Screening for pre-eclampsia in the first trimester: role of maternal hemodynamics and bioimpedance in non-obese patients.

OBJECTIVE: To test if maternal hemodynamics and bioimpedance, assessed at the time of combined screening for PE, are able to identify in the first trimester of gestation normotensive non-obese patients at risk for pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). METHODS: One hundred and fifty healthy nulliparous non-obese women (body mass index < 30 kg/m2 ) in the first trimester of pregnancy underwent assessment by UltraSonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters, bioimpedance analysis to characterize body composition, and combined screening for PE (assessment of maternal history, biophysical and maternal biochemical markers). Patients were followed until term, noting the appearance of PE and/or IUGR. RESULTS: One hundred and thirty-eight patients had an uneventful pregnancy (controls), while 12 (8%) developed complications (cases). USCOM showed, in cases compared with controls, lower cardiac output (5.6 ± 0.3 vs 6.7 ± 1.1 L/min, P < 0.001), lower inotropy index (1.54 ± 0.38 vs 1.91 ± 0.32 W/m2 , P < 0.001) and higher total vascular resistance (1279.8 ± 166.4 vs 1061.4 ± 179.5 dynes × s/cm5 , P < 0.001). Bioimpedance analysis showed, in cases compared with controls, lower total body water (53.7 ± 3.3% vs 57.2 ± 5.6%, P = 0.037). Combined screening was positive for PE in 8% of the controls and in 50% of the cases (P < 0.001). After identification of cut-off values for USCOM and bioimpedance parameters, forward multivariate logistic regression analysis identified as independent predictors of complications in pregnancy the inotropy index (derived by USCOM), fat mass (derived from bioimpedance analysis) and combined screening. CONCLUSIONS: Combined screening for PE and assessment of bioimpedance and maternal hemodynamics can be used to identify early markers of impaired cardiovascular adaptation and body composition that may lead to complications in the third trimester of pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Genome-wide evaluation and discovery of vertebrate A-to-I RNA editing sites.

RNA editing by adenosine deamination, catalyzed by adenosine deaminases acting on RNA (ADAR), is a post-transcriptional modification that contributes to transcriptome and proteome diversity and is widespread in mammals. Here we administer a bioinformatics search strategy to the human and mouse genomes to explore the landscape of A-to-I RNA editing. In both organisms we find evidence for high excess of A/G-type discrepancies (inosine appears as a guanosine in cloned cDNA) at non-polymorphic, non-synonymous codon sites over other types of discrepancies, suggesting the existence of several thousand recoding editing sites in the human and mouse genomes. We experimentally validate recoding-type A-to-I RNA editing in a number of human genes with high scoring positions including the coatomer protein complex subunit alpha (COPA) as well as cyclin dependent kinase CDK13.

Diagnostic obturator nerve block for inguinal and back pain: a recovered opinion.

Peripheral nerve blocks are very useful in diagnosing certain pain conditions. We report a case of chronic inguinal and back pain secondary to hip arthropathy. An obturator nerve block was used to help determine the origin of the pain.

Opioid agonist affinity in the guinea-pig ileum and mouse vas deferens.

The affinity of morphine, normorphine, methadone, Tyr-D-Ala-Gly-MePhe-NH(CH2)2(N-O)(CH3)2 (RX 783030), [D-Ala2,D-Leu5]enkephalin (DADLE), ketazocine and ethylketocyclazocine (EKC) were determined for their pharmacological receptors in two bioassay tissues, the guinea-pig ileum and the mouse vas deferens (MVD). The method involved the use of the irreversible antagonist, beta-chlornaltrexamine (beta-CNA), and the method of partial receptor blockade. The agonist concentration-effect curves were displaced to the right with decreasing maximum effect, a pattern typical of partial, irreversible blockade of receptors. The concentrations of beta-CNA required to produce a rightward displacement in the concentration-effect curves for different agonists, ranged between 2 and 3000 nM. No similarity was found between the IC50 and the dissociation constant (KA), values predicted to be equivalent only if a linear relationship exists between receptor occupation and observed effect; the dissociation constant for the agonists were between 3 and 218 times larger than the IC50 values. When methadone was used as the agonist in the guinea-pig ileum, beta-CNA produced parallel displacement of the concentration-effect curve, regardless of the blocking concentration chosen, preventing the determination of KA for this agonist, in this tissue; this problem was not encountered in the mouse vas deferens. The KA of morphine, RX 783030 and ketazocine were found not to differ in the guinea-pig ileum and mouse vas deferens. As expected, DADLE had significantly different affinity in the two tissues, showing 117-fold lower affinity in the guinea-pig ileum. Surprisingly, the normorphine affinity was found to be 7-fold higher in the guinea-pig ileum. While the difference in affinity of DADLE may be due to the suggested lack of functional delta receptors in the guinea-pig ileum, the difference in affinity seen with normorphine, but not morphine, in the two tissues is difficult to explain. Taken together with the insensitivity of methadone to beta-CNA blockade in the guinea-pig ileum, but not mouse vas deferens, the difference in the affinity of normorphine in these tissues may suggest the possibility of differences in local milieu of mu receptors or of mu receptor subtypes in the two tissues. The results provide fundamental information regarding opioid agonist affinity in two standard bioassays in vitro, and support the view of (1) a difference in receptors activated by DADLE in the guinea-pig ileum (mu) and mouse vas deferens (delta), as well as (2) possible differences in mu-receptors in these tissues.

Activity of mu- and delta-selective opioid agonists in the guinea pig ileum preparation: differentiation into peptide and nonpeptide classes with beta-funaltrexamine.

Previous studies have demonstrated that pretreatment of guinea pig longitudinal muscle-myenteric plexus ileal preparations with the highly selective noncompetitive mu antagonist beta-funaltrexamine (beta-FNA) causes an increase in the Ke value for the interaction of morphine with naloxone, suggesting that beta-FNA inactivates those receptors at which morphine interacts in the guinea pig ileum. The effect is selective for mu receptors since beta-FNA has no effect upon the interaction of naloxone with the kappa agonist nalorphine. In the present study, it was found that although beta-FNA attenuated the effects of morphine and other morphine-like agonists at mu receptors in the guinea pig longitudinal muscle-myenteric plexus ileal preparation, the mu-mediated actions of delta-selective peptide agonists and mu-selective peptide agonists were not completely attenuated by beta-FNA pretreatment. These data suggest that morphine-like mu agonists and other mu-selective and delta-selective peptide agonists in the guinea-pig ileum preparation either interact with similar opioid receptors but in a distinguishable manner or interact with different populations of opioid receptors or the peptides studied had greater intrinsic activity than the nonpeptides.