RESUMO
Despite the growing importance of oxygen-delivery devices worldwide, there are only a few reports of physiological data on various oxygen masks in children. The possibility of carbon dioxide (CO2) rebreathing has been a prevalent concern with the use of oxygen-delivery devices. OxyMask KidTM (Southmedic Inc. Canada; hereafter OxyMask) is expected to reduce CO2 rebreathing even at low oxygen flow rates because of its structural features. Biological data using OxyMask in children have not been well investigated. Measured respiratory parameters of OxyMask with those of a simple oxygen mask in healthy children were compared. Ten subjects were enrolled, with a median age of 5.4 years. All subjects used both OxyMask and a simple oxygen mask. The fraction of inspiratory oxygen (FIO2), partial pressure of inspiratory CO2 (PICO2), and partial pressure of end-tidal CO2 were measured using a sidestream gas-sampling monitor in all subjects. The oxygen flow rate was set at 1, 3, 5, and 10 L/min. FIO2 levels were higher with OxyMask than those with the simple oxygen mask at 3 L/min of oxygen. PICO2 levels were significantly lower with OxyMask than those with the simple oxygen mask (1.5 mmHg vs. 3.7 mmHg at 1 L/min, P = 0.005; 1.0 mmHg vs. 2.7 mmHg at 3 L/min, P = 0.005, respectively), whereas PICO2 levels were higher at low oxygen flow rates with both masks.Conclusion: Our results showed that higher FIO2 and less CO2 rebreathing were achieved with OxyMask than those with a simple oxygen mask at low flow rates of oxygen in healthy children. What is Known: ⢠OxyMask is expected to reduce carbon dioxide rebreathing even at low oxygen flow rates because of its structural features. ⢠Efficacy has been demonstrated in experimental models and adult data, but clinical data on the use of the OxyMask in children are limited. What is New: ⢠Higher fraction of inspiratory oxygen and lesser carbon dioxide rebreathing were achieved with OxyMask than with a simple oxygen mask at low flow rates of oxygen in healthy children.
Assuntos
Dióxido de Carbono , Oxigênio , Adulto , Canadá , Criança , Pré-Escolar , Humanos , Máscaras , Respiração ArtificialRESUMO
There are few biomarkers to predict efficacy of glucocorticoid treatment in childhood acute lymphoblastic leukemia (ALL) at diagnosis. Here, we demonstrate reciprocal regulation of 11beta-hydroxysteroid dehydrogenase (11ß-HSD), may predict the apoptotic response of ALL to glucocorticoid treatment. Our data may be useful to refine glucocorticoid treatment, to retain benefit while minimizing side effects.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/fisiologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/fisiologia , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisolona/uso terapêutico , Adolescente , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Resultado do TratamentoAssuntos
Paralisia de Bell , Paralisia Facial , Doença de Lyme , Síndrome da Leucoencefalopatia Posterior , Paralisia Facial/diagnóstico , Paralisia Facial/etiologia , Humanos , Doença de Lyme/complicações , Doença de Lyme/diagnóstico , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/etiologiaRESUMO
Genome-wide association studies have consistently implicated the interleukin-15 (IL-15) gene in acute lymphoblastic leukemia (ALL) biology, including associations with disease susceptibility, and increased risk of central nervous system (CNS) involvement. However, whether pre-B ALL blasts directly respond to IL-15 is unknown. Here, we show that most pre-B ALL primary samples and cell lines express IL-15 and components of its receptor and that primary pre-B ALL cells show increased growth in culture in response to IL-15. Investigation of mechanisms of action using IL-15-responsive SD-1 cells shows this growth advantage is maximal under low-serum conditions, mimicking those found in cerebrospinal fluid. IL-15 also upregulates PSGL-1 and CXCR3, molecules associated with CNS trafficking. Investigation of downstream signaling pathways indicates that IL-15 induces signal transducer and activator of transcription 5 (STAT5), extracellular signal-regulated kinase (ERK) 1/2, and to a lesser extent phosphatidylinositol 3-kinase (PI3K) and nuclear factor κB (NF-κB) phosphorylation. The IL-15-mediated growth advantage is abolished by mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK), PI3K, and NF-κB inhibitors but preserved in the presence of STAT5 inhibition. Together, these observations provide a mechanistic link between increased levels of IL-15 expression and leukemogenesis, high-risk disease, and CNS relapse and suggest potential therapeutic targets.
Assuntos
Sistema Nervoso Central/imunologia , Interleucina-15/imunologia , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Fosfatidilinositol 3-Quinases/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-15/genética , Glicoproteínas de Membrana/genética , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Inibidores de Fosfoinositídeo-3 Quinase , Inibidor 1 de Ativador de Plasminogênio/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Receptores CXCR3/genética , Fator de Transcrição STAT5/antagonistas & inibidores , Fator de Transcrição STAT5/imunologia , Transdução de Sinais , Regulação para CimaAssuntos
Glucocorticoides/metabolismo , Síndrome de Linfonodos Mucocutâneos/metabolismo , Transdução de Sinais , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Criança , Feminino , Humanos , Japão , Masculino , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/genéticaRESUMO
Pasteurella multocida, often found as part of the human oral flora and in finger/toenails, also exists in many animals, especially cats, dogs, and pigs. Although rare, pasteurella infection in neonates can cause serious systemic disease, such as meningitis. In this article, a 23-day-old girl presented with decreased appetite and irritability for >2 days. Eighteen days previously her pet cat had jumped onto the left side of her head while she was sleeping. On laboratory data C-reactive protein was high, and on cerebrospinal fluid (CSF) analysis leukocyte count was extremely high, with low glucose and high protein. P. multocida grew out of the blood and CSF cultures, and she was successfully treated with antibiotics for 3 weeks. Although pasteurellosis rarely occurs, it can sometimes lead to life-threatening situations, so parents should exercise caution when having pets around their children.
Assuntos
Bacteriemia/microbiologia , Meningites Bacterianas/microbiologia , Infecções por Pasteurella/etiologia , Pasteurella multocida , Animais , Bacteriemia/diagnóstico , Bacteriemia/terapia , Gatos , Feminino , Humanos , Recém-Nascido , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/terapia , Infecções por Pasteurella/diagnóstico , Infecções por Pasteurella/terapiaRESUMO
Anorexia nervosa (AN) is a psychiatric disorder with metabolic abnormalities. Prolonged cardiopulmonary resuscitation (CPR) is predicted to result in death and poor neurological outcomes. This report describes the case of a patient with AN who had an unexpectedly favorable outcome after prolonged CPR. A 12-year-old female with AN presented to the emergency department, requiring intubation due to worsening consciousness and respiratory distress. Refractory hypotension led to cardiac arrest. After 135 minutes of CPR, venoarterial extracorporeal membrane oxygenation (EMCO) was started, and the patient was treated for post-resuscitation management, refeeding syndrome, and sepsis. The cardiac function gradually improved, the patient was weaned from EMCO eight days after admission, and the patient was extubated 30 days after admission. The patient maintained a good central nervous system function. AN patients tend to be youngsters and have a lower metabolism, which may be associated with a favorable neurological prognosis after prolonged CPR.
RESUMO
Vascular complications, such as pseudoaneurysms and thrombosis, are uncommon in pediatric acute pancreatitis (AP); hence, treatment experience remains limited. Here, we report a case of adolescent AP complicated with pseudoaneurysms and venous thrombosis simultaneously. Even after multiple endovascular embolizations for pseudoaneurysms, the patient experienced hemorrhagic shock resulting from pseudoaneurysm rupture after taking anticoagulants for thrombus. Inevitably, a total pancreatectomy was performed to prevent bleeding and control local complications. In AP, even among the pediatric population, a therapeutic dilemma between bleeding prevention and anticoagulation for thrombosis may occur. Despite the lack of experience with AP and its complications, a total pancreatectomy may become an alternative therapy for refractory AP or its complications.
RESUMO
Kawasaki Disease (KD) is an acute inflammatory disorder associated with systemic vasculitis. Intravenous immunoglobulin (IVIG) is an effective therapy for KD, yet, about 20% of cases show IVIG resistance with persistent inflammation. The lipid profile in IVIG-resistant KD patients and the relationship between lipid characteristics and IVIG resistance remain unknown. In this study, serum samples from twenty KD patients with different IVIG responses (sensitive, intermediate, or resistant) were collected both before and after treatment, and lipidomic analysis was performed using high-performance liquid chromatography-mass spectrometry. As a result, before treatment, six lipid species were found as the most variant features, in which all the top decreased lipids in the IVIG-resistant group were lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), suggesting the potential to be IVIG-resistant markers in pretreatment diagnosis. During treatment, lipidomic changes showed a weaker response in the IVIG-resistant group. After treatment, LPC and LPE species exhibited lower in the IVIG-resistant group and negative correlation with the inflammatory markers, indicating that the unique metabolism may occur among IVIG-responsiveness. These results might contribute to diagnosing IVIG-resistant patients more accurately for alternative therapy and to a better understanding of how lipid metabolism is associated with IVIG sensitiveness/resistance in KD.
Assuntos
Síndrome de Linfonodos Mucocutâneos , Humanos , Criança , Lactente , Síndrome de Linfonodos Mucocutâneos/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Lipidômica , Lipídeos , Estudos RetrospectivosRESUMO
BACKGROUND: Pandemic influenza A (H1N1) causes severe pneumonia in children. The mechanism of development of respiratory failure in pneumonia patients remains unknown. This report describes clinical features of childhood influenza A pneumonia. METHODS: The clinical and laboratory findings of 31 H1N1 pneumonia patients hospitalized in Iwata City Hospital from 1 October 2009 to 31 January 2010 were reviewed. Intubation and mechanical ventilation were required due to respiratory failure in eight patients, who were classified as the intubation group. Other patients without mechanical ventilation were classified as the non-intubation group. Clinical features and laboratory findings were compared between the two groups. RESULTS: The median age was 6.3 years (range, 3-10 years). The male to female ratio was 22:9. Clinical manifestations of tachycardia, tachypnea and cyanosis were significant findings in the intubation group at admission. Lymphocytopenia was observed in both groups. Leukocytosis with neutrophilia was the risk factor for intubation. CONCLUSIONS: Tachycardia, tachypnea, cyanosis and leukocytosis with neutrophilia, could be useful predictors at admission to identify high-risk influenza A (H1N1) pneumonia in children.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Pneumonia Viral/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Influenza Humana/diagnóstico , Influenza Humana/terapia , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapiaRESUMO
OBJECTIVES: Thyroid storm (TS) is a rare but life-threatening condition caused by decompensated hyperthyroidism. There is no consensus on how to diagnose pediatric TS. We report three pediatric cases of TS presenting with central nervous system (CNS) and gastrointestinal (GI) symptoms as the initial presentation of Graves' disease. CASE PRESENTATION: They were previously healthy adolescents without family history of thyroid disease. CNS symptoms varied from agitation to coma. GI symptoms included abdominal pain, vomiting, and diarrhea. Their laboratory studies revealed thyrotoxicosis and positive result of thyroid-stimulating antibody (TSAb). They were admitted to the intensive care unit (ICU) and received the combination of an antithyroid drug, Lugol's solution, a beta antagonist, and hydrocortisone. The most severe case was a 13 year-old Japanese girl who presented with loss of consciousness and hemodynamic shock. She died after 5 days of intensive treatment. CONCLUSIONS: Pediatricians should consider TS in the differential diagnosis when a patient exhibits both CNS and GI symptoms.
Assuntos
Gastroenteropatias/diagnóstico , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Doenças do Sistema Nervoso/diagnóstico , Doenças da Glândula Tireoide/diagnóstico , Adolescente , Antitireóideos/uso terapêutico , Criança , Feminino , Gastroenteropatias/complicações , Gastroenteropatias/tratamento farmacológico , Humanos , Iodetos/uso terapêutico , Masculino , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/tratamento farmacológico , Prognóstico , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/tratamento farmacológicoRESUMO
11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert 11keto-glucocorticoids to active 11beta-hydroxy forms, thereby amplifying intracellular glucocorticoid action. Up-regulation of 11beta-HSD1 in adipose tissue and liver is of pathogenic importance in metabolic syndrome. However, the mechanisms controlling 11beta-HSD1 transcription are poorly understood. Glucocorticoids themselves potently increase 11beta-HSD1 expression in many cells, providing a potential feed-forward system to pathology. We have investigated the molecular mechanisms by which glucocorticoids regulate transcription of 11beta-HSD1, exploiting an A549 cell model system in which endogenous 11beta-HSD1 is expressed and is induced by dexamethasone. We show that glucocorticoid induction of 11beta-HSD1 is indirect and requires new protein synthesis. A glucocorticoid-responsive region maps to between -196 and -88 with respect to the transcription start site. This region contains two binding sites for CCAAT/enhancer-binding protein (C/EBP) that together are essential for the glucocorticoid response and that bind predominantly C/EBPbeta, with C/EBPdelta present in a minority of the complexes. Both C/EBPbeta and C/EBPdelta are rapidly induced by glucocorticoids in A549 cells, but small interfering RNA-mediated knockdown shows that only C/EBPbeta reduction attenuates the glucocorticoid induction of 11beta-HSD1. Chromatin immunoprecipitation studies demonstrated increased binding of C/EBPbeta to the 11beta-HSD1 promoter in A549 cells after glucocorticoid treatment. A similar mechanism may apply in adipose tissue in vivo where increased C/EBPbeta mRNA levels after glucocorticoid treatment were associated with increased 11beta-HSD1 expression. C/EBPbeta is a key mediator of metabolic and inflammatory signaling. Positive regulation of 11beta-HSD1 by C/EBPbeta may link amplification of glucocorticoid action with metabolic and inflammatory pathways and may represent an endogenous innate host-defense mechanism.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Dexametasona/farmacologia , Regiões Promotoras Genéticas/efeitos dos fármacos , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Proteína delta de Ligação ao Facilitador CCAAT/genética , Linhagem Celular , DNA/genética , DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Knockout , Pró-Opiomelanocortina/deficiência , Pró-Opiomelanocortina/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Childhood nephrotic syndrome, in which steroid-dependence occurs concurrently with steroid-resistance, requires aggressive therapy to prevent relapse. Predictive biomarkers that can be used to stratify treatment are urgently needed. Here we report that reciprocal regulation of the glucocorticoid metabolizing enzymes, 11ß-hydroxysteroid dehydrogenase types 1 and 2, is associated with steroid-responsiveness and disease remission in childhood nephrotic syndrome, potentially providing a marker to identify patients in which aggressive therapy is required.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/sangue , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/sangue , Anti-Inflamatórios/uso terapêutico , Resistência a Medicamentos , Tolerância a Medicamentos , Síndrome Nefrótica/tratamento farmacológico , Prednisolona/uso terapêutico , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Dexametasona/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Quimioterapia de Indução , Quimioterapia de Manutenção , Masculino , Síndrome Nefrótica/sangue , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/enzimologia , Receptores de Glucocorticoides/sangue , Recidiva , Resultado do TratamentoRESUMO
11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) converts inert glucocorticoids into active forms, thereby increasing intracellular glucocorticoid levels, important to restrain acute inflammation. 11ß-HSD1 is induced by pro-inflammatory cytokines in a variety of cells. Here, we show 11ß-HSD1 expression in human A549 epithelial cells is increased by pro-inflammatory cytokines (IL-1α/TNFα) via the P2 promoter of the HSD11B1 gene. Inhibition of p38 MAPK attenuated the pro-inflammatory cytokine induction of mRNA encoding 11ß-HSD1 as well as that encoding C/EBPß. IL-1α/TNFα-induced phosphorylation of C/EBPß at Thr235 was also attenuated by p38 MAPK inhibition suggesting involvement of a p38 MAPK-C/EBPß pathway. siRNA-mediated knock-down of C/EBPß and NF-κB/RelA implicated both transcription factors in the IL-1α/TNFα induction of HSD11B1 mRNA. Transient transfections of HSD11B1 promoter-reporter constructs identified the proximal region of the P2 promoter of HSD11B1 as essential for this induction. IL-1α increased binding of C/EBPß to the HSD11B1 P2 promoter, but this was not observed for NF-κB/RelA, suggesting indirect regulation by NF-κB/RelA. Ectopic expression of mutant chicken C/EBPß constructs unable to undergo phosphorylation at the threonine equivalent to Thr235 attenuated the IL-1α-induction of HSD11B1, whereas mimicking constitutive phosphorylation of Thr235 (by mutation to aspartate) increased basal expression of HSD11B1 mRNA without affecting IL-1α-induced levels. These data clearly demonstrate a role for both C/EBPß and NF-κB/RelA in the pro-inflammatory cytokine induction of HSD11B1 in human epithelial cells and show that p38 MAPK-induced phosphorylation of C/EBPß at Thr235 is critical in this.
Assuntos
11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Citocinas/metabolismo , Regulação da Expressão Gênica/imunologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Animais , Proteína beta Intensificadora de Ligação a CCAAT , Linhagem Celular Tumoral , Galinhas , Glucocorticoides/metabolismo , Humanos , Ligases/metabolismo , NF-kappa B/metabolismo , Fosforilação , Regiões Promotoras Genéticas/genéticaRESUMO
Synthetic glucocorticoids (GCs) form a crucial first-line treatment for childhood acute lymphoblastic leukemia (ALL). However prolonged GC therapy frequently leads to GC-resistance with an unclear molecular mechanism. 11ß-hydroxysteroid dehydrogenase (11ß-HSD) 2 inactivates GCs within cells. Here, we show the association between GC sensitivity and 11ß-HSD2 expression in human T-cell leukemic cell lines. 11ß-HSD2 mRNA and protein levels were considerably higher in GC-resistant MOLT4F cells than in GC-sensitive CCRF-CEM cells. The 11ß-HSD inhibitor, carbenoxolone pre-treatment resulted in greater cell death with prednisolone assessed by methyl-thiazol-tetrazolium assay and caspase-3/7 assay, suggesting that 11ß-HSD2 is a cause of GC-resistance in ALL.