RESUMEN
OBJECTIVE: To assess the incidence and impact of extracardiac anomalies on the prognosis of fetuses with heterotaxy syndrome. METHODS: All fetuses diagnosed with heterotaxy syndrome by three experienced examiners over a period of 14 years (1999-2013) were reviewed retrospectively. RESULTS: In total, 165 fetuses with heterotaxy syndrome were diagnosed in the study period. One hundred and fifty (90.9%) had cardiac defects; extracardiac anomalies that did not involve the spleen were present in 26/165 (15.8%) cases. Of the total study cohort, termination of pregnancy was performed in 49 (29.7%) cases, intrauterine death occurred in 11 (6.7%), postnatal death occurred in 38 (23.0%) and 67 (40.6%) were alive at the latest follow-up, resulting in a total perinatal and pediatric mortality of 59.4%. Among the 105 liveborn neonates, 15 (14.3%) had extracardiac anomalies with significant impact on the postnatal course: one neonate died following repair of an encephalocele, six had successful treatment for various types of intestinal malrotation and/or atresia and one underwent hiatal hernia repair; the remaining seven had biliary atresia, of which five died and the two survivors are awaiting liver transplantation. The status of the spleen was assessed in 93/105 liveborn children and was found to be abnormal in 84/93 (90.3%). There were three cases of lethal sepsis, all associated with asplenia. Of the 38 postnatal deaths, 29 (76.3%) had a cardiac cause, seven (18.4%) had an extracardiac cause and in two (5.2%) the reason was uncertain. CONCLUSIONS: Although the leading causes of death in fetuses and children with heterotaxy syndrome are cardiac, a small subset of fetuses have extracardiac anomalies with significant impact on outcome. These anomalies often escape prenatal detection, and therefore neonates at risk should be monitored for bowel obstruction, biliary atresia and immune dysfunction in order to allow timely intervention through a multidisciplinary approach. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Asunto(s)
Enfermedades Fetales/mortalidad , Feto/anomalías , Síndrome de Heterotaxia/mortalidad , Adulto , Femenino , Muerte Fetal/etiología , Enfermedades Fetales/diagnóstico por imagen , Edad Gestacional , Síndrome de Heterotaxia/diagnóstico por imagen , Síndrome de Heterotaxia/embriología , Humanos , Recién Nacido , Muerte Perinatal/etiología , Embarazo , Resultado del Embarazo , Pronóstico , Estudios Retrospectivos , Bazo/anomalías , Bazo/diagnóstico por imagen , Ultrasonografía Prenatal/métodosRESUMEN
Congenital diaphragmatic hernia is a malformation presenting with varying degrees of severity. An accurate prediction of outcome is crucial for parental counselling and therapeutic planning. In selected cases, foetal endoscopic tracheal occlusion (FETO) can improve foetal outcome. Timely referral to a highly specialised centre is important when the requirement for extracorporeal membrane oxygenation (ECMO) is expected.
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Oxigenación por Membrana Extracorpórea/métodos , Fetoscopía/métodos , Hernias Diafragmáticas Congénitas , Herniorrafia/métodos , Herniorrafia/rehabilitación , Ultrasonografía Prenatal/métodos , Terapia Combinada , Hernia Diafragmática/diagnóstico , Humanos , Recién Nacido , Pronóstico , Medición de RiesgoRESUMEN
The aetiology of urinary tract obstructions (LUTO) is heterogeneous. The most common entities are isolated posterior urethral valves or urethral atresia in male foetuses. In female foetuses LUTO is frequently a part of complex malformations. The natural history of LUTO is characterised by high morbidity and mortality due to the development of severe pulmonary hypoplasia caused by oligo- or anhydramnios affecting the cannalicular phase (16-24 weeks of gestation) of pulmonary development. The degree of renal damage is variable and ranges from mild renal impairment in infancy to end-stage renal insufficiency, necessitating dialysis and transplantation. Foetal interventions in order to bypass the obstruction are biologically plausible and technically feasible. Vesico-amniotic shunting as well as (currently less frequent) foetoscopic cystoscopy and laser ablation of posterior urethral valves are minimally invasive treatment options. Previous reports indicate that prenatal therapy is suitable to reduce perinatal mortality but does not improve postnatal renal function. Selection of foetuses who may profit from prenatal intervention is aggravated by the lack of reliable prognostic criteria for the prediction of postnatal renal function in both ultrasound and foetal urine analysis. Furthermore, there is no randomised trial available at the time of writing. Because of a relevant complication rate and still no clear evidence for foetal benefit, interventions should be performed in specialised centres. Further studies are necessary to improve case selection of affected foetuses and to evaluate the impact of interventions in earlier gestational weeks. The data from the PLUTO trial (percutaneous shunting in lower urinary tract obstruction) conducted by the University of Birmingham may help to answer these questions. In the meantime selection of foetuses for prenatal intervention puts high requirements on interdisciplinary counselling in every case. A general treatment algorithm for foetal therapy is not available at the moment.
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Cistoscopía/métodos , Fetoscopía/métodos , Síntomas del Sistema Urinario Inferior/diagnóstico , Síntomas del Sistema Urinario Inferior/cirugía , Ultrasonografía Prenatal/métodos , Obstrucción del Cuello de la Vejiga Urinaria/diagnóstico , Obstrucción del Cuello de la Vejiga Urinaria/cirugía , Femenino , Humanos , Terapia por Láser/métodos , Síntomas del Sistema Urinario Inferior/congénito , Masculino , Obstrucción del Cuello de la Vejiga Urinaria/congénitoRESUMEN
PURPOSE: The aim of this study was to evaluate the prevalence of an aberrant right subclavian artery (ARSA) in a mixed-risk population in the second trimester and to assess its potential as a new soft marker in the genetic scan. MATERIALS AND METHODS: Fetal echocardiography was performed prospectively in 1337 fetuses at 16 - 28 weeks of gestation during a 12-month period at two referral centers for prenatal diagnosis. The presence of ARSA was verified by visualization of the transverse 3-vessel trachea view with color Doppler sonography. RESULTS: The total rate of fetuses with an ARSA was 1.05 % (14 / 1337). The spectrum of associated findings in affected fetuses included: one trisomy 21, one unbalanced inversion of chromosome 9, one triploidy and two non-chromosomally related structural defects. Nine fetuses had no anomalies. The calculated odds ratio for the presence of an ARSA in the case of Down syndrome compared with healthy fetuses was 12.6 (95 % CI, 1.93 - 86.10). CONCLUSION: The presence of an ARSA is more common in fetuses with trisomy 21 and other chromosomal defects than in healthy fetuses. Although it can be considered as a weak marker, the second trimester diagnosis of an ARSA should prompt a detailed search for additional "soft markers" and structural defects.
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Aorta Torácica/anomalías , Aorta Torácica/diagnóstico por imagen , Trastornos de los Cromosomas/diagnóstico por imagen , Síndrome de Down/genética , Arteria Subclavia/anomalías , Arteria Subclavia/diagnóstico por imagen , Ultrasonografía Prenatal , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/genética , Adolescente , Adulto , Aberraciones Cromosómicas , Trastornos de los Cromosomas/genética , Inversión Cromosómica/genética , Cromosomas Humanos Par 9/genética , Síndrome de Down/diagnóstico por imagen , Femenino , Edad Gestacional , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/genética , Humanos , Recién Nacido , Cariotipificación , Persona de Mediana Edad , Embarazo , Segundo Trimestre del Embarazo , Embarazo Múltiple/genética , Estudios Prospectivos , Triploidía , Adulto JovenRESUMEN
PURPOSE: To assess the spectrum of underlying diseases in cases of fetal anemia in which the cause was unknown at the time of first and second transfusion or thereafter. MATERIALS AND METHODS: All patients who underwent intrauterine transfusion were identified in the perinatal databases of two tertiary referral centers for prenatal medicine and treatment between 2002 and June 2010. RESULTS: 82 fetuses received intrauterine transfusion in the study period. A total of 356 transfusions were performed in these patients. The causes of fetal anemia in our cohort were alloimmunization (32), parvovirus infection (23), feto-fetal transfusion syndrome (9), sacrococcygeal teratoma (2) and cytomegalovirus infection (1). In the remaining 15 cases, the cause of fetal anemia was unknown at the time of first and second transfusion, and could only be ascertained in the further course of pregnancy, in the postnatal period or was ultimately left in doubt. In all cases markedly elevated peak systolic velocities in the middle cerebral artery accurately predicted fetal anemia. The final diagnosis in these cases was fetomaternal hemorrhage (4), Blackfan-Diamond anemia (1), diffuse neonatal hemangiomatosis with chorangioma (1), kaposi-like hemangioendothelioma (1), elliptocytosis (1), neonatal hemochromatosis (1), mucopolysaccharidosis type VII (1) and in 5 cases the cause of fetal anemia remained unexplained. The latter 5 cases had an uneventful postnatal course and did not require further transfusions in infancy. CONCLUSION: In cases of fetal anemia with negative indirect Coombs test and TORCH serology, rare causes of anemia have to be considered. Fetal studies should therefore include reticulocyte count, parameters of hemolysis, peripheral blood smear and fetal liver function tests. Maternal studies should involve a search for fetal red cells using flow cytometry rather than Kleihauer-Betke test.
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Anemia Neonatal/etiología , Transfusión de Sangre Intrauterina , Enfermedades Fetales/etiología , Ultrasonografía Prenatal , Anemia Neonatal/epidemiología , Anemia Neonatal/terapia , Causalidad , Prueba de Coombs , Diagnóstico Diferencial , Femenino , Enfermedades Fetales/terapia , Edad Gestacional , Hemoglobinometría , Humanos , Recién Nacido , EmbarazoRESUMEN
A method is described for the determination of betaine and its metabolite N,N-dimethylglycine in human urine. The method involves a deamination step and a solid-phase extraction to isolate both substances from urine followed by high performance liquid chromatography (HPLC) separation on a 5-microns SCX column with UV absorbance detection. Limit of detection is about 0.9 micrograms for both substances. Recoveries were > 85%. The method appears to be suitable for monitoring betaine and its metabolite in urine of patients undergoing therapy with betaine.
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Betaína/orina , Sarcosina/análogos & derivados , Betaína/aislamiento & purificación , Betaína/uso terapéutico , Preescolar , Cromatografía Líquida de Alta Presión/métodos , Homocistinuria/tratamiento farmacológico , Homocistinuria/orina , Humanos , Reproducibilidad de los Resultados , Sarcosina/aislamiento & purificación , Sarcosina/orinaRESUMEN
Hypotonicity-induced Ca2+ signals and volume regulation were studied in proliferating and quiescent subpopulations of multicellular prostate cancer spheroids. Enzymatic dissociation of multicellular spheroids 100+/-19 microm in diameter, which are entirely proliferative, yielded a population of cells with a mean cell diameter of 17.5+/-1.4 microm. After dissociation of spheroids in a size class of 200+/-30, 300+/-60, and 400+/-65 microm in diameter, two subpopulations of cells with mean cell diameters corresponding to 12.9+/-1.9 microm and 16.7+/-2 microm were discriminated. The subpopulation of large cells was shown to be proliferative by positive Ki-67 antibody staining; the subpopulation of small cells was Ki-67 negative, indicating cell quiescence. In a spheroid size class of 100+/-19 microm, a distinct subpopulation of quiescent cells was absent. Superfusion by hypotonic solutions revealed that only the proliferating cell fraction showed a regulatory volume decrease (RVD) and a [Ca2+]i transient. Both effects were absent in the quiescent cell population. The [Ca2+]i transient persisted in low (10 nM) Ca2+ solution and in the presence of 4 mM extracellular Ni2+ but was abolished in the presence of the endoplasmic reticulum Ca2+-ATPase blocker 2,5-di-tert-butyl-hydrochinone (t-BHQ). The t-BHQ likewise inhibited RVD, indicating that Ca2+ release from intracellular stores was necessary for RVD. Moreover, [Ca2+]i and RVD were dependent on an intact microfilament cytoskeleton because after 30 min of preincubation with cytochalasin B the [Ca2+]i transient was significantly reduced and RVD was abolished. The absence of RVD and [Ca2+]i transient in quiescent cells may be due to differences in the amount and the cytosolic arrangement of F-actin observed in quiescent cells.
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Calcio/metabolismo , Tamaño de la Célula/fisiología , Soluciones Hipotónicas/farmacología , Actinas/análisis , Adenosina Trifosfato/farmacología , ATPasas Transportadoras de Calcio/antagonistas & inhibidores , División Celular/fisiología , Citocalasina B/farmacología , Citometría de Flujo , Humanos , Hidroquinonas/farmacología , Inmunohistoquímica , Inositol 1,4,5-Trifosfato/farmacología , Antígeno Ki-67/inmunología , Masculino , Níquel/farmacología , Neoplasias de la Próstata/metabolismo , Células Tumorales CultivadasRESUMEN
Growing multicellular prostate tumor spheroids develop quiescent cell subpopulations in central regions with features of intrinsic multicell-mediated drug resistance. Doxorubicin (dox) uptake was significantly reduced in large spheroids (diameter 400+/-70 microm), which consist predominantly of quiescent cells, as compared to small spheroids (diameter 100+/-50 microm), which consist entirely of proliferating cells. After removal of dox from the incubation medium, dox fluorescence declined more efficiently in large spheroids, which led to a decreased dox toxicity as revealed by colony-forming assays. Verapamil significantly increased dox retention in large spheroids and, consequently, augmented dox toxicity. At a depth 80 microm from the spheroid periphery, a significantly decreased dox fluorescence was observed in the deep, quiescent cell layers of large spheroids. The P-glycoprotein-mediated multidrug resistance (MDR)-reversing agents verapamil, cyclosporin A, quinidine, sodium orthovanadate and tamoxifen significantly increased dox fluorescence at this depth, whereas genistein, indomethacin, probenecid and brefeldin A, which reverse multidrug-resistance-associated protein (MRP) function, exerted no effect. Anti-P-glycoprotein immunohistochemistry of multicellular tumor spheroids revealed an increase of P-glycoprotein expression in large speroids as compared to small spheroids, which was most prominent in the Ki-67-negative, quiescent cell layers 60 to 100 microm distant from the periphery of the spheroid, indicating that the MDR phenotype is related to cell quiescence. This was corroborated by whole-cell patch-clamp experiments, where the C219 antibody, which is directed against the ATP-binding site of P-glycoprotein, significantly inhibited P-glycoprotein-associated, volume-activated chloride currents in quiescent, but not proliferating cells from multicellular tumor spheroids.