Magnetic resonance imaging for abnormally invasive placenta: the added value of intravenous gadolinium injection.

OBJECTIVES: To assess the added value of intravenous gadolinium injection to magnetic resonance imaging (MRI) -based diagnosis of abnormally invasive placenta (AIP) and to examine this in relation to the radiologist's experience. DESIGN: Retrospective study. SETTING: Between March 2009 and October 2012, 31 pregnant women who had previous caesarean delivery together with a placenta praevia and suspected placenta accreta on ultrasound in the third trimester of pregnancy. POPULATION: All were offered MRI examination, and made aware of the limited (but so far reassuring) data regarding fetal safety of gadolinium. Twenty pregnant women agreed to undergo prenatal MRI (1.5 T), with and without gadolinium injection. METHODS: Two sets of MRI examinations without and with gadolinium were reviewed independently 2 months apart by two senior and two junior radiologists; all were blinded to the outcome (known in all cases). Histopathological findings and clinical signs of AIP were considered as the defining criteria of diagnosis. MAIN OUTCOME MEASURE: accuracy of MRI with and without gadolinium was assessed. RESULTS: Eight of the 20 women had confirmed abnormal placental invasion. The overall performance of both sets of readers in detecting AIP increased with gadolinium-sensitivity and specificity of 75.0% (42.0-100%) and 47.9% (19.9-75.9%) increasing to 87.5% (57.1-100%) and 60.4% (33.9-86.9%), respectively (P = 0.04). The added value of gadolinium remained irrespective of radiologist's experience, although senior radiologists performed better overall (sensitivity and specificity of 87.5% and 62.5% versus 62.5% and 33.3%, respectively, increasing with injection to 93.8% and 70.8% versus 81.3% and 50%, respectively; P < 10-4 ). CONCLUSION: There was an association between gadolinium use and improvement in MRI-based diagnostic accuracy for the diagnosis of AIP, for both junior and senior radiologists. TWEETABLE ABSTRACT: Gadolinium injection improves MRI performance of radiologists for the diagnosis of placenta accreta.

Fetal intracerebral hemorrhage and cataract: think COL4A1.

The COL4A1 gene encodes the alpha1 chain of type IV collagen, a crucial component of nearly all basement membranes. Mutations in COL4A1 were first associated with cerebral microangiopathy and familial porencephaly. Recently, several authors have reported mutations in COL4A1 as a Mendelian cause of prenatal onset intracranial hemorrhage (ICH). We report two cases of prenatal ICH associated with cataract and suggest that COL4A1 mutation should be envisaged in fetuses with prenatal ICH, especially in the presence of lens abnormalities at ultrasound examination.

Mesenchymal stem cells protect CNS neurons against glutamate excitotoxicity by inhibiting glutamate receptor expression and function.

Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury. Their beneficial effects are attributed to the activation of endogenous CNS protection and repair processes as well as immune regulation but their mechanisms of action are poorly understood. Here we investigated the neuroprotective effects of mouse MSC in rodent MSC-neuron co-cultures and mice using models of glutamate excitotoxicity. A 24h pre-culture of mouse primary cortical neurons with MSC protected them against glutamate (NMDA) receptor-induced death and conditioned medium from MSC (MSC CM) was sufficient for this effect. Protection by MSC CM was associated with reduced mRNA levels of genes encoding NMDA receptor subunits, and increased levels for genes associated with non-neuronal and stem cell types, as shown by RT-PCR and cDNA microarray analyses. Changes in gene expression were not associated with alterations in cell lineage representation within the cultures. Further, MSC CM-mediated neuroprotection in rat retinal ganglion cells was associated with reduced glutamate-induced calcium influx. The adoptive transfer of EGFP(+)MSC in a mouse kainic acid epilepsy model also provided neuroprotection against glutamate excitotoxicity in vivo, as shown by reduced neuron damage and glial cell activation in the hippocampus. These results show that MSC mediate direct neuroprotection by reducing neuronal sensitivity to glutamate receptor ligands and altering gene expression, and suggest a link between the therapeutic effects of MSC and the activation of cell plasticity in the damaged CNS.

Benzodiazepine-like hypnotics and the associated risk of road traffic accidents.

The aim of the study was to investigate the association between the use of benzodiazepine or benzodiazepine-like hypnotics and the risk of road traffic accidents. Data from three French national databases were matched: the health-care insurance database, police reports, and the police database of injury-related traffic accidents. A total of 72,685 drivers involved in injury-related road traffic accidents in France, from 2005 to 2008, were included in the study. The risk of being responsible for a traffic accident was higher in users of benzodiazepine hypnotics (odds ratio (OR) = 1.39 (1.08-1.79)) and in the 155 drivers to whom a dosage of more than one pill of zolpidem a day had been dispensed during the 5 months before the collision (OR = 2.46 (1.70-3.56)). No association was found between the use of zopiclone and risk of traffic accidents. Although this study did not find any association between the use of zolpidem as recommended and causation of traffic accidents, the potential risk related to possible abuse of the drug and risky driving behaviors should be further investigated. The results related to benzodiazepine hypnotics are consistent with those of previous studies.

Functional, molecular and proteomic characterisation of bone marrow mesenchymal stem cells in rheumatoid arthritis.

OBJECTIVE: Bone marrow (BM) mesenchymal stem cells (MSCs) are being considered as potential therapeutic agents in various inflammatory autoimmune diseases for their tissue-repair and anti-inflammatory tissue-protective properties. This study investigates the reserves and function, the molecular and proteomic profile and the differentiation potential of BM MSCs in patients with active rheumatoid arthritis (RA). METHODS: We evaluated the frequency of MSCs in the BM mononuclear cell fraction using a limiting dilution assay, the proliferative/clonogenic potential and the capacity of cells to differentiate towards the osteogenic/chondrogenic/adipogenic lineages using appropriate culture conditions. We also assessed the molecular and proteomic characteristics in terms of inflammatory cytokine gene and protein expression, the relative telomere length and the survival characteristics of BM MSCs. RESULTS: MSCs from patients with RA (n = 26) and age- and sex-matched healthy individuals (n = 21) were similar in frequency, differentiation potential, survival, immunophenotypic characteristics, and protein profile. Patient MSCs, however, had impaired clonogenic and proliferative potential in association with premature telomere length loss. Transcriptome analysis revealed differential expression of genes related to cell adhesion processes and cell cycle progression beyond the G1 phase. Previous treatment with methotrexate, corticosteroids, anti-cytokine and biological agents or other disease-modifying anti-inflammatory drugs did not correlate with the clonogenic and proliferative impairment of BM MSCs. CONCLUSION: In spite of some restrictions related to the impaired clonogenic and proliferative potential, our findings support the use of autologous BM MSCs in RA and may have important implications for the ongoing efforts to repair tissue injury commonly seen in the course of the disease.

[MRI aspects of anoxic-ischemic encephalopathy of the term and premature newborn]. / Aspects IRM de l'encéphalopathie anoxo-ischémique du nouveau-né à terme et du prémature.

These past few years have seen an increasing role of MRI in the investigation of neonatal cerebral anoxic-ischemic pathology. This is due not only to greater precision in diagnosing lesion extension, but also to earlier detection of lesions with the diffusion of weighted imagery. The aim of this iconographic review is to illustrate the main MRI aspects of anoxic-ischemic encephalopathy in a pedagogical way. After a brief physiopathology reminder, the different cerebral lesions are studied in a first chapter on the premature newborn pathology and a second chapter on full-term newborn pathology.

Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia.

Septo-optic dysplasia (SOD; De Morsier syndrome) is a rare congenital disorder characterized by the absence of the septum pellucidum (SP), hypoplasia of the optic chiasma and nerves, and various types of hypothalamic-pituitary dysfunction. We report on two fetuses with absence of the SP diagnosed by ultrasound examination at 29 and 30 gestational weeks. In the first case the diagnosis of SOD was suspected in utero and confirmed postnatally; to the best of our knowledge this is the first report of the prenatal diagnosis of SOD. In the second case absence of the SP appeared to be isolated and no visual or endocrine impairment were detected after birth.

Expression pattern of connexin gene products at the early developmental stages of the mouse cardiovascular system.

The synchronized contraction of myocytes in cardiac muscle requires the structural and functional integrity of the gap junctions present between these cells. Gap junctions are clusters of intercellular channels formed by transmembrane proteins of the connexin (Cx) family. Products of several Cx genes have been identified in the mammalian heart (eg, Cx45, Cx43, Cx40, and Cx37), and their expression was shown to be regulated during the development of the myocardium. Cx43, Cx40, and Cx45 are components of myocyte gap junctions, and it has also been demonstrated that Cx40 was expressed in the endothelial cells of the blood vessels. The aim of the present work was to investigate the expression and regulation of Cx40, Cx43, and Cx37 during the early stages of mouse heart maturation, between 8.5 days post coitum (dpc), when the first rhythmic contractions appear, and 14.5 dpc, when the four-chambered heart is almost completed. At 8.5 dpc, only the reverse-transcriptase polymerase chain reaction technique has allowed identification of Cx43, Cx40, and Cx37 gene transcripts in mouse heart, suggesting a very low activity level of these genes. From 9.5 dpc, all three transcripts became detectable in whole-mount in situ-hybridized embryos, and the most obvious result was the labeling of the vascular system with Cx40 and Cx37 anti-sense riboprobes. Cx40 and Cx37 gene products (transcript and/or protein) were demonstrated to be expressed in the vascular endothelial cells at all stages examined. By contrast, only Cx37 gene products were found in the endothelial cells of the endocardium. In heart, Cx37 was expressed exclusively in these cells, which rules out any direct involvement of this Cx in the propagation of electrical activity between myocytes and the synchronization of contractions. Between 9.5 and 11.5 dpc, Cx40 gene activation in myocytes was demonstrated to proceed according to a caudorostral gradient involving first the primitive atrium and the common ventricular chamber (9.5 dpc) and then the right ventricle (11.5 dpc). During this period of heart morphogenesis, there is clearly a temporary and asymmetrical regionalization of the Cx40 gene expression that is superimposed on the functional regionalization. In addition, comparison of Cx40 and Cx43 distribution at the above developmental stages has shown that these Cxs have overlapping (left ventricle) or complementary (atrial tissue and right ventricle) expression patterns.

Developmental regulation of connexin 40 gene expression in mouse heart correlates with the differentiation of the conduction system.

In adult mouse heart, CX40 is expressed in the atria and the proximal part of the ventricular conduction system (the His bundle and the upper parts of the bundle branches). This cardiac tissue is specialized in the conduction of the electrical impulse. CX40 is the only mouse connexin known to be expressed in these parts of the adult conductive tissue and is thus considered as a marker of the conduction system. In the present report, we investigated CX40 expression and distribution during mouse heart development. We first demonstrate that CX40 mRNA is regulated throughout development, as are other heart connexin transcripts, i.e., CX37, CX43, and CX45, with a decreasing abundance as development proceeds. We also show that the CX40 transcript and protein are similarly regulated, CX40 being expressed as two different phosphorylated and un-phosphorylated forms of 41 and 40 kDa, respectively. Surprisingly, distribution studies demonstrated that CX40 is widely expressed in 11 days post-coitum (dpc) embryonic heart, where it is detected in both the atria and ventricle primordia. As development proceeds, the CX40 distribution pattern in the atria is maintained, whereas a more dynamic pattern is observed in the ventricles. From 14 dpc onwards, as the adult ventricular conduction system differentiates, CX40 decreases in the trabecular network and it is preferentially distributed in the ventricular conduction system. CX40 is thus the marker of the early differentiating conduction system. It is hypothesized that the conduction system is present in unorganized "embryonic" form at 11 dpc and transdifferentiates by 14 dpc into the adult conduction system.

Varying heparin requirements in hemodialysis patients receiving erythropoietin.

A two-phase study was undertaken to investigate the incidence, extent, and management of increased heparin needs occurring during erythropoietin (EPO) therapy in the hemodialysis patient. Individual heparin doses and activated clotting time (ACT) test values were the parameters used to indicate changes in heparin requirements. It appears that increased heparin requirements are frequently associated with EPO therapy, and awareness of this finding, coupled with close ACT monitoring, may possibly prevent complications associated with undetected increases in heparin requirement.

Learned caloric adjustment of human intake.

The time course of caloric compensation of food intake was studied in human subjects presented with a new calorically dilute snack food under naturalistic conditions. In a preliminary test, two versions of the snack food, normal in calories (NC) or low in calories (LC), were found equally palatable by the subjects (15 to 17-year-old boys). In the first part of the experiment two groups were presented with a 125g serving of either NC or LC version as an afternoon snack. Intakes during the subsequent dinner (1 h later) were measured. In the second part of the experiment, the same subjects were allowed to habituate to NC or LC, i.e. on five consecutive days, subjects were served NC or LC food ad libitum at afternoon snack-time; servings and left-overs were weighed. On the sixth day, the snack was a 125 g serving of the habitual food and dinner intakes were measured. It was shown that in these adolescent males a 200 kcal difference in the afternoon snack was not immediately compensated for by dinner intake. However, precise caloric adjustment occurred after habituation. This casts in question the value for weight control of such a use of food products having lower caloric content than conventional products.

Lipotropic effect of estradiol-17 beta in fed and fasted lactating cows.

The lipotropic effect of estradiol-17 beta was measured in seven nonpregnant Holstein-Friesian cows 2 to 5 wk into lactation. The experiment was divided into an initial 3-day control period, 19 days treatment, and 2 days fast. Jugular blood samples were taken twice daily during the control period, the last 2 days of treatment, and the fast. After the control period, four cows received daily injections of estradiol-17 beta benzoate (15 mg) in sesame oil for the remainder of the experiment whereas three cows received injections of sesame oil only. Estradiol-17 beta did not change triglyceride concentration of plasma during the treatment period but increased it markedly during fast. Estradiol-17 beta increased the free glycerol concentration of plasma during treatment. Cholesterol concentrations of plasma showed a consistent trend lower in the estradiol group during treatment and fast. No differences were apparent in glucose and blood ketone concentrations. The concentration of insulin in plasma was lower for the estradiol group during treatment. Estradiol-17 beta appears to have a similar effect on lipid metabolism in dairy cows to other species. However, it exerted a strong lipotropic effect only under fasting.