Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development.

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation, and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF. Our results provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.

Conocimientos sobre la lectoescritura emergente y prácticas en las aulas para su promoción: Un estudio con docentes de Educación preescolar en Costa Rica / Emergent Literacy Knowledge and Classroom Practices for its promotion: a Study with Preschool Education Teachers in Costa Rica

Resumen Las concepciones y los conocimientos docentes afectan la práctica docente y esta, a su vez, influye en los logros de desarrollo en lectoescritura emergente de los niños preescolares. Esta investigación explora las valoraciones docentes de prácticas efectivas en el aula para la promoción de la lectoescritura emergente y sus conocimientos sobre conciencia fonológica y fonemas. Una muestra conformada por 284 docentes a cargo de salones de educación preescolar contestó un cuestionario en línea. Los resultados indicaron diferencias según tipo de universidad en la cual se tituló la docente. Las docentes graduadas de universidades públicas otorgaron mayor importancia a prácticas efectivas en el aula para la promoción de la lectoescritura emergente que las docentes graduadas de universidades privadas. Si bien la mayoría de participantes consideró la conciencia fonológica como un factor importante para el desarrollo de la lectoescritura, los conocimientos sobre esta fueron deficientes en toda la muestra. Igualmente, los conocimientos docentes sobre los fonemas y su habilidad para identificarlos en palabras concretas también fueron deficientes. Estos y otros hallazgos se discuten a la luz de sus implicaciones para la promoción de la calidad en la educación preescolar costarricense.

Abstract Teachers' conceptions and knowledge affect their practices, and teachers' practices influence preschoolers' early literacy development. This study explores how much teachers value classroom practices previously proven to be effective in promoting early literacy development, and how much teachers know about phonological awareness and phonemes. A sample of 284 preschool teachers filled out an online questionnaire. Results showed differences as a function of the kind of university where teachers obtained their university degree. Teachers who graduated from public universities considered practices proven to be effective to promote early literacy more important than teachers who graduated from private universities. Although most participants considered phonological awareness an important factor for early literacy development, knowledge about it was deficient across the whole sample. Teachers' knowledge about phonemes and their abilities to identify phonemes in specific words were deficient. Findings are discussed in light of their implications for promoting quality preschool education in Costa Rica.

Incisión axilar para el cierre quirúrgico de la comunicación interauricular / Axillary approach for surgical closure of atrial septal defect

La esternotomía media es el acceso habitual para la corrección quirúrgica de las cardiopatías congénitas. Sin embargo, la cicatriz visible recuerda siempre que se trata de un cardiópata. Diversos abordajes alternativos han sido explorados en afecciones simples con objeto de ocultar la cicatriz. Presentamos una serie de 26 pacientes intervenidos de comunicación interauricular por vía axilar. La media de edad fue de 5,45 años (rango 3-13) y de peso 19,84 kg (rango 13-37). En 13 casos el defecto se cerró directamente (sutura) y en los 13 restantes, mediante parche de pericardio propio. Los pasos y los tiempos quirúrgicos son superponibles a la técnica clásica. La recuperación funcional, estancia en cuidados intensivos y planta hospitalaria hasta el alta han sido estándar. El resultado estético, valorado por pacientes y familiares, ha sido excelente (AU)

Mid-line sternotomy is the routine approach for surgical repair of congenital heart diseases. However, its noticeable scar is a constant reminder of having undergone heart surgery. Several alternative approaches have been developed for simple cardiac conditions to hide the scar. Our series, consisting of 26 patients with axillary closure of atrial septal defect, is presented. The median age was 5.45 years (range 3-13), and median weight was 19.84 Kg. (range 13-37). The defect was closed directly in 13 cases, and with an autologous pericardial patch in the other 13. The number of surgical steps and time taken were the same as in median sternotomy. Functional recovery, intensive care unit stay, and hospital discharge were also standard. The cosmetic result, assessed both by patients and relatives, was excellent (AU)

[Axillary approach for surgical closure of atrial septal defect]. / Incisión axilar para el cierre quirúrgico de la comunicación interauricular.

Mid-line sternotomy is the routine approach for surgical repair of congenital heart diseases. However, its noticeable scar is a constant reminder of having undergone heart surgery. Several alternative approaches have been developed for simple cardiac conditions to hide the scar. Our series, consisting of 26 patients with axillary closure of atrial septal defect, is presented. The median age was 5.45 years (range 3-13), and median weight was 19.84 Kg. (range 13-37). The defect was closed directly in 13 cases, and with an autologous pericardial patch in the other 13. The number of surgical steps and time taken were the same as in median sternotomy. Functional recovery, intensive care unit stay, and hospital discharge were also standard. The cosmetic result, assessed both by patients and relatives, was excellent.

[Dehiscence of a composite aortic graft (Bono and Bentall technique) secondary to Acinetobacter endocarditis]. / Dehiscencia de un injerto valvulado aórtico (técnica de Bono y Bentall) secundaria a endocarditis por Acinetobacter.

Acinetobacter sp. are gram-negative bacteria and usually resistant to multiple antibiotics. They are a customary cause of nosocomial infections, but are uncommon etiologic agents of endocarditis. We present a case of endocarditis caused by Acinetobacter iwoffi in a composite aortic graft with a St. Jude prosthetic valve, using the Bono and Bentall procedure, complicated with multiple graft dehiscenses causing first a peritube pseudoaneurysm and finally severe paraprosthetic valve regurgitation to the left ventricle which required emergency surgery.

[Asymptomatic aortic dissection in a patient with aortic valve prosthesis]. / Disección aórtica asintomática en paciente con prótesis valvular aórtica.

The occurrence of iatrogenic aortic dissection after aortic valve replacement is uncommon, usually late, and exceptionally asymptomatic. We present here a case of dissecting aneurysm suspected by excessive mediastinal dilatation observed in the routine annual roentgenogram exam of a patient who has had an aortic valve prosthesis for thirteen years. The confirmation with other diagnostic methods and its successful surgical treatment are also described.

Histamine H2-receptor antagonist action of ebrotidine. Effects on gastric acid secretion, gastrin levels and NSAID-induced gastrotoxicity in the rat.

The antagonism of histamine H2-receptors by ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl ] amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) was assessed on isolated guinea-pig right atrium. The dose-response curves obtained by histamine on the positive chronotropic effect in guinea-pig atrium were displaced to the right in parallel depending on the concentration of ebrotidine and ranitidine without change in the maximum response with pA2 values of 7.12 and 7.26, respectively. The slope of the regression line of log (DR-1) against log ebrotidine concentration was not significantly different from unity: 0.96 (95% confidence limits: 0.89-1.03). These results indicate that ebrotidine is a competitive H2-receptor antagonist. Following intravenous administration to rats, ebrotidine inhibited histamine- and pentagastrin-stimulated acid secretion in a dose-dependent manner, ED50 being 0.21 and 0.44 mg/kg, respectively. After oral administration to fasting rats 3 h before their sacrifice, ebrotidine decreased the total acid contents of the stomach in a dose-dependent manner, ED50 being 7.5 mg/kg. After a single dose of 100 mg/kg in fasting rats, ebrotidine increased significantly serum gastrin levels within 2 and 5 h after administration, but 8 h after administration serum gastrin levels returned to normal values. In contrast, ranitidine at a single oral dose of 100 mg/kg increased serum gastrin levels more markedly within 2 and 5 h after administration, while after 8 h, this increase still persisted although without significant differences with respect to control, and after 24 h levels returned to normal values. Both ebrotidine and ranitidine were administered orally at a dose of 100 mg/kg for 26 days showing significant increments in plasma gastrin levels 5 h after administration. Such increments were not so marked after ebrotidine and normal values were attained at 24 h after administration. The results obtained after repeated oral administration for 15 days of ebrotidine and ranitidine at the doses of 15 and 50 mg/kg demonstrated that ebrotidine did not increase significantly serum gastrin levels with respect to control 2 h after administration, and no dose-related effect was observed. In contrast, ranitidine increased serum gastrin levels significantly and in a dose-dependent manner with respect to control group. ED50 values of ebrotidine obtained in the experiments on the prevention of NSAID-induced gastrotoxicity in the rat were 12.2, 12.5, 11.5 and 9.8 mg/kg against diclofenac, ketoprofen, indometacin and naproxen, respectively. ED50 values of ranitidine were of the same order: 20.6, 13.9, > 50 and 15.1 mg/kg.

Effect of ebrotidine on ethanol-induced gastric mucosal damage in the rat. Comparative study with other H2-receptor antagonists.

Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl ] amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is a novel H2-receptor antagonist with additional gastroprotective effect. The gastroprotective effect of oral doses of ebrotidine against ethanol-induced mucosal damage in female rats was compared with the effect of cimetidine, ranitidine and famotidine. Macroscopically, ebrotidine showed dose-dependent inhibition of the lesion, with significant differences from that of controls at doses of > or = 12.50 mg/kg (ED50 was 26.54 mg/kg). None of the other drugs tested showed gastroprotective effect under the same conditions. The histopathological study revealed significant reduction in the number of deep and superficial ulcers in ebrotidine-treated animals. The gastroprotective effect of ebrotidine is patent even in the presence of indometacin suggesting that prostaglandins play a rather negligible role in gastroprotective action. These results suggest that ebrotidine may be more useful than the classically known H2-antagonists in the treatment of peptic ulcers.

Involvement of endogenous nitric oxide and sulfhydryl compounds in ebrotidine-induced gastroprotection.

The role of endogenous nitric oxide and sulfhydryl compounds in the prevention by ebrotidine (N-[(E)- [[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl]amino] methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) (100 mg/kg i.g.) of ethanol-induced gastric damage in rats was demonstrated. When the animals were pretreated with N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, at the dose of 10 mg/kg i.v., the mucosal lesions were aggravated and the gastroprotective action of ebrotidine decreased from 85% to 24%. This decrease in ebrotidine protection was antagonized by L-arginine (200 mg/kg i.v.), the lesion inhibition rate being 69%. D-arginine (200 mg/kg i.v.) was ineffective and the inhibition afforded by ebrotidine was only 14%. Pretreatment with N-ethylmaleimide, a sulfhydryl blocker, at the dose of 50 mg/kg s.c., increased the mucosal lesion induced by ethanol, and the gastroprotective action of ebrotidine decreased from 75% to 9%. These results suggest that endogenous nitric oxide and sulfhydryl compounds play a crucial role in the gastroprotective activity of ebrotidine.