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1.
Pediatr Dev Pathol ; 27(2): 198-204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37903135

RESUMO

Caseinolytic peptidase B homolog (CLPB) is a mitochondrial protein which is highly expressed in brain. Its deficiency may be associated with severe neonatal encephalopathy. This report describes a case of fatal neonatal encephalopathy associated with biallelic stop-gain mutation in CLPB (NM_001258392.3:c.1159C>T/p.Arg387*). Neurologic disorder encompasses pre- and post-natal features including polyhydramnios, intrauterine growth restriction, respiratory insufficiency, lethargy, excessive startle reflex, generalized hypertonia, and epileptic seizures. Brain macroscopic examination demonstrates frontal severe periventricular cystic leukoencephalopathy, along with mild ex-vacuo tri-ventricular dilatation. The most striking immunohistopathologic features are striato-thalamic neurodegeneration and deep white matter loss associated with strong reactive astrogliosis. This report supports that CLPB deficiency should be considered among the neurometabolic disorders associated with severe prenatal-onset neurologic impairment that may result from cystic leukoencephalopathy.


Assuntos
Epilepsia , Doenças do Recém-Nascido , Leucoencefalopatias , Recém-Nascido , Feminino , Gravidez , Humanos , Endopeptidase Clp/genética , Endopeptidase Clp/metabolismo , Encéfalo/patologia , Epilepsia/metabolismo , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/genética , Leucoencefalopatias/metabolismo , Códon sem Sentido/metabolismo , Doenças do Recém-Nascido/patologia
2.
Fetal Pediatr Pathol ; 42(5): 746-752, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37341537

RESUMO

OBJECTIVE: We evaluated what placental pathologies were associated with adverse preterm births. MATERIALS AND METHODS: Placental findings, classified according to the Amsterdam criteria, were correlated with infant outcomes. The fetal vascular lesions, inflammatory responses other than histological chorioamnionitis (HCA), and placentas with combined maternal vascular malperfusion (MVM) and HCA were excluded. RESULTS: A total of 772 placentas were evaluated. MVM was present in 394 placentas, HCA in 378. Early neonatal sepsis, retinopathy of prematurity, necrotizing enterocolitis, and neonatal death occurred more often in the MVM-only group than HCA-only group. The frequency of bronchopulmonary dysplasia (BPD) was 38.6% in the HCA-only group, and it was 20.3% in the MVM-only group (p < 0.001). HCA was the most important independent risk factor for BPD (OR 3.877, 95% CI 2.831-5.312). CONCLUSION: Inflammation in the placenta influences fetal and neonatal outcomes. HCA is an independent risk factor for BPD.


Assuntos
Corioamnionite , Doenças Fetais , Doenças do Recém-Nascido , Morte Perinatal , Lactente , Recém-Nascido , Gravidez , Feminino , Humanos , Recém-Nascido Prematuro , Placenta/patologia , Inflamação/patologia , Doenças Fetais/patologia , Doenças do Recém-Nascido/patologia , Idade Gestacional
3.
Semin Pediatr Surg ; 32(3): 151309, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37290338

RESUMO

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disorder in premature infants that causes significant morbidity and mortality. Research efforts into the pathogenesis of NEC have discovered a pivotal role for the gram-negative bacterial receptor, Toll-like receptor 4 (TLR4), in its development. TLR4 is activated by dysbiotic microbes within the intestinal lumen, which leads to an exaggerated inflammatory response within the developing intestine, resulting in mucosal injury. More recently, studies have identified that the impaired intestinal motility that occurs early in NEC has a causative role in disease development, as strategies to enhance intestinal motility can reverse NEC in preclinical models. There has also been broad appreciation that NEC also contributes to significant neuroinflammation, which we have linked to the effects of gut-derived pro-inflammatory molecules and immune cells which activate microglia in the developing brain, resulting in white matter injury. These findings suggest that the management of the intestinal inflammation may secondarily be neuroprotective. Importantly, despite the significant burden of NEC on premature infants, these and other studies have provided a strong rationale for the development of small molecules with the capability of reducing NEC severity in pre-clinical models, thus guiding the development of specific anti-NEC therapies. This review summarizes the roles of TLR4 signaling in the premature gut in the pathogenesis of NEC, and provides insights into optimal clinical management strategies based upon findings from laboratory studies.


Assuntos
Enterocolite Necrosante , Doenças do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Mucosa Intestinal/patologia , Receptor 4 Toll-Like/uso terapêutico , Enterocolite Necrosante/terapia , Enterocolite Necrosante/microbiologia , Intestinos , Recém-Nascido Prematuro , Doenças do Recém-Nascido/patologia
4.
Cell Rep Med ; 2(6): 100320, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34195684

RESUMO

Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown. We investigated the role of IL-22 in the neonatal intestine under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning, and both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or lacking the IL-22 receptor in the intestine display a similar susceptibility to NEC, consistent with the lack of endogenous IL-22 during development. Strikingly, treatment with recombinant IL-22 during NEC substantially reduces inflammation and enhances epithelial regeneration. These findings may provide a new therapeutic strategy to attenuate NEC.


Assuntos
Enterocolite Necrosante/imunologia , Interleucinas/genética , Mucosa Intestinal/imunologia , Proteínas Recombinantes/farmacologia , Regeneração/imunologia , Animais , Animais Recém-Nascidos , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL2/genética , Quimiocina CXCL2/imunologia , Modelos Animais de Doenças , Enterocolite Necrosante/tratamento farmacológico , Enterocolite Necrosante/microbiologia , Enterocolite Necrosante/patologia , Microbioma Gastrointestinal/imunologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Recém-Nascido , Doenças do Recém-Nascido/imunologia , Doenças do Recém-Nascido/microbiologia , Doenças do Recém-Nascido/patologia , Recém-Nascido Prematuro , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucinas/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Knockout , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Receptores de Interleucina/genética , Receptores de Interleucina/imunologia , Regeneração/genética , Transdução de Sinais , Desmame , Interleucina 22
5.
Front Endocrinol (Lausanne) ; 12: 673755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093443

RESUMO

Background: Mutations in GLIS3 cause a rare syndrome characterized by neonatal diabetes mellitus (NDM), congenital hypothyroidism, congenital glaucoma and cystic kidneys. To date, 14 mutations in GLIS3 have been reported, inherited in an autosomal recessive manner. GLIS3 is a key transcription factor involved in ß-cell development, insulin expression, and development of the thyroid, eyes, liver and kidneys. Cases: We describe non-identical twins born to consanguineous parents presenting with NDM, congenital hypothyroidism, congenital glaucoma, hepatic cholestasis, cystic kidney and delayed psychomotor development. Sequence analysis of GLIS3 identified a novel homozygous nonsense mutation, c.2392C>T, p.Gln798Ter (p.Q798*), which results in an early stop codon. The diabetes was treated with a continuous subcutaneous insulin infusion pump and continuous glucose monitoring. Fluctuating blood glucose and intermittent hypoglycemia were observed on follow-up. Conclusions: This report highlights the importance of early molecular diagnosis for appropriate management of NDM. We describe a novel nonsense mutation of GLIS3 causing NDM, extend the phenotype, and discuss the challenges in clinical management. Our findings provide new areas for further investigation into the roles of GLIS3 in the pathophysiology of diabetes mellitus.


Assuntos
Biomarcadores/sangue , Hipotireoidismo Congênito/patologia , Proteínas de Ligação a DNA/genética , Diabetes Mellitus/patologia , Doenças do Recém-Nascido/patologia , Mutação , Proteínas Repressoras/genética , Transativadores/genética , Glicemia/análise , Pré-Escolar , Hipotireoidismo Congênito/etiologia , Hipotireoidismo Congênito/metabolismo , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Recém-Nascido , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/metabolismo , Masculino , Fenótipo , Prognóstico
6.
Am J Surg ; 222(5): 1034-1039, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33958200

RESUMO

BACKGROUND: Abdominal ultrasound (AUS) is a promising adjunct to abdominal x-ray (AXR) for evaluating necrotizing enterocolitis (NEC). We developed a multivariable risk score incorporating AUS to predict surgical NEC. METHODS: 83 patients were evaluated by AXR and AUS for suspected NEC. A subset had surgical NEC. Multivariate logistic regression determined predictors of surgical NEC, which were incorporated into a risk score. RESULTS: 14/83 patients (16.9%) had surgical NEC. 10/83 (12.0%) patients required acute intervention, while 4/83 (4.8%) patients only required delayed surgery. Four predictors of surgical NEC were identified: abdominal wall erythema (OR: 8.2, p = 0.048), portal venous gas on AXR (OR: 29.8, p = 0.014), and echogenic free fluid (OR: 17.2, p = 0.027) and bowel wall thickening (OR: 12.5, p = 0.030) on AUS. A multivariable risk score incorporating these predictors had excellent area-under-the-curve of 0.937 (95% CI: 0.879-0.994). CONCLUSIONS: AUS, as an adjunct to physical exam and AXR, has utility for predicting surgical NEC.


Assuntos
Enterocolite Necrosante/diagnóstico por imagem , Abdome/diagnóstico por imagem , Parede Abdominal/diagnóstico por imagem , Parede Abdominal/patologia , Área Sob a Curva , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/patologia , Enterocolite Necrosante/cirurgia , Eritema/complicações , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico por imagem , Doenças do Recém-Nascido/patologia , Doenças do Recém-Nascido/cirurgia , Modelos Logísticos , Masculino , Projetos Piloto , Radiografia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Ultrassonografia
7.
Lipids Health Dis ; 20(1): 38, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879184

RESUMO

BACKGROUND: Neonatal severe hypertriglyceridemia is rarely reported in the literature and there is no consensus for hypertriglyceridemia management at this age group. METHODS: The index case is a 4-week-old male infant with severe hypertriglyceridemia accidentally discovered during a circumcision surgery. His clinical and genetic characteristics and his successful management strategy are described. Furthermore, a detailed ophthalmological examination of the proband was conducted at 3 and 6 months of age using Fourier-domain-optical coherence tomography. RESULTS: Triglycerides level at presentation was extremely high 33,727 mg/dL (380.8 mmol/L). Two sessions of exchange blood transfusion on two consecutive days successfully reduced triglycerides to 382 mg/dL (4.3 mmol/L) with no adverse effects. The infant was discharged 3 days later. At discharge, the mother was advised to continue breastfeeding together with a medium-chain triglycerides formula. Satisfactory growth parameters and lipid profile values were obtained for a follow-up duration of 5 months with no reported attacks of acute pancreatitis. Lipoprotein lipase deficiency was confirmed by the detection of the LPL homozygous pathogenic variant c.805G > A; p.(Glu269Lys). Early corneal and macular lesions were detected and persisted on follow-up despite relatively good lipemic control. CONCLUSION: This case highlights the importance of the early discovery of severe hypertriglyceridemia during the neonatal period, which is needed for prompt management and prevention of severe complications. Rationalized breastfeeding can be tolerated within the diet plan of the disease with satisfactory outcomes. To our knowledge, it is the first study reporting early corneal and macular affection by severe hypertriglyceridemia in a neonate. Prolonged follow-up is needed to determine the extent of ophthalmological lesions.


Assuntos
Hiperlipoproteinemia Tipo IV/terapia , Doenças do Recém-Nascido/terapia , Retina/patologia , Transfusão Total , Humanos , Hiperlipoproteinemia Tipo IV/patologia , Recém-Nascido , Doenças do Recém-Nascido/patologia , Masculino , Tomografia de Coerência Óptica , Triglicerídeos/sangue
9.
Invest New Drugs ; 39(3): 775-784, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33411210

RESUMO

Infantile hemangioma is the most common vascular tumor of childhood. It is characterized by clinical expansion of endothelial cells and promoted by angiogenic factors. Luteolin is a flavonoid compound that carries anti-cancer and anti-angiogenesis properties. The study aimed to investigate the effect of luteolin in treating infantile hemangioma. We first tested the effect of luteolin on cell proliferative potential and VEGFA expression in hemangioma-derived stem cells (HemSCs). We then examined the efficacy of systemic application of luteolin in a murine hemangioma model. We then identified the downstream factor regulated by luteolin in HemSCs and validated its causative relationship with knock-down method in both in vitro and in vivo models. We also investigated the protein expression change of this targeting factor in proliferating hemangiomas. Luteolin inhibited HemSC growth and suppressed VEGF-A expression in a dose-dependent manner. Luteolin inhibited microvessel formation and de novo vasculogenesis in the murine model. FZD6 was induced by luteolin and exerted the anti-angiogenesis effect in our tumor models. Lastly, FZD6 level was repressed in the clinical tissues of human proliferating hemangiomas. Luteolin is a promising new agent to treat infantile hemangioma. Targeting the Wnt pathway may represent a potential therapeutic strategic to inhibit angiogenesis in proliferating hemangiomas.


Assuntos
Antineoplásicos/uso terapêutico , Receptores Frizzled/antagonistas & inibidores , Hemangioma/tratamento farmacológico , Doenças do Recém-Nascido/tratamento farmacológico , Luteolina/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Hemangioma/genética , Hemangioma/metabolismo , Hemangioma/patologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/metabolismo , Doenças do Recém-Nascido/patologia , Luteolina/farmacologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos Nus , Microvasos/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
10.
Diagn Cytopathol ; 49(4): 533-539, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33369154

RESUMO

OBJECTIVE: Sternocleidomastoid tumor of infancy (SCMI) is a rare, benign self-limiting condition which occurs in the perinatal period. The goal of our study is to highlight clinicoradiological and cytopathological findings in these cases. MATERIAL AND METHODS: A study was done at a tertiary level hospital, from January 2016 to December 2019. Thirteen cases were studied, out of which 11 were clinically suspected cases of SCMI tumor and two cases were clinically suspected as cervical lymph node tuberculosis which were finally diagnosed as SCMI on fine needle aspiration cytology (FNAC) evaluation. Drs. N. K., S. Z., S. S. K., and S. R. independently reviewed the original diagnosis. Clinical, ultrasonographical, and cytopathological features are highlighted along with follow-up of the cases. RESULTS: There were a total of 13 cases, out of which 11 cases were neonates and two cases were more than 1 month of age (2 months and 2.5 months). Male: female ratio was 10:3 and swelling was present more commonly on the right side of the neck. Ultrasonography predominantly showed non-cystic, bulky, and heterogenous echotexture of the sternocleidomastoid muscle. Smears were moderately cellular showing mainly singly scattered oval to spindle shaped fibroblasts along with degenerating and regenerating muscle fibers. CONCLUSION: FNAC along with adequate clinic-radiological correlation aids in early and reliable diagnosis and can help curtail complications.


Assuntos
Fibroma/patologia , Neoplasias de Cabeça e Pescoço/patologia , Doenças do Recém-Nascido/patologia , Músculos do Pescoço/patologia , Biópsia por Agulha Fina/métodos , Biópsia por Agulha Fina/normas , Diagnóstico Diferencial , Feminino , Fibroblastos/patologia , Fibroma/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico por imagem , Masculino , Fibras Musculares Esqueléticas/patologia , Músculos do Pescoço/diagnóstico por imagem , Ultrassonografia/métodos
11.
J Med Genet ; 58(4): 247-253, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32487539

RESUMO

INTRODUCTION: TMEM16A is a calcium-activated chloride channel expressed in various secretory epithelia. Two siblings presented in early infancy with reduced intestinal peristalsis and recurrent episodes of haemorrhagic diarrhoea. In one of them, the episodes were characterised by hepatic pneumatosis with gas bubbles in the portal vein similar to necrotising enterocolitis of the newborn. METHODS: Exome sequencing identified a homozygous truncating pathogenic variant in ANO1. Expression analysis was performed using reverse transcription PCR, western blot and immunohistochemistry. Electrophysiological and cell biological studies were employed to characterise the effects on ion transport both in patient respiratory epithelial cells and in transfected HEK293 cells. RESULTS: The identified variant led to TMEM16A dysfunction, which resulted in abolished calcium-activated Cl- currents. Secondarily, CFTR function is affected due to the close interplay between both channels without inducing cystic fibrosis (CF). CONCLUSION: TMEM16A deficiency is a potentially fatal disorder caused by abolished calcium-activated Cl- currents in secretory epithelia. Secondary impairment of CFTR function did not cause a CF phenotyp, which may have implications for CF treatment.


Assuntos
Anoctamina-1/genética , Canais de Cloreto/genética , Predisposição Genética para Doença , Doenças do Recém-Nascido/genética , Proteínas de Neoplasias/genética , Anoctamina-1/deficiência , Transporte Biológico/genética , Cálcio/metabolismo , Canais de Cloreto/metabolismo , Cloretos/metabolismo , Fibrose Cística/genética , Fibrose Cística/patologia , Feminino , Células HEK293 , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/patologia , Masculino , Proteínas de Neoplasias/deficiência
12.
Semin Pediatr Surg ; 29(4): 150939, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32861443

RESUMO

Liver and biliary pathology in the neonate are rare and include a broad range of structural, neoplastic, infectious, genetic, and metabolic diseases. While most conditions present postnatally, antenatal detection is increasing given recent advances in antenatal imaging capabilities. In certain structural or obstructive liver diseases, antenatal detection now proves essential to help guide treatment and prevent morbidity. We review the epidemiology, pathophysiology, common antenatal diagnostic findings, and recommendations for surgical liver and biliary pathology in the neonate.


Assuntos
Doenças Biliares/diagnóstico , Doenças Fetais/diagnóstico , Doenças do Recém-Nascido/diagnóstico , Hepatopatias/diagnóstico , Diagnóstico Pré-Natal , Doenças Biliares/epidemiologia , Doenças Biliares/patologia , Doenças Biliares/terapia , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/patologia , Doenças Fetais/terapia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/patologia , Doenças do Recém-Nascido/terapia , Hepatopatias/epidemiologia , Hepatopatias/patologia , Hepatopatias/terapia , Gravidez
13.
J Cell Physiol ; 235(4): 3690-3697, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31566734

RESUMO

Neonatal pneumonia is a high neonatal mortality disease. We studied the function and mechanism of long noncoding RNA myocardial infarction-associated transcript 2 (lncRNA MIAT2) on lipopolysaccharide (LPS)-induced inflammation in WI-38 cells. Cell Counting Kit-8 and apoptosis assay were respectively used to detect the functions of LPS, MIAT2, and microRNA-15 (miR-15) on viability and apoptosis. MIAT2 and miR-15 expressions were changed by cell transfection. Moreover, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot, and enzyme-linked immunosorbent assay were used to detect the expressions of interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1). The levels of Bax, cleaved-caspase-3, and cell pathways-related proteins were tested by western blot. Besides, the levels of miR-15 and MIAT2 were tested by RT-qPCR. We found that LPS declined cell viability and heightened apoptosis and levels of Bax, cleaved-caspase-3, IL-6, and MCP-1. MIAT2 was negatively regulated by LPS and it alleviated LPS-induced damage. Furthermore, MIAT2 reversely regulated miR-15 and miR-15 mimic could reverse the effects of MIAT2. Finally, MIAT2 restrained the p38MAPK and NF-κB pathways by downregulating miR-15. In conclusion, MIAT2 alleviated LPS-induced inflammation damage in WI-38 cells by sponging miR-15 via p38MAPK and NF-κB pathways.


Assuntos
Inflamação/genética , MicroRNAs/genética , Pneumonia/genética , RNA Longo não Codificante/genética , Apoptose , Caspase 3/genética , Linhagem Celular , Sobrevivência Celular/genética , Quimiocina CCL2 , Regulação da Expressão Gênica/genética , Humanos , Recém-Nascido , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/patologia , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Pneumonia/patologia , Transdução de Sinais/genética , Fator de Transcrição RelA/genética , Proteína X Associada a bcl-2/genética
14.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 37(3): 297-304, July-Sept. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1041348

RESUMO

ABSTRACT Objective: To evaluate the prevalence of neonatal dermatoses in the early neonatal period and to associate them with neonatal, demographic and obstetric variables. Methods: A cross-sectional study with neonates and their respective mothers, who were hospitalized in a public maternity hospital in Curitiba, PR, Brazil. Data collection was performed using information present in the medical records and a physical examination of the newborn during the period between April 2015 and May 2016. Results: 350 neonates were evaluated. 54.8% were male, and 94.8% (332/350) presented a dermatosis. Among them, 84.6% had, concomitantly, two or more dermatoses. A total of 23 types of dermatoses were diagnosed. The most prevalent were: sebaceous hyperplasia (66%); fluff (42.6%); and salmon patches (41.4%). The mean age of the mothers was 24.9±4.9 years old, and they were predominately white (57.7%). Vernix caseosa was associated with the female gender (p=0.034). Nonwhite mothers were associated with genital hyperpigmentation (p=0.03) and Mongolian spots (p=0.001). Physiological flaking was associated with cesarean deliveries (p=0.03) and a gestational age of over 40 weeks (p=0.054). Salmon patches was associated with primiparity (p=0.0001). Conclusions: There was a high prevalence of neonatal dermatosis in the studied population. Each newborn had, on average, three different dermatoses. Dermatosis in neonates was associated with primiparity, nonwhites, a gestational age of over 40 weeks, and the sex of the newborn.


RESUMO Objetivo: Avaliar a prevalência de dermatoses no período neonatal precoce e associar sua ocorrência a variáveis neonatais, demográficas e obstétricas. Métodos: Estudo transversal com neonatos e respectivas puérperas internados em alojamento conjunto de uma maternidade pública de Curitiba (PR). A coleta de dados foi realizada por meio de informações presentes nos prontuários e no exame físico do recém-nato durante o período de abril de 2015 a maio de 2016. Resultados: Foram avaliados 350 recém-nascidos, 54,8% do sexo masculino, e 332 (94,8%) apresentaram dermatoses. Desses 332, 84,6% tiveram, concomitantemente, duas ou mais dermatoses. Diagnosticou-se o total de 23 tipos de dermatoses, sendo mais prevalentes: hiperplasia sebácea (66,6%); lanugem (42,6%); e mancha salmão (41,4%). A média de idade das puérperas foi de 24,9±4,9 anos, com predomínio de etnia branca (57,7%). Vérnix foi associado a sexo feminino (p=0,034). A etnia materna não branca associou-se à hiperpigmentação genital (p=0,030) e mancha mongólica (p=0,001). A descamação fisiológica associou-se ao parto cesáreo (p=0,030) e à idade gestacional acima de 40 semanas (p=0,054); e mancha salmão, à primiparidade (p=0,0001). Conclusões: Verificou-se alta prevalência de dermatose neonatal na população estudada, sendo cada recém-nascido acometido em média por três tipos. Houve associação da presença de dermatoses com primiparidade, mães não brancas, idade gestacional superior a 40 semanas e sexo do neonato.


Assuntos
Humanos , Masculino , Feminino , Gravidez , Recém-Nascido , Adulto , Paridade/fisiologia , Dermatopatias/epidemiologia , Doenças do Recém-Nascido/epidemiologia , Dermatopatias/patologia , Brasil/epidemiologia , Prevalência , Estudos Transversais , Idade Gestacional , Doenças do Recém-Nascido/patologia , Mães
15.
Nat Commun ; 10(1): 3494, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375667

RESUMO

Necrotizing enterocolitis (NEC) is an idiopathic, inflammatory bowel necrosis of premature infants. Clinical studies have linked NEC with antecedent red blood cell (RBC) transfusions, but the underlying mechanisms are unclear. Here we report a neonatal murine model to investigate this association. C57BL/6 mouse pups rendered anemic by timed phlebotomy and then given RBC transfusions develop NEC-like intestinal injury with prominent necrosis, inflammation, and submucosal edema/separation of the lamina propria in the ileocecal region and colon within 12-24 h. The anemic intestine is infiltrated by inflammatory macrophages, which are activated in situ by RBC transfusions via a Toll-like receptor (TLR)-4-mediated mechanism and cause bowel injury. Chelation of RBC degradation products with haptoglobin, absence of TLR4, macrophage depletion, and inhibition of macrophage activation is protective. Intestinal injury worsens with increasing severity and the duration of anemia prior to transfusion, indicating a need for the re-evaluation of current transfusion guidelines for premature infants.


Assuntos
Anemia/complicações , Enterocolite Necrosante/etiologia , Transfusão de Eritrócitos/efeitos adversos , Doenças do Recém-Nascido/etiologia , Anemia/terapia , Animais , Animais Recém-Nascidos , Ceco/patologia , Colo/patologia , Modelos Animais de Doenças , Enterocolite Necrosante/patologia , Humanos , Íleo/patologia , Recém-Nascido , Doenças do Recém-Nascido/patologia , Recém-Nascido Prematuro , Mucosa Intestinal/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo
17.
Sci Rep ; 9(1): 4438, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30872799

RESUMO

Our goal was to assess whether quantitative fetal fibronectin (qfFN) is associated with spontaneous preterm birth (sPTB) after laser surgery for twin-twin transfusion syndrome (TTTS). qfFN was collected within 24 hours before and after laser surgery. Aims were: (1) To determine if qfFN changed with operative fetoscopy; and (2) To estimate the number of patients needed to study the predictive value of qfFN for sPTB <28 and <32 weeks. Results are reported as median (range). Among 49 patients, there was no net difference in qfFN levels after laser surgery [0.0 ng/mL (-37 to +400), p = 0.6041]. However, patients with a qfFN increase >10 ng/mL were 19 times more likely to undergo sPTB at <28 weeks (OR = 19.5). We determined that 383 and 160 patients would be needed to achieve adequate statistical power for qfFN to be predictive of sPTB at a GA <28 weeks and <32 weeks, respectively. In conclusion, laser surgery did not alter the qfFN level within the entire cohort, but qfFN may be useful in identifying a subset of patients at increased risk of preterm delivery.


Assuntos
Transfusão Feto-Fetal/cirurgia , Fibronectinas/metabolismo , Doenças do Recém-Nascido/diagnóstico , Terapia a Laser/efeitos adversos , Nascimento Prematuro/diagnóstico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/metabolismo , Doenças do Recém-Nascido/patologia , Gravidez , Gravidez de Gêmeos , Nascimento Prematuro/etiologia , Nascimento Prematuro/metabolismo , Nascimento Prematuro/patologia , Estudos Prospectivos , Estudos em Gêmeos como Assunto
18.
Eur J Paediatr Neurol ; 23(2): 280-287, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30744982

RESUMO

BACKGROUND: Punctate white matter lesions (PWMLs) are small focal patches of increased signal intensity (SI) on T1- and decreased SI on T2-weighted magnetic resonance imaging (MRI). To date, there have been few reports of PWMLs in term born infants. OBJECTIVE: To identify associated diagnoses and factors predictive of clinical outcome in (near) term infants with PWMLs. METHODS: MRI studies and clinical records of (near) term infants, with PWMLs on MRI scans performed in two institutions in the first 28 postnatal days were reviewed. The PWMLs were classified according to their number, pattern and distribution. The medical records were examined to assess the associated diagnoses and determine the neurodevelopmental outcome at >12 months of age. Infants with congenital heart defect(s), those who had neonatal surgery, or those with perinatal arterial ischemic stroke were not eligible for the study. RESULTS: Forty-two (near) term infants with PWMLs were included. The major clinical association was perinatal asphyxia, present in 19/42 (45%). Ten (24%) had a history of seizures unrelated to asphyxia or a genetic diagnosis. Eleven (26%) had pathological genetic mutations. Other diagnoses, without seizures were identified in 2 (5%). The lesion load of PWMLs was high (>6) in 30/42 (71%). Evidence of irreversible white matter injury was present in 5 infants who had follow-up MRI performed between 18 and 24 months of age, because of clinical concerns. Five infants died and 37 had follow-up at a median age of 24 months. Neurodevelopmental outcome was poorest amongst 6 infants (16%) whose PWMLs occurred in the setting of a genetic disorder. CONCLUSION: PWMLs in (near) term infants represent white matter injury that may evolve into gliosis and/or white matter loss. Infants with PWMLs in the setting of a genetic disorder appeared at most risk of a poor outcome.


Assuntos
Encéfalo/patologia , Doenças do Recém-Nascido/patologia , Substância Branca/patologia , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Substância Branca/diagnóstico por imagem
19.
Am J Hum Genet ; 104(2): 213-228, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30639323

RESUMO

Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping ∼2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung.


Assuntos
Fator 10 de Crescimento de Fibroblastos/genética , Doenças do Recém-Nascido/genética , Doenças do Recém-Nascido/mortalidade , Pneumopatias/genética , Pneumopatias/mortalidade , Transdução de Sinais/genética , Proteínas com Domínio T/genética , Variações do Número de Cópias de DNA/genética , Feminino , Fator 10 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Recém-Nascido/metabolismo , Doenças do Recém-Nascido/patologia , Pulmão/embriologia , Pulmão/crescimento & desenvolvimento , Pneumopatias/metabolismo , Pneumopatias/patologia , Masculino , Herança Materna , Organogênese , Herança Paterna , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Proteínas com Domínio T/metabolismo
20.
Pediatr Blood Cancer ; 66(4): e27603, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30609257

RESUMO

Hepatocellular malignant neoplasm, not otherwise specified (HCN-NOS) is a provisional entity describing a subset of rare malignant pediatric liver tumors with overlapping features of hepatoblastoma and hepatocellular carcinoma. We present a case illustration of metastatic HCN-NOS successfully treated with a backbone of hepatoblastoma chemotherapy, pulmonary metastastectomy, and liver transplantation, along with a literature review of the clinical outcomes of HCN.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatoblastoma/cirurgia , Doenças do Recém-Nascido/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Carcinoma Hepatocelular/patologia , Hepatoblastoma/patologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/patologia , Neoplasias Hepáticas/patologia , Masculino , Metástase Neoplásica
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