RESUMEN
INTRODUCTION: The objective was to assess the prognostic value of the systolic flow through the aortic isthmus in monochorionic pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated by placental laser ablation. MATERIAL AND METHODS: Fetal echocardiography and outcome data of 105 cases of TTTS treated by laser photocoagulation of placental anastomoses were reviewed. Hemodynamic parameters were collected before and after treatment. The isthmic systolic index (ISI) was calculated as the peak systolic velocity/systolic nadir ratio. RESULTS: A total of 105 laser coagulations were studied. Fetal echocardiography pre- and post-laser were available in 68 cases, including 55 with data on aortic isthmic Doppler. Survival rates were 17, 22, and 61% for 0, 1, or 2 twins, respectively. At least 1 twin was delivered alive in 83% of the pregnancies. The mean gestational age at surgery was 21 weeks (range 16-26). Median ISI values were similar for donor and recipient twins, before and after laser ablation (all p > 0.05). A lower recipient ISI before laser was related to early recipient demise within 24 h (p = 0.04). DISCUSSION: A lower ISI before placental laser ablation for TTTS is associated with postoperative demise of the recipient twin.
Asunto(s)
Aorta/diagnóstico por imagen , Velocidad del Flujo Sanguíneo , Muerte Fetal , Transfusión Feto-Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/cirugía , Coagulación con Láser/efectos adversos , Gemelos , Aorta/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Ecocardiografía Doppler , Femenino , Muerte Fetal/etiología , Fetoscopía/métodos , Humanos , Coagulación con Láser/métodos , Valor Predictivo de las Pruebas , Embarazo , Resultado del TratamientoRESUMEN
INTRODUCTION: Our objective was to determine the impact of simple transposition of the great arteries (TGA) on fetal left ventricular (LV) and right ventricular (RV) performances and central circulatory dynamics including the aortic isthmus. MATERIAL AND METHODS: Ventricular stroke volumes were calculated as the product of the cross-sectional area of the corresponding semi-lunar valve and the flow velocity integral through these valves. Volume flow in ductus arteriosus (QDA ) was evaluated using the same technique. Flow through the lungs (QLUNGS ) was calculated by subtracting net QDA from flow in main pulmonary artery [net QDA = QDA minus retrograde ductus arteriosus (DA) diastolic flow]. Relative performance of each ventricle expressed as percentage of combined cardiac output was also indirectly assessed by the aortic isthmus systolic index (ISI) (nadir of incisura/peak systolic of the Doppler waveforms in the isthmus); the relation between ISI and QLUNGS was investigated. RESULTS: Fifty-one fetuses with TGA were compared with 74 normal controls matched for gestational age. TGA fetuses had higher QLV at T2 (58.6 ± 9.4% vs. 43.4 ± 5.0%, p < 0.001) and T3 (53.7 ± 8.9% vs. 43.9 ± 5.7%, p < 0.001). QLUNGS was higher in fetuses with TGA, in the second (50.4 ± 16.3% vs. 39.0 ± 16.8%, p = 0.007) and third trimesters of gestation (52.8 ± 22.0% vs. 37.1 ± 16.3%, p = 0.005). No difference was found between ISI values from normal and TGA groups. A significant inverse correlation was observed between ISI and QLUNGS (r = -0.55, p = 0.006). CONCLUSIONS: Central distribution of combined cardiac output of fetuses with simple TGA is characterized by a greater QLUNGS leading to a dominant LV. In prenatal TGA, changes in QLUNGS could be monitored by measuring ISI. The clinical importance of this last observation deserves further investigations.
Asunto(s)
Aorta Torácica/fisiopatología , Corazón Fetal/fisiopatología , Ventrículos Cardíacos/fisiopatología , Transposición de los Grandes Vasos/fisiopatología , Aorta Torácica/diagnóstico por imagen , Velocidad del Flujo Sanguíneo , Gasto Cardíaco , Ecocardiografía Doppler en Color , Femenino , Corazón Fetal/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Embarazo , Estudios Retrospectivos , Transposición de los Grandes Vasos/diagnóstico por imagen , Ultrasonografía PrenatalRESUMEN
BACKGROUND: Visible vascular and pigmentary conditions have a negative impact on children's and adolescents' quality of life (QoL). We sought to quantitate the effect of visible skin anomalies and their camouflage on QoL. METHODS: In all, 41 patients, 5 years of age and older, were taught to use cosmetic camouflage. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) before and 6 months after the intervention. Satisfaction and use were evaluated after 1 and 6 months. RESULTS: Baseline QoL scores revealed a small impact of vascular anomalies (CDLQI score 4.2) and a small to moderate effect of pigmentary anomalies (CDLQI score 6.1). Six months after the intervention, QoL improved in the study population as a whole (CDLQI score 5.1 vs 2.1, P<.001), with significant improvements documented for facial lesions and vascular malformations. Cosmetic camouflage was well tolerated and patients with pigmentary anomalies were more likely to continue using the products. LIMITATIONS: Limitations include small study population, few male patients, cultural influences not addressed, and limited range of conditions. CONCLUSIONS: Children and teenagers with visible vascular and pigmentary anomalies experience an impairment of QoL that is abrogated by introduction to use of cosmetic camouflage.
Asunto(s)
Cosméticos/uso terapéutico , Trastornos de la Pigmentación/tratamiento farmacológico , Calidad de Vida/psicología , Enfermedades Cutáneas Vasculares/tratamiento farmacológico , Malformaciones Vasculares/tratamiento farmacológico , Adolescente , Niño , Preescolar , Cara , Femenino , Humanos , Extremidad Inferior , Masculino , Satisfacción del Paciente , Trastornos de la Pigmentación/psicología , Enfermedades Cutáneas Vasculares/psicología , Encuestas y Cuestionarios , Tórax , Extremidad Superior , Malformaciones Vasculares/psicologíaRESUMEN
In humans, chromosome-number abnormalities have been associated with altered recombination and increased maternal age. Therefore, age-related effects on recombination are of major importance, especially in relation to the mechanisms involved in human trisomies. Here, we examine the relationship between maternal age and recombination rate in humans. We localized crossovers at high resolution by using over 600,000 markers genotyped in a panel of 69 French-Canadian pedigrees, revealing recombination events in 195 maternal meioses. Overall, we observed the general patterns of variation in fine-scale recombination rates previously reported in humans. However, we make the first observation of a significant decrease in recombination rates with advancing maternal age in humans, likely driven by chromosome-specific effects. The effect appears to be localized in the middle section of chromosomal arms and near subtelomeric regions. We postulate that, for some chromosomes, protection against non-disjunction provided by recombination becomes less efficient with advancing maternal age, which can be partly responsible for the higher rates of aneuploidy in older women. We propose a model that reconciles our findings with reported associations between maternal age and recombination in cases of trisomies.
Asunto(s)
Edad Materna , Recombinación Genética , Trisomía/genética , Adulto , Factores de Edad , Aneuploidia , Canadá , Centrómero/genética , Mapeo Cromosómico , Cromosomas Humanos Par 21/genética , Femenino , Genoma Humano , Genotipo , Humanos , Meiosis , Persona de Mediana Edad , No Disyunción Genética , LinajeRESUMEN
AIMS: Although ventricular septal defects (VSD) are the most common congenital heart lesion, familial clustering has been described only in rare instances. The aim of this study was to identify genetic factors and chromosomal regions contributing to VSD. METHODS AND RESULTS: A unique, large kindred segregating various forms of septal pathologies-including VSD, ventricular septal aneurysms, and atrial septal defects (ASD)-was ascertained and characterized clinically and genetically. Eighteen family members in three generations could be studied, out of whom 10 are affected (2 ASD, 3 septal aneurysm, 4 VSD, and 1 tetralogy of Fallot). Parametric multipoint LOD scores reach significance on chromosome 10p15.3-10p15.2 (max. 3.29). The LOD score support interval is in a gene-poor region where deletions have been reported to associate with septal defects, but that is distinct from the DiGeorge syndrome 2 region on 10p. Multiple linkage analysis scenarios suggest that tetralogy of Fallot is a phenocopy and genetically distinct from the autosomal dominant form of septal pathologies observed in this family. CONCLUSION: This study maps a rare familial form of VSD/septal aneurysms to chromosome 10p15 and extends the spectrum of the genetic heterogeneity of septal pathologies. Fine mapping, haplotype construction, and resequencing will provide a unique opportunity to study the pathogenesis of septal defects and shed light on molecular mechanisms of septal development.
Asunto(s)
Cromosomas Humanos Par 10/genética , Ligamiento Genético/genética , Aneurisma Cardíaco/genética , Defectos del Tabique Interventricular/genética , Femenino , Humanos , Masculino , Linaje , Fenotipo , Tetralogía de Fallot/genéticaRESUMEN
BACKGROUND: Congenital cardiac disease is the most common malformation, and a substantial source of mortality and morbidity in children and young adults. A role for genetic factors is recognised for these malformations, but overall few predisposing loci have been identified. Here we report the rationale, design, and first results of a multi-institutional congenital cardiac disease cohort, assembled mainly from the French-Canadian population of the province of Quebec and centred on families with multiple affected members afflicted by cardiac malformations. METHODS: Families were recruited into the study, phenotyped and sampled for DNA in cardiology clinics over the first 3 years of enrolment. We performed segregation analysis and linkage simulations in the subgroup of families with left ventricular outflow tract obstruction (LVOTO). RESULTS: A total of 1603 participants from 300 families were recruited, with 169 out of 300 (56.3%) families having more than one affected member. For the LVOTO group, we estimate heritability to be 0.46-0.52 in our cohort. Simulation analysis demonstrated sufficient power to carry out linkage analyses, with an expected mean log-of-odds (LOD) score of 3.8 in 67 pedigrees with LVOTO. CONCLUSION: We show feasibility and usefulness of a population-based biobank for genetic investigations into the causes of congenital cardiac disease. Heritability of LVOTO is high and could be accounted for by multiple loci. This platform is ideally suited for multiple analysis approaches, including linkage analysis and novel gene sequencing approaches, and will allow to establish segregation of risk alleles at family and population levels.
Asunto(s)
Predisposición Genética a la Enfermedad , Cardiopatías Congénitas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Familia , Femenino , Ligamiento Genético , Defectos de los Tabiques Cardíacos/genética , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Linaje , Quebec , Proyectos de Investigación , Tetralogía de Fallot/genética , Obstrucción del Flujo Ventricular Externo/genética , Adulto JovenRESUMEN
OBJECTIVES: To explore the efficacy and safety of imiquimod 5% cream as a treatment for infantile hemangioma. DESIGN: Phase II, open-label, noncomparative study of imiquimod applied during 16 weeks, with posttherapy follow-up 16 weeks later (8 months total). SETTING: Outpatient pediatric tertiary care referral center in Quebec, Canada. PARTICIPANTS: Healthy infants up to 8.8 months of age with previously untreated, nonulcerated, proliferative superficial or mixed infantile hemangioma, excluding periorbital, or perineal localization, > or =100 cm2 in size. INTERVENTION: Topical imiquimod applied three to seven times per week for 16 weeks to infantile hemangioma. MAIN OUTCOME MEASURES: Lesion area, volume, depth (Doppler ultrasound), and color (erythema), serum drug, and interferon-alpha levels. RESULTS: Sixteen infants (11 girls, 5 boys) with a mean age at entry of 4.1 months and mean lesion area of 32.89 cm2, and volume of 39.98 cm3 were enrolled. Two participants discontinued treatment early, one for an adverse event (crying upon application), the other because of the lack of compliance. Local skin reactions were consistent with those reported in adults. Two cases had a decrease and three had an increase in lesion parameters; otherwise no meaningful changes in lesion area, volume, or depth were observed. At the 4-month posttreatment visit, 11 of 14 subjects had improvement in erythema (marginal homogeneity test = 2.668, p = 0.008). Measured serum drug and interferon-alpha levels were low or undetectable. CONCLUSIONS: Treatment of infants with infantile hemangioma with imiquimod up to seven times per week for 16 weeks was generally well tolerated with low systemic exposure. Improvement was observed in hemangioma coloration, but not lesion size, suggesting effects were limited to the superficial component.
Asunto(s)
Aminoquinolinas/uso terapéutico , Antineoplásicos/uso terapéutico , Hemangioma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Aminoquinolinas/sangre , Antineoplásicos/sangre , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Humanos , Imiquimod , Lactante , Interferón-alfa/sangre , Masculino , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/orinaRESUMEN
Children with hypoplastic left heart syndrome (HLHS) have an increased prevalence of central nervous system (CNS) abnormalities. The extent to which this problem is due to CNS maldevelopment, prenatal ischemia, postnatal chronic cyanosis and/or multiple exposures to cardiopulmonary bypass is unknown. To better understand the etiology of CNS abnormalities in HLHS, we evaluated 68 neonates with HLHS; in 28 cases, both fetal ultrasound and echocardiogram data were available to assess head size, head growth and aortic valve anatomy (atresia or stenosis). In addition, we evaluated neuropathology in 11 electively aborted HLHS fetuses. The mean head circumference percentile in HLHS neonates was significantly smaller than HLHS fetuses (22 +/- 2% versus 40 +/- 4%, p < 0.001). A significant decrease in head growth, defined as a 50% reduction in head circumference percentile, was observed in half (14/28) of HLHS fetuses and nearly a quarter (6/28) were already growth restricted (Asunto(s)
Válvula Aórtica/patología
, Cabeza/embriología
, Síndrome del Corazón Izquierdo Hipoplásico/complicaciones
, Cefalometría
, Ecocardiografía
, Cabeza/diagnóstico por imagen
, Humanos
, Síndrome del Corazón Izquierdo Hipoplásico/patología
, Recién Nacido
, Ohio
RESUMEN
The mucosal immune system is overactivated in Crohn disease (CD) and viral infections have been associated with clinical exacerbations. To investigate the potential association between mucosal inflammation and the cytokines involved in the early response to viruses, we analyzed colonic tissue levels of IL-2Ralpha, interferon-alpha, and IL-15 in CD. Patients undergoing diagnostic colonoscopy were classified into controls (n = 22) and three CD groups based on the histologic severity of inflammation and clinical activity: a) severely active CD (n = 3); b) mild to moderately active CD (n = 14); and c) quiescent CD (n = 23). Rectal biopsies (two per patient) were homogenized and cytokine levels determined by ELISA kits. Statistical analysis was performed by ANOVA with Tukey and Scheffé tests. IL-2Ralpha levels were increased in the active CD group compared with the quiescent CD group: a) 405 +/- 87, b) 159 +/- 31, and c) 33 +/- 15 pg/mg DNA (p < 0.001). The latter group was similar to controls (39 +/- 20 pg/mg DNA). Furthermore, a linear correlation (r = 0.98) between IL-2Ralpha and disease activity (Van Hees index) was observed. IL-15 levels were also higher in active compared with quiescent CD and controls: a) 0.69 +/- 0.23 and b) 0.72 +/- 0.31 versus c) 0.28 +/- 0.21 and 0.28 +/- 0.14 pg/mg DNA for controls (p < 0.05). Interferon-alpha levels were undetectable in all samples. Our data suggest that IL-2Ralpha tissue levels correlate with CD activity. IL-15 is also overproduced in inflamed CD tissue. The lack of a parallel elevation of interferon-alpha does not support a role for viral induction of IL-15 in inflamed CD samples.