Resolution of hydrops fetalis caused by atrioventricular block: good postnatal evolution with terbutaline treatment.

INTRODUCTION: Complete atrioventricular block (CAVB) is rarely seen, as it occurs in only 1:11 000 to 1:20 000 newborns. There is a serious risk of mortality in CAVB, mainly in those cases associated with hydrops, fetal cardiac frequency ≤ 55 beats/minute, and premature delivery. CASE REPORT: Case of complete atrioventricular block with a poor prognosis (hydrops fetalis and foetal cardiac frequency < 5 beats/minute) caused by anti-La and anti-Ro antibodies. Intrauterine symptoms improved after treatment with terbutaline, permit- ting foetal viability and successful postnatal treatment with a cardiac pacemaker. DISCUSSION: In case of complete atrioventricular block of cause autoimmune with poor prognosis should be treated with positive inotropic drugs, anticholinergics or b-mimetic in the attempt to maintain adequate ventricular frequency, and thus prevent hydrops fetalis from occurring.

Cribado prenatal de cardiopatías congénitas en población de bajo riesgo de defectos congénitos. Una realidad en la actualidad / Prenatal screening of congenital heart defects in population at low risk of congenital defects. A reality today

INTRODUCCIÓN: Nos proponemos demostrar que es posible la implantación de un cribado prenatal de cardiopatías congénitas de garantía (sensibilidad diagnóstica para malformaciones cardíacas mayores del 90%) y universal (aplicado a más del 90% de las gestantes). MATERIAL Y MÉTODO: Estudio prospectivo. Hemos valorado a 12.478 gestantes (enero del 2008-diciembre del 2010). Realizamos un cribado de cardiopatías congénitas aplicando una ecocardiografía fetal básica ampliada. RESULTADOS: La prevalencia de los defectos congénitos en general y de las cardiopatías congénitas es del 2,5% (2,2-2,7%) y el 0,9% (0,7-1%), respectivamente. Las cardiopatías congénitas presentan una tasa de asociación a otras malformaciones estructurales del 11,5% (5,6-17,4%), 21% en caso de cardiopatía congénita mayor (9,9-32%) y a cromosomopatías del 15,9% (9,1- 22,7%), 32,6% en caso de cardiopatía congénita mayor (19,8-45,3%). Hemos logrado realizar una valoración ecográfica cardiaca fetal al 99,2% de las gestantes. La ecocardiografía fetal presenta, para el diagnóstico de las cardiopatías congénitas en general y de las cardiopatías congénitas mayores, una sensibilidad 42,8% (33,5-52,5%) y el 90,4% (78,9-96,8%), respectivamente, y una especificidad para ambas del 99,9% (99,8-99,9%). CONCLUSIONES: Es posible realizar un cribado prenatal de garantías y universal de las cardiopatías congénitas mayores

INTRODUCTION: We propose to demonstrate that it is possible to implement a valid (diagnostic sensitivity for major cardiac malformations 90%), and universal (applied to over 90% of pregnant women), prenatal screening method for congenital heart defects. MATERIALS AND METHODS: Prospective study. A total of 12478 pregnant women were evaluated between January 2008 and December 2010. Congenital heart diseases were screened using fetal extended basic echocardiography (cardiac ultrasound). RESULTS: The prevalence of birth defects in general and congenital heart disease was 2.5% (2.2- 2.7%) and 0.9% (0.7-1%) respectively. Congenital heart disease had a higher rate of association with other structural abnormalities with 11.5% (5.6-17.4%), 21% for major congenital heart disease (9.9-32%), and chromosomal abnormalities of 15.9% (9.1-22.7%), with 32.6% for major congenital heart disease (19.8-45.3%). A fetal cardiac ultrasound assessment was performed on 99.2% of pregnant women. The fetal echocardiography is useful for the diagnosis of congenital heart disease in general, and major congenital heart disease, with a sensitivity of 42.8% (33.5- 52.5%) and 90.4% (78.9-96.8%), respectively, and a specificity for both of 99.9% (99.8-99.9%). CONCLUSIONS: It is possible to perform a valid prenatal and universal screening of major congenital heart disease

[Prenatal screening of congenital heart defects in population at low risk of congenital defects. A reality today]. / Cribado prenatal de cardiopatías congénitas en población de bajo riesgo de defectos congénitos. Una realidad en la actualidad.

INTRODUCTION: We propose to demonstrate that it is possible to implement a valid (diagnostic sensitivity for major cardiac malformations 90%), and universal (applied to over 90% of pregnant women), prenatal screening method for congenital heart defects. MATERIALS AND METHODS: Prospective study. A total of 12478 pregnant women were evaluated between January 2008 and December 2010. Congenital heart diseases were screened using fetal extended basic echocardiography (cardiac ultrasound). RESULTS: The prevalence of birth defects in general and congenital heart disease was 2.5% (2.2-2.7%) and 0.9% (0.7-1%) respectively. Congenital heart disease had a higher rate of association with other structural abnormalities with 11.5% (5.6-17.4%), 21% for major congenital heart disease (9.9-32%), and chromosomal abnormalities of 15.9% (9.1-22.7%), with 32.6% for major congenital heart disease (19.8-45.3%). A fetal cardiac ultrasound assessment was performed on 99.2% of pregnant women. The fetal echocardiography is useful for the diagnosis of congenital heart disease in general, and major congenital heart disease, with a sensitivity of 42.8% (33.5-52.5%) and 90.4% (78.9-96.8%), respectively, and a specificity for both of 99.9% (99.8-99.9%). CONCLUSIONS: It is possible to perform a valid prenatal and universal screening of major congenital heart disease.

Diagnóstico precoz del embarazo cervical: factor más importante para la conservación de la fertilidad con tratamiento conservador / Early diagnosis of cervical pregnancy: The most important factor for preservation of fertility with conservative treatment

El embarazo cervical supone un 1% de los embarazos ectópicos. En el pasado se asociaba a una alta incidencia de hemorragias intensas e histerectomías. En la actualidad el diagnóstico precoz ecográfico y el tratamiento con metotrexate posibilita la preservación de la fertilidad (AU)

Cervical pregnancy represents less than 1% of all ectopic pregnancies. In the past, this event was associated with a high incidence of hysterectomies due to intense hemorrhage. Currently, due to early ultrasonographic diagnosis and medical treatment with metotrexate, future fertility can usually be preserved (AU)

Implementación universal del «consecutive combined test» en el área sur de Sevilla (Hospital Universitario Valme) / Universal implementation of the “Consecutive Combined Test” in the South Seville area (Valme University Hospital)

La universalización debe ser un objetivo en el cribado de cromosomopatía además de lograr una adecuada sensibilidad y una tasa de falsos positivos (F+) del método de cribado aplicado. Objetivos Nos proponemos implementar un cribado de cromosomopatías en el área sur de Sevilla con la característica de universal (cobertura mayor del 90%) y manteniendo la tasa de diagnóstico del 80% para un 5% de F+. Método A nuestras gestantes, entre julio de 2005 y septiembre de 2008, se les oferta un test combinado consecutivo. En los casos de edad gestacional >13 semanas se les aplica un doble test. Resultados Al 95,1%, de las 12.478 gestantes se les oferta un cribado. Al 86,85% de las gestantes se les realiza un test combinado consecutivo y el 6,43% de las gestantes han revocado el cribado. Se han observado 35 cromosomopatías (prevalencia de 0,28%), con una tasa de diagnóstico del 88,5% para un 4,31% de F+. Conclusiones La universalización debe ser un objetivo en el cribado de cromosomopatías además de lograr una adecuada sensibilidad y tasa de F+ (AU)

Universal application should be an aim in chromosomal abnormality screening, in addition to achieving adequate sensitivity and an acceptable false positive rate of the screening method applied. Objectives We aimed to implement universal chromosomal abnormality screening (coverage greater than 90% of pregnancies) in the southern area of Seville and to maintain the rate of diagnosis at 80% and the false-positive rate at 5%.MethodBetween July 2005 and September 2008, chromosomal abnormality screening through the consecutive combined test was offered to pregnant women in the southern area of Seville. The Double Test was used in women accessing screening later than 13 weeks of pregnancy. Results Of 12,478 pregnant women, chromosomal abnormality screening was offered to 95.1%. The consecutive combined test was performed in 86.86% of the pregnancies and screening was rejected by 6.32% of patients. Thirty-five chromosomal abnormalities were detected (a prevalence of 0.28%), of which 31 (88.5%) were diagnosed prenatally. The false-positive rate was 4.31%.ConclusionsUniversal application should be an objective of chromosomal abnormality screening, in addition to achieving adequate sensitivity and an acceptable false-positive rate in the screening method applied (AU)

Gestación triple con feto acardio / Triple pregnancy with acardiac fetus

El feto acardio es una complicación rara, de etiología incierta, que dificulta las gestaciones múltiples y especialmente las gemelares univitelinas. Se trata de un parásito que requiere aporte sanguíneo del feto normal, poniendo a éste en riesgo de padecer un fallo cardíaco. Presentamos un caso de gestación triple con feto acardio identificado en la semana 13, con diferencia de peso entre fetos normales y acardio mayor del 50 por ciento, tratado de forma expectante y con finalización de la gestación favorable para los dos fetos normales (AU)

New azole antifungals. 2. Synthesis and antifungal activity of heterocyclecarboxamide derivatives of 3-amino-2-aryl-1-azolyl-2-butanol.

A series of 92 azole antifungals containing an amido alcohol unit was synthesized. The nature and substitution of the amide portion was systematically modified in search of improved antifungal activity, especially against filamentous fungi. The compounds were tested in vitro against a variety of clinically important pathogens and in vivo (po) in a murine candidosis model. Thiazole and thiophene carboxamides carrying both a substituted phenyl ring and a small alkyl group were best suited for activity against filamentous fungi. In a subset of these compounds, the amide portion was conformationally locked by means of a pyrimidone ring and it was proven that only an orthogonal orientation of the phenyl ring yields bioactive products. A tendency to display long plasma elimination half-lives was observed in both series. Two compounds, 74 and 107, representative of the open and cyclic amides, respectively, were chosen for further studies, based on their excellent activity in in vivo murine models of candidosis and aspergillosis. This work describes the SARs found within this series. The next paper displays the results obtained in a related series of compounds, the quinazolinones.

New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)-quinazolinones.

A series of azole antifungal agents featuring a quinazolinone nucleus have been subjected to studies of structure-activity relationships. In general, these compounds displayed higher in vitro activities against filamentous fungi and shorter half-lives than the structures described in our preceding paper. The most potent products in vitro carried a halogen (or an isostere) at the 7-position of the quinazolinone ring. Using a murine model of systemic candidosis, oral activity was found to be dependent on hydrophobicity, which, in turn, modulated the compound's half-life. The 7-Cl derivative, (1R,2R)-7-chloro-3-[2-(2, 4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2, 4-triazol-1-yl)propyl]quinazolin-4(3H)-one (20, UR-9825), was selected for further testing due to its high in vitro activity, low toxicity, good pharmacokinetic profile, and ease of obtention. Compound 20 is the (1R,2R) isomer of four possible stereoisomers. The other three isomers were also prepared and tested. The enantiomer (1S,2S) and the (1R,2S) epimer were inactive, whereas the (1S,2R) epimer retained some activity. In vitro 20 was superior to fluconazole, itraconazole, SCH-42427, and TAK-187 and roughly similar to voriconazole and ER-30346. In vivo, 20 was only moderately active in a mouse model of systemic candidosis when administration was limited to the first day. This was attributed to its short half-life in that species (t1/2 = 1 h po). Protection levels comparable to or higher than those of fluconazole, however, were observed in systemic candidosis models in rat and rabbit, where the half-life of the compound was found to be 6 and 9 h, respectively. Finally, 20 showed excellent protection levels in an immunocompromised rat model of disseminated aspergillosis. The compound showed low toxicity signs when administered to rats at 250 mg/kg qd or at 100 mg/kg bid during 28 days.

Synthesis and antifungal activity of new azole derivatives containing an N-acylmorpholine ring.

A series of azole derivatives carrying an N-acylmorpholine ring are described. The compounds were chemically designed to simulate the lanosterol D ring, taking advantage of the conformational preferences of 2-alkyl-1-acylmorpholines. Three structural variables, the nature of the N-benzoyl group, the phenyl substituents, and the degree of oxidation at carbon 2 of the morpholine, were optimized for maximum activity. Only the (5R,6R) isomers showed antifungal activity. Cyclic hemiacetal (-)-39a (UR-9746) and cyclic ether (-)-41 (UR-9751) were selected for further development. In vitro, (-)-41 was clearly more active than (-)-39a and somewhat less active than the acyclic counterpart (-)-7. In vivo activity was assessed by a systemic (mouse) and a vaginal (rat) candidosis model. In the former, (-)-39a, (-)-41, and (-)-7 at 1 mg/kg given 1, 4, and 24 h postinfection displayed 90-100% protection from mortality on day 9. Compound (-)-39a was slightly more potent than (-)-41 and similar in potency to (-)-7. The three compounds were superior in potency to fluconazole and similar in potency in SCH-42427 in this test. In the vaginal model, (-)-39a and (-)-41 given daily during 3 days after infection at 0.5 mg/kg showed high levels of protection on days 10 and 15. At 0.25 mg/kg, (-)-39a was slightly more potent than SCH-42427 and (-)-7 and superior in potency to (-)-41 and fluconazole in this model. Preliminary 28-day toxicity tests at 100 mg/kg/day po in rats indicated no or very mild adverse effects for the two UR compounds.