RESUMEN
Non-nucleoside reverse transcriptase inhibitors are important antiretroviral agents for the treatment of human immunodeficiency virus. Some non-nucleoside reverse transcriptase inhibitors, in particular efavirenz, have prominent effects on sleep, cognition and psychiatric variables that limit their tolerability. To avoid confounds due to drug-drug and drug-disease interactions, we assessed the effects of efavirenz in healthy volunteers on sleep, cognition and psychological endpoints during the first week of treatment. Forty healthy male subjects were randomized to receive placebo or efavirenz 600 mg nightly for 7 days after completion of a 3-day placebo run-in period. Treatment with efavirenz was associated with reduced time to sleep onset in the Maintenance of Wakefulness Test, an increase in non-rapid eye movement sleep, a large exposure-related decrease in sigma band spectral density and sleep spindle density during non-rapid eye movement sleep, and reduced performance on an attention switching task. Because efavirenz has been shown to have serotonin 2A receptor partial-agonist properties, we reasoned that antagonism of serotonin 2A receptor signalling in the thalamic reticular nucleus, which generates sleep spindles and promotes attention, may be responsible. Consistent with predictions, treatment of healthy volunteers with a single dose of a serotonin 2A receptor antagonist was found to significantly suppress sigma band spectral density in an exposure-related manner and modulated the overall spectral profile in a manner highly similar to that observed with efavirenz, consistent with the notion that efavirenz exhibits serotonin 2A receptor partial-agonist pharmacology in humans.
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Benzoxazinas/farmacología , Sueño/efectos de los fármacos , Sueño/fisiología , Adulto , Alquinos , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacología , Atención/efectos de los fármacos , Atención/fisiología , Benzoxazinas/efectos adversos , Cognición/efectos de los fármacos , Cognición/fisiología , Ciclopropanos , Agonismo Parcial de Drogas , Humanos , Masculino , Persona de Mediana Edad , Placebos , Receptor de Serotonina 5-HT2A/metabolismo , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/farmacología , Antagonistas del Receptor de Serotonina 5-HT2/farmacología , Vigilia/efectos de los fármacos , Vigilia/fisiología , Adulto JovenRESUMEN
BACKGROUND: Preoperative brain injury is common in neonates with complex congenital heart disease. Increasing evidence suggests a complex interaction of prenatal and postnatal risk factors for development of brain white matter injury, called periventricular leukomalacia (PVL), in neonates with complex congenital heart disease. To date, there remains a limited understanding of the risk factors contributing to preoperative PVL in hypoplastic left heart syndrome (HLHS). METHODS: Neonates with HLHS or HLHS variants from 3 prospective magnetic resonance imaging studies (2003-2010) were selected for this cohort. Preoperative brain magnetic resonance imaging was performed the morning of the surgery. Stepwise multilogistic regression of patient characteristics, mode of delivery (cesarean section vs vaginal), time of diagnosis (prenatal vs postnatal), HLHS subtypes, brain total maturation score, time to surgery, individual averaged daily preoperative blood gases, and complete blood cell count values was used to determine significant associations. RESULTS: A total of 57 neonates with HLHS were born at 38.7 ± 2.3 weeks; 86% (49/57) had a prenatal diagnosis, with 31% (18/57) delivered by cesarean section. HLHS with aortic atresia (AA) was common in this cohort, 71% (41/57). Preoperative PVL was identified in 19% (11/57). Male patients with AA (P = .004) were at higher risk for PVL. Lower total brain maturation score was also identified as a strong predictor for preoperative PVL (P = .005). CONCLUSIONS: In neonates with HLHS, nonmodifiable patient-related factors, including male sex with AA (lack of antegrade blood flow) and lower total brain maturation score, placed neonates at the greatest risk for preoperative white matter injury.
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Síndrome del Corazón Izquierdo Hipoplásico/complicaciones , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Leucomalacia Periventricular/complicaciones , Femenino , Humanos , Recién Nacido , Leucomalacia Periventricular/epidemiología , Masculino , Periodo Preoperatorio , Estudios Prospectivos , Factores de RiesgoRESUMEN
Canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to loss of enzyme activity and increased concentrations of the substrate N-acetyl-aspartate (NAA) in the brain. Accumulation of NAA results in spongiform degeneration of white matter and severe impairment of psychomotor development. The goal of this prospective cohort study was to assess long-term safety and preliminary efficacy measures after gene therapy with an adeno-associated viral vector carrying the ASPA gene (AAV2-ASPA). Using noninvasive magnetic resonance imaging and standardized clinical rating scales, we observed Canavan disease in 28 patients, with a subset of 13 patients being treated with AAV2-ASPA. Each patient received 9 × 10(11) vector genomes via intraparenchymal delivery at six brain infusion sites. Safety data collected over a minimum 5-year follow-up period showed a lack of long-term adverse events related to the AAV2 vector. Posttreatment effects were analyzed using a generalized linear mixed model, which showed changes in predefined surrogate markers of disease progression and clinical assessment subscores. AAV2-ASPA gene therapy resulted in a decrease in elevated NAA in the brain and slowed progression of brain atrophy, with some improvement in seizure frequency and with stabilization of overall clinical status.
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Enfermedad de Canavan/terapia , Terapia Genética , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/metabolismo , Enfermedad de Canavan/metabolismo , Niño , Preescolar , Humanos , Lactante , Estudios ProspectivosRESUMEN
BACKGROUND: A blood-based test that could be used as a screen for Alzheimer disease (AD) may enable early intervention and better access to treatment. OBJECTIVE: To apply a multiplex immunoassay panel to identify plasma biomarkers of AD using plasma samples from the Alzheimer's Disease Neuroimaging Initiative cohort. DESIGN: Cohort study. SETTING: The Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project. PARTICIPANTS: Plasma samples at baseline and at 1 year were analyzed from 396 (345 at 1 year) patients with mild cognitive impairment, 112 (97 at 1 year) patients with AD, and 58 (54 at 1 year) healthy control subjects. MAIN OUTCOME MEASURES: Multivariate and univariate statistical analyses were used to examine differences across diagnostic groups and relative to the apolipoprotein E (ApoE) genotype. RESULTS: Increased levels of eotaxin 3, pancreatic polypeptide, and N-terminal protein B-type brain natriuretic peptide were observed in patients, confirming similar changes reported in cerebrospinal fluid samples of patients with AD and MCI. Increases in tenascin C levels and decreases in IgM and ApoE levels were also observed. All participants with Apo ε3/ε4 or ε4/ε4 alleles showed a distinct biochemical profile characterized by low C-reactive protein and ApoE levels and by high cortisol, interleukin 13, apolipoprotein B, and gamma interferon levels. The use of plasma biomarkers improved specificity in differentiating patients with AD from controls, and ApoE plasma levels were lowest in patients whose mild cognitive impairment had progressed to dementia. CONCLUSIONS: Plasma biomarker results confirm cerebrospinal fluid studies reporting increased levels of pancreatic polypeptide and N-terminal protein B-type brain natriuretic peptide in patients with AD and mild cognitive impairment. Incorporation of plasma biomarkers yielded high sensitivity with improved specificity, supporting their usefulness as a screening tool. The ApoE genotype was associated with a unique biochemical profile irrespective of diagnosis, highlighting the importance of genotype on blood protein profiles.
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Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Biomarcadores/sangre , Disfunción Cognitiva/genética , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Apolipoproteínas B/sangre , Apolipoproteínas E/metabolismo , Proteína C-Reactiva/líquido cefalorraquídeo , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Quimiocina CXCL9/sangre , Disfunción Cognitiva/sangre , Estudios de Cohortes , Femenino , Genotipo , Humanos , Inmunoensayo , Interleucina-3/sangre , Masculino , Curva ROCRESUMEN
PURPOSE: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. METHODS AND MATERIALS: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29 nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. RESULTS: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. CONCLUSIONS: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.
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Trastornos del Conocimiento/diagnóstico , Trastornos de la Memoria/diagnóstico , Memoria/efectos de la radiación , Radioterapia Conformacional/efectos adversos , Neoplasias Supratentoriales/radioterapia , Adulto , Anciano , Trastornos del Conocimiento/etiología , Humanos , Estudios Longitudinales , Memoria/fisiología , Trastornos de la Memoria/etiología , Recuerdo Mental/efectos de la radiación , Persona de Mediana Edad , Pruebas Neuropsicológicas , Traumatismos por Radiación/complicaciones , Radioterapia Conformacional/métodos , Neoplasias Supratentoriales/patología , Adulto JovenRESUMEN
PURPOSE: Obesity and cigarette smoking are two of the most frequent and preventable causes of disease and death in the United States; both are often established during youth. We hypothesized that obese, adolescent girls would be at higher risk for nicotine addiction in young adulthood, and that particular individual and social factors would mediate this association. METHODS: Students surveyed in the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative school-based and in-home survey conducted in three waves, comprised the sample. More than 4,000 respondents were used for the multivariate linear and logistic regression analyses used to determine the association between obesity and level of nicotine addiction. Potential mediation effects of the association were also examined. RESULTS: Obesity doubled the risk of the highest level of nicotine addiction after controlling for demographic factors, parent and friend smoking, and baseline smoking (OR, 2.12; 95% CI, 1.22-3.68). Family smoking was the strongest predictor of nicotine addiction (OR, 4.72; 95% CI, 2.89-7.72). Grade point average was a partial mediator of this relationship (OR, .48; 95% CI, .32-.74). CONCLUSIONS: Obese, adolescent females are at increased risk for high-level nicotine addiction in young adulthood as compared with their nonobese peers. Grade point average partially mediates the association, and may represent a confluence of factors including increased absenteeism, social marginalization, biases, and lack of confidence in academic ability. Obese, adolescent females may require targeted interventions to address their risk of subsequent high-level nicotine addiction, especially if risk factors such as parental smoking and poor school performance are present.
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Conducta del Adolescente , Obesidad/epidemiología , Autoimagen , Fumar/epidemiología , Tabaquismo/epidemiología , Adolescente , Comorbilidad , Intervalos de Confianza , Femenino , Humanos , Incidencia , Relaciones Interpersonales , Obesidad/psicología , Oportunidad Relativa , Grupo Paritario , Fumar/psicología , Medio Social , Tabaquismo/psicología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
To understand how normal variations in white matter relate to cognition, magnetization transfer imaging ratios (MTR) of a hypothesized neural network were associated with a test of visual selective attention (VST). Healthy adults (N = 16) without abnormal signal on brain scans viewed a version of DeSchepper and Treisman's test of VST (1996) with two levels of processing (novel shape matching with and without distractors, contingency feedback). A hypothesized neural network and component regions was significantly associated with accuracy and response times when distractors were present, with betas predicting 55% of variance in accuracy, and 59% of response times. MTR for anterior and posterior cingulate, prefrontal region, and thalami comprised a model predicting 55% of accuracy when distractors were present, and the anterior cingulate accounted for the majority of this effect. Prefrontal MTR predicted longer response times which was associated with increased accuracy. Distal neural areas involved in complex, processing-driven tasks (error processing, response selection, and variable response competition and processing load) may be dependent on white matter fibers to connect distal brain regions/nuclei of a macronetwork, including prefrontal executive functions.
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Atención/fisiología , Encéfalo/anatomía & histología , Encéfalo/fisiología , Percepción Visual/fisiología , Adolescente , Adulto , Anciano , Envejecimiento/fisiología , Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Cognición/fisiología , Femenino , Percepción de Forma/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Pruebas Neuropsicológicas , Lóbulo Parietal/anatomía & histología , Lóbulo Parietal/fisiología , Desempeño Psicomotor/fisiología , Análisis de Regresión , Tálamo/fisiología , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this multicenter study was to confirm the validity and reliability of the Pediatric Cardiac Quality of Life Inventory (PCQLI). METHODS: Seven centers recruited pediatric patients (8-18 years of age) with heart disease (HD) and their parents to complete the PCQLI and generic health-related quality of life (Pediatric Quality of Life Inventory [PedsQL]) and non-quality of life (Self-Perception Profile for Children [SPPC]/Self-Perception Profile for Adolescents [SPPA] and Youth Self-Report [YSR]/Child Behavior Checklist [CBCL]) tools. PCQLI construct validity was assessed through correlations of PCQLI scores between patients and parents and with severity of congenital HD, medical care utilization, and PedsQL, SPPC/SPPA, and YSR/CBCL scores. PCQLI test-retest reliability was evaluated. RESULTS: The study enrolled 1605 patient-parent pairs. Construct validity was substantiated by the association of lower PCQLI scores with Fontan palliation and increased numbers of cardiac operations, hospital admissions, and physician visits (P<.001); moderate to good correlations between patient and parent PCQLI scores (r=0.41-0.61; P<.001); and fair to good correlations between PCQLI total scores and PedsQL total (r=0.70-0.76), SPPC/SPPA global self-worth (r=0.43-0.46), YSR/CBCL total competency (r=0.28-0.37), and syndrome and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-oriented scale (r=-0.58 to -0.30; P<.001) scores. Test-retest reliability correlations were excellent (r=0.78-0.90; P<.001). CONCLUSIONS: PCQLI scores are valid and reliable for children and adolescents with congenital and acquired HD and may be useful for future research and clinical management.
Asunto(s)
Cardiopatías , Calidad de Vida , Encuestas y Cuestionarios , Adolescente , Adulto , Niño , Estudios Transversales , Femenino , Cardiopatías/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Concern for effects of gestational cocaine exposure (GCE) on human neurocognitive (NC) development is based on effects of cocaine on blood flow to the fetus and impact of cocaine on developing monoaminergic systems. GCE has been shown to affect language, attention and perceptual reasoning skills. OBJECTIVE: Our objective was to investigate effects of GCE on 7 NC systems, assessed behaviorally in middle school-aged, low socioeconomic status subjects followed prospectively since birth. METHODS: 55 GCE and 65 non-exposed Control subjects were tested with a battery of 14 tasks adapted from neuroimaging and lesion literature designed to tap 3 frontal systems (Cognitive Control, Working Memory, and Reward Processing) and 4 non-frontal systems (Language, Memory, Spatial Cognition, and Visual Cognition). Using multivariate analysis of covariance, we assessed the relation between NC functioning and GCE status with the following covariates: age at testing; gender; gestational exposure to cigarettes, alcohol and marijuana; foster care placement; caregiver current cocaine use; and two indices of childhood environment. RESULTS: None of the analyses showed an effect of GCE on NC function. In contrast, child characteristics, including age at testing and childhood environment, were associated with NC function. CONCLUSIONS: In this cohort there is either no effect of GCE on NC function at middle school age, or that effect is less pronounced than the effect of age or childhood environment.
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Trastornos Relacionados con Cocaína/complicaciones , Cocaína/toxicidad , Cognición/efectos de los fármacos , Complicaciones del Embarazo , Efectos Tardíos de la Exposición Prenatal/psicología , Adulto , Niño , Desarrollo Infantil/efectos de los fármacos , Trastornos Relacionados con Cocaína/psicología , Femenino , Humanos , Lenguaje , Estudios Longitudinales , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Embarazo , RecompensaRESUMEN
BACKGROUND: There is an urgent need for the development of a topical microbicide to protect against sexually transmitted infections. We compared distribution and acceptability of four different gel formulations to be used as a vehicle for a microbicide. STUDY DESIGN: This is a randomized, double-blind comparative study. Six women tested each of the four gels at two different time points. Magnetic resonance imaging (MRI) scans were taken both within 10-15 min following intravaginal gel insertion and 4 h following gel insertion, before and after simulated intercourse at both time points. RESULTS: Vaginal surface contact immediately after insertion ranged from 68% to 92%. Simulated intercourse increased surface contact for all gels (range, 90-106%). After 4 h, surface contact ranged from 86% to 102%. Simulated intercourse at that time resulted in decreased coverage for two gels and increased coverage for two gels. One gel was noted to have consistent broad coverage of the vagina both immediately and 4 h after insertion, increased coverage with simulated intercourse at both time points and the lowest standard deviation of disruption at all time points. CONCLUSION: MRI used in combination with qualitative assessments of acceptability can be used to select optimal gels for use as vehicles for potential spermicides or microbicides. We conclude that a gel consisting of 3% hydroxypropyl methylcellulose and 1.5% of methyl cellulose is the most promising candidate gel.
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Antiinfecciosos Locales/administración & dosificación , Vagina/metabolismo , Administración Intravaginal , Adolescente , Adulto , Antiinfecciosos Locales/farmacocinética , Método Doble Ciego , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Cremas, Espumas y Geles Vaginales/administración & dosificación , Cremas, Espumas y Geles Vaginales/farmacocinética , Adulto JovenRESUMEN
OBJECTIVE: Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in populations of infants with severe forms of congenital heart defects. This study tests the hypothesis that congenital heart defects delay in utero structural brain development. METHODS: Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospectively evaluated with preoperative brain magnetic resonance imaging. Patients with independent risk factors for abnormal brain development (shock, end-organ injury, or intrauterine growth retardation) were excluded. Outcome measures included head circumferences and the total maturation score on magnetic resonance imaging. Total maturation score is a previously validated semiquantitative anatomic scoring system used to assess whole brain maturity. The total maturation score evaluates 4 parameters of maturity: (1) myelination, (2) cortical infolding, (3) involution of glial cell migration bands, and (4) presence of germinal matrix tissue. RESULTS: The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 +/- 1.1 weeks. Mean head circumference was 1 standard deviation below normal. The mean total maturation score for the cohort was 10.15 +/- 0.94, significantly lower than reported normative data in infants without congenital heart defects, corresponding to a delay of 1 month in structural brain development. CONCLUSION: Before surgery, term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected. This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative, intraoperative, and postoperative periods.
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Encéfalo/crecimiento & desarrollo , Retardo del Crecimiento Fetal/etiología , Cardiopatías Congénitas/complicaciones , Síndrome del Corazón Izquierdo Hipoplásico/complicaciones , Transposición de los Grandes Vasos/complicaciones , Femenino , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Factores de TiempoRESUMEN
OBJECTIVE: To determine availability of and test whether on-site mental health providers (MHP) is associated with greater odds of reported mental health consultation and referral among primary care pediatricians. METHODS: Pediatricians were identified from the American Medical Association's 2004 physician directory and stratified by region. Six hundred were randomly selected to receive a mail survey. The main independent variable was on-site MHP. The dependent variable was reported frequency (4-point rating) of mental health consultation and referral. Estimates were weighted to account for survey design and nonresponse. RESULTS: Overall response rate was 51%. The majority of respondents were male (56%), age > or =46 years old (59%), white (68%), and practicing in suburban locations (52%). Approximately half reported consultation with (44%) or referral to (51%) MHP always or often, but a few (17%) reported on-site MHP. After adjustment for demographic and practice characteristics, pediatricians with on-site MHP were more likely to consult (odds ratio [OR] 6.58, 95% confidence interval [95% CI] 3.55- 12.18) or refer (OR 4.25, 95% CI 2.19-8.22) than those without on-site MHP. Among those without on-site MHP, pediatricians with greater practice burden were less likely to consult (OR 0.69, 95% CI 0.48-0.99) or refer (OR 0.75, 95% CI 0.54-1.04) than those with lesser burden. CONCLUSIONS: Most pediatricians in the United States experienced practice-related burdens that limit mental health collaboration, but those with co-located services reported a greater likelihood of consultation and referral. Policy changes that encourage co-location of mental health services and limit practice burden may facilitate mental health consultation and referral.
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Trastornos Mentales/terapia , Servicios de Salud Mental/estadística & datos numéricos , Pediatría , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud , Derivación y Consulta/estadística & datos numéricos , Actitud del Personal de Salud , Competencia Clínica , Femenino , Humanos , Modelos Logísticos , Masculino , Encuestas y Cuestionarios , Estados UnidosRESUMEN
OBJECTIVE: In "true" parachute mitral valve, mitral valve chordae insert into one papillary muscle. In parachute-like asymmetric mitral valve, most or all chordal attachments are to one papillary muscle. This study compared morphologic features, associated lesions, and palliation strategies of the two parachute mitral valve and dominant papillary muscle types and examined interventions and midterm outcomes in patients with biventricular circulation. METHODS: Echocardiography and autopsy databases were reviewed to identify patients with "true" parachute mitral valve or parachute-like asymmetric mitral valve from January 1987 to January 2006. Predictors of palliation strategy in the entire cohort, mitral stenosis on initial echocardiogram, and mortality in the biventricular cohort were determined with logistic regression. RESULTS: Eighty-six patients with "true" parachute mitral valve (n = 49) or parachute-like asymmetric mitral valve (n = 37) were identified. Chordal attachments to the posteromedial papillary muscle were more common (73%). The presence "true" parachute mitral valve (P = .008), hypoplastic left ventricle (P < .001), and two or more left-sided obstructive lesions (P = .002) predicted univentricular palliation. Among 49 patients maintaining biventricular circulation at follow-up, 8 died median follow-up 6.4 years (7 days-17.8 years). Multivariate analysis revealed that "true" parachute mitral valve was associated with mitral stenosis on initial echocardiogram (P = .03), and "true" parachute mitral valve (P = .04) and conotruncal anomalies (P = .0003) were associated with mortality. Progressive mitral stenosis was found in 11 patients; 2 underwent mitral valve interventions, and 1 died. CONCLUSION: Nearly two thirds of this parachute mitral valve cohort underwent biventricular palliation. Some progression of mitral stenosis occurred, although mitral valve intervention was rare. "True" parachute mitral valve was associated with mitral stenosis on initial echocardiogram. "True" parachute mitral valve and conotruncal anomalies were associated with mortality in the biventricular population.
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Válvula Mitral/anomalías , Válvula Mitral/cirugía , Músculos Papilares/anomalías , Adolescente , Procedimientos Quirúrgicos Cardíacos , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estenosis de la Válvula Mitral/cirugía , Análisis Multivariante , Músculos Papilares/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: Preoperative brain injury is an increasingly recognized phenomenon in neonates with complex congenital heart disease. Recently, reports have been published that associate preoperative brain injury in neonates with transposition of the great arteries with the performance of balloon atrial septostomy (BAS), a procedure that improves systemic oxygenation preoperatively. It is unclear whether BAS is the cause of brain injury or is a confounder, because neonates who require BAS are typically more hypoxemic. We sought to determine the relationship between preoperative brain injury in neonates with transposition of the great arteries and the performance of BAS. We hypothesized that brain injury results from hypoxic injury, not from the BAS itself. METHODS AND RESULTS: Infants with transposition of the great arteries (n=26) were retrospectively included from a larger cohort of infants with congenital heart disease who underwent preoperative brain MRI as part of 2 separate prospective studies. Data collected included all preoperative pulse oximetry recordings, all values from preoperative arterial blood gas measurements, and BAS procedure data. MRI scans were performed on the day of surgery, before the surgical repair. Of the 26 neonates, 14 underwent BAS. No stroke was seen in the entire cohort, whereas 10 (38%) of 26 patients were found to have hypoxic brain injury in the form of periventricular leukomalacia. Periventricular leukomalacia was not associated with BAS; however, neonates with periventricular leukomalacia had lower preoperative oxygenation (P=0.026) and a longer time to surgery (P=0.028) than those without periventricular leukomalacia. CONCLUSIONS: Preoperative brain injury in neonates with transposition of the great arteries is associated with hypoxemia and longer time to surgery. We found no association between BAS and brain injury.
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Cateterismo , Defectos del Tabique Interatrial/cirugía , Hipoxia Encefálica/etiología , Oxígeno/sangre , Transposición de los Grandes Vasos/cirugía , Cateterismo/efectos adversos , Cateterismo/estadística & datos numéricos , Femenino , Edad Gestacional , Atrios Cardíacos/cirugía , Defectos del Tabique Interatrial/epidemiología , Defectos del Tabique Interventricular/epidemiología , Defectos del Tabique Interventricular/cirugía , Tabiques Cardíacos/cirugía , Humanos , Hipoxia Encefálica/epidemiología , Hipoxia Encefálica/patología , Recién Nacido , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Cuidados Preoperatorios , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/patología , Transposición de los Grandes Vasos/epidemiologíaRESUMEN
The effects of environmental stimulation and parental nurturance on brain development have been studied extensively in animals. Much less is known about the relations between childhood experience and cognitive development in humans. Using a longitudinally collected data set with ecologically valid in-home measures of childhood experience and later in-laboratory behavioral measures of cognitive ability, we were able to test hypotheses concerning the effects of environmental stimulation and parental nurturance. A double dissociation was found: On the one hand, there was a selective relation between parental nurturance and memory development, consistent with the animal literature on maternal buffering of stress hormone effects on hippocampal development. On the other hand, there was a selective relation between environmental stimulation and language development. The relevance of these findings to socioeconomic gradients in cognitive ability is discussed.
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Desarrollo Infantil/fisiología , Cognición/fisiología , Ambiente , Relaciones Padres-Hijo , Niño , Femenino , Humanos , Masculino , Responsabilidad Parental/psicología , Conducta SocialRESUMEN
Gambling has increased in the past decade, with growing opportunities for initiation by adolescents. More limited data, however, are available regarding gambling in preadolescents. In the investigation reported here, gambling for money was the most common risk behavior in 10- to 12-year-olds. Gamblers were more likely to be white, have tried alcohol, have positive affect toward gambling, and have friends who gamble.
Asunto(s)
Conducta Infantil , Juego de Azar , Niño , Cognición , Femenino , Humanos , Conducta Impulsiva , Masculino , Philadelphia , Estudios Prospectivos , Asunción de Riesgos , Autorrevelación , Interfaz Usuario-ComputadorRESUMEN
OBJECTIVE: Neo-aortic insufficiency (neo-AI) has been noted following the Ross procedure. The purpose of this study was to evaluate the ability of intraoperative transesophageal echocardiography (TEE) to predict future neo-AI in pediatric patients undergoing the Ross from January 1995 to December 2003, who had an intraoperative TEE, and discharge and follow-up transthoracic (TTE) echocardiograms. DESIGN: Retrospective case series. PATIENTS: All patients who underwent the Ross procedure at Children's Hospital of Philadephia between January 1995 and December 2003, and had an intraoperative TEE, discharge, and follow-up (>6 months) transthoracic echocardiogram (TTE) (by July 1, 2004) were included. OUTCOME MEASURES: Grade of neo-AI was assessed on intraoperative TEE, discharge, and follow-up TTE echocardiogram reports. RESULTS: Follow-up was available in 99/115 (86%) survivors. Median age at Ross was 9.3 years (4 days-34 years). No patient had more than mild neo-AI on intraoperative TEE. At discharge, 2 patients (2%) had moderate neo-AI. At most recent follow-up (median 4.2 years, 8 months-9.3 years), 21 patients (21%) had moderate or greater neo-AI; 9 underwent neo-aortic reintervention. The presence of any neo-AI on intraoperative TEE had 100% sensitivity and negative predictive value for diagnosing moderate or greater neo-AI at discharge. Patients who had mild neo-AI on TEE were more likely to have moderate or greater neo-AI at most recent follow-up than those patients with no neo-AI on TEE (9% vs. 30%, P = 0.01). CONCLUSION: Intraoperative TEE is an excellent screening tool for the presence of significant neo-AI at the time of hospital discharge. Neo-AI progresses over time after Ross procedure and is more likely to progress in those patients with neo-AI on intraoperative TEE. However, predictive validity decreases over time as neo-AI progresses.
Asunto(s)
Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Ecocardiografía Transesofágica , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Monitoreo Intraoperatorio/métodos , Adolescente , Adulto , Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/etiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Humanos , Lactante , Recién Nacido , Masculino , Valor Predictivo de las Pruebas , Reoperación , Reproducibilidad de los Resultados , Proyectos de Investigación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
OBJECTIVE: Mortality after surgery for congenital heart disease (CHD) has decreased. Quality of life (QOL) assessment in survivors has become increasingly important. The purpose of this project was to create the Pediatric Cardiac Quality of Life Inventory (PCQLI). METHODS: Items were generated through nominal groups of patients, parents, and providers. The pilot PCQLI was completed by children (age 8-12), adolescents (age 13-18), and their parents at three cardiology clinics. Item reduction was performed through analysis of items, principal components, internal consistency (IC), and patterns of correlation. RESULTS: A total of 655 patient-parent pairs completed the pilot PCQLI. Principal components identified included: impact of disease (ID); psychosocial impact (PI); and emotional environment (EE). After item reduction ID and PI had excellent IC (ID = 0.88-0.91; PI = 0.78-0.85) and correlated highly with each other (0.81-0.90) and with the total score (TS) (ID = 0.95-0.96; PI = 0.87-0.93). EE was not correlated with ID, PI, or TS and was removed from the final forms. Two-ventricle CHD patients had a higher TS than single-ventricle CHD patients across all forms (P < 0.001). CONCLUSION: The PCQLI has patient and parent-proxy forms, has wide age range, and discriminates between CHD subgroups. The ID and PI subscales of the PCQLI have excellent IC and correlate well with each other and the TS.
Asunto(s)
Adaptación Psicológica , Cardiopatías/psicología , Calidad de Vida , Adolescente , Instituciones Cardiológicas , Niño , Protección a la Infancia , Bases de Datos como Asunto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Proyectos Piloto , Psicometría , Calidad de Vida/psicologíaRESUMEN
OBJECTIVE: To assess the effect of gestational cocaine exposure on the prefrontal cortex (PFC) with functional magnetic resonance imaging (fMRI). STUDY DESIGN: Using an n-back task, we obtained fMRI with a 3T Siemens scanner on 49 adolescents, 25 who were exposed to cocaine and 24 who were not exposed. The primary outcome was PFC activation during task performance. Five functionally derived regions of interest (ROI) were defined; in addition, 2 a priori anatomical ROIs were generated for Brodmann regions 10 and 46. RESULTS: Of the 49 adolescents who underwent imaging, data from 17 who were exposed to cocaine and 17 who were not exposed were in the final analysis. Groups had similar performance on the n-back task (P >/= .4), with both showing a fewer number of correct responses on the 2-back than the 1-back (P < .001), indicating increased demands on working memory with greater task difficulty. In functionally derived ROIs, imaging results showed increased activation for both groups in the 2-back versus the 1-back condition. In anatomical ROIs, both groups showed greater activation in the 2-back versus the 1-back condition, with activation in the non-exposed group proportionally greater for the left prefrontal region (P = .05). CONCLUSION: In this sample of adolescents, participants who were exposed to cocaine and participants who were not exposed were similar in performance on an executive function task and in fMRI activation patterns during task performance.