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BACKGROUND: Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities. METHODS: We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174. FINDINGS: We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25-0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78). INTERPRETATION: Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG. FUNDING: Japan Agency for Medical Research and Development (grant CCT-B-2503).
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Anomalias dos Vasos Coronários/prevenção & controle , Ciclosporina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Criança , Pré-Escolar , Anomalias dos Vasos Coronários/epidemiologia , Ciclosporina/administração & dosagem , Resistência a Medicamentos/imunologia , Quimioterapia Combinada , Feminino , Indicadores Básicos de Saúde , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/uso terapêutico , Incidência , Japão/epidemiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/imunologia , Resultado do TratamentoRESUMO
Tipepidine hibenzate (Asverin) is commonly used as an antitussive drug for acute and chronic cough in various age groups and is generally safe and well-tolerated. However, we experienced a case of tipepidine hibenzate-induced anaphylactic shock in a 1-year-old boy. After ingesting cold medication including tipepidine hibenzate, the patient presented with generalized erythema and urticaria, swollen face, coughing, wheezing and vomiting, together with hypotension and a decreased level of consciousness. To identify the culprit drug, we performed skin prick tests (SPTs) and oral drug provocation tests (DPTs). SPTs revealed a negative reaction for all drugs, but DPTs caused a positive reaction only for a full therapeutic dose of tipepidine hibenzate. Physicians need to consider tipepidine hibezate as a culprit drug when anaphylaxis occurs after taking anticough or common cold medication.
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Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca(2+)/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca(2+) release activated Ca(2+) (CRAC) channel mediating store-operated Ca(2+) entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair in-frame insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca(2+)/NFAT pathway in the pathogenesis of this disorder.
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Povo Asiático/genética , Canais de Cálcio/genética , Síndrome de Linfonodos Mucocutâneos/genética , Mutagênese Insercional , Polimorfismo de Nucleotídeo Único , Adolescente , Cálcio/metabolismo , Cromossomos Humanos Par 12/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Humanos , Japão , Masculino , Síndrome de Linfonodos Mucocutâneos/patologia , Proteína ORAI1 , Irmãos , População Branca/genética , Adulto JovemRESUMO
INTRODUCTION: Kawasaki disease (KD) is the most common multisystem vasculitis in childhood. Pathogens can be associated with the onset of KD. However, a lack of consistency prevails among reports about this disease. CASE PRESENTATION: For this case of a 1-year-old boy with four recurrent episodes of KD within a year, we analysed profiles of pathogen reads in his serum and pharynx specimens using next-generation sequencing. Comparative analysis of the identified bacterial reads from serum samples found significant correlation of bacteria such as Streptococcus and Haemophilus spp. with the first and fourth episodes (R2 = 0.9506) before treatment. In the first convalescent phase, the number of Streptococcus spp. was reduced remarkably (P < 0.0001). From sequencing of the pharynx specimen from the fourth episode, a similar correlation was found with serum from the fourth episode (R2 = 0.6633). CONCLUSION: In this case, Streptococcus spp. may have been associated with onset of KD. Further studies must be undertaken to evaluate the putative association of micro-organism infection with KD pathogenesis.
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INTRODUCTION: Kawasaki disease (KD) is an acute, self-limited vasculitis of unknown aetiology that predominantly affects infants and young children. We hypothesise that cyclosporin A (CsA) may be effective in treating KD by regulating the Ca(2+)/NFAT signalling pathway. This trial compares the current standard therapy of intravenous immunoglobulin (IVIG) and the combined IVIG+CsA therapy in paediatric patients with severe KD. METHODS AND ANALYSIS: This trial is a phase III, multicentre, randomised, open-label, blinded-end point trial that evaluates the efficacy and safety of IVIG+CsA therapy. Patients with severe KD who satisfy the eligibility criteria are randomised (1:1) to receive either CsA (5 mg/kg/day for 5 days; Neoral) plus high-dose IVIG (2 g/kg for 24 h and aspirin 30 mg/kg/day), or high-dose IVIG alone (2 g/kg for 24 h and aspirin 30 mg/kg/day). The primary end point is the frequency of occurrence of coronary artery abnormalities during the trial period. An independent end point review committee will be in charge of the trial assessment. ETHICS AND DISSEMINATION: The protocol was approved by the Institutional Review Board of each institution. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, in Japan. The trial is currently on-going and is scheduled to finish in April 2017. The findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: JMA-IIA00174; Pre-results.
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Aspirina/uso terapêutico , Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Projetos de Pesquisa , Inibidores de Calcineurina/efeitos adversos , Pré-Escolar , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Lactente , Japão , Masculino , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
INTRODUCTION: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of AESD; excitotoxicity is postulated to be the pathogenesis based on elevated glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx, or whether MR spectroscopy is useful for an early diagnosis. METHODS: Five Japanese patients with AESD (three boys and two girls, 1 year of age) were enrolled in this study. MR spectroscopy was acquired from the frontal white matter (repetition time (TR) of 5000 ms, echo time (TE) of 30 ms) with a 1.5- or 3.0-T scanner. MR spectroscopy was performed four times for two patients, three times for one patient, and two times for two patients. Quantification of Glu and Gln was performed using LCModel. RESULTS: Glu was elevated in three of four studies on days 1-4 and became normal or low afterward. Gln was normal in three studies on days 1-2, elevated in all seven studies on days 4-12, and became normal or low afterward. CONCLUSION: These findings suggest that MR spectroscopy may be useful for an early diagnosis. Acute Glu elevation changes to subacute Gln elevation, suggesting that a disrupted Glu-Gln cycle may play an important role.
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Epilepsia Tônico-Clônica/metabolismo , Lobo Frontal/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Substância Branca/metabolismo , Biomarcadores/sangue , Epilepsia Tônico-Clônica/patologia , Feminino , Lobo Frontal/patologia , Humanos , Recém-Nascido , Masculino , Taxa de Depuração Metabólica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Substância Branca/patologiaRESUMO
The etiologic role of recently identified respiratory viruses for lower respiratory tract disease (LRTD) remains unclear in Japan. The purpose of this study was to investigate the prevalence of respiratory viruses in young children with LRTD. We prospectively examined 721 children who were under two years old and admitted to a single medical center in Japan with LRTD between April 2007 and March 2012. Viral nucleotic acids were taken from their nasal swabs. Each sample was examined with (RT-) PCR for respiratory syncytial virus (RSV), enterovirus (EV), human metapuemovirus (hMPV), human bocavirus (HBoV), parainfluenzavirus (PIV), and adenovirus (AdV). We detected at least one virus agent in 466 (65%); 83 patients (12%) were co-infected with different viruses. No virus was detected in 255 patients (35%). RSV (27%) was most common, followed by EV (11%), hMPV (6.9%), HBoV (3.3%), PIV (2.9%), and AdV (2.2%). Seasonal distribution was seen in each virus. Infants under 6 months old were frequently positive for RSV or EV. In 20 patients (2.8%) who required mechanical ventilation because of respiratory failure, 18 patients were positive for RSV nospace between "and/or" EV.
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Metapneumovirus/isolamento & purificação , Vírus Sinciciais Respiratórios/isolamento & purificação , Doenças Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Japão/epidemiologia , Masculino , Doenças Respiratórias/diagnóstico , Infecções Respiratórias/diagnóstico , Fatores de TempoRESUMO
To investigate systemic cytokine responses in human bocavirus (HBoV)-associated lower respiratory tract infection, serum cytokine profiles were analyzed in HBoV positive-children (n=14) using multiplex immunoassay. Concentrations of TNF-a, IL-2, IL-5 and IL-8 on admission were significantly different from those of respiratory syncytial virus-positive children (n=28). This unique cytokine response might partly explain some characteristic clinical features of HBoV-associated respiratory infection.
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Citocinas/sangue , Bocavirus Humano/isolamento & purificação , Infecções por Parvoviridae/sangue , Infecções Respiratórias/sangue , Pré-Escolar , Citocinas/imunologia , Feminino , Bocavirus Humano/genética , Humanos , Lactente , Masculino , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/virologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologiaRESUMO
BACKGROUND: Most infants with pneumothorax have underlying conditions. Pneumocystis jirovecii pneumonia (PCP) frequently occurs in patients with severe combined immunodeficiency (SCID). The aim of this study was to determine clinical features of PCP-associated pneumothorax in SCID patients. METHODS: The medical records of four SCID patients with pneumothorax were retrospectively reviewed. RESULTS: All four patients were diagnosed as having SCID at the time of contracting PCP. All patients received mechanical ventilation because of severe respiratory failure. Only one patient was successfully extubated and was alive following hematopoietic stem cell transplantation (HSCT); of the remaining patients, however, two died of respiratory failure, and one patient died of early HSCT-related complications. CONCLUSIONS: Pneumothorax associated with PCP can occur in SCID patients, and they may have a poor prognosis. If pneumothorax occurs in infants, both respiratory management and prompt investigation of the underlying conditions are needed, considering the possibility of PCP associated with SCID.
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Pneumocystis carinii , Pneumonia por Pneumocystis/complicações , Pneumotórax/complicações , Imunodeficiência Combinada Severa/complicações , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Polyomaviruses (PyV) WU and KI are reportedly associated with respiratory tract disease (RTD) worldwide but their incidence is unclear in Japan. In a 2 year prospective study, WU/KIPyV were detected in 48 (13.9%) and in five (1.4%) of 345 children hospitalized with lower RTD, respectively. The seasonal distribution was observed in spring and early summer. Other respiratory viruses were co-detected in 51% of PyV-positive patients, but eight (2.3%) of the WUPyV-positive patients were negative for other known pathogens.
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DNA Viral/genética , Mucosa Nasal/virologia , Nasofaringe/virologia , Polyomavirus/genética , Infecções Respiratórias/virologia , Feminino , Humanos , Lactente , Japão/epidemiologia , Masculino , Reação em Cadeia da Polimerase , Polyomavirus/isolamento & purificação , Prevalência , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Análise de Sequência de DNARESUMO
BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis occurring in medium-sized arteries, especially coronary arteries. Patients with KD who fail to respond to standard therapy with intravenous immunoglobulin (IVIG) face a higher risk of developing coronary artery lesions. Cyclosporin A (CsA) is one treatment option for IVIG-resistant KD. However, the mechanism of its suppression of inflammation in patients with KD remains unknown. METHODS AND RESULTS: We analyzed time-line profiles of multiple inflammatory cytokines in sera of 19 patients treated with CsA (4 mg/kg/day, p.o., 14 days) after additional IVIG. Trough concentration of CsA in blood was maintained between 60 and 200 ng/ml. We examined serum samples before, on day 7, and at the end (day 14) of CsA treatment. Assays were conducted using a Milliplex kit®. Fourteen patients responded to CsA and became afebrile within 5 days (Responders), although five patients were regarded as Non-responders. Serum transitional levels of IL-6 (p<0.001), sIL-2R (p<0.001), sTNFRII (p<0.001), and G-CSF (p<0.001) reflect disease severity. In Non-responders, average levels of IL-6 at day 7 (43.5 vs. 13.8 pg/ml, p<0.001) and average levels of sIL-2R at day 14 (21.3 vs. 3.31 pg/ml, p=0.014) were significantly higher than those in Responders. CONCLUSION: CsA treatment effectively reduced the persisting serum inflammatory cytokines in most of the IVIG-resistant KD patients. Soluble IL-2R suppression implies a mechanism explaining the effects of CsA.
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Ciclosporina/uso terapêutico , Citocinas/sangue , Imunossupressores/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/metabolismo , Síndrome de Linfonodos Mucocutâneos/terapia , Projetos Piloto , Resultado do TratamentoRESUMO
We performed a genome-wide association study (GWAS) of Kawasaki disease in Japanese subjects using data from 428 individuals with Kawasaki disease (cases) and 3,379 controls genotyped at 473,803 SNPs. We validated the association results in two independent replication panels totaling 754 cases and 947 controls. We observed significant associations in the FAM167A-BLK region at 8p22-23 (rs2254546, P = 8.2 × 10(-21)), in the human leukocyte antigen (HLA) region at 6p21.3 (rs2857151, P = 4.6 × 10(-11)) and in the CD40 region at 20q13 (rs4813003, P = 4.8 × 10(-8)). We also replicated the association of a functional SNP of FCGR2A (rs1801274, P = 1.6 × 10(-6)) identified in a recently reported GWAS of Kawasaki disease. Our findings provide new insights into the pathogenesis and pathophysiology of Kawasaki disease.
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Povo Asiático/genética , Loci Gênicos , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Receptores de IgG/genéticaRESUMO
Encephalopathy with reversible lesion of the corpus callosum splenium has a favorable prognosis, but that in 2009 influenza A/H1N1 is unknown. We report a case of clinically mild encephalopathy with a reversible lesion of the corpus callosum splenium in which 2009 influenza A/H1N1 virus was confirmed by laboratory tests. A 15-year-old Japanese girl seen at the emergency unit for loss of consciousness 18 hours after fever onset had been diagnosed with influenza A, and administered zanamivir. Diffusion-weighted magnetic resonance imaging (MRI) indicated lesions of the corpus callosum splenium, and electroencephalography showed slow basic activity, suggesting influenza A related to encephalopathy. She required intensive care with ventilation for two days. Her consciousness had become normal by day 6 after onset, and MRI findings improved on day 7. She recovered without adverse sequelae.
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Encefalopatias/etiologia , Corpo Caloso , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Adolescente , Feminino , HumanosRESUMO
BACKGROUND: There are still no definite treatments for refractory Kawasaki disease (KD). In this pilot study, we evaluated the use of cyclosporin A (CyA) treatment in patients with refractory KD. METHODS: We prospectively collected clinical data of CyA treatment (4-8 mg/kg/d, oral administration) for refractory KD patients using the same protocol among several hospitals. Refractory KD is defined as the persistence or recurrence of fever (37.5°C or more of an axillary temperature) at the end of the second intravenous immunoglobulin (2 g/kg) following the initial one. RESULTS: Subjects were enrolled out of 329 KD patients who were admitted to our 8 hospitals between January 2008 and June 2010. Among a total of 28 patients of refractory KD treated with CyA, 18 (64.3%) responded promptly to be afebrile within 3 days and had decreased C-reactive protein levels, the other 4 became afebrile within 4 to 5 days. However, 6 patients (21.4%) failed to become afebrile within 5 days after the start of CyA and/or high fever returned after becoming afebrile within 5 days. Although hyperkalemia developed in 9 patients at 3 to 7 days after the start of CyA treatment, there were no serious adverse effects such as arrhythmias. Four patients (1.2%), 2 before and the other 2 after the start of CyA treatment, developed coronary arterial lesions. CONCLUSION: CyA treatment is considered safe and well tolerated, and a promising option for patients with refractory KD. Further investigations will be needed to clarify optimal dose, safety, and timing of CyA treatment.
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Ciclosporina/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/administração & dosagem , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Pré-Escolar , Ciclosporina/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Lactente , Masculino , Projetos PilotoRESUMO
BACKGROUND: Kawasaki disease (KD) is characterized by systemic vasculitis with tissue edema. During the healing process of inflammation, lymphangiogenesis is essential for reducing tissue edema. One potential responsible candidate for the induction of lymphangiogenesis in the healing process of acute KD is vascular endothelial growth factor-D (VEGF-D). METHODS AND RESULTS: Sequential changes in serum VEGF-D levels in patients with acute KD (n = 47) using an enzyme-linked immunosorbent assay were investigated. Cross-sectional areas of lymphatic vessels and VEGF-D protein expression were evaluated immunohistochemically in cardiac tissues of patients (n = 6) who died of KD. Regulation of VEGF-D messenger RNA (mRNA) expression in cultured fibroblasts was assessed using quantitative real-time polymerase chain reaction. Serum VEGF-D levels increased after intravenous immunoglobulin therapy in patients with acute KD (P < 0.001). In addition, they were significantly lower in patients with coronary artery lesions (CAL) than in those without CAL (P < 0.05). The cross-sectional areas of lymphatic vessels in cardiac tissues were enlarged in patients with acute KD. VEGF-D protein was detected on the endothelium of the enlarged lymphatic vessels. In vitro, tumor necrosis factor- significantly down-regulated VEGF-D mRNA expression in cultured fibroblasts (P = 0.004). CONCLUSIONS: This study indicates that the production of VEGF-D increases and is related to lymphangiogenesis in patients with acute KD. In addition, low VEGF-D production appears to be associated with the development of CAL.
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Doença da Artéria Coronariana/sangue , Linfangiogênese , Vasos Linfáticos/metabolismo , Síndrome de Linfonodos Mucocutâneos/sangue , Fator D de Crescimento do Endotélio Vascular/sangue , Doença Aguda , Biomarcadores/sangue , Estudos de Casos e Controles , Células Cultivadas , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/metabolismo , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imuno-Histoquímica , Fatores Imunológicos/uso terapêutico , Lactente , Japão , Linfangiogênese/genética , Vasos Linfáticos/patologia , Vasos Linfáticos/fisiopatologia , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/patologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima , Fator D de Crescimento do Endotélio Vascular/genéticaRESUMO
A novel influenza A (2009 H1N1) virus has led to a worldwide pandemic. A significant number of patients with pneumonia have been reported, although its pathogenesis remains to be elucidated. To determine its pathogenesis, we evaluated serum interleukin (IL)-5 and peripheral eosinophil counts in patients with acute pneumonia caused by the 2009 H1N1 virus. During the period from October to December 2009, 40 patients with laboratory-confirmed 2009 H1N1 pneumonia were under investigation. Their mean age at presentation was 6.8 years. The most characteristic finding was the early development of hypoxemic respiratory distress in the first 24 hr after the onset of fever. Bronchial mucous plugs included eosinophils in addition to neutrophils, even in patients without allergies. Serum IL-5 levels were elevated in 20 out of 24 patients (83%) whose samples were obtained in the first 24 hr after the onset of fever (26.5 ± 20.1 pg/mL), independent of the presence of underlying allergies. In contrast, induction of IL-5 was not documented in sera from eight patients with laboratory-confirmed 2009 H1N1 virus who developed neurological complications, but without lower respiratory infection (2.1 ± 0.7 pg/mL, P < 0.001 vs acute pneumonia). Peripheral eosinophilia was characteristic in acute pneumonia, but not in patients without a lower respiratory infection. There was a marked difference in the induction of IL-5 in 2009 H1N1 patients who developed acute pneumonia, compared with those without a lower respiratory infection. IL-5 may play a role in the early phase of acute pneumonia caused by the 2009 H1N1 virus in Japanese children.
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Eosinofilia/complicações , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/complicações , Interleucina-5/sangue , Pandemias , Pneumonia Viral/virologia , Doença Aguda , Criança , Pré-Escolar , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Tóquio/epidemiologiaRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization during the winter among infants and young children. In 2002 palivizumab was introduced to high-risk infants for RSV hospitalization in Japan. It is important to characterize the hospitalized children due to RSV infection after the introduction of palivizumab. METHODS: A survey was conducted to collect the data from the hospitalized children at 12 participating hospitals during the winter of 2007. RESULTS: From October 2007 through April 2008, 8163 children were admitted to participating hospitals, with RSV infection accounting for 811 of those hospitalizations. Mean age in children with RSV infection at hospitalization was 12.4 ± 12.7 months, and children under 24 months of age accounted for 86.4%. The mean gestational age of those at birth was 38.0 ± 2.6 weeks, with 82.4% of the children born at term. Palivizumab was administered in 24 cases of RSV infection, while there were 28 patients who were not treated with palivizumab, even though they met the indication for palivizumab. Death, in a total of five cases, occurred in children who were not treated with palivizumab. CONCLUSIONS: Palivizumab has been widely used in high-risk infants who were covered by health insurance, and most of the hospitalized children with RSV infection in the study hospitals were not treated with palivizumab.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Hospitalização/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sinciciais Respiratórios/imunologia , Anticorpos Antivirais/análise , Antivirais/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/virologia , Japão/epidemiologia , Masculino , Palivizumab , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/virologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Today most patients with congenital heart disease (CHD) can be expected to survive into adulthood. Reports regarding the number of adults with CHD in Japan are scarce. Our study aims to define the number of these adults. MATERIAL AND METHODS: The estimated number of infants born in Japan with major CHDs since 1947 was calculated together with mortality rates. We estimated the number of CHD survivors from data on survival rates of unoperated and postoperative patients. The number of deaths from 1968 to 1997 was analyzed using individual death certificates held by the Japanese Government. RESULTS: In 1967, 163,058 patients with CHD including 53,846 adults were assumed to be alive. From 1968 to 1997, 548,360 patients with CHD were born and 82,919 died. A total of 622,800 patients, including 304,474 children (49%) and 318,326 adults (51%) were estimated to be alive in 1997. From 1997 to 2007, there has been an estimated increase of 9000 adults every year, and in 2007, 409,101 adults are estimated to be alive. CONCLUSIONS: The prevalence in adults with CHD in Japan has explosively increased from 1967 to 2007. There were 409,101 adults with CHD in 2007 with an annual increase of 9000. These data are crucial for planning the establishment in Japan of special facilities and resources necessary for the care of these patients.
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Cardiopatias Congênitas/epidemiologia , Adulto , Fatores Etários , Feminino , Cardiopatias Congênitas/mortalidade , Humanos , Japão/epidemiologia , Masculino , Prevalência , Taxa de Sobrevida/tendênciasRESUMO
Kawasaki disease (KD; OMIM 611775) is an acute vasculitis syndrome which predominantly affects small- and medium-sized arteries of infants and children. Epidemiological data suggest that host genetics underlie the disease pathogenesis. Here we report that multiple variants in the caspase-3 gene (CASP3) that are in linkage disequilibrium confer susceptibility to KD in both Japanese and US subjects of European ancestry. We found that a G to A substitution of one commonly associated SNP located in the 5' untranslated region of CASP3 (rs72689236; P = 4.2 x 10(-8) in the Japanese and P = 3.7 x 10(-3) in the European Americans) abolished binding of nuclear factor of activated T cells to the DNA sequence surrounding the SNP. Our findings suggest that altered CASP3 expression in immune effecter cells influences susceptibility to KD.
Assuntos
Caspase 3/genética , Predisposição Genética para Doença , Síndrome de Linfonodos Mucocutâneos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Sítios de Ligação/genética , Estudos de Casos e Controles , Caspase 3/metabolismo , Caspase 3/fisiologia , Criança , Pré-Escolar , Feminino , Frequência do Gene , Testes Genéticos , Humanos , Lactente , Desequilíbrio de Ligação , Masculino , Fatores de Transcrição NFATC/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Ligação Proteica , População Branca/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Clinical characteristics of human bocavirus (HBoV) infection have been studied worldwide, but their importance of those characteristics remains unknown. We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection (LRTI). METHODS AND RESULTS: During April 2007-July 2009, for 402 hospitalized children younger than 2 years with LRTI, we prospectively examined virus genomes in nasopharyngeal swabs for HBoV, respiratory syncytial virus (RSV), rhinovirus, metapneumovirus, parainfluenzavirus, and adenovirus. The HBoV genomes were identified in 34 patients (8.5%). Clinical and laboratory data of HBoV-positive and other virus/bacteria-negative patients (n = 18) were analyzed and compared with data of RSV-single positive patients (n = 99). The seasonal distribution of HBoV exhibits a concentration of cases during March-September, with most RSV cases occurring during winter in Japan. The minimum age of HBoV-positive patients was 5 months, although 44 patients (44%) with RSV were younger than 6 months. The main clinical features were respiratory distress and hypoxia. Hypoxia advances within 3 days after onset. The mean oxygen saturation on arrival was 92.8%, which was significantly lower than that in patients with RSV (p < 0.001). White blood cell counts were similar among groups. However, the percentage of neutrophils in white blood cells were significantly higher in HBoV-positive patients (62 vs. 45%, p < 0.001). Their prognoses were good. Their hospital stays were 6.6 days. CONCLUSIONS: HBoV-single positive patients show several clinical characteristics, such as seasonality, age, hypoxia, and neutrophilia, which differ from those with RSV infection.