T4-mediated rescue of aortic malformations in hypothyroid rats indicates maternal thyroid status can affect great vessel development.

Pexacerfont is a corticotrophin-releasing factor subtype 1 receptor (CRF-1) antagonist developed for potential treatment of anxiety and stress-related disorders. In male rats, pexacerfont caused hepatic enzyme induction leading to increased thyroxine (T4) clearance. When administered to pregnant rats on gestation day 6 to 15, pexacerfont at 300 mg/kg/day (30× mean AUC in humans at 100 mg/day) produced similar effects on thyroid homeostasis with serum T4 and thyroid-stimulating hormone levels that were 0.3-0.5× and 3.3-3.7× of controls, respectively. At this dose, fetuses of pexacerfont-treated dams presented findings associated with maternal hypothyroidism including growth retardation and increased skeletal alterations. Additionally, there were unexpected great vessel malformations that were mostly derived from the 4th pharyngeal arch artery in 5 (4.3%) fetuses from 3 (15.8%) litters. The etiology was unclear whether the vascular malformations were related to insufficient thyroid hormones or another mechanism. To better understand this relationship, pregnant rats were implanted with a subcutaneous L-thyroxine pellet designed to provide a sustained release of T4 throughout organogenesis in rat embryos (GD 6 to 15; the dosing period of pexacerfont). T4 supplementation produced a near euthyroid state in pexacerfont-treated dams and completely prevented the fetal vascular malformations. These results suggest maternal T4 levels during organogenesis may have a role in great vessel morphogenesis associated with patterning and/or regression of pharyngeal arch arteries. Although previous clinical reports have speculated a potential relationship between thyroid hormone homeostasis and early cardiovascular development, this is the first report to experimentally demonstrate this relationship in great vessel morphogenesis.

Primary palliative stenting against obstructive mixed-type total anomalous pulmonary venous connection associated with right atrial isomerism.

This case report presents a low-birth-weight neonate who received primary stent implantation as a long-term palliative intervention for obstructive mixed-type total anomalous pulmonary venous connection (TAPVC) without common pulmonary venous chamber associated with right atrial isomerism, which was considered difficult to surgically repair in the neonatal period. Stent redilation with balloon catheters was repeated for in-stent stenosis from neointimal proliferation, resulting in successful TAPVC repair with cavopulmonary connection at 17 months of age.

Role of mutation and pharmacologic block of human KCNH2 in vasculogenesis and fetal mortality: partial rescue by transforming growth factor-ß.

BACKGROUND: N629D KCNH2 is a human missense long-QT2 mutation. Previously, we reported that the N629D/N629D mutation embryos disrupted cardiac looping, right ventricle development, and ablated IKr activity at E9.5. The present study evaluates the role of KCNH2 in vasculogenesis. METHODS AND RESULTS: N629D/N629D yolk sac vessels and aorta consist of sinusoids without normal arborization. Isolated E9.5 +/+ first branchial arches showed normal outgrowth of mouse ERG-positive/α-smooth muscle actin coimmunolocalized cells; however, outgrowth was grossly reduced in N629D/N629D. N629D/N629D aortas showed fewer α-smooth muscle actin positive cells that were not coimmunolocalized with mouse ERG cells. Transforming growth factor-ß treatment of isolated N629D/N629D embryoid bodies partially rescued this phenotype. Cultured N629D/N629D embryos recapitulate the same cardiovascular phenotypes as seen in vivo. Transforming growth factor-ß treatment significantly rescued these embryonic phenotypes. Both in vivo and in vitro, dofetilide treatment, over a narrow window of time, entirely recapitulated the N629D/N629D fetal phenotypes. Exogenous transforming growth factor-ß treatment also rescued the dofetilide-induced phenotype toward normal. CONCLUSIONS: Loss of function of KCNH2 mutations results in defects in cardiogenesis and vasculogenesis. Because many medications inadvertently block the KCNH2 potassium current, these novel findings seem to have clinical relevance.

Oral pyridoxine during pregnancy : potential protective effect for cardiovascular malformations.

OBJECTIVE: To study the human risk and benefit of oral pyridoxine (vitamin B6) treatment during pregnancy. DESIGN AND SETTING: The analysis of cases with 25 congenital abnormality (CA) groups and their all-matched controls without CAs in the population-based dataset of the large Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. STUDY PARTICIPANTS: 22,843 cases of pregnant women who had newborns or fetuses with CAs and 38,151 pregnant women who had newborn infants without any CAs (control group). MAIN OUTCOME MEASURES: Prevalence of pyridoxine use in early pregnancy among mothers of cases with different CAs and control mothers with infants without any CA. RESULTS: 2013 (8.8%) case mothers and 4086 (10.7%) control mothers were treated with pyridoxine (adjusted prevalence odds ratio [POR] 0.8; 95% confidence interval [CI] 0.7, 0.9). The analysis of cases with different defects and their all-matched controls did not indicate any obvious teratogenic potential of pyridoxine use during the second and third months of gestation, i.e. in the critical period for the development of most major CAs. However, some protective effect was found for cardiovascular malformations (adjusted POR 0.8; 95% CI 0.7, 0.9). CONCLUSION: Treatment with pyridoxine during pregnancy does not indicate a teratogenic risk to the fetus, but may provide some protective effect for cardiovascular malformations.

[Superficial venous malformations]. / Malformations veineuses superficielles ou "angiomes veineux".

Superficial venous malformations are part of a larger group now called superficial vascular anomalies and previously known as angiomas. These include vascular tumors or infantile hemangioma, low-flow vascular malformations (capillary, lymphatic, and superficial venous malformations) and high-flow vascular malformations (arteriovenous malformations). Some of these lesions are complex. This classification facilitates their multidisciplinary therapeutic management. Embolization is an effective curative treatment for malformations of small and intermediate size. The objective for large or complex malformations is to restore anatomic function and improve cosmetic results.

Malformaciones capilares tratadas con aplicación secuencial de láser de colorante pulsado y Nd:YAG: estudio retrospectivo / Capillary Malformations Treated With Sequential Pulsed Dye and Nd:YAG Laser Therapy: A Retrospective Study

INTRODUCCIÓN Y OBJETIVO: Las malformaciones capilares son las malformaciones vasculares más frecuentes en la infancia. El tratamiento de elección sigue siendo el láser de colorante pulsado (LCP), sin embargo, la resolución completa con este habitualmente no se consigue, motivo por el que se siguen buscando otras alternativas terapéuticas. En este estudio comunicamos nuestra experiencia con el láser dual secuencial de LCP y Nd:YAG. MATERIAL Y MÉTODOS: Se efectuó un estudio retrospectivo y descriptivo de los pacientes con malformaciones capilares tratados con el láser dual de LCP y Nd:YAG desde 2006 hasta 2011. Cuatro dermatólogos valoraron el grado de eficacia en una escala del 10 al 0. Se analizó la posibilidad de factores predictores de mejor respuesta al tratamiento: sexo, color de la lesión, existencia de hipertrofia asociada y tamaño de la malformación. Se recogieron igualmente los efectos secundarios. RESULTADOS: Se incluyeron 71 pacientes, presentando el conjunto de ellos una mejoría estadísticamente significativa tras el tratamiento. Las malformaciones de coloración violácea que tenían hipertrofia asociada y las de menor tamaño se asociaron con una mejor respuesta. Se produjeron efectos adversos en un 26,76% de los pacientes, siendo la presencia de zonas atróficas puntuales el más frecuente. CONCLUSIONES: Consideramos que el láser dual de LCP y Nd:YAG es una alternativa eficaz para el tratamiento de malformaciones capilares en paciente seleccionados

INTRODUCTION AND OBJECTIVE: Capillary malformations are the most common vascular malformations in childhood. The current treatment of choice is pulsed dye laser (PDL) therapy, but this frequently does not result in complete resolution. The search for alternative treatment strategies thus continues. In this study we describe our experience with the use of sequential dual-wavelength PDL and Nd:YAG laser therapy in patients with capillary malformations. MATERIAL AND METHODS: We conducted a retrospective, descriptive study of patients with capillary malformations treated with dual-wavelength PDL and Nd:YAG laser therapy between 2006 and 2011. Four dermatologists rated the effectiveness of treatment on a scale of 10 to 0. We also investigated the potential value of the following factors as predictors of better treatment response: sex, malformation size and color, and presence of associated hypertrophy. Adverse effects were also analyzed. RESULTS: We studied 71 patients and most of them experienced a statistically significant improvement after treatment. More favorable responses were observed for violaceous malformations, lesions with associated hypertrophy, and smaller lesions. Adverse effects were reported for 26.76% of patients, and the most common effect was the appearance of isolated areas of skin atrophy. CONCLUSIONS: We consider that sequential dual-wavelength PDL and ND:YAG laser therapy is an effective alternative for treating capillary malformations in selected patients