Clinical application of a micro multiplane transoesophageal probe in congenital cardiac disease.

AIM: To assess the quality of imaging modalities of a new micro multiplane transoesophageal echocardiogram probe. METHOD: This is a prospective study of micro transoesophageal echocardiogram S8-3t probe used at a single institution between 15 December, 2009 and 15 March, 2010. The images were compared with standard paediatric or adult probes where possible. Assessors prospectively rated imaging quality - two dimensional, colour flow imaging, pulse wave, and continuous wave Doppler - with a subjective 4-point scale (1 = poor to 4 = excellent). RESULTS: A total of 24 studies were performed on 23 patients, with a median weight = 11.7 kilograms (2.6-72 kilograms) and a median age of 3 years (0.16-60 years). Of the 23 patients, one neonate (2.8 kilograms) had transient bradycardia on probe insertion. Imaging in patients less than 10 kilograms was of full diagnostic value and new information was obtained in eight out of ten patients. Pulse wave and continuous wave Doppler was consistently good across all weight groups. There were high frame rates and good imaging quality to a depth of 4-6 centimetres in all studies. A comparison with a larger alternative probe was available for 12 studies (weight 11.9-72 kilograms). The median micro transoesophageal two-dimensional image quality score was 3 (2-4) and 4 (3-4) with the comparative probe. For the 10- to 30-kilogram group, image quality with the micro transoesophageal echocardiogram probe was judged as inferior to larger standard probes. Adult sized patients had good imaging of near the field, allowing guidance for percutaneous device closure of the atrial septum. CONCLUSION: The micro multiplane transoesophageal echocardiogram probe provides imaging of diagnostic quality in neonates. In larger patients, it offers good imaging of near field structures. In the intermediate-sized child (10-30 kilograms), standard paediatric probes provide better imaging.

Ecdysteroid ligand-receptor selectivity--exploring trends to design orthogonal gene switches.

A set of thirty-two natural and ten semisynthetic ecdysteroids was assayed in murine 3T3 cells across ten different ecdysteroid receptor (EcR) ligand-binding domains derived from nine arthropod species in an engineered gene switch format. Among the ecdysteroids tested, the most biologically widespread ecdysteroid, 20-hydroxyecdysone (20E), was moderately and consistently potent across the tested EcRs. The most potent ligand-receptor combination (EC(50) = 0.3 nm) was ponasterone A (PoA) actuating the Nephotettix cincticeps EcR switch. The most robust ligand-receptor combination, as measured by potency and efficacy, was PoA actuating either the Bombyx mori EcR or a 'VY' (E274V/V390I/Y410E) mutant of Choristoneura fumiferana EcR. Parallel ecdysteroid structure-activity relationships were observed across species; addition of hydroxyl groups at positions 2, 3, 14, 20 and 22 incrementally enhanced potency, whereas hydroxylation at position 25 retarded potency. Nevertheless, several outlier ligand-EcR combinations, such as cyasterone actuating the VY C. fumiferana EcR mutant and canescensterone activating Bemisia argentifolii EcR, exhibited an inversion of relative potency, and therefore lend themselves to construction of orthogonal duplex gene switches. The potency inversion between these two ligand-receptor pairs can be accounted for by steroid-tail contact residues Tyr411 and Met502 in VY C. fumiferana EcR corresponding to two threonines in B. argentifolii EcR. Another potency inversion was also observed with cyasterone operating on the VY mutant of C. fumiferana EcR and polypodine B activating Aedes aegypti EcR. The ecdysteroid-EcR dataset, generated in a non-natural system, nevertheless invites conjecture regarding relative ecdysteroid potencies, plant species distribution of certain phytoecdysteroids, and the role of phytoecdysteroids as chemodefense against relevant insect herbivores.

Morphologic and functional predictors of eventual circulation in the fetus with pulmonary atresia or critical pulmonary stenosis with intact septum.

OBJECTIVES: The purpose of this study was to determine the morphologic and physiological predictors of post-natal surgical pathway in a longitudinal series of fetuses with pulmonary atresia with intact ventricular septum (PAIVS) and/or critical pulmonary stenosis with reversal of ductal flow (CPS) using statistical modeling. BACKGROUND: Pulmonary atresia with intact ventricular septum is rarely associated with chromosomal or extra cardiac malformations, so decisions about continuing a pregnancy are strongly influenced by the prediction of univentricular (UV) or biventricular (BV) circulation. METHODS: Predictive scores were derived, using a combination of z-scores of fetal cardiac measurements (for femoral length) and tricuspid/mitral valve (TV/MV) ratios, to facilitate early prediction of UV or BV circulation in 21 fetuses with PAIVS (18 fetuses) or CPS (3 fetuses) between 1998 and 2004. We also assessed the predictive value of coronary fistulae and right atrial pressure (RAP) score (comprising the tricuspid valve, foramen ovale, and ductus venosus Doppler). RESULTS: One-half of the cohort was first assessed before 23 gestational weeks (range 15.7 to 33.7 weeks). The TV z-score was a good predictor at all gestations, but the best predictive scores for specific gestations were pulmonary valve (PV) z-score (<23 weeks), median TV z-score (<26 weeks), the combination of median PV z-score and the median TV/MV ratio (26 to 31 weeks), and the combination of median TV z-score and median TV/MV ratio (>31 weeks). The RAP score and coronary fistulae were good independent predictors: RAP score >3 predicted BV with area under the curve of 0.833, and detection of fistulae usually predicted a UV route. CONCLUSIONS: The best predictive scores for post-natal outcome in fetal PAIVS/CPS are a combination of morphologic and physiological variables, which predict a BV circulation with a sensitivity of 92% and specificity of 100% before 26 weeks.

Myocardial tissue Doppler and long axis function in the fetal heart.

UNLABELLED: Current echocardiographic assessment of fetal ventricular function uses relatively crude measures and this has led to inconsistencies in assessment of diastolic function. Long axis parameters may be more insightful. OBJECTIVE: To describe fetal long axis cardiac function and construct reference ranges. DESIGN: 159 normal fetuses were studied cross-sectionally using long axis M-mode to measure displacement of the atrioventricular ring and pulsed wave Doppler ultrasound to record myocardial tissue Doppler velocities at the base of the heart. RESULTS: There was a strong, almost linear gestational relationship for all but late left basal myocardial velocities. Systolic amplitude of the atrioventricular ring increased significantly. Wall thickness increased with gestation and heart rate reduced. Late diastolic mitral and tricuspid flow velocities showed no age-dependence. Right ventricular filling (p<0.0001) and myocardial lengthening (p<0.0001) and shortening velocities (p<0.0001) were higher than left. Aortic velocities were higher than pulmonary (p<0.0001). Right ventricular long axis amplitude was greater than left (p<0.0001). There were no significant differences in right (RV) and left (LV) ventricular and septal thicknesses (RV 2.5 mm [1.2-4.1]; LV (2.4 mm [1.0-4.0] and septum 2.6 mm [1.0-4.3]). Left and right myocardial tissue Doppler velocities showed similar maturation in systole (LV 0.14 vs. RV 0.10 cm/s/week) and early diastole (LV 0.16 vs. RV 0.14 cm/s/week). CONCLUSIONS: This study demonstrates maturational changes occur in both fetal systolic and diastolic ventricular function and moreover the maturational rate of myocardial tissue velocities is similar in both ventricles, despite differential loading conditions.

Sesquiterpenes from the New Zealand Liverwort Lepidolaena hodgsoniae.

NMR studies have shown that seven new sesquiterpenoids, 3, 4, 5a, and 7-10, isolated from dried samples of the New Zealand liverwort Lepidolaena hodgsoniae have the same substituted cyclopentapyran ring system as the previously described insecticidal sesquiterpene diene hodgsonox (1), which has been reported only from this plant. In all but one compound, 10, the 1,1-disubstituted double bond of hodgsonox has migrated into an endocyclic position, but only two, 5a and 9, have the double bonds in conjugation. These seven new compounds represent a variety of different oxidation levels. Two of the new derivatives, 9 and 10, were isolated only from an aged sample and are presumably artifacts. The only other terpenoid isolated in significant quantity was (7R,10R)-calamenene (2).

Synthesis of the 3-methylene-2-vinyltetrahydropyran unit; the hallmark of the sesquiterpene, hodgsonox.

[structure: see text] The synthesis of some simple compounds containing the previously unreported 3-methylene-2-vinyltetrahydropyran system, a unique feature of the liverwort metabolite, hodgsonox is reported. Key features are the creation of an acrolein substituted in the alpha-position with a three-carbon chain bearing a terminal electrophilic site, addition of a vinyl group, and cyclization.

Determination of the absolute configuration of Anisotome irregular diterpenes: application of CD and NMR methods.

Several Anisotome diterpene derivatives were synthesized in an attempt to obtain a crystalline compound for X-ray analysis. Although we were unable to obtain a suitable crystal, the absolute configuration of the irregular diterpene skeleton was determined using two other techniques: a circular dichroism (CD) protocol based on a tetraarylporphyrin molecular tweezer that allowed prediction of the absolute stereochemistry on a microscale level, and a method employing differences in NMR shifts from derivatization of the naturally occurring acid 1 with enantiomers of a phenylglycine methyl ester (PGME) chiral anisotropic reagent. The excellent agreement between the CD and NMR methods led to the assignment of a 2S-absolute configuration for anisotomenoic acid 1.

Biosynthesis of the sesquiterpene hodgsonox from the New Zealand liverwort Lepidolaena hodgsoniae.

The incorporation of [1-13C] labelled glucose into hodgsonox, a sesquiterpene epoxide with a unique, doubly allylic ether functionality has been studied in axenic cultures of the liverwort Lepidolaena hodgsoniae. Quantitative 13C NMR spectroscopic analysis showed that the isoprene units are derived exclusively from the methylerythritol phosphate pathway.