Blood lead levels and risk factors in young children in France, 2008–2009

BackgroundThe exposure of children to lead has decreased in recent years, thanks notably to the banning of leaded gasoline. However, lead exposure remains a matter of public health concern, because no toxicity threshold has been observed, cognitive effects having been demonstrated even at low levels. It is therefore important to update exposure assessments. A national study was conducted, in 2008–2009, to determine the blood lead level (BLL) distribution in children between the ages of six months and six years in France. We also assessed the contribution of environmental factors.MethodsThis cross-sectional survey included 3831 children recruited at hospitals. Two-stage probability sampling was carried out, with stratification by hospital and French region. Sociodemographic characteristics were recorded, and blood samples and environmental data were collected by questionnaire. Generalized linear model and quantile regression were used to quantify the association between BLL and environmental risk factors.ResultsThe geometric mean BLL was 14.9 μg/l (95% confidence interval (CI) = [14.5–15.4]) and 0.09% of the children (95% CI = [0.03–0.15]) had BLLs exceeding 100 μg/l, 1.5% (95% CI = [0.9–2.1] exceeding 50 μg/l. Only slight differences were observed between French regions. Environmental factors significantly associated with BLL were the consumption of tap water in homes with lead service connections, peeling paint or recent renovations in old housing, hand-mouth behavior, passive smoking and having a mother born in a country where lead is often used.ConclusionsIn children between the ages of one and six years in France, lead exposure has decreased over the last 15 years as in the US and other European countries. Nevertheless still 76,000 children have BLL over 50 μg/l and prevention policies must be pursued, especially keeping in mind there is no known toxicity threshold.     

Status and prospect of current inotropic agents

Critical reassessment of established inotropic drugs such as the phosphodiesterase inhibitors and the digitalis glycosides has reaffirmed the need for novel cardiotonic agents that will not only beneficially affect the haemodynamic and functional impairment of patients with overt congestive heart failure, but also prevent its clinical manifestation and reduce the high mortality. None of the drugs examined in these directions - calcium sensitisers, β-receptor blockers, sodium channel modulators, digitalis derivatives - have been shown to achieve these goals. The research on endogenous digitalis did not, as was hoped, reveal a general strategy for improving the therapeutic index of cardiac glycosides. The proof that Na+/K+-transporting ATPase of cardiac muscle is the molecular point of attack (receptor) for the inotropic and toxic effects of digitalis-like acting C/D-cis and C/D-trans steroids revealed the cyclopentano-perhydrophenanthrene nucleus as their common pharmacophoric lead structure. This has opened a wide field for lead development in the direction of derivatives that favourably discriminate between the inotropy-linked α1-isoform and the toxicity-linked α3-isoform of Na+/K+-ATPase as the basis for the design of inotropic agents with high therapeutic margin.     

Preprocedural computed tomography before cardiac implanted electronic device lead extraction: Indication,technique, and approach to interpretation

Cardiac implantable electronic devices (CIEDs) frequently need to be extracted due to infection, hardware failure, and other causes. The extraction of the CIED is typically performed using percutaneous methods. While these procedures are mostly performed without incident there is a small risk of significant complications. Dedicated imaging pre‐CEID removal to include the central veins and heart with multidetector computed tomography (MDCT) can be utilized to evaluate the lead course and termination, the integrity of the central veins and cardiac chambers, and identify potential complications that may alter the lead extraction procedure as well as reimplantation of subsequent leads. Indications for preprocedural imaging, the technique of dedicated preprocedural lead extraction MDCT, and the approach to the interpretation of the images is discussed in this review.     

The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer

Breast cancer is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer still represent a real unmet medical challenge. Previous studies have shown that chloropyramine ( C4 ) inhibits FAK‐VEGFR3 signalling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μm ) that would not be compatible with further drug development against invasive breast cancer driven by FAK signalling. In this study, molecular modelling guided structural modifications have been introduced to the chloropyramine C4 scaffold to improve its activity in breast cancer cell lines. Seventeen compounds were designed and synthesized, and their antiproliferative activity was evaluated against three human breast cancer lines (MDA‐MB‐231, BT474 and T47D). Compound 5c was identified to display an average activity of IC₅₀ = 23.5–31.3 μm , which represents a significant improvement of C4 activity in the same assay model. Molecular modelling and pharmacokinetic studies provided more promising insights into the mechanistic features of this new series.     

Long-term survival following transvenous lead extraction: Importance of indication and comorbidities

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