RESUMO
OBJECTIVE: Current guidelines for percutaneous endoscopic gastrostomy (PEG) placement focus largely on maintaining enteral feeding when oral feeding is no longer possible or adequate with an emphasis on nutrition and quality of life (QOL). Previous publications have also alluded to potential benefits in medication adherence, for example, in children with HIV, renal disease and neurodisability. We describe a cohort of children with refractory epilepsy who refused oral medication and in whom PEG tube placement was initiated for the purpose of drug administration. DESIGN: We identified children from the medical records of two tertiary paediatric units over a 9-year period who had PEG tube placement for administration of antiepileptic drug (AED) therapy and collected demographic and clinical details from chart reviews. We assessed parent-reported changes in seizure control and QOL using a structured questionnaire. RESULTS: Ten patients met the inclusion criteria. All families reported an improvement in ease of administering medications and eight reported a significant improvement in QOL. Nine children had a decrease in seizure frequency (lasting more than 12 months) following PEG tube placement, including two who underwent surgical intervention for their epilepsy during that period. Four had either a decrease in the number of drugs administered or their doses and four went on to receive fluids and nutrition through their tube on a regular basis. Seven reported PEG complications, which did not require removal of the PEG. CONCLUSIONS: This case series of children with resistant epilepsy demonstrates improvement in seizure control and QOL following PEG tube placement for AED administration.
Assuntos
Epilepsia Resistente a Medicamentos/terapia , Intubação Gastrointestinal , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia Resistente a Medicamentos/psicologia , Nutrição Enteral , Feminino , Humanos , Lactente , Entrevistas como Assunto , Irlanda , Masculino , Prontuários Médicos , Estado Nutricional , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e Questionários , Recusa do Paciente ao TratamentoRESUMO
Neurologic complications can occur with varicella-zoster virus (VZV) infection, usually after vesicular exanthem. We report the case of a previously healthy 14-year-old boy with aseptic meningitis as a result of reactivated-VZV infection without exanthem. Diagnosis was made by detection of VZV-DNA in cerebrospinal fluid. VZV should be considered in cases of aseptic meningitis, even without a history of exanthem or immune compromise.
Assuntos
Encefalite por Varicela Zoster/virologia , Exantema , Herpesvirus Humano 3/isolamento & purificação , Adolescente , DNA Viral/líquido cefalorraquidiano , Humanos , MasculinoRESUMO
A case of central hypoventilation syndrome was identified in a child with brainstem and cervical cord injury following Haemophilus influenzae type b meningitis and extensive herpes simplex infection. This process resulted in a spastic tetraplegia, and the child continues to require respiratory support. Possible mechanisms of causation are discussed including an evolving, progressive inflammatory or vasculitic process in the setting of transient immunosuppression.
Assuntos
Haemophilus influenzae tipo b , Herpes Simples/complicações , Hipoventilação/microbiologia , Hipoventilação/virologia , Meningite por Haemophilus/complicações , Pré-Escolar , Humanos , Hipoventilação/patologia , Lactente , Infarto/microbiologia , Infarto/patologia , Infarto/virologia , Imageamento por Ressonância Magnética , Masculino , Ponte/patologia , Quadriplegia/microbiologia , Quadriplegia/patologia , Quadriplegia/virologia , Insuficiência Respiratória/microbiologia , Insuficiência Respiratória/patologia , Insuficiência Respiratória/virologia , Medula Espinal/patologiaRESUMO
Facilitated glucose transporter isoform 1 deficiency syndrome (GLUT1 DS), caused by impaired GLUT1-mediated glucose transport into the brain, is characterized by hypoglycorrhachia. The defect in the facilitative glucose transporter isoform 1 (GLUT1) can be confirmed by functional, quantitative, and molecular analyses. Diagnostic difficulties arise when these analyses are normal and hypoglycorrhachia remains unexplained. Three infants presenting with seizures and hypoglycorrhachia at 2, 4, and 6 weeks of age, which suggests GLUT1 deficiency syndrome, are reported. The seizures responded to a ketogenic diet in Patients 1 and 3 and phenobarbitone in Patient 2. Repeated GLUT1 analyses were normal. When treatment was discontinued, all patients remained seizure-free and developed normally. Subsequent lumbar punctures showed the return to normoglycorrhachia. We conclude that these cases might represent a transient disturbance in GLUT1-mediated glucose transport. The biomolecular basis for this clinical observation remains unknown. Though no treatment is required, clinical follow-up and repeated lumbar punctures are necessary to distinguish this benign condition from the original GLUT1 deficiency syndrome.
Assuntos
Glucose/líquido cefalorraquidiano , Proteínas de Transporte de Monossacarídeos/líquido cefalorraquidiano , Transporte Biológico/fisiologia , Feminino , Glucose/deficiência , Transportador de Glucose Tipo 1 , Humanos , Lactente , Recém-Nascido , Cetose/líquido cefalorraquidiano , Cetose/dietoterapia , Masculino , Proteínas de Transporte de Monossacarídeos/deficiênciaRESUMO
OBJECTIVES: To identify clinical features and therapeutic decisions that influence admission to the Intensive Care unit (ICU) in children presenting with convulsive status epilepticus (CSE). METHODS: We evaluated 47 admissions with status epilepticus to a tertiary paediatric hospital A&E over a three year period (2003-2006). Following initial management 23 episodes required admission to ICU and 24 were managed on a paediatric ward. We compared clinical, demographic data and compliance with our CSE protocol between the ICU and ward groups. RESULTS: Median age at presentation in the ICU group was 17 months (range 3 months-11 years) compared to 46 months in the ward group (range 3 months-10 years). Fifty per cent of patients in both groups had a previous history of seizures. Median duration of pre-hospital seizure activity was 30 min in both groups. More than two doses of benzodiazepines were given as first line medication in 62% of the ICU group and 33% of the ward group. Among children admitted to ICU with CSE, 26% had been managed according to the CSE protocol, compared to 66% of children who were admitted to a hospital ward. Febrile seizures were the most common aetiology in both groups. CONCLUSION: Younger age at presentation, administration of more than two doses of benzodiazepines and deviation from the CSE protocol appear to be factors which influence admission of children to ICU. Recognition of pre-hospital administration of benzodiazepines and adherence to therapeutic guidelines may reduce the need for ventilatory support in this group.
Assuntos
Fidelidade a Diretrizes , Unidades de Terapia Intensiva/normas , Admissão do Paciente/normas , Estado Epiléptico/tratamento farmacológico , Anticonvulsivantes/administração & dosagem , Benzodiazepinas/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Guias de Prática Clínica como AssuntoRESUMO
Systemic hypoxia-ischemia at birth may alter the neonatal neutrophil phenotype. In this study, we evaluated alterations in perinatal neutrophil phenotype following systemic hypoxia-ischemia compared with normal controls. Neutrophils from adults (n = 15), normal newborns (n = 20), newborns requiring resuscitation at birth (n = 17), and their respective maternal samples were incubated alone or with lipopolysaccharide (LPS). Surface receptor CD11b (neutrophil activation) and the percentage apoptosis (persistence of inflammatory response) were assessed using flow cytometry. Neutrophil apoptosis was decreased in neonates requiring resuscitation at birth and was further exaggerated in infants who developed mild neurological signs. All infants who required resuscitation were LPS hyporesponsive irrespective of neurological findings. Newborns with severe neurological signs had increased apoptosis and decreased CD11b. Maternal neutrophils were LPS hyporesponsive only if their infants had moderate/severe neurological signs. Infants with mild encephalopathy may display a predominantly proinflammatory neutrophil response with a persistent inflammatory response, whereas those with moderate/severe encephalopathy have a tendency toward immunosuppression.
Assuntos
Apoptose , Antígeno CD11b/biossíntese , Hipóxia-Isquemia Encefálica/fisiopatologia , Neutrófilos/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipóxia-Isquemia Encefálica/imunologia , Recém-Nascido , MasculinoRESUMO
BACKGROUND: Dysfunctional inflammatory responses have been implicated in several neonatal inflammatory disorders following infection and hypoxia. OBJECTIVES: We aimed to study the effects of in vitro hypoxia and heat shock (HS) on normal adult and newborn neutrophil migration (CD11b) and persistence (apoptosis) following lipopolysaccharide (LPS) stimulation. METHODS: The mechanism for altered LPS responses was assessed at the level of the LPS signalling receptors, Toll-like receptor-4 (TLR-4), TLR-2 and CD14 expression in normal neonates and adults. RESULTS: In adults, although hypoxia delayed neutrophil apoptosis, LPS enhanced this response. In contrast, HS (42 degrees C) increased adult apoptotic rates and abrogated the LPS responses. Both hypoxia and HS prevented the LPS-induced increase in adult CD11b although it was unaltered in neonates. Adult TLR-4 neutrophil expression was increased by LPS and hypoxia, and decreased in HS, possibly explaining their variable LPS responsiveness. In contrast, neonatal neutrophils were LPS hyporesponsive which may be mediated by failure of TLR-4 upregulation with LPS. CONCLUSIONS: Neonates do not have increased LPS responsiveness in hypoxia or heat shock in vitro, which may prevent hyperinflammation and thereby minimise tissue damage in inflammation or infection.
Assuntos
Antígeno CD11b/genética , Lipopolissacarídeos/farmacologia , Neutrófilos/citologia , Neutrófilos/fisiologia , Receptor 4 Toll-Like/genética , Adulto , Envelhecimento/fisiologia , Apoptose/efeitos dos fármacos , Hipóxia Celular , Feminino , Sangue Fetal/citologia , Idade Gestacional , Temperatura Alta , Humanos , Recém-Nascido , Masculino , Neutrófilos/efeitos dos fármacosRESUMO
Neutropenia is a common sequela of neonatal sepsis. Recent clinical trials have shown the beneficial effects of colony-stimulating factors (CSFs) on outcome in this group, but the exact mechanism remains unknown. Neonates and mothers who were at high-risk for infection were recruited for cord blood sampling in a university tertiary referral maternity hospital. Neonatal and adult neutrophils were evaluated for their ability to combat bacterial infection by examining their functional activity (CD11b and reactive oxygen intermediates) and their persistence at inflammatory sites (apoptosis). The mechanism for altered apoptotic responses was assessed by caspase activation assays, X chromosome-linked inhibitor of apoptosis protein expression, and cytosolic cytochrome c release. Although granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly delayed neutrophil apoptosis in normal adults, only G-CSF had a similar effect in normal neonates. Neutrophils from neonates who are at high risk for infection are unresponsive to the antiapoptotic effects of G-CSF or GM-CSF, unlike maternal neutrophils, which have delayed apoptosis in response to GM-CSF. However, CD11b expression and reactive oxygen intermediate production were significantly increased in normal neonatal neutrophils that were incubated with GM-CSF versus controls but not G-CSF or lipopolysaccharide. Decreased cytosolic cytochrome c release and caspases 3 and 9 activity are associated with the CSF-mediated delay in apoptosis in adults but not in newborns. The antiapoptotic X chromosome-linked inhibitor of apoptosis protein is up-regulated in neonates compared with adults and may mediate their differential spontaneous apoptosis. These results have important implications for the use of CSFs in neonatal sepsis, as responses differ from those seen in adults. Further delineation of neonatal neutrophil responses to CSFs may improve their therapeutic potential.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Neutrófilos/efeitos dos fármacos , Adulto , Apoptose/efeitos dos fármacos , Sequência de Bases , Caspase 3 , Caspase 9 , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Feminino , Sangue Fetal/citologia , Humanos , Técnicas In Vitro , Recém-Nascido , Masculino , Neutrófilos/citologia , Neutrófilos/fisiologia , Gravidez , Proteínas/genética , Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/farmacologia , Sepse/sangue , Sepse/tratamento farmacológico , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo XRESUMO
Labor is a mild proinflammatory state that is associated with fetal leukocytosis. Elective cesarean section has been linked with increased neonatal morbidity, which may be partially immune mediated. We hypothesized that labor may alter neutrophil phenotype and thereby decrease neonatal complications. We characterized neutrophil function and survival in normal neonates after either uncomplicated vaginal delivery (VD) or elective cesarean section (CS) without labor. Spontaneous neutrophil apoptosis is delayed in cord blood neutrophils of neonates after normal labor (VD) compared with CS, as assessed by propidium iodide DNA incorporation using flow cytometry. This demonstrates their ability to maintain an inflammatory response. CD11b expression on neonatal neutrophils after CS is decreased, providing further evidence of altered activation or priming. Lipopolysaccharide responsiveness, characterized by CD11b and apoptosis, is similar in VD and adults, but CS-derived neutrophils are unresponsive. Baseline TLR-4 levels are elevated in CS in contrast to the other groups, although expression is not up-regulated by lipopolysaccharide co-incubation. Neonatal neutrophil survival and function are altered by labor and may increase antibacterial function and neutrophilia. This suggests that labor of any duration may be immunologically beneficial to the normal term neonate.
Assuntos
Trabalho de Parto/imunologia , Lipopolissacarídeos/farmacologia , Neutrófilos/citologia , Neutrófilos/imunologia , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Cesárea , Parto Obstétrico , Feminino , Humanos , Técnicas In Vitro , Recém-Nascido , Glicoproteínas de Membrana/metabolismo , Neutrófilos/metabolismo , Fenótipo , Gravidez , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Receptor 4 Toll-Like , Receptores Toll-Like , VaginaRESUMO
OBJECTIVE: We studied the effect of labor on maternal neutrophil phenotype. STUDY DESIGN: Neutrophil apoptosis with inflammatory cytokines and the expression of CD11b, CD34 and toll-like receptor 4 (TLR4) were assessed with flow cytometry in women at uncomplicated vaginal delivery (VD), and elective cesarean section (ElCS) without labor, emergency cesarean section with (EmCSL+) or without (EmCSL-) labor. RESULTS: Spontaneous neutrophil apoptosis is delayed in maternal neutrophils after VD, EmCSL+ or EmCSL- versus ElCS. In all groups lipopolysaccharide delayed apoptosis and increased CD11b expression. Elevated TLR4 expression in ElCS was associated with lipopolysaccharide responsiveness. CD34 was diminished in VD, indicating increased cell maturity. CONCLUSION: Normal labor primes the neutrophil and may enhance antibacterial function by inducing a mild maternal inflammatory response syndrome. Delayed neutrophil apoptosis may promote the neutrophilia seen in women after VD. We suggest that labor of any duration may be immunologically beneficial to the parturient.
Assuntos
Trabalho de Parto/imunologia , Neutrófilos/fisiologia , Antígenos de Superfície/metabolismo , Apoptose , Cesárea , Parto Obstétrico , Feminino , Citometria de Fluxo , Humanos , Glicoproteínas de Membrana/metabolismo , Fenótipo , Gravidez , Receptores de Superfície Celular/metabolismo , Receptor 4 Toll-Like , Receptores Toll-LikeRESUMO
Women are conferred with greater immunologic and survival benefits compared to men. Female sex steroids contribute to this sexual dimorphism. Furthermore, during human pregnancy when female sex hormones are elevated, neutrophil apoptosis is delayed. This study examines the specific effects of estradiol and progesterone on neutrophil apoptosis and function in healthy adult men and women. We also examined the contribution of these hormones to the persistence and resolution of an inflammatory response. Spontaneous apoptosis was significantly decreased in women compared with men. Physiologic doses of estradiol and progesterone caused a further delay in spontaneous apoptosis in both men and women but did not diminish Fas antibody-induced apoptosis. The delay in apoptosis was mediated at the level of the mitochondria with decreased release of cytochrome c, which may alter caspase cleavage and activity. There were no associated alterations in neutrophil CD11b, but production of reactive oxygen intermediates (ROIs) in women was increased. Thus, female sex hormones mediate delayed neutrophil apoptosis in both sexes and enhance female intracellular production of ROIs. Modulating hormonal responses may be an effective therapeutic tool in combating inflammatory diseases.