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1.
Neurodiagn J ; 59(3): 163-168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411943

RESUMO

Collodion remover, a solvent blend used to remove collodion glue after long-term video EEG monitoring, was implicated as a potential causative factor in patient safety events at our institution during which damage to plastic components of medical devices was noted in the intensive care unit. We sought to determine experimentally whether collodion remover could lead to degradation of multiple plastic-containing medical devices commonly used in the intensive care unit to determine whether workflow changes were needed during electrode removal. We exposed devices to collodion remover for brief, intermediate, and prolonged durations. We report that collodion remover is capable of degrading the hard plastic components of multiple medical devices after prolonged exposure; however, intermediate duration exposure was also capable of producing damage to clave connectors used with intravenous and central lines, which could plausibly lead to adverse events given the widespread use of these devices. These data suggest a pathway-based approach to collodion remover use might be beneficial in minimizing the potential impact of this solvent on plastic-containing medical devices.

2.
Neurotherapeutics ; 16(3): 848-857, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054119

RESUMO

Pathogenic variants in KCNT1 represent an important cause of treatment-resistant epilepsy, for which an effective therapy has been elusive. Reports about the effectiveness of quinidine, a candidate precision therapy, have been mixed. We sought to evaluate the treatment responsiveness of patients with KCNT1-related epilepsy. We performed an observational study of 43 patients using a collaborative KCNT1 patient registry. We assessed treatment efficacy based upon clinical seizure reduction, side effects of quinidine therapy, and variant-specific responsiveness to treatment. Quinidine treatment resulted in a > 50% seizure reduction in 20% of patients, with rare patients achieving transient seizure freedom. Multiple other therapies demonstrated some success in reducing seizure frequency, including the ketogenic diet and vigabatrin, the latter particularly in patients with epileptic spasms. Patients with the best quinidine response had variants that clustered distal to the NADP domain within the RCK2 domain of the protein. Half of patients did not receive a quinidine trial. In those who did, nearly half did not achieve therapeutic blood levels. More favorable response to quinidine in patients with KCNT1 variants distal to the NADP domain within the RCK2 domain may suggest a variant-specific response.

3.
J Clin Neurophysiol ; 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30383719

RESUMO

PURPOSE: Many neonates undergo electroencephalogram (EEG) monitoring to identify and manage acute symptomatic seizures. Information about brain function contained in the EEG background data may also help predict neurobehavioral outcomes. For EEG background features to be useful as prognostic indicators, the interpretation of these features must be standardized across electroencephalographers. We aimed at determining the interrater and intrarater agreement among electroencephalographers interpreting neonatal EEG background patterns. METHODS: Five neonatal electroencephalographers reviewed 5-to-7.5-minute epochs of EEG from full-term neonates who underwent continuous conventional EEG monitoring. The EEG assessment tool used to classify background patterns was based on the American Clinical Neurophysiology Society's guideline for neonatal EEG terminology. Interrater and intrarater agreement were measured using Kappa coefficients. RESULTS: Interrater agreement was consistently highest for voltage (binary: substantial, kappa = 0.783; categorical: moderate, kappa = 0.562), seizure presence (fair-substantial; kappa = 0.375-0.697), continuity (moderate; kappa = 0.481), burst voltage (moderate; kappa = 0.574), suppressed background presence (moderate-substantial; kappa = 0.493-0.643), delta activity presence (fair-moderate; kappa = 0.369-0.432), theta activity presence (fair-moderate; kappa = 0.347-0.600), presence of graphoelements (fair; kappa = 0.381), and overall impression (binary: moderate, kappa = 0.495; categorical: fair-moderate, kappa = 0.347, 0.465). Agreement was poor or inconsistent for all other patterns. Intrarater agreement was variable, with highest average agreement for voltage (binary: substantial, kappa = 0.75; categorical: substantial, kappa = 0.714) and highest consistent agreement for continuity (moderate-substantial; kappa = 0.43-0.67) and overall impression (moderate-substantial; kappa = 0.42-0.68). CONCLUSIONS: This study demonstrates substantial variability in neonatal EEG background interpretation across electroencephalographers, indicating a need for educational and technological strategies aimed at improving performance.

4.
Seizure ; 61: 221-226, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30227341

RESUMO

PURPOSE: Electroencephalographic seizures (ES) are common among neonates with hypoxic-ischemic encephalopathy (HIE), and they represent a treatable complication that might improve neurodevelopmental outcomes. We aimed to establish whether higher ES exposure was predictive of unfavorable outcomes while adjusting for other important clinical and electroencephalographic parameters. METHODS: We performed a single-center, retrospective study of consecutive neonates with HIE managed with therapeutic hypothermia from June 2010 through December 2016. Neonates underwent continuous electroencephalographic (cEEG) monitoring during and after therapeutic hypothermia. Outcome measures included abnormal MRIs after rewarming and abnormal motor and language development. RESULTS: Clinical data from the perinatal period were available for 116 neonates. Follow-up data were available for 93 of 116 (80%) neonates who survived to discharge, with a median follow-up period of 23 months (interquartile range 1236 months). Multivariate analysis demonstrated that high ES exposure (OR 5.2, 95% CI 1.3-21.2, p = 0.02) and moderate/severely abnormal EEG background (OR 8.3, 95% CI 1.6-43.9, p = 0.01) were independent predictors of abnormal motor development. High ES exposure was an independent predictor of abnormal language development (OR 4.2, 95% CI 1.1-15.9, p = 0.04). High ES exposure (OR 7.0, 95% CI 2.2-22.5, p = 0.01) and severe encephalopathy (OR 7.9, 95% CI 1.5-42.7, p = 0.02) were independent predictors of abnormal MRIs. CONCLUSIONS: Among neonates with HIE managed with therapeutic hypothermia, high ES exposure was the most important predictor of abnormal developmental and neuroimaging outcomes, even after adjustment for multiple clinical and EEG variables. Adequate identification and management of ES with judicious use of anti-seizure medications may optimize outcomes.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia , Hipóxia-Isquemia Encefálica/complicações , Transtornos do Neurodesenvolvimento/etiologia , Convulsões/etiologia , Feminino , Seguimentos , Humanos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Lactente , Masculino , Estudos Retrospectivos
5.
Neurology ; 91(12): e1112-e1124, 2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-30171078

RESUMO

OBJECTIVE: To delineate the electroclinical features of SCN8A infantile developmental and epileptic encephalopathy (EIEE13, OMIM #614558). METHODS: Twenty-two patients, aged 19 months to 22 years, underwent electroclinical assessment. RESULTS: Sixteen of 22 patients had mildly delayed development since birth. Drug-resistant epilepsy started at a median age of 4 months, followed by developmental slowing, pyramidal/extrapyramidal signs (22/22), movement disorders (12/22), cortical blindness (17/22), sialorrhea, and severe gastrointestinal symptoms (15/22), worsening during early childhood and plateauing at age 5 to 9 years. Death occurred in 4 children, following extreme neurologic deterioration, at 22 months to 5.5 years. Nonconvulsive status epilepticus recurred in 14 of 22 patients. The most effective antiepileptic drugs were oxcarbazepine, carbamazepine, phenytoin, and benzodiazepines. EEG showed background deterioration, epileptiform abnormalities with a temporo-occipital predominance, and posterior delta/beta activity correlating with visual impairment. Video-EEG documented focal seizures (FS) (22/22), spasm-like episodes (8/22), cortical myoclonus (8/22), and myoclonic absences (1/22). FS typically clustered and were prolonged (<20 minutes) with (1) cyanosis, hypomotor, and vegetative semiology, sometimes unnoticed, followed by (2) tonic-vibratory and (3) (hemi)-clonic manifestations ± evolution to a bilateral tonic-clonic seizure. FS had posterior-temporal/occipital onset, slowly spreading and sometimes migrating between hemispheres. Brain MRI showed progressive parenchymal atrophy and restriction of the optic radiations. CONCLUSIONS: SCN8A developmental and epileptic encephalopathy has strikingly consistent electroclinical features, suggesting a global progressive brain dysfunction primarily affecting the temporo-occipital regions. Both uncontrolled epilepsy and developmental compromise contribute to the profound impairment (increasing risk of death) during early childhood, but stabilization occurs in late childhood.

6.
Mol Cancer Res ; 16(12): 1952-1964, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30082484

RESUMO

: Breast cancer remains the most common malignant disease in women worldwide. Despite advances in detection and therapies, studies are still needed to understand the mechanisms underlying this cancer. Cancer stem cells (CSC) play an important role in tumor formation, growth, drug resistance, and recurrence. Here, it is demonstrated that the transcription factor RUNX1, well known as essential for hematopoietic differentiation, represses the breast cancer stem cell (BCSC) phenotype and suppresses tumor growth in vivo. The current studies show that BCSCs sorted from premalignant breast cancer cells exhibit decreased RUNX1 levels, whereas ectopic expression of RUNX1 suppresses tumorsphere formation and reduces the BCSC population. RUNX1 ectopic expression in breast cancer cells reduces migration, invasion, and in vivo tumor growth (57%) in mouse mammary fat pad. Mechanistically, RUNX1 functions to suppress breast cancer tumor growth through repression of CSC activity and direct inhibition of ZEB1 expression. Consistent with these cellular and biochemical results, clinical findings using patient specimens reveal that the highest RUNX1 levels occur in normal mammary epithelial cells and that low RUNX1 expression in tumors is associated with poor patient survival. IMPLICATIONS: The key finding that RUNX1 represses stemness in several breast cancer cell lines points to the importance of RUNX1 in other solid tumors where RUNX1 may regulate CSC properties.

7.
Epilepsia ; 58(6): 1047-1053, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28401998

RESUMO

OBJECTIVE: Neonates with hypoxic-ischemic encephalopathy (HIE) managed with therapeutic hypothermia (TH) often experience acute symptomatic seizures, prompting treatment with antiseizure medications (ASMs). Because the risk of seizure occurrence after hospital discharge is unknown, the optimal ASM treatment duration is unclear. We aimed to determine the risk of seizure occurrence after hospital discharge and the impact of ASM treatment duration on this outcome. METHODS: We performed a single-center, retrospective study of consecutive neonates with HIE managed with TH who received ASMs for acute symptomatic seizures from June 2010 through December 2014. Neonates were monitored with continuous electroencephalography (EEG) during TH. RESULTS: Follow-up data were available for 59 (82%) of 72 neonates who survived to discharge, with a median follow-up period of 19 months (interquartile range [IQR] 11-25). Acute symptomatic seizures occurred in 35 neonates (59%), including electrographic seizures in 21 neonates (36%). ASMs were continued upon discharge in 17 (49%) of 35 neonates. Seizures occurred in follow-up in four neonates (11%). No patient for whom ASMs were discontinued prior to discharge experienced seizures during the follow-up period. SIGNIFICANCE: Among neonates with HIE, seizures after hospital discharge were rare in those with acute symptomatic seizures and did not occur in neonates without acute symptomatic seizures. ASM discontinuation prior to discharge did not increase the risk of seizures during the follow-up period, suggesting that ASMs may be discontinued in many neonates prior to discharge.


Assuntos
Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Alta do Paciente , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Feminino , Seguimentos , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Funções Verossimilhança , Imagem por Ressonância Magnética , Masculino , Monitorização Fisiológica , Recidiva , Estudos Retrospectivos
8.
Mol Biol Cell ; 27(24): 3903-3912, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27708137

RESUMO

The Nxf1 protein is a major nuclear export receptor for the transport of mRNA, and it also is essential for export of retroviral mRNAs with retained introns. In the latter case, it binds to RNA elements known as constitutive transport elements (CTEs) and functions in conjunction with a cofactor known as Nxt1. The NXF1 gene also regulates expression of its own intron-containing RNA through the use of a functional CTE within intron 10. mRNA containing this intron is exported to the cytoplasm, where it can be translated into the 356-amino acid short Nxf1(sNxf1) protein, despite the fact that it is a prime candidate for nonsense-mediated decay (NMD). Here we demonstrate that sNxf1 is highly expressed in nuclei and dendrites of hippocampal and neocortical neurons in rodent brain. Additionally, we show that sNxf1 localizes in RNA granules in neurites of differentiated N2a mouse neuroblastoma cells, where it shows partial colocalization with Staufen2 isoform SS, a protein known to play a role in dendritic mRNA trafficking. We also show that sNxf1 forms heterodimers in conjunction with the full-length Nxf1 and that sNxf1 can replace Nxt1 to enhance the expression of CTE-containing mRNA and promote its association with polyribosomes.


Assuntos
Proteínas de Transporte Nucleocitoplasmático/metabolismo , Transporte Ativo do Núcleo Celular/genética , Processamento Alternativo , Animais , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Expressão Gênica , Hipocampo/metabolismo , Íntrons , Camundongos , Neocórtex/metabolismo , Proteínas do Tecido Nervoso , Neurônios/metabolismo , Proteínas de Transporte Nucleocitoplasmático/genética , Polirribossomos/metabolismo , Isoformas de RNA , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo
10.
Pediatr Nephrol ; 31(2): 227-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25634549

RESUMO

A 17-year-old girl recently diagnosed with systemic lupus erythematosus (SLE) presented to the Emergency Room with acute onset of psychosis. A variety of potential etiologies, including those related to SLE, to the treatment of her SLE, or to another psychiatric condition, are discussed. In addition, the work-up and management decisions for this patient are reviewed in detail.


Assuntos
Glucocorticoides/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/tratamento farmacológico , Prednisolona/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Psicoses Induzidas por Substâncias/diagnóstico
11.
Mol Cell Biol ; 36(4): 615-27, 2016 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-26644406

RESUMO

Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotency.


Assuntos
Cromatina/genética , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Histonas/genética , Células-Tronco Embrionárias Humanas/citologia , Ciclo Celular , Diferenciação Celular , Linhagem Celular , Cromatina/metabolismo , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Estudo de Associação Genômica Ampla , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas de Neoplasias/metabolismo
12.
Psychol Rep ; 94(3 Pt 2): 1393-403, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15362423

RESUMO

Previous investigators have suggested that the personality variable tolerance for error is related to success in computational estimation. However, this suggestion has not been tested directly. This study examined the relationship between performance on a computational estimation test and scores on the NEO-Five Factor Inventory, a measure of the Big Five personality traits, including Openness, an index of tolerance for ambiguity. Other variables included SAT-I Verbal and Mathematics scores and self-rated mathematics ability. Participants were 65 college students. There was no significant relationship between the tolerance variable and computational estimation performance. There was a modest negative relationship between Agreeableness and estimation performance. The skepticism associated with the negative pole of the Agreeableness dimension may be important to pursue in further understanding of estimation ability.


Assuntos
Adaptação Psicológica , Escolaridade , Matemática , Inventário de Personalidade/estatística & dados numéricos , Resolução de Problemas , Adolescente , Adulto , Aptidão , Testes de Aptidão , Feminino , Humanos , Masculino , Psicometria/estatística & dados numéricos , Estudantes/psicologia
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