Fetal cardiac malposition: incidence and outcome of associated cardiac and extracardiac malformations

Cardiac malposition is a rare but important finding when detected on fetal ultrasound. The purpose of this study was to evaluate the incidence of fetal cardiac malposition, associated abnormalities, and clinical outcome in a tertiary-care medical center. Records of fetuses (1993 to 2006) with dextroposition, dextrocardia, mesocardia, ectopia cordis, or heterotaxy were reviewed. The presence of congenital heart disease (CHD), extracardiac anomalies, and outcome were noted. Cardiac malposition was present in 101 fetuses among a total of 3313 (3%) pregnancies. In 78 (78%) patients, the heart was positioned in the right hemithorax. Of those, 26 (33%) had dextrocardia (CHD = 21), and 52 (67%) had dextroposition (CHD = 14). Sixteen (16%) patients had mesocardia (CHD = 8), and 7 (7%) had ectopia cordis (CHD = 6). The majority (58%) of fetal cardiac malposition was caused by intrathoracic masses. Concomitant CHD occurred in 50%. Outcome was available in 97%. The perinatal and neonatal mortality rate was 30%; the elective termination rate was 4%. Patients with CHD had higher mortality rates. The highest mortality rates occurred in ectopia cordis and combined disease of diaphragmatic hernia and CHD.     

Ultrasonography and computed tomography of inflammatory abdominal wall lesions

Twenty-four patients with inflammatory lesions of the abdominal wall were examined by ultrasonography. Nine of these patients underwent computed tomographic (CT) scanning as well. Both ultrasonography and CT clearly delineated the exact location and extent of abdominal wall abscesses. Abscesses were easily differentiated from cellulitis or phlegmon with ultrasound. The peritoneal line was more clearly delineated on ultrasonograms than on CT scans; abscesses were also more distinct on the ultrasonograms because of their low echogenicity compared with the surrounding structures. Gas bubbles, fat density with specific low attenuation values, and underlying inflamed bowel loops in obese patients with Crohn's disease were better delineated by CT.     

Biochemical and behavioural characterization of EMPA,a novel high-affinity,selective antagonist for the OX2 receptor

Background and purpose:

The OX₂ receptor is a G-protein-coupled receptor that is abundantly found in the tuberomammillary nucleus, an important site for the regulation of the sleep-wake state. Herein, we describe the in vitro and in vivo properties of a selective OX₂ receptor antagonist, N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA).

Experimental approach:

The affinity of [³H]EMPA was assessed in membranes from HEK293-hOX₂-cells using saturation and binding kinetics. The antagonist properties of EMPA were determined by Schild analysis using the orexin-A-or orexin-B-induced accumulation of [³H]inositol phosphates (IP). Quantitative autoradiography was used to determine the distribution and abundance of OX₂ receptors in rat brain. The in vivo activity of EMPA was assessed by reversal of [Ala¹¹,D-Leu¹⁵]orexin-B-induced hyperlocomotion during the resting phase in mice and the reduction of spontaneous locomotor activity (LMA) during the active phase in rats.

Key results:

[³H]EMPA bound to human and rat OX₂-HEK293 membranes with K_D values of 1.1 and 1.4 nmol·L⁻¹ respectively. EMPA competitively antagonized orexin-A-and orexin-B-evoked accumulation of [³H]IP at hOX₂ receptors with pA₂ values of 8.6 and 8.8 respectively. Autoradiography of rat brain confirmed the selectivity of [³H]EMPA for OX₂ receptors. EMPA significantly reversed [Ala¹¹,D-Leu¹⁵]orexin-B-induced hyperlocomotion dose-dependently during the resting phase in mice. EMPA, injected i.p. in rats during the active phase, reduced LMA dose-dependently. EMPA did not impair performance of rats in the rotarod procedure.

Conclusions and implications:

EMPA is a high-affinity, reversible and selective OX₂ receptor antagonist, active in vivo, which should prove useful for analysis of OX₂ receptor function.     

Comparative 13-week cigarette smoke inhalation study in Sprague-Dawley rats: evaluation of cigarettes with two banded cigarette paper technologies.

This study compared the toxicological responses of Sprague-Dawley rats exposed nose-only to mainstream smoke (MS) from Test cigarettes (1, 2, and 3) to those of Control cigarettes without banded cigarette paper technologies (BCPT). Test cigarettes 1 and 2 had bands based on one technology (different band weight application) while Test cigarette 3 had bands based on another technology. The banded papers are representative of current marketed technologies. Rats were exposed to humidified HEPA filtered air (Sham) or to MS at concentrations of 0.06, 0.20, or 0.80 mg wet total particulate matter per liter air. Each exposure group contained 30 animals/sex (sentinel had 20 animals/sex). The study had two phases (13 weeks each): MS exposure (1 h/day, 5 days/week) and recovery without smoke exposure. Endpoints included clinical observations, respiratory physiology, hematology, serum chemistry, blood carboxyhemoglobin (COHb), serum nicotine, body/organ weights, gross pathology, and histopathology. Comparisons conducted were: Sham exposed vs. all cigarettes, Control cigarette vs. all Test cigarettes, and Test 1 vs. Test 2. Control and Test MS had comparable effects on respiratory physiology, COHb, serum nicotine, serum chemistry, and hematology. While some minor differences were observed, Control and Test MS had comparable effects on clinical signs, body/organ weights, and gross pathology/histopathology. Consequently, exposure of rats to equivalent MS concentrations from the four cigarettes induced similar toxicological responses in this study.     

Premature closure of the foramen ovale associated with aortic stenosis, left ventricular dilation with thrombus, and early mortality

Premature foramen ovale (FO) closure has been postulated as a cause of hypoplastic left heart syndrome. We suggest that premature FO closure is also associated with left ventricular (LV) dilation and LV thrombus formation, and that FO closure in patients with aortic stenosis and LV dilation is a secondary event that occurs later in gestation than that seen with the hypoplastic left heart.