comparisons of the biophysical properties and underlying mechanisms have only been rarely made between these two channels. However, the recent determination of their molecular structures by X-ray crystallography has revealed unexpected parallels in the architecture of the two pores, providing a basis for possible functional analogies. In this review, we analyze the structural and functional similarities that are shared by these trimeric ion channels, and we outline key unanswered questions that, if addressed experimentally, may help us to elucidate how two unrelated ion channels have adopted a similar fold of the pore.

High sensitivity of immature GABAergic neurons to blockers of voltage-gated calcium channels.

The involvement of voltage-gated calcium channels in the survival of immature CNS neurons was studied in aggregating brain cell cultures by examining cell type-specific effects of various channel blockers. Nifedipine (10 microM), a specific blocker of L-type calcium channels, caused a pronounced and irreversible decrease of glutamic acid decarboxylase activity, whereas the activity of choline acetyltransferase was significantly less affected. Flunarizine (1-10 microM, a relatively unspecific ion channel blocker) elicited similar effects, that were attenuated by NMDA. The glia-specific marker enzymes, glutamine synthetase and 2',3'-cyclic nucleotide 3'-phosphohydrolase, were affected only after treatment with high concentrations of nifedipine (50 microM) or NiCl2 (100 microM, shown to block T-type calcium channels). Nifedipine (50 microM), NiCl2 (100 microM), and flunarizine (5 microM) also caused a significant increase in the soluble nucleosome concentration, indicating increased apoptotic cell death. This effect was prevented by cycloheximide (1 microM). Furthermore, the combined treatment with calcicludine (10 nM, blocking L-type calcium channels) and funnel-web spider toxin-3.3 (100 nM, blocking T-type channels) also caused a significant increase in free nucleosomes as well as a decrease in glutamic acid decarboxylase activity. In contrast, cell viability was not affected by peptide blockers specific for N-, P-, and/or Q-type calcium channels. Highly differentiated cultures showed diminished susceptibility to nifedipine and flunarizine. The present data suggest that the survival of immature neurons, and particularly that of immature GABAergic neurons, requires the sustained entry of Ca2+ through voltage-gated calcium channels.

Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

Simultaneous Optical Recording in Multiple Cells by Digital Holographic Microscopy of Chloride Current Associated to Activation of the Ligand-Gated Chloride Channel GABA(A) Receptor.

Chloride channels represent a group of targets for major clinical indications. However, molecular screening for chloride channel modulators has proven to be difficult and time-consuming as approaches essentially rely on the use of fluorescent dyes or invasive patch-clamp techniques which do not lend themselves to the screening of large sets of compounds. To address this problem, we have developed a non-invasive optical method, based on digital holographic microcopy (DHM), allowing monitoring of ion channel activity without using any electrode or fluorescent dye. To illustrate this approach, GABA(A) mediated chloride currents have been monitored with DHM. Practically, we show that DHM can non-invasively provide the quantitative determination of transmembrane chloride fluxes mediated by the activation of chloride channels associated with GABA(A) receptors. Indeed through an original algorithm, chloride currents elicited by application of appropriate agonists of the GABA(A) receptor can be derived from the quantitative phase signal recorded with DHM. Finally, chloride currents can be determined and pharmacologically characterized non-invasively simultaneously on a large cellular sampling by DHM.

Markedly reduced blood pressure responsiveness in endotoxemic rats; reversal by neuropeptide Y.

This study in conscious normotensive rats was performed to assess the effect of the vasoconstrictor peptide, neuropeptide Y (NPY), on blood pressure responsiveness to exogenous norepinephrine in endotoxaemia. NPY and endotoxin were infused at doses which had no effect on blood pressure, whether given alone or in combination. Endotoxin markedly reduced the pressor responses to bolus injections of norepinephrine. However, blood pressure responsiveness could be enhanced by infusing NPY simultaneously with the endotoxin. It is suggested that low dose NPY infusions may be clinically useful in reversing the reduced vascular responsiveness to pressor amines in shock.