RESUMO
Although both natural and induced regulatory T (nTreg and iTreg) cells can enforce tolerance, the mechanisms underlying their synergistic actions have not been established. We examined the functions of nTreg and iTreg cells by adoptive transfer immunotherapy of newborn Foxp3-deficient mice. As monotherapy, only nTreg cells prevented disease lethality, but did not suppress chronic inflammation and autoimmunity. Provision of Foxp3-sufficient conventional T cells with nTreg cells reconstituted the iTreg pool and established tolerance. In turn, acute depletion of iTreg cells in rescued mice resulted in weight loss and inflammation. Whereas the transcriptional signatures of nTreg and in vivo-derived iTreg cells were closely matched, there was minimal overlap in their T cell receptor (TCR) repertoires. Thus, iTreg cells are an essential nonredundant regulatory subset that supplements nTreg cells, in part by expanding TCR diversity within regulatory responses.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Especificidade do Receptor de Antígeno de Linfócitos T , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Transferência Adotiva , Animais , Animais Recém-Nascidos , Autoimunidade/genética , Células Cultivadas , Fatores de Transcrição Forkhead/genética , Tolerância Imunológica , Inflamação , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Mutação/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Especificidade do Receptor de Antígeno de Linfócitos T/genética , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologiaRESUMO
OBJECTIVES: The cystic fibrosis transmembrane conductance regulator regulates fluid balance in alveolar epithelial cells and appears to modulate the inflammatory response. To determine whether more severe lung injury in children who develop community-acquired pneumonia is associated with variations known to affect function in the gene coding for cystic fibrosis transmembrane conductance regulator. DESIGN: A prospective cohort genetic association study of lung injury in children with community-acquired pneumonia. SETTING: Three major tertiary care children's hospitals. SUBJECTS: Caucasian and African American children with community-acquired pneumonia either evaluated in the emergency department or admitted to the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Caucasian and African American children with pneumonia were genotyped for the most common variants reported to affect cystic fibrosis transmembrane conductance regulator function, the p.508del mutation, the (TG)mTn variable repeat region, and the M470V polymorphism in the cystic fibrosis transmembrane conductance regulator gene. Genotypes and haplotypes were determined, and the association of high-risk alleles or high-risk haplotypes (defined as the presence of at least one variant known to decrease the level of functional cystic fibrosis transmembrane conductance regulator) with the need for mechanical ventilation or the development of acute lung injury was evaluated. Forty-two children in the Caucasian cohort (n = 304) required mechanical ventilation; 32 developed acute lung injury. Forty-three children in the African American cohort (n = 474) required mechanical ventilation; 29 developed acute lung injury. In African American children, high-risk (TG)mTn alleles known to result in decreased levels of functional cystic fibrosis transmembrane conductance regulator were associated with the need for mechanical ventilation (p = .0013) and the development of acute lung injury (p = .0061). Multivariable analysis demonstrated that high-risk (TG)mTn alleles were independently associated with mechanical ventilation (odds ratios = 3.19; 95% confidence interval, 1.63-6.26) and acute lung injury (odds ratios = 3.36; 95% confidence interval, 1.50-7.53) in African American children. CONCLUSION: Genetic variation in cystic fibrosis transmembrane conductance regulator is associated with acute lung injury in African American children with community-acquired pneumonia.
Assuntos
Lesão Pulmonar Aguda/genética , Negro ou Afro-Americano/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Pneumonia/genética , Lesão Pulmonar Aguda/etnologia , Adolescente , Alelos , Sequência de Bases , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/etnologia , Infecções Comunitárias Adquiridas/genética , Primers do DNA , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pneumonia/etnologia , Polimorfismo Genético/genética , Estudos ProspectivosRESUMO
Oxidative stress and mitochondrial permeability transition (MPT) are important mechanisms in acetaminophen (APAP) toxicity. The MPT inhibitor trifluoperazine (TFP) reduced MPT, oxidative stress, and toxicity in freshly isolated hepatocytes treated with APAP. Since hypoxia inducible factor-one alpha (HIF-1α) is induced very early in APAP toxicity, a role for oxidative stress in the induction has been postulated. In the present study, the effect of TFP on toxicity and HIF-1α induction in B6C3F1 male mice treated with APAP was examined. Mice received TFP (10mg/kg, oral gavage) prior to APAP (200mg/kg IP) and at 7 and 36h after APAP. Measures of metabolism (hepatic glutathione and APAP protein adducts) were comparable in the two groups of mice. Toxicity was decreased in the APAP/TFP mice at 2, 4, and 8h, compared to the APAP mice. At 24 and 48h, there were no significant differences in toxicity between the two groups. TFP lowered HIF-1α induction but also reduced the expression of proliferating cell nuclear antigen, a marker of hepatocyte regeneration. TFP can also inhibit phospholipase A(2), and cytosolic and secretory PLA(2) activity levels were reduced in the APAP/TFP mice compared to the APAP mice. TFP also lowered prostaglandin E(2) expression, a known mechanism of cytoprotection. In summary, the MPT inhibitor TFP delayed the onset of toxicity and lowered HIF-1α induction in APAP treated mice. TFP also reduced PGE(2) expression and hepatocyte regeneration, likely through a mechanism involving PLA(2).
Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Hepatócitos/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Regeneração Hepática/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Trifluoperazina/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Dinoprostona/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Imuno-Histoquímica , Indicadores e Reagentes , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/patologia , Permeabilidade , Antígeno Nuclear de Célula em Proliferação/biossíntese , Prostaglandina-Endoperóxido Sintases/metabolismo , Receptores da Fosfolipase A2/antagonistas & inibidores , Receptores da Fosfolipase A2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Ambulatory blood pressure monitoring (ABPM) has been proposed as a useful tool for more accurately diagnosing hypertension (HTN) and evaluating blood pressure (BP) response in pediatric anti-hypertensive trials. ABPM captures multiple BP measurements during routine daily activities and is thus an excellent method for identifying white-coat HTN. Additionally, ABPM measurements in adults do not demonstrate the placebo effect commonly seen with casual BP measurements, although this has yet to be evaluated in children. Therefore,, the aim of this study was to assess the effect of placebo on ABPM measurements in children. METHODS: A total of 141 children aged 5-16 years with elevated BP were randomized into a multi-center, single-blind, cross-over trial. Subjects received a placebo pill prior to wearing a 24-h ABPM device at one of two visits separated by 1-2 weeks. Study procedures were otherwise identical at both visits. RESULTS: Mean systolic and diastolic BP for all measured time periods were similar between visits, as was the number of children diagnosed with HTN at each visit. CONCLUSION: Having confirmed HTN at baseline did not affect the impact of placebo on mean BP. If confirmed, this lack of placebo effect on ABPM measurements may allow for the design of direct comparison pediatric anti-hypertensive trials without a placebo arm.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Hipertensão/diagnóstico , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos Cross-Over , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Visita a Consultório Médico , Efeito Placebo , Valor Preditivo dos Testes , Método Simples-Cego , Estados UnidosRESUMO
Residual right ventricular (RV) outflow tract pathology is universal among patients with repaired tetralogy of Fallot, and pulmonary regurgitation (PR) is also commonly present. Although tolerated in early life, by the second decade of life PR is associated with an increased risk of death because of ventricular arrhythmias. Pulmonary valve replacement (PVR) is a safe procedure that will eliminate PR, but timing and indications are evolving. Patients with arrhythmias or prolonged QRS duration are candidates for PVR. Patients with symptomatic exercise intolerance are likely to have improvement in symptoms and quality of life and should be offered PVR. Cardiac magnetic resonance has become an essential component of the management of the patient with tetralogy of Fallot with PR, and has identified the potential for and limitations of RV remodeling following PVR. Among patients with severe RV enlargement, particularly those with diminished RV or left ventricular function, there is an increased risk of adverse events and even asymptomatic patients with severe PR should be considered for PVR. Valve replacement is accomplished with homografts or heterografts, either stented bioprosthetic valves or valved conduits. In a retrospective analysis of the Children's Hospital of Wisconsin experience with PVR, there was no difference in survival or freedom from reintervention between heterografts and homografts.
Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Pulmonar/cirurgia , Tetralogia de Fallot/cirurgia , Adolescente , Adulto , Fatores Etários , Bioprótese , Criança , Próteses Valvulares Cardíacas , Humanos , Seleção de Pacientes , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/fisiopatologia , Estudos Retrospectivos , Tetralogia de Fallot/complicações , Tetralogia de Fallot/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Historically, HIDA is the initial diagnostic test in the evaluation of biliary atresia (BA). Non-excreting HIDA scans can yield false-positive results leading to negative laparotomy. OBJECTIVE: Cholestatic infants must be evaluated promptly to exclude biliary atresia (BA) and other treatable hepatic conditions. Intraoperative cholangiogram (IOC) is the gold standard for diagnosing BA, but requires surgical intervention. Percutaneous transhepatic cholecysto-cholangiography (PTCC) and liver biopsy are less invasive and have been described in small case series. We hypothesized that PTCC and liver biopsy effectively exclude BA, thus avoiding unnecessary IOC. MATERIALS AND METHODS: Retrospective review of cholestatic infants who underwent PTCC, biopsy or cholescintigraphy at a tertiary children's hospital from August 1998 to January 2009. Group differences were evaluated and the receiver operator curve and safety of PTCC determined. RESULTS: One-hundred twenty-eight cholestatic infants were reviewed. Forty-six (36%) underwent PTCC. Forty-one out of 46 (89%) had simultaneous PTCC and liver biopsy. PTCC was completed successfully in 19/23 (83%) children despite a small or absent GB on initial US. Negative laparotomy rate was 1/6 (17%) for simultaneous PTCC/liver biopsy. Complications occurred in 4/46 including bleeding (n=2), fever with elevated transaminases (n=1) and oxygen desaturations (n=1). CONCLUSION: PTCC, particularly when performed in combination with simultaneous liver biopsy, effectively excludes BA in cholestatic infants with acceptable morbidity. PTCC can frequently be performed when a contracted gallbladder is seen on initial US exam. Negative laparotomy rate is lowest when PTCC is coupled with simultaneous liver biopsy.
Assuntos
Biópsia/estatística & dados numéricos , Colangiografia/estatística & dados numéricos , Colecistografia/estatística & dados numéricos , Icterícia/diagnóstico , Icterícia/epidemiologia , Laparotomia/estatística & dados numéricos , Procedimentos Desnecessários/estatística & dados numéricos , Doença Crônica , Feminino , Humanos , Iminoácidos , Lactente , Recém-Nascido , Icterícia/cirurgia , Masculino , Prevalência , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Wisconsin/epidemiologiaRESUMO
After stage 1 palliation (S1P) with a Norwood operation, infants commonly experience growth failure during the initial interstage period. Growth failure during this high-risk period is associated with worse outcomes. This study evaluated the growth patterns of patients enrolled in the authors' interstage home-monitoring program (HMP), which uses a multidisciplinary team approach to nutrition management. From 2000 to 2009, 148 infants were enrolled in the HMP after S1P. Families recorded daily weights during the interstage period and alerted the interstage monitoring team about protocol violations of nutritional goals. Interstage monitoring and inpatient data from the S1P hospitalization were reviewed to identify risk factors for poor growth. Growth outcomes were compared with published norms from the Centers for Disease Control. Interstage survival for patients in the HMP was 98 % (145/148). Growth velocity during the interstage period was 26 ± 8 g/day. The weight-for-age z-scores decreased from birth to discharge after S1P (-0.4 ± 0.9 to -1.3 ± 0.9; p < 0.001) but then increased during the interstage period to the time of S2P (-0.9 ± 1; p < 0.001). The factors associated with improved growth during the interstage period included male gender, greater birth weight, full oral feeding at S1P discharge, and a later birth era. After S1P, infants enrolled in an HMP experienced normal growth velocity during the interstage period. Daily observation of oxygen saturation, weight change, and enteral intake together with implementation of a multidisciplinary feeding protocol is associated with excellent interstage growth and survival.
Assuntos
Insuficiência de Crescimento/etiologia , Insuficiência de Crescimento/prevenção & controle , Cardiopatias Congênitas/cirurgia , Serviços Hospitalares de Assistência Domiciliar , Monitorização Fisiológica/métodos , Procedimentos de Norwood , Apoio Nutricional , Peso Corporal , Continuidade da Assistência ao Paciente , Oxigenação por Membrana Extracorpórea , Feminino , Gastrostomia , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Reoperação/estatística & dados numéricos , Fatores de RiscoRESUMO
OBJECTIVE: To determine whether genetic variations in the gene coding for surfactant protein B are associated with lung injury in African American children with community-acquired pneumonia. DESIGN: A prospective cohort genetic association study of lung injury in children with community-acquired pneumonia. SETTING: Two major tertiary care children's hospitals. SUBJECTS: African American children with community-acquired pneumonia (n = 395) either evaluated in the emergency department or admitted to the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-five African American children (14 days to 18 yrs of age) with community-acquired pneumonia were enrolled. Thirty-seven patients required mechanical ventilation and 26 of these were diagnosed with acute lung injury or acute respiratory distress syndrome. Genotyping was performed on seven linkage disequilibrium-tag single nucleotide polymorphisms in the surfactant protein B gene. Univariate analysis demonstrated two linkage disequilibrium-tag single nucleotide polymorphisms, rs1130866 (also known as SP-B + 1580 C/T) and rs3024793, were associated with the need for mechanical ventilation in African American children (p = .016 and p = .030, respectively). Multivariable analysis indicated that both of these single nucleotide polymorphisms are independently associated with need for mechanical ventilation (p = .040 and p = .012, respectively) as was rs7316 when its interaction with age was considered (p = .015). Multivariable analysis examining acute lung injury demonstrated a significant association of rs7316 with acute lung injury (p = .031). Haplotype analysis was also performed. Two haplotypes, GTGCGCG and ATATAAG, were associated with need for mechanical ventilation using either univariate (p = .041 and p = .043, respectively) or multivariable analysis (odds ratios of 2.62, p = .048, and 3.12, p = .033, respectively). CONCLUSIONS: Genetic variations in the gene coding for surfactant protein B are associated with more severe lung injury as indicated by the association of specific single nucleotide polymorphism genotypes and haplotypes with the need for mechanical ventilation in African American children with community-acquired pneumonia.
Assuntos
Lesão Pulmonar Aguda/genética , Negro ou Afro-Americano/genética , Predisposição Genética para Doença/etnologia , Variação Genética , Pneumonia/genética , Proteína B Associada a Surfactante Pulmonar/genética , Lesão Pulmonar Aguda/etnologia , Lesão Pulmonar Aguda/terapia , Adolescente , Distribuição por Idade , Análise de Variância , Criança , Pré-Escolar , Estudos de Coortes , Infecções Comunitárias Adquiridas/etnologia , Infecções Comunitárias Adquiridas/genética , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Genótipo , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Pneumonia/etnologia , Pneumonia/microbiologia , Polimorfismo Genético , Estudos Prospectivos , Respiração Artificial , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não ParamétricasRESUMO
In addition to thymus-derived or natural T regulatory (nT(reg)) cells, a second subset of induced T regulatory (iT(reg)) cells arises de novo from conventional CD4(+) T cells in the periphery. The function of iT(reg) cells in tolerance was examined in a CD45RB(high)CD4(+) T cell transfer model of colitis. In situ-generated iT(reg) cells were similar to nT(reg) cells in their capacity to suppress T cell proliferation in vitro and their absence in vivo accelerated bowel disease. Treatment with nT(reg) cells resolved the colitis, but only when iT(reg) cells were also present. Although iT(reg) cells required Foxp3 for suppressive activity and phenotypic stability, their gene expression profile was distinct from the established nT(reg) "genetic signature," indicative of developmental and possibly mechanistic differences. These results identified a functional role for iT(reg) cells in vivo and demonstrated that both iT(reg) and nT(reg) cells can act in concert to maintain tolerance.
Assuntos
Colite/imunologia , Colite/patologia , Tolerância Imunológica , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Transferência Adotiva , Animais , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Células Cultivadas , Colite/genética , Colite/terapia , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/fisiologia , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Transgênicos , Regiões Promotoras Genéticas/imunologiaRESUMO
OBJECTIVES: Racial disparities in therapies and outcomes in adult and neonatal ICUs are well documented; however, little is known regarding racial disparities in pediatric intensive care unit (PICU). Our objective was to determine whether racial disparities exist in the admission of critically ill children to the PICU. METHODS: We retrospectively analyzed admissions to a PICU in a tertiary care pediatric hospital. Summarized demographic data was analyzed from the county health department. RESULTS: Of the 4676 admissions to the PICU between January 1, 1997 and December 31, 1999, 1030 children were <48 months of age, lived in Shelby County, TN, and were either African American (789, 76.6%) or non-Hispanic white (241, 23.4%). The surrounding county was comprised of approximately 58% African American and 41% non-Hispanic white children ≤ 48 months of age. A history of premature birth was more common in African American children than non-Hispanic white children (46.8% vs. 32.8%; P < 0.0001). Mortality was 5.7% overall and was not significantly different between African Americans and non-Hispanic whites but was higher for those children with a history of premature birth (4.6% vs. 7.1%, P < 0.026). The overall relative risk of admission to the PICU for African American children was 2.12 (95% CI, 1.66-2.74), for African American children with a history of premature birth was 1.44 (95% CI, 0.96-2.21), and for full-term African American children was 1.82 (95% CI, 1.33 -2.49). CONCLUSIONS: Racial differences in admission to the PICU exist with African American children having a greater risk for PICU admission than non-Hispanic white children.
Assuntos
Estado Terminal/epidemiologia , Disparidades em Assistência à Saúde , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva Pediátrica/ética , Admissão do Paciente/estatística & dados numéricos , Grupos Raciais , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Tennessee/epidemiologiaRESUMO
OBJECTIVE: To conduct a meta-analytic review of psychosocial adjustment of youth with inflammatory bowel disease (IBD). METHODS: Nineteen studies with a total of 1167 youth with IBD (M age = 14.33, 50% female) were included. Effect size (ES) estimates were calculated for anxiety symptoms & disorders, depressive symptoms & disorders, internalizing symptoms & disorders, externalizing symptoms, quality of life (QOL), social functioning, and self-esteem. Separate ESs were calculated for comparisons between IBD and youth with chronic illnesses versus healthy youth. RESULTS: Youth with IBD had higher rates of depressive disorders and internalizing disorders than youth with other chronic conditions. Youth with IBD had higher parent-reported internalizing symptoms, lower parent- and youth-reported QOL, and lower youth-reported social functioning compared to healthy youth. CONCLUSIONS: Clinical attention to depressive disorders, QOL, and social functioning may be particularly salient in the context of pediatric IBD.
Assuntos
Adaptação Psicológica , Doenças Inflamatórias Intestinais/psicologia , Qualidade de Vida/psicologia , Ajustamento Social , Adolescente , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Criança , Depressão/psicologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , AutoimagemRESUMO
OBJECTIVE: To investigate whether selected single nucleotide polymorphisms in the myosin light chain kinase gene are associated with more severe lung injury in children and adults with community-acquired pneumonia. Previous studies have demonstrated an association between single nucleotide polymorphisms in the myosin light chain kinase gene and increased severity of acute lung injury in adults. DESIGN: Prospective, case-control genetic association study. SETTING: Three tertiary children's hospitals and one adult healthcare system. PATIENTS: A total of 800 pediatric patients and 393 adult patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Genetic variation in the myosin light chain kinase gene was examined. The pediatric cohort was predominantly composed of African American (n = 443) and Caucasian (n = 253) children. A total of 393 patients made up the adult cohort. Within the pediatric cohort, single nucleotide polymorphisms rs16834493, rs820463, and rs9840993 were genotyped in the African American patients, whereas single nucleotide polymorphisms rs960224, rs33264, rs11718105, and rs9289225 were genotyped in the Caucasian patients. One single nucleotide polymorphism (rs820336) was genotyped in both groups. Genotyping in the adult cohort included rs820336, rs860224, rs33264, and rs11718105. Genotyping was performed using the Taqman Assay. Data were analyzed separately for African Americans and Caucasians and for children and adults. No associations were observed between the myosin light chain kinase gene single nucleotide polymorphisms genotyped in children with community-acquired pneumonia and increased severity of lung injury. Similarly, no associations were observed between myosin light chain kinase gene single nucleotide polymorphisms genotyped in adults with community-acquired pneumonia and increased severity of lung injury. CONCLUSIONS: No association between the selected single nucleotide polymorphisms in the myosin light chain kinase gene and either the need for positive-pressure ventilation or the development of acute lung injury/acute respiratory distress syndrome was observed in children with community-acquired pneumonia. This suggests that variation in this gene may play less of a role in lung injury in children or adults with community-acquired pneumonia than in adults with sepsis or trauma.
Assuntos
Variação Genética , Lesão Pulmonar/genética , Quinase de Cadeia Leve de Miosina/genética , Pneumonia/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Lactente , Recém-Nascido , Lesão Pulmonar/enzimologia , Lesão Pulmonar/etnologia , Masculino , Pneumonia/enzimologia , Pneumonia/etnologia , Polimorfismo de Nucleotídeo Único , Respiração com Pressão Positiva , Estudos ProspectivosRESUMO
BACKGROUND AND OBJECTIVE: Reported rates of recurrence after enema reduction for intussusception are variable. Concerns for recurrence influence postreduction management. The objective of this study was to conduct a systematic review and meta-analysis to estimate overall, 24-hour, and 48-hour recurrence rates after enema reduction in children. METHODS: PubMed, Cochrane Database, and OVID Medline were searched from 1946 through December 2011 using the search terms: intussusception, recurrence, and enema. Sixty-nine studies of patients age 0 to 18 years with radiographically proven intussusception reduced by enema that report the number of enema reductions and the number of recurrences were included. Extraction was done by the primary author (M.P.G.) with 10% of included studies independently audited to ensure concordance. RESULTS: Overall recurrence rates were 12.7% (95% confidence interval [CI]: 11.1%-14.4%, I2 = 28.8%) for contrast enema (CE), 7.5% (95% CI: 5.7%-9.8%, I2 = 52.4%) for ultrasound-guided noncontrast enema (UGNCE), and 8.5% (95% CI: 6.9%-10.4%, I2 = 50.1%) for fluoroscopy-guided air enema (FGAE). Recurrence rates within 24 hours were 3.9% (95% CI: 2.2%-6.7%, I2 = 47.0%) for CE, 3.9% (95% CI: 1.5%-10.1%, I2 = 0.0%) for UGNCE, and 2.2% (95% CI: 0.7%-6.5%, I2 = 59.8%) for FGAE. Recurrence rates within 48 hours were 5.4% (95% CI 3.7%-7.8%, I2 = 32.3%) for CE, 6.6% (95% CI: 4.0%-10.7%, I2 = 0.0%) for UGNCE, and 2.7% (95% CI: 1.2%-6.5%, I2 = 73.8%) for FGAE. Most included studies are retrospective and vary in quality of reporting. Few studies reported detailed patient characteristics including timing of recurrences. CONCLUSIONS: The risk of early (within 48 hours) recurrence after enema reduction is low, suggesting outpatient management of well-appearing patients should be considered.
Assuntos
Enema , Doenças do Íleo/terapia , Intussuscepção/terapia , Criança , Humanos , Recidiva , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVE: Poor oral intake is a common presenting symptom among infants hospitalized with bronchiolitis. The prevalence, degree, and duration of iminished caloric intake in these infants have not been studied. Our goal was to determine the daily caloric intake among infants admitted with bronchiolitis and to evaluate the relationship between early hospital caloric intake and length of stay (LOS). METHODS: We conducted a retrospective chart review of infants aged <1 year admitted to Children's Hospital of Wisconsin with bronchiolitis who were placed in the bronchiolitis treatment protocol during the 2004-2005 season. Patient-, disease-, respiratory-, and nutrition-specific data were abstracted. RESULTS: A total of 273 patients with bronchiolitis were admitted between November 1, 2004, and April 15, 2005; placed on the bronchiolitis protocol; and included in the study. Median caloric intake was diminished on day 1 (53 kcal/kg per day) and day 2 (64 kcal/kg per day). Caloric intake was slower to normalize in infants with progressively longer LOS, and a slower rate of increase from day 1 to day 2 was significantly correlated with longer LOS (r= -0.18; P= .002). Subgroup analysis revealed significant correlations between hospital day 2 caloric intake and LOS in formula-fed infants, breastfed infants, infants aged <183 days, and infants aged > or =183 days. CONCLUSIONS: Caloric intake was diminished in the early course of hospitalization for infants who had bronchiolitis and slowest to normalize in infants with the longest LOS. Interventions aimed at decreasing LOS among infants admitted with bronchiolitis should consider the potential significance of nutrition for severely affected infants with this condition.
Assuntos
Bronquiolite/terapia , Ingestão de Energia , Tempo de Internação/estatística & dados numéricos , Estudos de Coortes , Progressão da Doença , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine if maternal knowledge of prematurity is improved when verbal gestational age-specific counseling is supplemented with written gestational age-specific information. METHODS: Prospective, randomized study of 60 pregnant participants assessed to be at risk for premature delivery between 23 and 34 weeks' gestation. Counseling in the control group consisted of gestational age-specific verbal information, and counseling in the intervention group consisted of written gestational age-specific information 1 hour before the verbal gestational age-specific information. Both groups completed a Prematurity Knowledge Questionnaire after counseling and the State-Trait Anxiety Inventory before and after counseling. The Prematurity Knowledge Questionnaire consisted of questions regarding short-term problems (immature lungs, intraventricular hemorrhage, retinopathy, feeding problems, infection, apnea, and jaundice), long-term problems (chronic lung disease, postdischarge respiratory infections, visual impairment, hearing impairment, brain damage, and learning and behavior problems), and numerical outcome data (probabilities of survival, survival without significant morbidity, severe intraventricular hemorrhage, severe retinopathy, and chronic lung disease). RESULTS: Knowledge of short-term problems was not statistically different between the intervention (82%) and control groups (67%). Knowledge of long-term problems was better in the intervention (71%) than the control group (45%). Knowledge of numerical data was better in the intervention (48%) than the control group (29%). State-Trait Anxiety Inventory scores decreased after counseling in the intervention group. CONCLUSIONS: Supplementation of face-to-face verbal counseling with written information improved knowledge of long-term problems and knowledge of numerical outcome data, and it also decreased anxiety in women expecting a premature delivery.
Assuntos
Aconselhamento/métodos , Trabalho de Parto Prematuro/prevenção & controle , Folhetos , Educação de Pacientes como Assunto/métodos , Cuidado Pré-Natal/métodos , Adaptação Psicológica , Ansiedade/psicologia , Compreensão , Feminino , Idade Gestacional , Humanos , Rememoração Mental , Trabalho de Parto Prematuro/psicologia , Gravidez , Cuidado Pré-Natal/psicologia , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , TexasRESUMO
BACKGROUND: In a mouse model of viral induced atopic disease, expression of FcεRI on dendritic cells is critical. While adult human conventional (cDC) and plasmacytoid (pDC) dendritic cells have been shown to express FcεRI, it is not known if this receptor is expressed in childhood and how its expression is governed by IgE. METHODS: Following informed consent of subjects (n = 27, aged 12-188 months), peripheral blood was stained for surface expression of CD19, ILT7, CD1c, IgE, FcεRI and analyzed by flow cytometry (cDC: CD19(-) ILT7(-) CD1c(+); pDC: CD19(-) ILT7(+) CD1c(-)). Total and specific serum IgE levels to food and inhalant allergens were determined by ImmunoCAP, and the relationship between FcεRI expression on dendritic cells and sensitization, free IgE, cell bound IgE, and age was determined. RESULTS: Independent of sensitization status, FcεRI expression was noted on cDC and pDC as early as 12 months of age. Serum IgE level correlated with expression of FcεRI on cDC, but not pDC. Based on the concentration of IgE, a complex relationship was found between surface bound IgE and expression of FcεRI on cDC. pDC exhibited a linear relationship of FcεRI expression and bound IgE that was consistent through all IgE concentrations. CONCLUSIONS: In children, FcεRI expression on cDC and pDC is modulated differently by serum and cell bound IgE. IgE governance of FcεRI expression on cDC depends upon a complex relationship. Further studies are needed to determine the functional roles of FcεRI on cDC and pDC.
Assuntos
Células Dendríticas/citologia , Regulação da Expressão Gênica , Receptores de IgE/biossíntese , Receptores de IgE/química , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Citometria de Fluxo/métodos , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/química , Lactente , Masculino , Receptores de IgE/metabolismoRESUMO
BACKGROUND: Prior prediction models for length of stay (LOS) in bronchiolitis have focused more on birth- and disease-related risk factors than on early hospital course factors, particularly common clinical markers including respiratory status and caloric intake. OBJECTIVES: 1) Study the associations of various clinical markers and LOS; and 2) develop a LOS prediction model. DESIGN: Retrospective cohort study. SETTING: Children's Hospital of Wisconsin. PATIENTS: Inclusion criteria were: age < 365 days old; admission between November 1, 2004 and April 15, 2005; final diagnosis of bronchiolitis; placement on the bronchiolitis treatment protocol; and lack of concurrent condition impacting LOS. RESULTS: During the study period, 272/347 infants admitted with bronchiolitis met inclusion criteria. On hospital day 2, infants in the prolonged LOS group (≥ 108 hours) had a significantly greater number of hours on supplemental oxygen, maximum supplemental oxygen use, minimum supplemental oxygen use, maximum respiratory rate, mean respiratory score, and number of times suctioned. They had significantly lower minimum oxygen saturation and caloric intake. Recursive partitioning demonstrated five variables (hours of supplemental oxygen, maximum respiratory rate, minimum supplemental oxygen use, gestation, and caloric intake) to predict short or prolonged LOS with an area under the receiver-operator characteristic curve of 0.89/0.72 in the learning/test trees; sensitivity, 0.85; and specificity, 0.82. CONCLUSIONS: There are important differences between infants with bronchiolitis having short and prolonged hospital stays, including several clinical markers identifiable on hospital day 2. This model may be a useful prediction tool for targeting early interventions for high-risk infants.
Assuntos
Bronquiolite/epidemiologia , Bronquiolite/terapia , Tempo de Internação/tendências , Bronquiolite/fisiopatologia , Estudos de Coortes , Feminino , Previsões , Hospitalização/tendências , Humanos , Lactente , Masculino , Oxigenoterapia/métodos , Oxigenoterapia/tendências , Estudos RetrospectivosRESUMO
OBJECTIVE: To identify if 1,6-hexamethylene diisocyanate (HDI) workers demonstrated an increased prevalence of occupational asthma or accelerated decline in pulmonary function. METHODS: Employees from two plants manufacturing or producing 1,6-HDI monomer and/or HDI polyisocyanates were matched to a control population by age, gender, race, and smoking status. A random coefficient regression analysis compared the decline in pulmonary function test values over time. Retrospective medical review was used to identify potential cases of occupationally induced asthma. RESULTS: No significantly accelerated annual decline in force expiratory volume after 1 second in the HDI exposure group compared to the matched control group was observed. No cases of adult onset asthma, beyond those present at time of hire, and no cases of occupational asthma were identified. CONCLUSIONS: This study provides support for the current American Conference of Governmental Industrial Hygienists threshold limit value time-weighted average of 5 ppb.
Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Asma/epidemiologia , Cianatos/toxicidade , Exposição Ocupacional/efeitos adversos , Respiração , Adulto , Asma/induzido quimicamente , Estudos de Coortes , Feminino , Humanos , Isocianatos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Microbial water contamination after periods of heavy rainfall is well described, but its link to acute gastrointestinal illness (AGI) in children is not well known. OBJECTIVES: We hypothesize an association between rainfall and pediatric emergency department (ED) visits for AGI that may represent an unrecognized, endemic burden of pediatric disease in a major U.S. metropolitan area served by municipal drinking water systems. METHODS: We conducted a retrospective time series analysis of visits to the Children's Hospital of Wisconsin ED in Wauwatosa, Wisconsin. Daily visit totals of discharge International Classification of Diseases, 9th Revision codes of gastroenteritis or diarrhea were collected along with daily rainfall totals during the study period from 2002 to 2007. We used an autoregressive moving average model, adjusting for confounding variables such as sewage release events and season, to look for an association between daily visits and rainfall after a lag of 1-7 days. RESULTS: A total of 17,357 AGI visits were identified (mean daily total, 7.9; range, 0-56). Any rainfall 4 days prior was significantly associated with an 11% increase in AGI visits. Expected seasonal effects were also seen, with increased AGI visits in winter months. CONCLUSIONS: We observed a significant association between rainfall and pediatric ED visits for AGI, suggesting a waterborne component of disease transmission in this population. The observed increase in ED visits for AGI occurred in the absence of any disease outbreaks reported to public health officials in our region, suggesting that rainfall-associated illness may be underestimated. Further study is warranted to better address this association.
Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Gastroenteropatias/terapia , Pediatria , Chuva , Doença Aguda , Criança , Humanos , Análise de Regressão , Estudos Retrospectivos , WisconsinRESUMO
The first wave of the 2009 influenza H1N1 pandemic (H1N1pdm) in Milwaukee, WI has been recognized as the largest reported regional outbreak in the United States. The epidemiologic and clinical characteristics of this large first wave outbreak from April 28(th) 2009-July 25(th) 2009, studied using both passive and targeted surveillance methodologies are presented. A total of 2791 individuals with H1N1pdm infection were identified; 60 % were 5-18 years old. The 5-18 year and 0-4 year age groups had high infection (1131 and 1101 per 100,000) and hospitalization (49 and 12 per 100,000) rates respectively. Non-Hispanic blacks and Hispanics had the highest hospitalization and infection rates. In targeted surveillance, infected patients had fever (78%), cough (80%), sore throat (38%), and vomiting or diarrhea (8%). The "influenza like illness" definition captured only 68 % of infected patients. Modeling estimates that 10.3 % of Milwaukee population was infected in the first wave and 59% were asymptomatic. The distinct epidemiologic profile of H1N1pdm infections observed in the study has direct implications for predicting the burden of infection and hospitalization in the next waves of H1N1pdm. Careful consideration of demographic predictors of infection and hospitalization with H1N1pdm will be important for effective preparedness for subsequent influenza seasons.