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INTRODUCTION: Maxillomandibular advancement (MMA) and genioglossus advancement (GA) are surgeries for patients with obstructive sleep apnea (OSA). Postoperative evaluation is primarily based on the apnea-hypopnea index (AHI) measured by polysomnography. The purpose of this study was to identify the timing of hyoid bone relocation after MMA and GA surgery and to investigate whether or not hyoid bone relocation can be an indicator of postoperative evaluation of OSA. METHODS: Patients with OSA underwent MMA and GA surgery. Changes in hyoid bone position and tongue-to-oral volume ratio were analyzed on lateral radiographs before, immediately after, and 1 year after surgery. Then, a correlation was verified between these changes and postoperative AHI. RESULTS: In 18 patients studied, the position of the hyoid bone did not show a constant tendency immediately after surgery. One year after surgery, the bone had moved anteriorly and toward the oral cavity in all patients compared to its preoperative position. And AHI correlated with the movement of the hyoid bone to the oral side. DISCUSSION: One year after surgery, the tongue was adapted to the newly enlarged oral space, and as a result, the low position of the hyoid bone before the operation was improved. The findings suggest that the degree of lowering of the hyoid bone may be an indicator of the improvement of AHI.
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Avanço Mandibular , Apneia Obstrutiva do Sono , Humanos , Osso Hioide/diagnóstico por imagem , Osso Hioide/cirurgia , Língua/diagnóstico por imagem , Língua/cirurgia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Apneia Obstrutiva do Sono/cirurgia , Músculos FaciaisRESUMO
Azithromycin displays immunomodulatory and anti-inflammatory effects in addition to broad-spectrum antimicrobial activity and is used to treat inflammatory diseases, including respiratory and odontogenic infections. Few studies have reported the effect of azithromycin therapy on bone remodeling processes. The aim of this study was to examine the effects of azithromycin on the osteogenic function of osteoblasts using osteoblast-like MC3T3-E1 cells. Cells were cultured in the presence of 0, 0.1, 1, and 10 µg/mL azithromycin, and cell proliferation and alkaline phosphatase (ALPase) activity were determined. In vitro mineralized nodule formation was detected with alizarin red staining. The expression of collagenous and non-collagenous bone matrix protein was determined using real-time PCR or enzyme-linked immunosorbent assays. In cells cultured with 10 µg/mL azithromycin, the ALPase activity and mineralized nodule formation decreased, while the type I collagen, bone sialoprotein, osteocalcin, and osteopontin mRNA expression as well as osteopontin and phosphorylated osteopontin levels increased. These results suggest that a high azithromycin concentration (10 µg/mL) suppresses mineralized nodule formation by decreasing ALPase activity and increasing osteopontin production, whereas low concentrations (≤l.0 µg/mL) have no effect on osteogenic function in osteoblastic MC3T3-E1 cells.
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Azitromicina/farmacologia , Calcificação Fisiológica/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores , Matriz Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteopontina/genética , Osteopontina/metabolismo , RNA Mensageiro/genéticaRESUMO
The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential components of the enzyme catalyzing the first step of diphthamide formation on eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally modified histidine residue on EEF2 that promotes protein chain elongation in the ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2, leading to growth defects, embryonic lethality, and cell death. In humans, DPH1 mutations cause developmental delay with a short stature, dysmorphic features, and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901). To date, only two homozygous missense mutations in DPH1 (c.17T>A, p.Met6Lys and c.701T>C, p.Leu234Pro) have been reported. We used WES to identify novel compound heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C, p.Leu164Pro) in a patient from a nonconsanguineous family presenting with intellectual disability, a short stature, craniofacial abnormalities, and external genital abnormalities. The clinical phenotype of all patients with DPH1 mutations, including the current patient, revealed core features, although the external genital anomaly was newly recognized in our case.
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Obstrução das Vias Respiratórias/diagnóstico , Obstrução das Vias Respiratórias/genética , Heterozigoto , Antígenos de Histocompatibilidade Menor/genética , Mutação , Fenótipo , Proteínas Supressoras de Tumor/genética , Anormalidades Urogenitais/diagnóstico , Anormalidades Urogenitais/genética , Alelos , Substituição de Aminoácidos , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Análise Mutacional de DNA , Fácies , Humanos , Recém-Nascido , Masculino , Linhagem , SíndromeRESUMO
INTRODUCTION: Multi-organ injury causes leakage of several intracellular enzymes into the circulation. We evaluated the correlation between the serum-leaked intracellular enzyme levels at the beginning of treatment and the outcome in perinatally stressed neonates. MATERIALS AND METHODS: We retrospectively studied neonates whose 1 minute Apgar score was < 7. We collected initial venous blood sample data, including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, and correlated these with patient short-term outcomes. RESULTS: Of 60 neonates, nine patients were treated with therapeutic hypothermia, and 32 needed mechanical ventilation. The therapeutic hypothermia group showed significantly larger base deficit, and higher lactate, AST, ALT, LDH, and CK (all p < 0.01). The duration of mechanical ventilation significantly correlated with AST, ALT, LDH, and CK levels (all p < 0.01). CONCLUSION: Initial enzyme levels are useful for predicting the duration of mechanical ventilation in stressed neonates.
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Asfixia Neonatal/embriologia , Recém-Nascido/metabolismo , Síndrome de Aspiração de Mecônio/enzimologia , Taquipneia/enzimologia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Asfixia Neonatal/sangue , Asfixia Neonatal/enzimologia , Creatina Quinase/sangue , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Ácido Láctico/sangue , Síndrome de Aspiração de Mecônio/sangue , Gravidez , Estudos Retrospectivos , Taquipneia/sangueRESUMO
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction and ceroid deposition. We report suspected ocular albinism in two Japanese sisters, caused by mutations in the HPS6 (Hermansky-Pudlak syndrome 6) gene. Trio-based whole-exome sequencing (WES) identified novel compound heterozygous mutations in HPS6 (c.1898delC: mother origin and c.2038C>T: father origin) in the two sisters. To date, 10 associated mutations have been detected in HPS6. Although we detected no general manifestations, including platelet dysfunction, in the sisters, even in long-term follow-up, we established a diagnosis of HPS type 6 based on the HPS6 mutations and absence of dense bodies in the platelets, indicating that WES can identify cases of HPS type 6. To the best of our knowledge, this is the first report of HPS6 mutations in Japanese patients.
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Albinismo Ocular/diagnóstico , Albinismo Ocular/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Irmãos , Alelos , Pré-Escolar , Exoma , Feminino , Angiofluoresceinografia , Genes Recessivos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Japão , Linhagem , Fenótipo , Tomografia de Coerência ÓpticaRESUMO
Duodenal stenosis is a type of congenital intestinal atresia syndrome. Most patients are diagnosed during the neonatal period based on recurrent vomiting, but some cases develop symptoms at an older age. We report a case with an unusual pathogenic mechanism: sudden ileus due to food impaction.A 15-month-old boy was admitted to our institution with a history of recurrent vomiting and diarrhea for 7 days and fever for 2 days. Abdominal distention was found upon physical examination but other congenital anomalies were not. He was initially treated for acute gastroenteritis, but vomiting resumed after starting oral ingestion. Congenital membranous duodenal stenosis and impaction of a shimeji mushroom into the narrow section of the duodenum was recognized upon endoscopy. Dilatation was successful and restenosis was not seen. Food impaction is a rare (but important) initial event in congenital duodenal stenosis, and this disorder should be included in the differential diagnosis, especially for infants/toddlers with recurrent vomiting that develops at the time of eating solid and more diverse types of food.
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Duodenopatias/etiologia , Obstrução Duodenal/congênito , Obstrução Duodenal/complicações , Alimentos , Íleus/etiologia , Humanos , Lactente , Atresia Intestinal , MasculinoRESUMO
Mitochondrial diseases are associated with defects of adenosine triphosphate production and energy supply to organs as a result of dysfunctions of the mitochondrial respiratory chain. Biallelic mutations in the YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase cause myopathy, lactic acidosis, and sideroblastic anemia 2 (MLASA2), a type of mitochondrial disease. Here, we report a consanguineous Turkish family with two siblings showing severe metabolic decompensation including recurrent hypoglycemia, lactic acidosis, and transfusion-dependent anemia. Using whole-exome sequencing of the proband and his parents, we identified a novel YARS2 mutation (c.1303A>G, p.Ser435Gly) that was homozygous in the patient and heterozygous in his parents. This mutation is located at the ribosomal protein S4-like domain of the gene, while other reported YARS2 mutations are all within the catalytic domain. Interestingly, the proband showed more severe symptoms and an earlier onset than previously reported patients, suggesting the functional importance of the S4-like domain in tyrosyl-tRNA synthetase.
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Acidose Láctica/genética , Anemia Sideroblástica/genética , Doenças Musculares/genética , Mutação , Tirosina-tRNA Ligase/genética , Acidose Láctica/complicações , Adolescente , Adulto , Anemia Sideroblástica/complicações , Criança , Pré-Escolar , Evolução Fatal , Feminino , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Doenças Musculares/complicações , Linhagem , Adulto JovemRESUMO
OBJECTIVE: While human epidermal growth factor receptor 2 (HER2) is upregulated in endometrial carcinoma-especially in the p53 aberrant type- conventional anti-HER2 therapy is not typically used for this cancer type. Recently, HER2-targeted antibody-drug conjugates have shown antitumor effects against HER2 low-expressing cancers. Therefore, we analyzed the clinicopathological characteristics of HER2-positive endometrial carcinomas including those with low expression, as well as the prognostic significance of p53 and HER2 co-expression. METHODS: Immunohistochemistry for HER2 and p53 was performed in 530 patients with endometrial carcinoma; 124 cases (23%) were HER2-positive. RESULTS: Of the HER2-positive cases, >50% were 1+. A high prevalence of HER2 expression was observed in serous (64%), clear-cell (73%), and mixed (64%) carcinomas. Notably, 19% of endometrioid carcinomas were HER2-positive. HER2 positivity was significantly associated with age ≥60 years, high-grade histological subtype, deep myometrium invasion, stage III/IV, recurrence, and death. Univariate analysis showed that HER2-positive cases had reduced progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.012). However, after adjusting for stage, HER2 positivity was not associated with survival. In the early stage, co-expression of HER2-positive and p53 aberrant types was associated with shorter PFS (p<0.001) and OS (p<0.001) compared with at least one negative result. Multivariate analysis of PFS showed HER2 and p53 co-expression (hazard ratio, 1.891; 95% confidence interval, 1.183-5.971, p=0.008) as an independent prognostic factor. CONCLUSIONS: This study presents detailed clinicopathological characteristics and the prognostic impact of HER2-positivity in endometrial carcinomas. HER2-targeted antibody-drug conjugate therapy may be broadly applicable to endometrial carcinoma.
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Yunis-Varon syndrome (YVS, MIM 216340) is a rare autosomal recessive disorder characterized by skeletal abnormalities and severe neurological impairment with vacuolation of the central nervous system, skeletal muscles and cartilages. Very recently, mutations of the FIG4 (FIG4 homolog, SAC1 lipid phosphatase domain containing (Saccharomyces cerevisiae)) gene, which encodes a 5'-phosphoinositide phosphatase essential for endosome/lysosome function have been identified as the cause for YVS. Interestingly, FIG4 mutations were previously reported to be responsible for other neurodegenerative diseases such as autosomal recessive Charcot-Marie-Tooth disease type 4J and autosomal dominant amyotrophic lateral sclerosis/primary lateral sclerosis. We analyzed a YVS patient using whole-exome sequencing, and identified novel biallelic FIG4 mutations: c.1750+1delG and c.2284_2285delCT (p.S762Wfs*3). These two mutations were mutations supposed to have null function. To our knowledge, this is the second report of FIG4 mutations in YVS and our result supports the idea that biallelic null mutations of FIG4 cause YVS in human.
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Displasia Cleidocraniana/genética , Displasia Ectodérmica/genética , Flavoproteínas/genética , Deformidades Congênitas dos Membros/genética , Micrognatismo/genética , Mutação/genética , Pré-Escolar , Feminino , Humanos , Monoéster Fosfórico HidrolasesRESUMO
Premature closure of the ductus arteriosus (PCDA) and transposition of the great arteries (TGA) cause persistent pulmonary hypertension of the newborn (PPHN). We present a case of a newborn who demonstrated d-TGA with ventricular septal defect (VSD) and pulmonary stenosis (PS) complicated by PCDA. The neonate showed severe cyanosis resistant to resuscitation soon after birth, and was diagnosed with d-TGA with VSD by echocardiography. PPHN was also suspected based on physical symptoms and results of echocardiography. The neonate was given inhaled nitric oxide, prostaglandin E1, and catecholamines under sedation, and underwent a balloon atrial septostomy (BAS). His condition gradually improved, and he was extubated on day 7, but his pulmonary subvalvular stenosis gradually worsened and pulmonary blood flow was markedly decreased. A second BAS was performed on day 27 and he showed no improvement. Blalock-Taussig shunt surgery was performed on day 34, which markedly improved his condition. The co-existence of d-TGA and PCDA is generally a lethal state. In our patient, an increase in pulmonary blood flow during the fetal period was restricted because of PS and outlet flow from the left ventricle to the right ventricle via the VSD. This restricted blood flow through the ductus arteriosus, which led to narrowing of the DA. At the same time, damage to and constrictive changes of the pulmonary vessels were prevented. The ductus arteriosus should be carefully evaluated to exclude PCDA in cases of d-TGA. The presence of both VSD and PS may be a prognostic factor in such cases.
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Anormalidades Múltiplas , Canal Arterial/anormalidades , Comunicação Interventricular/fisiopatologia , Síndrome da Persistência do Padrão de Circulação Fetal/fisiopatologia , Estenose da Valva Pulmonar/fisiopatologia , Pressão Propulsora Pulmonar , Transposição dos Grandes Vasos/fisiopatologia , Adulto , Diagnóstico Diferencial , Ecocardiografia Doppler em Cores , Feminino , Comunicação Interventricular/diagnóstico , Humanos , Recém-Nascido , Masculino , Síndrome da Persistência do Padrão de Circulação Fetal/diagnóstico , Síndrome da Persistência do Padrão de Circulação Fetal/etiologia , Gravidez , Estenose da Valva Pulmonar/diagnóstico , Índice de Gravidade de Doença , Transposição dos Grandes Vasos/diagnósticoRESUMO
We report prolonged valganciclovir (VGCV) treatment of a symptomatic cytomegalovirus infection case. Automated auditory brainstem evoked response performed at 5 days of age revealed severe hearing impairment. Cranial magnetic resonance (MR) imaging at 11 days of age showed abnormal findings. At 5 weeks of age, VGCV was started. The viral load in blood cells, plasma, and urine decreased during the 6-week treatment. Because of improvement of hearing level and no adverse effects, VGCV was restarted for an additional 6 weeks. Neither the patient's hearing impairment nor results of cranial MR imaging have become worse in 6 months. It is crucial to gather information from as many cases as possible treated with VGCV to establish a standard protocol for VGCV treatment.
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Antivirais/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/análogos & derivados , Doenças do Recém-Nascido/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico por imagem , Infecções por Citomegalovirus/virologia , DNA Viral/sangue , DNA Viral/urina , Potenciais Evocados Auditivos do Tronco Encefálico , Ganciclovir/administração & dosagem , Perda Auditiva/virologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico por imagem , Doenças do Recém-Nascido/virologia , Imageamento por Ressonância Magnética , Masculino , Radiografia , Valganciclovir , Carga ViralRESUMO
Backsliding is a major problem when moving the maxilla significantly forward in orthognathic surgery. For example, in sleep surgery, maxillomandibular advancement is an application of orthognathic surgery, and it is well known that the anterior movement of the maxilla back and forth is an important factor that greatly widens the pharyngeal airway. However, postoperative backsliding is a major problem in this surgery. Therefore, a surgical method was devised to prevent the maxilla from retracting by adjusting the bone when moving the maxilla forward.
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Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Cefalometria , Maxila/cirurgia , Osteotomia de Le FortRESUMO
A neonate with severe neonatal asphyxia was treated with therapeutic hypothermia. He developed hypothermia-induced respiratory deterioration, after which congenital tracheal stenosis and pulmonary artery sling were diagnosed. Even low-grade hypothermia is likely to induce bronchial narrowing in neonates, especially in neonates with congenital respiratory tract anomalies. Congenital tracheal stenosis represents a potential pitfall in differential diagnosis and should be carefully ruled out in cases of bronchial narrowing episode induced by therapeutic hypothermia. Pediatr Pulmonol. 2017;52:E7-E10. © 2016 Wiley Periodicals, Inc.
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Hipotermia Induzida , Artéria Pulmonar/anormalidades , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Estenose Traqueal/diagnóstico , Asfixia Neonatal/terapia , Humanos , Hipóxia-Isquemia Encefálica/prevenção & controle , Recém-Nascido , Masculino , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Estenose Traqueal/congênitoRESUMO
BACKGROUND: Symptoms of congenital cytomegalovirus infection remains unclear. CASE CHARACTERISTICS: Extremely low birth weight twins with twin-to-twin transfusion syndrome were infected with cytomegalovirus congenitally. OBSERVATION: The donor showed neuronal impairment, whereas the recipient showed hepatic dysfunction. MESSAGE: Intrauterine hemodynamics may be important in pathophysiology of congenital cytomegalovirus infection.
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Infecções por Citomegalovirus , Transfusão Feto-Fetal , Complicações Infecciosas na Gravidez , Gêmeos Monozigóticos , Adulto , Encéfalo/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Resultado do TratamentoAssuntos
Agonistas de Receptores Adrenérgicos beta 2 , Doenças do Recém-Nascido/tratamento farmacológico , Procaterol , Síndrome do Nó Sinusal/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Eletrocardiografia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Procaterol/administração & dosagem , Procaterol/uso terapêutico , Síndrome do Nó Sinusal/diagnósticoRESUMO
Various pathological conditions can cause fatty liver in children. Nonalcoholic steatohepatitis (NASH) in children has been known since 1983. However, NASH diagnosed in childhood does not have a favorable outcome. The pathological characteristics of NASH are significantly different between children and adults. Nonalcoholic fatty liver disease (NAFLD)/NASH is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both children and adults. In NASH, a "two-hit" model involving triglyceride accumulation (first hit) and liver damage (second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis or NAFLD activity score in children. Therefore, insulin resistance may be important in the first hit. Because there is obvious familial clustering in NASH, genetic predisposition as well as environmental factors including diet might be the second hit of NAFLD/NASH.
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AIM: Central nervous system involvement represents a serious and common complication of systemiclupus erythematosus (SLE). We describe the characteristics of patients with neuropsychiatric (NP) SLE complicated with reversible basal ganglia lesions. METHODS: We describe the cases of three NPSLE patients. RESULTS: They presented with NP manifestations such as headache, cognitive dysfunction, tremors, seizures, and mood disorder. The levels of autoantibodies to NMDA (N-methyl-d-aspartate) receptor antibodies and antiribosomal-P antibodies were elevated, indicating the presence of an acute phase. Marked elevation of interleukin-6 in cerebrospinal fluid was noted when these patients showed NP symptoms. Moreover, the patients presented with high-intensity lesions in the basal ganglia on T2-weighted images, fluid-attenuated inversion recovery (FLAIR) images, diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps. Following immunosuppressive treatment, almost complete improvement of the lesions was noted. CONCLUSION: The reported cases indicate that reversible vasculopathies represent vasogenic edema localized in basal ganglia lesions and that activation of the autoimmune system and inflammation could lead to NP manifestations in SLE.