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BACKGROUND: We recently reported on a late preterm infant born at 36 weeks' gestation with serious arrhythmia due to hyperkalemia associated with long-term maternal ritodrine administration. It is unknown whether ritodrine alone increases the risk of neonatal hyperkalemia in infants born at 34-36 weeks' gestation. METHODS: This single-center, retrospective, cohort study enrolled late preterm infants (34-36 gestational weeks) born between 2004 and 2018. Cases with maternal magnesium sulfate use were not sufficient for statistical analysis and so were excluded from the study. Risk factors for the occurrence of hyperkalemia were determined based on clinical relevance and previous reports. RESULTS: In all, 212 late preterm infants with maternal ritodrine use and 400 infants without tocolysis were included in the study. Neonatal hyperkalemia occurred in 5.7% (12/212) in the ritodrine group and 1.8% (7/400) in the control group. The risk of neonatal hyperkalemia was significantly increased by maternal ritodrine administration with a crude odds ratio (OR) of 3.37 (95% confidence interval [CI]: 1.30-8.69; p < 0.01) and an adjusted OR of 3.71 (95% CI: 1.41-9.74; p < 0.01) on multivariable analysis. Long-term tocolysis (≥28 days) with ritodrine increased the risk of neonatal hyperkalemia with 9.3% (11/118) of infants developing hyperkalemia (adjusted OR 4.86; 95% CI: 1.59-14.83; p < 0.01). Neonatal hyperkalemia was not found within 2 weeks of ritodrine administration. CONCLUSION: This research suggests that late preterm infants born after long-term ritodrine administration are at risk of neonatal hyperkalemia and require special attention.
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Hiperpotasemia , Trabajo de Parto Prematuro , Ritodrina , Embarazo , Lactante , Femenino , Recién Nacido , Humanos , Ritodrina/efectos adversos , Trabajo de Parto Prematuro/inducido químicamente , Estudios Retrospectivos , Estudios de Cohortes , Hiperpotasemia/inducido químicamente , Hiperpotasemia/epidemiología , Recien Nacido PrematuroRESUMEN
Costello syndrome (CS) is an autosomal-dominant disorder characterized by distinctive facial features, hypertrophic cardiomyopathy, skeletal abnormalities, intellectual disability, and predisposition to cancers. Germline variants in HRAS have been identified in patients with CS. Intragenic HRAS duplications have been reported in three patients with a milder phenotype of CS. In this study, we identified two known HRAS variants, p.(Glu63_Asp69dup), p.(Glu62_Arg68dup), and one novel HRAS variant, p.(Ile55_Asp57dup), in patients with CS, including a patient with craniosynostosis. These intragenic duplications are located in the G3 domain and the switch II region. Cells expressing cDNA with these three intragenic duplications showed an increase in ELK-1 transactivation. Injection of wild-type or mutant HRAS mRNAs with intragenic duplications in zebrafish embryos showed significant elongation of the yolk at 11 h postfertilization, which was improved by MEK inhibitor treatment, and a variety of developmental abnormalities at 3 days post fertilization was observed. These results indicate that small in-frame duplications affecting the G3 domain and switch II region of HRAS increase the activation of the ERK pathway, resulting in developmental abnormalities in zebrafish or patients with CS.
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Anomalías Múltiples , Síndrome de Costello , Anomalías Múltiples/genética , Animales , Síndrome de Costello/genética , Humanos , Sistema de Señalización de MAP Quinasas , Fenotipo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Pez Cebra/genéticaRESUMEN
BACKGROUND: Urinary titin N-fragment levels have been used to assess the catabolic state, and we used this biomarker to evaluate the catabolic state of infants. METHODS: We retrospectively measured urinary titin N-fragment levels of urinary samples. The primary outcome was its changes according to postmenstrual age. The secondary outcomes included differences between gestational age, longitudinal change after birth, influence on growth, and relationship with blood tests. RESULTS: This study included 219 patients with 414 measurements. Urinary titin N-fragment exponentially declined with postmenstrual age. These values were 12.5 (7.1-19.6), 8.1 (5.1-13.0), 12.8 (6.0-21.3), 26.4 (16.4-52.0), and 81.9 (63.3-106.4) pmol/mg creatinine in full, late, moderate, very, and extremely preterm infants, respectively (p < 0.01). After birth, urinary levels of titin N-fragment exponentially declined, and the maximum level within a week was associated with the time to return to birth weight in preterm infants (ρ = 0.39, p < 0.01). This was correlated with creatine kinase in full-term infants (ρ = 0.58, p < 0.01) and with blood urea nitrogen in preterm infants (ρ = 0.50, p < 0.01). CONCLUSIONS: The catabolic state was increased during the early course of the postmenstrual age and early preterm infants. IMPACT: Catabolic state in infants, especially in preterm infants, was expected to be increased, but no study has clearly verified this. In this retrospective study of 219 patients with 414 urinary titin measurements, the catabolic state was exponentially elevated during the early postmenstrual age. The use of the urinary titin N-fragment clarified catabolic state was prominently increased in very and extremely preterm infants.
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Recien Nacido Prematuro , Peso al Nacer , Conectina/orina , Edad Gestacional , Humanos , Lactante , Recién Nacido , Estudios RetrospectivosRESUMEN
Many transgender men receive testosterone therapy to achieve virilization. The therapy is often mistaken for having a contraceptive effect because it causes amenorrhea. However, some treated patients become pregnant, which is not well known. A 25-year-old transgender man who had received testosterone for 3 years had an unplanned pregnancy during discontinuation of treatment. He was unaware of his pregnancy, resumed testosterone, and continued treatment until pregnancy was confirmed. His female child was exposed to androgens during the fetal period; thus, careful, long-term observation was required. He developed insomnia and depression during the postpartum, and giving birth made it difficult for him to change his family register to male. Transgender men can become pregnant through sexual intercourse with biological men, even during hormone replacement therapy, so correct contraception is necessary to avoid unwanted pregnancies. Transgender sex education is important to increase awareness of this issue among individuals and medical professionals.
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Personas Transgénero , Adulto , Andrógenos , Niño , Anticoncepción , Femenino , Humanos , Masculino , Embarazo , Embarazo no Planeado , Testosterona/efectos adversosRESUMEN
We report a very rare case of monochorionic dizygotic twins conceived spontaneously. The fetuses were sex-discordant in ultrasonography despite being monochorionic twins. After birth, the girl and boy showed normal phenotypes but they showed blood chimerism in karyotype and blood group type.
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Antígenos de Grupos Sanguíneos , Gemelos Dicigóticos , Quimerismo , Femenino , Humanos , Cariotipo , Cariotipificación , Masculino , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genéticaRESUMEN
BACKGROUND: Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this agent, including newborn hypoglycemia and hypokalemia, as well as maternal hypokalemia and rebound hyperkalemia; however, cases of neonatal rebound hyperkalemia are not described in the literature. CASE PRESENTATION: A male infant born at 36 weeks of gestation by cesarean section at a local maternity clinic suddenly entered cardiopulmonary arrest with ventricular tachycardia and fibrillation due to hyperkalemia (K+, 8.7 mmol/L). No monitoring, examination of blood electrolyte levels, or infusions had been performed prior to this event. Maternal infusion of ritodrine (maximum dose, 170 µg/min) had been performed for 7 weeks prior to cesarean section. After resuscitation combined with calcium gluconate, the infant died at 4 months old due to serious respiratory failure accompanied by acute lung injury following shock. No cause of hyperkalemia other than rebound hyperkalemia associated with ritodrine was identified. CONCLUSIONS: This case report serves as a warning regarding the potential risk of neonatal rebound hyperkalemia in association with maternal long-term ritodrine administration.
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Hiperpotasemia , Trabajo de Parto Prematuro , Ritodrina , Tocolíticos , Cesárea , Femenino , Humanos , Hiperpotasemia/inducido químicamente , Lactante , Recién Nacido , Masculino , Embarazo , Ritodrina/efectos adversos , Tocolíticos/efectos adversosRESUMEN
BACKGROUND: We recently demonstrated that preterm neonates have higher urinary angiotensinogen (AGT) levels than full-term neonates. Here, we tested the hypothesis that enhanced neonatal AGT expression is associated with intrarenal renin-angiotensin system (RAS) status during kidney development. METHODS: We prospectively recruited neonates born at our hospital and healthy children with minor glomerular abnormalities between April 2013 and March 2017. We measured neonatal plasma and urinary AGT levels at birth and 1 year later and assessed renal AGT expression in kidney tissues from neonates and healthy children using immunohistochemical (IHC) analysis. RESULTS: Fifty-four neonates and eight children were enrolled. Although there were no changes in plasma AGT levels, urinary AGT levels were significantly decreased 1 year after birth. Urinary AGT levels at birth were inversely correlated with gestational age, and urinary AGT levels at birth and 1 year later were inversely correlated with estimated glomerular filtration rate 1 year after birth. IHC analysis showed that renal AGT expression in neonates was higher than that in healthy children and inversely correlated with gestational age. CONCLUSIONS: Enhanced AGT expression and urinary AGT excretion may reflect intrarenal RAS activation associated with kidney development in utero.
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Angiotensinógeno/sangre , Angiotensinógeno/orina , Riñón/crecimiento & desarrollo , Angiotensinógeno/metabolismo , Biopsia , Niño , Preescolar , Creatinina/orina , Femenino , Edad Gestacional , Tasa de Filtración Glomerular , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Riñón/patología , Riñón/fisiología , Glomérulos Renales/anomalías , Masculino , Parto , Estudios ProspectivosAsunto(s)
Ascitis Quilosa , Hipofosfatasia , Lactante , Humanos , Hipofosfatasia/complicaciones , Hipofosfatasia/diagnóstico , Hipofosfatasia/terapia , Terapia de Reemplazo Enzimático , Ascitis Quilosa/diagnóstico , Ascitis Quilosa/etiología , Ascitis Quilosa/terapia , Respiración , Inmunoglobulina G , Fosfatasa Alcalina/uso terapéuticoAsunto(s)
Fiebre/etiología , Hemangioma/congénito , Hemangioma/diagnóstico por imagen , Hepatomegalia/congénito , Hepatomegalia/diagnóstico por imagen , Neoplasias Hepáticas/congénito , Niño , Fiebre/diagnóstico por imagen , Hemangioma/complicaciones , Hepatomegalia/complicaciones , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: Recently, we demonstrated that urinary angiotensinogen (AGT) levels are increased and reflect intrarenal renin-angiotensin system (RAS) status in pediatric patients with chronic glomerulonephritis. Therefore, this study was performed to test the hypothesis that urinary AGT (UAGT) levels provide a specific index of intrarenal RAS status associated with RAS blockade treatment in pediatric IgA nephropathy (IgAN) patients. METHODS: We measured plasma and UAGT levels and urinary transforming growth factor beta (TGF-ß) levels, after which we performed immunohistochemical analysis of AGT, angiotensin II (Ang II), and TGF-ß in 24 pediatric IgAN patients treated with RAS blockades for 2 years. Paired tests were used to analyze the changes from baseline to study end. RESULTS: Although there was no change in plasma AGT levels, UAGT and TGF-ß levels were significantly decreased after RAS blockade, which was accompanied by the expression levels of AGT, Ang II, and TGF-ß, as well as the magnitude of glomerular injury. Baseline UAGT levels positively correlated with diastolic blood pressure, urinary protein levels, scores for mesangial hypercellularity, and the expression levels of AGT, Ang II, and TGF-ß in renal tissues. CONCLUSIONS: These data indicate that UAGT is a useful biomarker of intrarenal RAS activation, which is associated with glomerular injury during RAS blockade in pediatric IgAN patients.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Angiotensinógeno/orina , Glomerulonefritis por IGA/tratamiento farmacológico , Riñón/efectos de los fármacos , Sistema Renina-Angiotensina/efectos de los fármacos , Adolescente , Angiotensina II/sangre , Angiotensina II/orina , Angiotensinógeno/sangre , Biomarcadores/sangre , Biomarcadores/orina , Biopsia , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/fisiopatología , Glomerulonefritis por IGA/orina , Humanos , Inmunohistoquímica , Riñón/metabolismo , Riñón/patología , Riñón/fisiopatología , Masculino , Valor Predictivo de las Pruebas , Factores de Tiempo , Factor de Crecimiento Transformador beta/sangre , Factor de Crecimiento Transformador beta/orina , Resultado del Tratamiento , UrinálisisRESUMEN
Measles-rubella-mumps vaccination is routine in many countries, but the mumps vaccine remains voluntary and is not covered by insurance in Japan. A 5-year-old Japanese boy who had not received the mumps vaccine was affected by mumps parotitis. Several days later, he presented with various neurological abnormalities, including akinesia, mutism, dysphagia, and uncontrolled respiratory disorder. Mumps encephalitis was diagnosed. Despite steroid pulse and immunoglobulin treatment, the disease progressed. Magnetic resonance imaging showed necrotic changes in bilateral basal ganglia, midbrain, and hypothalamus. At 1 year follow up, he was bedridden and required enteral feeding through a gastric fistula and tracheostomy. Mumps vaccination should be made routine as soon as possible in Japan, because mumps encephalitis carries the risk of severe sequelae.
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Mutismo Acinético/etiología , Encefalitis Viral/complicaciones , Paperas/complicaciones , Mutismo Acinético/diagnóstico , Preescolar , Combinación de Medicamentos , Encefalitis Viral/diagnóstico por imagen , Encefalitis Viral/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Japón , Imagen por Resonancia Magnética , Masculino , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Metilprednisolona/uso terapéutico , Paperas/diagnóstico por imagen , Paperas/tratamiento farmacológico , Prednisolona/uso terapéuticoRESUMEN
OBJECTIVES: Osteomyelitis (OM) and septic arthritis (SA) in childhood might cause complications, sequelae, or even death if diagnosis and treatment are delayed. Here, we examined the outcomes of OM/SA at a pediatric emergency core hospital in Japan. METHODS: This was a single-center, retrospective, observational cohort study at a pediatric emergency core hospital in Japan. Pediatric outpatients who underwent magnetic resonance imaging at the hospital in the period 2012?2020 were recruited. Primary outcomes were sequelae, recurrent symptoms, chronicity, and death. RESULTS: Fifteen OM/SA patients (9 OM, 4 SA, 2 OM+SA) were recruited. The identified major pathogens included methicillin-susceptible Staphylococcus aureus (40.0 %, n=6) and methicillin-resistant S. aureus (13.3 %, n=2). Mean time from onset to first hospital visit, hospitalization, and initiation of effective antibiotics was 2 days, 3.9?±?1.8 days, and 4.9±2.2 days, respectively. All OM/SA patients recovered without complications or sequelae. CONCLUSIONS: In this study, all patients with OM/SA showed a good prognosis. Despite the small sample size, this pilot study suggests that the pediatric emergency core system in Japan provides early treatment and a good prognosis for patients diagnosed with OM/SA. J. Med. Invest. 70 : 236-240, February, 2023.
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Artritis Infecciosa , Staphylococcus aureus Resistente a Meticilina , Osteomielitis , Infecciones Estafilocócicas , Niño , Humanos , Estudios Retrospectivos , Japón/epidemiología , Proyectos Piloto , Artritis Infecciosa/terapia , Artritis Infecciosa/complicaciones , Artritis Infecciosa/diagnóstico , Progresión de la Enfermedad , Osteomielitis/terapia , Osteomielitis/complicaciones , Osteomielitis/diagnóstico , Antibacterianos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/diagnósticoRESUMEN
The outbreak of coronavirus disease (COVID-19) resulted in implementation of social distancing and other public health measures to control the spread of infection and improve prevention, resulting in a decrease in respiratory syncytial virus (RSV) and pediatric respiratory tract infection rates. However, there was a rapid and large re-emergence of RSV infection in Japan. Notably, we were faced with a difficult situation wherein there was a shortage of hospital beds. This study aimed to examine the epidemiological patterns of RSV-related hospitalizations among children before and after the COVID-19 pandemic onset at two pediatric emergency referral hospitals covering the entire Tokushima Prefecture. Data were extracted from electronic medical records of children hospitalized with RSV infection between January 1, 2018, and December 31, 2021. All patients meeting the eligibility criteria were included in this study. The rates of study outcomes were documented annually during 2018-2021 and compared between the 2018-2020 and 2021 periods. In 2020, there was no RSV infection outbreak. Hospitalizations at the peak week in 2021 were 2.2- and 2.8-fold higher than those in 2018 and 2019, respectively. Hospitalizations in 2021 were concentrated within a short period. In addition, there was a significant increase in hospitalizations among children aged 3-5 months and those older than 24 months. The high-flow nasal cannula (HFNC) use rate nearly doubled in 2021. A new pandemic in the future may cause an outbreak of RSV infection that can result in an intensive increase in the number of hospitalizations of pediatric patients requiring respiratory support, especially in infants aged <6 months. There is an urgent need to improve the preparedness of medical systems, particularly in terms of the number of inpatient beds and the immediate availability of HFNC.
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BACKGROUND/AIMS: Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor-ß(1) (TGF-ß(1))- and hydrogen peroxide (H(2)O(2))-inducible focal adhesion protein that may be necessary for maintaining the myofibroblastic phenotype in pathological scar formation. To investigate the involvement of Hic-5 in the pathogenesis of glomerulonephritis (GN), we examined the glomerular expression of Hic-5 in human and rat GN as well as the regulation of Hic-5 by TGF-ß(1) in vitro. METHODS AND RESULTS: Immunohistochemical analyses showed that the expression of Hic-5 was increased in mesangial cells (MCs) in human mesangial proliferative GN. Hic-5 expression was significantly correlated not only with the levels of α-smooth muscle actin (α-SMA) and TGF-ß(1), the accumulation of extracellular matrix, and the number of glomerular cells, but also with the urinary protein level in patients with GN. Glomerular Hic-5 expression increased in parallel with α-SMA expression in a rat model of mesangial proliferative GN. Combined therapy with an angiotensin type I receptor blocker and an antioxidant in this model improved the histology and the expression of Hic-5 and α-SMA. TGF-ß(1) upregulated Hic-5 and α-SMA protein levels in human cultured MCs. CONCLUSION: Our findings suggest that Hic-5 is involved in changes in the MC phenotype to produce abnormal extracellular matrix remodeling in GN.
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Glomerulonefritis Membranoproliferativa/metabolismo , Glomérulos Renales/metabolismo , Proteínas con Dominio LIM/biosíntesis , Actinas/biosíntesis , Adolescente , Adulto , Anciano , Animales , Western Blotting , Células Cultivadas , Niño , Preescolar , Proteínas del Citoesqueleto/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Femenino , Mesangio Glomerular/metabolismo , Mesangio Glomerular/patología , Glomerulonefritis Membranoproliferativa/patología , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular , Glomérulos Renales/efectos de los fármacos , Masculino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Microscopía Fluorescente , Persona de Mediana Edad , Músculo Liso/química , Ratas , Factor de Crecimiento Transformador beta1/biosíntesis , Factor de Crecimiento Transformador beta1/farmacología , Adulto JovenRESUMEN
The patient was a 15 months-old boy who had been diagnosed CHARGE syndrome, which is a multiple congenital anomaly syndrome caused by mutations in the CHD7 gene. Mechanical ventilation management was initiated 2 hours after birth for dysphagia and respiratory failure, and tracheotomy was performed 3 months after birth for dysphagia and failed extubation. He was repeatedly hospitalized due to pneuomoniae. Approximately 1 year after birth, the boy had two consecutive episodes of sudden ventilatory insufficiency while replacing the tracheotomy cannula. A bronchoscopic examination under general anesthesia revealed a tracheoesophageal fistula directly below the tracheostomy. The patient was diagnosed with Gross E esophageal atresia, and we speculated that the cannula migrated to the esophagus via the fistula during tracheostomy cannula replacement. Gross E esophageal atresia is a rare disease. Its diagnosis is often delayed, and it is discovered by recurrent pneumonia in many cases. A tracheoesophageal fistula may also be found in children with deformities of the respiratory system. Furthermore, tracheoesophageal fistulae are often found in the neck. Therefore, when sudden ventilatory insufficiency occurs in a child with a tracheostomy after replacing the tracheostomy cannula, caution must be exercised since the cannula may have migrated to the esophagus via a fistula. J. Med. Invest. 69 : 141-144, February, 2022.
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Anomalías Múltiples , Trastornos de Deglución , Atresia Esofágica , Fístula Traqueoesofágica , Niño , Atresia Esofágica/diagnóstico , Humanos , Lactante , Masculino , Fístula Traqueoesofágica/congénito , Fístula Traqueoesofágica/diagnósticoRESUMEN
Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia that is characterized by thoracic hypoplasia, polydactyly, oral abnormalities, and congenital heart disease. It is caused by pathogenic variants in the EVC or EVC2 genes. We report a case of a newborn with a compound heterozygous variant comprising NM_147127.5: c.1991dup:[p.Lys665Glufs*10] in the EVC2 gene and a novel large deletion involving exon 1 in EVC and exons 1-7 in EVC2.
RESUMEN
A 6-year-old girl was admitted to our hospital with proteinuria, hematuria, skin rash and joint pain of the lower limbs. Due to rapid progression of renal insufficiency, hemodialysis and peritoneal dialysis were performed. She was diagnosed with rapidly progressive glomerulonephritis. Kidney biopsy showed severe crescent formation (50% of glomeruli) and no deposition of any immunoglobulins or complements. Serologically, anti-neutrophil cytoplasmic autoantibody (ANCA) was negative not only by ELISA against proteinase-3 and myeloperoxidase-ANCA but also by indirect immunofluorescent assay against cytoplasmic and perinuclear ANCA. Anti-glomerular basement membrane antibody was also negative. In the acute phase, proinflammatory cytokines such as soluble tumor necrosis factor receptor 1 (sTNFR1), soluble interleukin (IL)-2 receptor (sIL2R), IL-6 and chemokine IL-8 were elevated. The patient was diagnosed with ANCA-negative pauci-immune crescentic glomerulonephritis (CrGN). Intensive treatment with methylprednisolone pulse therapy, plasma exchange, and multiple drug therapy including prednisolone and cyclophosphamide resulted in histopathological improvement and complete remission of proteinuria. There was a possibility that sTNFR1, sIL2R, IL-6 and IL-8 might be involved in the initiation and progression of ANCA-negative pauci-immune CrGN, and to remove and suppress these cytokines might be an effective way to treat ANCA-negative pauci-immune CrGN.
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Glomerulonefritis/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Autoanticuerpos/análisis , Niño , Ciclofosfamida/administración & dosificación , Quimioterapia Combinada , Femenino , Glomerulonefritis/tratamiento farmacológico , Humanos , Metilprednisolona/administración & dosificación , Plasmaféresis , Prednisolona/administración & dosificación , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Quimioterapia por PulsoRESUMEN
The purpose of this study was to clarify the effects of individual infection control measures and physical distancing on pediatric medical care in a local prefecture in Japan, where the incidence of coronavirus disease (COVID-19) in pediatric patients was extremely low. We extracted data from hospital records on the number of outpatients, inpatients, infectious disease consultations, and consultations for representative pediatric diseases. We compared attendance in 2017-2019, before the COVID-19 pandemic, with 2020, when COVID-19 spread to Japan. There were no COVID-19 patients in the pediatric department during the study period. The total number outpatient visits decreased by 24.4%, and the number of hospital admissions, excluding neonatal care unit admissions, decreased by approximately 35%. There was a marked reduction in the number of hospitalizations for infectious diseases such as influenza (-74.8%) and respiratory syncytial virus infection (-93.5%), and the number of hospitalizations for bronchitis/pneumonia, Kawasaki disease, and bronchial asthma decreased. In contrast, the number of clinical psychological interventions and cases reported to the child guidance center increased. In the context of pandemic infectious diseases, it is important to control the spread of problematic infectious diseases by individual infection control measures and physical distancing. However, it is necessary to maintain social life as much as possible for the mental health and physical development of children.
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COVID-19/epidemiología , Servicio de Urgencia en Hospital/normas , Hospitalización/estadística & datos numéricos , Hospitales Pediátricos/estadística & datos numéricos , Infecciones del Sistema Respiratorio/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Pandemias , Infecciones del Sistema Respiratorio/epidemiología , Factores SexualesRESUMEN
A disintegrin and metalloprotease 17 (ADAM17) is the major sheddase that processes more than 80 substrates, including tumour necrosis factor-α (TNFα). The homozygous genetic deficiency of ADAM17 causing a complete loss of ADAM17 expression was reported to be linked to neonatal inflammatory skin and bowel disease 1 (NISBD1). Here we report for the first time, a family with NISBD1 caused by functionally confirmed compound heterozygous missense variants of ADAM17, namely c.1699T>C (p.Cys567Arg) and c.1799G>A (p.Cys600Tyr). Both variants were detected in two siblings with clinical features of NISBD1, such as erythroderma with exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17-/- mEFs) exogenously expressing each of these mutants, phorbol 12-myristate 13-acetate-stimulated shedding was strongly reduced compared with wild-type ADAM17. Thus, in vitro functional assays demonstrated that both missense variants cause the loss-of-function of ADAM17, resulting in the development of NISBD1. Our study further expands the spectrum of genetic pathology underlying ADAM17 in NISBD1 and establishes functional assay systems for its missense variants.
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Proteína ADAM17/genética , Enfermedades del Recién Nacido/genética , Enfermedades Inflamatorias del Intestino/genética , Enfermedades de la Piel/genética , Animales , Femenino , Células HEK293 , Heterocigoto , Humanos , Recién Nacido , Masculino , Ratones , Mutación Missense , Mutación PuntualRESUMEN
The mitogen-activated protein kinase (MAPK) cascade plays an important role in the regulation of various cellular functions in glomerulonephritis (GN). Here, we investigated whether extracellular signal-regulated kinase 5 (ERK5), a member of the MAPK family, is involved in the pathogenesis of chronic mesangioproliferative GN, using a rat model induced by uninephrectomy and anti-Thy-1 antibody injection. Immunostaining of kidneys obtained at different time points revealed that phospho-ERK5 was weakly expressed in control glomeruli but dramatically increased in a typical mesangial pattern after 28 and 56 days of GN. A semiquantitative assessment indicated that glomerular phospho-ERK5 expression closely paralleled the accumulation of extracellular matrix (ECM), collagen type I, as well as glomerular expression of reactive oxygen species (ROS) and ANG II. On the other hand, phospho-ERK1/2 expression increased on day 7 during the phase of enhanced mesangial cell (MC) proliferation and decreased thereafter. H(2)O(2) and ANG II each induced ERK5 phosphorylation by cultured rat MCs. Costimulation with both H(2)O(2) and ANG II synergistically increased ERK5 phosphorylation in MCs. Cultured MCs transfected with ERK5-specific small interference RNA showed a significant decrease in H(2)O(2) or ANG II-induced cell viability and soluble collagen secretion compared with control cells. Treatment of GN rats with an ANG II type 1 receptor blocker resulted in significant decreases in phospho-ERK5 expression and collagen accumulation accompanied by remarkable histological improvement. Taken together, these results suggest that MC ERK5 phosphorylation by ANG II or H(2)O(2) enhances cell viability and ECM accumulation in an experimental model of chronic GN.