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BACKGROUND: Total colonic and small bowel aganglionosis (TCSA) occurs in less than 1% of all Hirschsprung's disease patients. Currently, the mainstay of treatment is surgery. However, in patients with TCSA, functional outcomes are often poor. A characteristic transition zone in TCSA can be difficult to identify which may complicate surgery and may often require multiple operations. CASE PRESENTATION: We present the case of a male infant who was diagnosed with biopsy-proven total colonic aganglionosis with extensive small bowel involvement as a neonate. The patient was diverted at one month of age based on leveling biopsies at 10 cm from the Ligament of Treitz. At 7 months of age, during stoma revision for a prolapsed stoma, intra-operative peristalsis was observed in nearly the entire length of the previously aganglionic bowel, and subsequent biopsies demonstrated the appearance of mature ganglion cells in a previously aganglionic segment. CONCLUSIONS: TCSA remains a major challenge for pediatric surgeons. Our case introduces new controversy to our understanding of aganglionosis. Our observations warrant further research into the possibility of post-natal ganglion maturation and encourage surgeons to consider a more conservative surgical approach.
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Gânglios/patologia , Doença de Hirschsprung/cirurgia , Intestino Delgado/inervação , Biópsia , Colo/anormalidades , Colo/patologia , Colo/cirurgia , Doença de Hirschsprung/patologia , Humanos , Recém-Nascido , Enteropatias/diagnóstico por imagem , Enteropatias/patologia , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Masculino , RadiografiaRESUMO
Following publication of the original article [1], the authors reported error on the images/figures used which also resulted in un-sequential order. The updated figures and captions are provided below.
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Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare congenital disorder, in which heterozygous missense variants in the Enteric Smooth Muscle actin γ-2 (ACTG2) gene have been recently identified. To investigate the mechanism by which ACTG2 variants lead to MMIHS, we screened a cohort of eleven MMIHS patients, eight sporadic and three familial cases, and performed immunohistochemistry, molecular modeling and molecular dynamics (MD) simulations, and in vitro assays. In all sporadic cases, a heterozygous missense variant in ACTG2 was identified. ACTG2 expression was detected in all intestinal layers where smooth muscle cells are present in different stages of human development. No histopathological abnormalities were found in the patients. Using molecular modeling and MD simulations, we predicted that ACTG2 variants lead to significant changes to the protein function. This was confirmed by in vitro studies, which showed that the identified variants not only impair ACTG2 polymerization, but also contribute to reduced cell contractility. Taken together, our results confirm the involvement of ACTG2 in sporadic MMIHS, and bring new insights to MMIHS pathogenesis.
Assuntos
Anormalidades Múltiplas/genética , Actinas/genética , Colo/anormalidades , Mucosa Intestinal/metabolismo , Pseudo-Obstrução Intestinal/genética , Contração Muscular/genética , Músculo Liso/metabolismo , Mutação de Sentido Incorreto , Bexiga Urinária/anormalidades , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/patologia , Actinas/química , Actinas/metabolismo , Colo/metabolismo , Colo/patologia , Evolução Fatal , Feminino , Expressão Gênica , Heterozigoto , Humanos , Recém-Nascido , Pseudo-Obstrução Intestinal/metabolismo , Pseudo-Obstrução Intestinal/patologia , Intestinos/patologia , Masculino , Simulação de Dinâmica Molecular , Músculo Liso/patologia , Linhagem , Multimerização Proteica , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Adulto JovemAssuntos
Deficiência de Vitaminas/prevenção & controle , Anormalidades do Sistema Digestório , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Coeficiente Internacional Normatizado/métodos , Nutrição Parenteral , Síndrome do Intestino Curto , Vitaminas , Varfarina , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Deficiência de Vitaminas/etiologia , Colo/anormalidades , Colo/fisiopatologia , Colo/cirurgia , Anormalidades do Sistema Digestório/diagnóstico , Anormalidades do Sistema Digestório/fisiopatologia , Anormalidades do Sistema Digestório/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Endocardite Bacteriana/complicações , Endocardite Bacteriana/microbiologia , Enterococcus faecalis/isolamento & purificação , Feminino , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Lactente , Atresia Intestinal/diagnóstico , Atresia Intestinal/cirurgia , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/fisiopatologia , Obstrução Intestinal/cirurgia , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Avaliação Nutricional , Nutrição Parenteral/efeitos adversos , Nutrição Parenteral/métodos , Síndrome do Intestino Curto/etiologia , Síndrome do Intestino Curto/fisiopatologia , Síndrome do Intestino Curto/terapia , Vitaminas/administração & dosagem , Vitaminas/efeitos adversos , Varfarina/administração & dosagem , Varfarina/farmacocinéticaAssuntos
Doença Celíaca/complicações , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Doença de Hirschsprung/cirurgia , Jejunostomia , Síndrome do Intestino Curto/cirurgia , Biópsia , Doença Celíaca/diagnóstico , Doença Celíaca/dietoterapia , Doença Celíaca/fisiopatologia , Criança , Transtornos da Nutrição Infantil/dietoterapia , Transtornos da Nutrição Infantil/etiologia , Transtornos da Nutrição Infantil/fisiopatologia , Fenômenos Fisiológicos da Nutrição Infantil , Dieta Livre de Glúten , Feminino , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/fisiopatologia , Humanos , Desnutrição/dietoterapia , Desnutrição/etiologia , Desnutrição/fisiopatologia , Estado Nutricional , Nutrição Parenteral Total , Síndrome do Intestino Curto/diagnóstico , Síndrome do Intestino Curto/etiologia , Síndrome do Intestino Curto/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: It is well known that small bowel length is a dominant prognostic indicator in patients with short bowel syndrome (SBS). The relative importance of jejunum, ileum, and colon is less well defined in children with SBS. Here we review the outcome of children with SBS with respect to the type of remnant intestine. METHODS: A retrospective review of 51 children with SBS was conducted at a single institution. The duration of parenteral nutrition use was the main outcome variable. The length of the remaining intestine as well as the type of intestine were recorded for each patient. Kaplan-Meier analyses were conducted to compare the subgroups. RESULTS: Children with greater than 10% expected small bowel length or more than 30 cm of small bowel achieved enteral autonomy faster than those with less. The presence of ileocecal valve enhanced the ability to wean from parenteral nutrition. The presence of ileum significantly enhanced the ability to wean from parenteral nutrition. Patients with the entire colon also achieved enteral autonomy sooner than those with partial colon. CONCLUSIONS: The preservation of ileum and colon is important in patients with SBS. Approaches to preserve or lengthen ileum and colon may be beneficial for these patients. LEVEL OF EVIDENCE: IV.
Assuntos
Síndrome do Intestino Curto , Humanos , Criança , Síndrome do Intestino Curto/terapia , Íleo , Intestino Delgado , Nutrição Parenteral , ColoAssuntos
Cálculos Biliares/etiologia , Atresia Intestinal/cirurgia , Síndrome de Mirizzi/etiologia , Nutrição Parenteral Total/efeitos adversos , Complicações Pós-Operatórias/terapia , Síndrome do Intestino Curto/terapia , Colecistectomia Laparoscópica/métodos , Procedimentos Cirúrgicos do Sistema Digestório , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/cirurgia , Humanos , Masculino , Síndrome de Mirizzi/diagnóstico , Síndrome de Mirizzi/cirurgia , Complicações Pós-Operatórias/etiologia , Síndrome do Intestino Curto/etiologia , Adulto JovemRESUMO
BACKGROUND AND AIM: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by upper gastrointestinal symptoms and the presence of high numbers of eosinophils in the esophagus. Although eosinophils in the esophagus have been found to be activated in subjects with EoE, detailed studies of intracellular signaling pathways involved in the mechanism of activation of eosinophils in EoE have heretofore been limited. The aim of the study was to assess whether any surface molecules or transcription factors are activated in peripheral eosinophils in subjects with EoE. METHODS: Eosinophils and CD3+ lymphocytes were identified directly from 50 µL of whole blood of EoE and control subjects. Using Hi-FACS, levels of surface activation markers, including CD66b, and intracellular phosphoepitopes, including phosphorylated forms of signal transducer and activator of transcription (phospho-STAT) 1 and 6, were measured within each cell subset. RESULTS: Levels of surface CD66b as well as levels of intracellular phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were significantly higher for untreated subjects with EoE vs healthy controls (P < 0.05). Levels of phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were lower in subjects with EoE on therapy versus untreated subjects with EoE (P < 0.05). CONCLUSIONS: Levels of phospho-STAT1 and phospho-STAT6, transcription factors involved in inflammatory processes, were both significantly higher in peripheral eosinophils from untreated (ie, newly diagnosed) subjects with EoE versus subjects with EoE on therapy, healthy controls. Blood-based measurements of CD66b and phospho-STAT levels in peripheral eosinophils may be beneficial for identifying EoE.
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Esofagite Eosinofílica/imunologia , Eosinófilos/imunologia , Ativação Linfocitária , Adolescente , Antígenos CD/metabolismo , Complexo CD3/metabolismo , Moléculas de Adesão Celular/metabolismo , Criança , Pré-Escolar , Esofagite Eosinofílica/metabolismo , Esofagite Eosinofílica/terapia , Eosinófilos/metabolismo , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Imunofenotipagem , Terapia de Imunossupressão , Linfócitos/metabolismo , Masculino , Fosforilação , Processamento de Proteína Pós-Traducional , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Índice de Gravidade de Doença , Adulto JovemAssuntos
Acidose Láctica/diagnóstico , Beriberi/diagnóstico , Colite Ulcerativa/diagnóstico , Nutrição Parenteral Total/efeitos adversos , Índice de Gravidade de Doença , Acidose Láctica/sangue , Acidose Láctica/induzido quimicamente , Adolescente , Beriberi/sangue , Beriberi/induzido quimicamente , Colite Ulcerativa/sangue , Colite Ulcerativa/terapia , Humanos , MasculinoRESUMO
OBJECTIVE: The aim of the study was to investigate whether eosinophils have increased human leukocyte antigen (HLA)-DR expression in subjects with eosinophilic esophagitis (EoE) compared with controls. PATIENTS AND METHODS: Patients who were undergoing an upper endoscopy with biopsies for suspected gastroesophageal reflux disease (GERD) or EoE at Lucile Packard Children's Hospital were enrolled. In total, the blood and tissue samples of 10 healthy controls (HC), 11 subjects with GERD, and 10 with EoE were studied. Multiple tissue staining to identify eosinophils (via eosinophil cationic protein-clone EG2) and major histocompatibility complex class II cell surface receptors (via HLA-DR) was performed via immunohistochemistry. The peripheral blood was analyzed using flow cytometry to detect eosinophil HLA-DR expression among these subjects. RESULTS: In the tissue, a greater proportion of eosinophils expressed HLA-DR among the subjects with EoE (mean 0.83 +/- 0.14, n = 9) relative to those with GERD (mean 0.18 +/- 0.19, n = 8, P < 0.01) and HC (mean 0.18 +/- 0.13, n = 6, P < 0.01). In total, 6 participants (4 HC subjects and 2 subjects with GERD) did not have any eosinophils identified on tissue staining and were unable to be included in the present statistical analysis. In the blood, there was no statistically significant difference in eosinophil HLA-DR expression among HC subjects (mean 415 +/- 217, n = 6), subjects with GERD (mean 507 +/- 429, n = 2), and those with EoE (mean 334 +/- 181, n = 6). CONCLUSIONS: These data demonstrate that the eosinophils from the esophagus of subjects with EoE have increased HLA-DR expression within this tissue.
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Esofagite Eosinofílica/imunologia , Eosinófilos/metabolismo , Esôfago/imunologia , Refluxo Gastroesofágico/imunologia , Antígenos HLA-DR/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Esofagite Eosinofílica/metabolismo , Eosinófilos/imunologia , Esôfago/metabolismo , Feminino , Refluxo Gastroesofágico/metabolismo , Humanos , Lactente , Masculino , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Aluminum (Al) is associated with significant central nervous system toxicity and bone and liver damage. Because Al is a contaminant of parenteral nutrition (PN) components including calcium and phosphate additives, premature infants are at potentially high risk for toxicity. The US Food and Drug Administration (FDA) has mandated PN component product labeling and recommended maximum Al daily exposure limits. The objective of this article is to determine the actual Al content of neonatal PN solutions, compare these values to the calculated amounts from manufacturers' PN product labels, and ascertain whether the actual Al exposure exceeds the FDA recommended maximum of 5 microg . kg(-1) . day(-1). MATERIALS AND METHODS: Samples from 40 neonatal patient PN solutions were selected for sampling and Al content determination. Samples were also taken from 16 manufacturer's component products used in PN formulation. All of the samples were sent to Mayo Laboratories for Al content measurement. The calculated Al concentrations in PN samples were determined from the manufacturer's labeled content. RESULTS: Both measured and calculated Al concentrations exceeded the FDA recommended safe limit of <5 microg . kg(-1) . day(-1). The actual measured Al content was significantly lower than the calculated Al content in both the patient PN solutions and the component product samples. CONCLUSIONS: Al exposure exceeded the FDA recommended maximum limit for all patient samples; however, the actual measured Al content of all the samples was significantly less than the calculated Al content based on manufacturer's labels. These findings suggest that manufacturers label their products with actual Al content at the time of product release rather than at time of expiration. Periodic monitoring of Al levels should be considered with prolonged PN therapy. Changes in manufacturing processes, including the use of better raw materials, are essential to reduce Al contamination to meet FDA mandates.
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Alumínio/análise , Qualidade de Produtos para o Consumidor , Contaminação de Alimentos/análise , Rotulagem de Alimentos , Fórmulas Infantis/química , Nutrição Parenteral , Alumínio/administração & dosagem , Alumínio/efeitos adversos , Rotulagem de Alimentos/legislação & jurisprudência , Regulamentação Governamental , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Estados Unidos , United States Food and Drug AdministrationRESUMO
OBJECTIVES: There are limited data on the role of regulatory T cells (Treg) in the disease pathology of eosinophilic esophagitis (EoE). We tested the differences in Treg in subjects with EoE compared with those with gastroesophageal reflux disease (GERD) and healthy controls (HC). PATIENTS AND METHODS: Pediatric patients evaluated by endoscopy were recruited for our study. Participants were categorized into 3 groups: EoE, GERD, and HC. RNA purified from esophageal biopsies were used for real-time quantitative polymerase chain reaction assays and tested for forkhead box P3 (FoxP3) mRNA expression. Treg were identified as CD4+CD25hiCD127lo cells in peripheral blood and as CD3+/FoxP3+cells in esophageal tissue. RESULTS: Forty-eight subjects were analyzed by real-time quantitative polymerase chain reaction: EoE (n = 33), GERD (n = 7), and HC (n = 8). FoxP3 expression was higher by up to 1.5-fold in the EoE group compared with the GERD and HC groups (P < 0.05). Protein levels of FoxP3 in blood and tissue were then investigated in 21 subjects: EoE (n = 10), GERD (n = 6), and HC (n = 5). The percentage of Treg and their subsets in peripheral blood were not significant between groups (P > 0.05). The amount of Treg in esophageal tissue was significantly greater in the EoE group (mean 10.7 CD3+/FoxP3+cells/high power field [HPF]) compared with the other groups (GERD, mean 1.7 CD3+/FoxP3+cells/HPF and HC, mean 1.6 CD3+/FoxP3+cells/HPF) (P < 0.05). CONCLUSIONS: We show that Treg are increased in esophageal tissue of EoE subjects compared with GERD and HC subjects. The present study illustrates another possible mechanism involved in EoE that implicates impairment of immune homeostasis.
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Esofagite Eosinofílica/imunologia , Esôfago/imunologia , Fatores de Transcrição Forkhead/metabolismo , Refluxo Gastroesofágico/imunologia , Linfócitos T Reguladores/metabolismo , Adolescente , Adulto , Antígenos CD/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Esofagite Eosinofílica/metabolismo , Esôfago/metabolismo , Feminino , Fatores de Transcrição Forkhead/genética , Refluxo Gastroesofágico/metabolismo , Humanos , Lactente , Masculino , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease. METHOD: Real-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8). RESULT: Of the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects. CONCLUSION: We describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.
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BACKGROUND: Children with short bowel syndrome (SBS) receiving home parenteral nutrition (HPN) are predisposed to ambulatory central line-associated bloodstream infection (A-CLABSI). Data describing risk factors of this infection in children are limited. METHODS: Retrospective cohort, single-center, case-crossover study of children ≤18 years old with SBS receiving HPN from January 2012 to December 2016. Univariate and multivariate mixed effect Poisson regression identified the relative risk (RR) of A-CLABSI with proposed risk factors. RESULTS: Thirty-five children were identified; median follow-up was 30 months. A-CLABSI rate was 4.2 per 1000 central line (CL) days. Univariate analysis identified younger age (RR: 0.92 per 12-month increase [95% confidence interval {CI}: 0.85-0.99; P = 0.036]), shorter small intestine length (RR: 0.96 per 10-cm increase [95% CI: 0.92-0.99; P = 0.008]), lower citrulline level (RR: 0.86 per 5-nmol/mL increase [95% CI: 0.75-0.99; P = 0.036]), and recent CL break (RR: 1.55 [95% CI: 1.06-2.28; P = 0.024]) as risk factors for A-CLABSI. Multivariate analysis showed increased A-CLABSI with clinical diagnosis of small intestine bacterial overgrowth (SIBO) (RR: 1.87 [95% CI: 1.1-3.17; P = 0.021]) and CL breaks (RR: 1.49 [95% CI: 1-2.22; P = 0.024]). CONCLUSIONS: Factors influencing gut integrity increase A-CLABSI rate, supporting translocation as an important mechanism and target for prevention. Clinical diagnosis of SIBO increases A-CLABSI rate, but whether dysbiosis or diarrhea is responsible is an area for future research. CL maintenance is crucial, and prevention of breaks would likely decrease A-CLABSI rate.
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Bacteriemia , Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Síndrome do Intestino Curto , Bacteriemia/etiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Criança , Estudos Cross-Over , Humanos , Estudos Retrospectivos , Fatores de Risco , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/terapiaAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Hodgkin/etiologia , Adalimumab , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Criança , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , HumanosAssuntos
Infecções por Citomegalovirus/diagnóstico , Erros de Diagnóstico , Falência Hepática/genética , Falência Hepática/virologia , Deficiência de alfa 1-Antitripsina/diagnóstico , Infecções por Citomegalovirus/complicações , Feminino , Genótipo , Humanos , Lactente , Falência Hepática/cirurgia , Transplante de Fígado , Fenótipo , Viremia/complicaçõesAssuntos
Linfadenite Histiocítica Necrosante/diagnóstico , Doença de Leigh/diagnóstico , Deficiência de Tiamina/diagnóstico , Acidose Láctica/etiologia , Adolescente , Colite Ulcerativa/cirurgia , Dispneia/etiologia , Fadiga/etiologia , Febre/etiologia , Cefaleia/etiologia , Linfadenite Histiocítica Necrosante/terapia , Humanos , Lactente , Doença de Leigh/genética , Masculino , Hipotonia Muscular/etiologia , Complicações Pós-Operatórias , Redução de PesoRESUMO
OBJECTIVES: Unnecessary use of antibiotics is an increasing problem. In this study, we sought to determine the diagnostic accuracy of procalcitonin in predicting bacteremia in children with a central line and fever, and we sought to determine optimal cutoff values to maximize sensitivity and specificity. This is the largest study to date in which procalcitonin is examined as a predictive marker of bacteremia in pediatric patients with a central line and fever. METHODS: We conducted a retrospective cohort study of children aged 0 to 23 years with a central line and fever of 38°C who had procalcitonin and blood cultures drawn before initiation of antibiotics and had no other identified bacterial infection. Patients were also prospectively monitored via a custom-built electronic medical record dashboard for eligibility. RESULTS: There were 523 patients and >2500 procalcitonin values reviewed for eligibility. Of these, 169 (47%) patients and 335 blood cultures with procalcitonin were included. There were 94 (28%) positive bacterial blood cultures and 241 (72%) negative bacterial blood cultures. In bacteremic cultures, the mean procalcitonin level was 9.96 ± 15.96 ng/mL, and the median procalcitonin level was 4.85 ng/mL (interquartile range 18.5). In nonbacteremic cultures, the mean procalcitonin level was 1.23 ± 10.37 ng/mL, and the median procalcitonin level was 0.3 ng/mL (interquartile range 0.7). A receiver operating characteristic analysis indicated a procalcitonin level of ≥0.6 ng/mL as the best cutoff point that produced a sensitivity of 85.6% and a specificity of 65.7% (area under the curve 0.85). CONCLUSIONS: Procalcitonin is a sensitive biomarker in predicting bacteremia in children with a central line and fever.
Assuntos
Bacteriemia , Infecções Relacionadas a Cateter/diagnóstico , Cateteres Venosos Centrais , Febre , Pró-Calcitonina/sangue , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Bacteriemia/etiologia , Biomarcadores/sangue , Hemocultura/métodos , Hemocultura/estatística & dados numéricos , California/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Criança , Diagnóstico Diferencial , Febre/diagnóstico , Febre/etiologia , Humanos , Recém-Nascido , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto JovemRESUMO
We have reported that nordihydroguaiaretic acid (NDGA) inhibits the tyrosine kinase activities of the IGF-1 receptor (IGF-1R) and the HER2 receptor in breast cancer cells. Herein, we studied the effects of NDGA on the growth of estrogen receptor (ER) positive MCF-7 cells engineered to overexpress HER2 (MCF-7/HER2-18). These cells are an in vitro model of HER2-driven, ER positive, tamoxifen resistant breast cancer. NDGA was equally effective at inhibiting the growth of both parental MCF-7 and MCF-7/HER2-18 cells. Half maximal effects for both cell lines were in the 10-15 microM range. The growth inhibitory effects of NDGA were associated with an S phase arrest in the cell cycle and the induction of apoptosis. NDGA inhibited both IGF-1R and HER2 kinase activities in these breast cancer cells. In contrast, Gefitinib, an epidermal growth factor receptor inhibitor but not an IGF-1R inhibitor, was more effective in MCF-7/HER2-18 cells than in the parental MCF-7 cells and IGF binding protein-3 (IGFBP-3) was more effective against MCF-7 cells compared to MCF-7/HER2-18. MCF-7/HER2-18 cells are known to be resistant to the effects of the estrogen receptor inhibitor, tamoxifen. Interestingly, NDGA not only inhibited the growth of MCF-7/HER2-18 on its own, but it also demonstrated additive growth inhibitory effects when combined with tamoxifen. These studies suggest that NDGA may have therapeutic benefits in HER2-positive, tamoxifen resistant, breast cancers in humans.