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1.
BMC Pediatr ; 24(1): 269, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38658852

RESUMO

BACKGROUND: There have been few studies evaluating the control of hypertension (HT) in children. This study aimed to assess the control of HT using ambulatory blood pressure monitoring (ABPM) and to compare the parameters between the uncontrolled HT and controlled HT groups. METHODS: Hypertensive patients aged ≥ 5 years who underwent ABPM to assess the control of HT were enrolled. Demographics, office blood pressure (BP), ABPM, and echocardiographic data were collected. Controlled HT was defined using a BP goal recommended by the 2016 European Society of Hypertension guidelines. RESULTS: There were 108 patients (64.8% males) with a mean age of 14.3 years and 51.9% had primary HT. Controlled HT was detected in 41.1% and 33.3% by office BP and ABPM, respectively. Based on ABPM, there was a greater prevalence of controlled HT in the primary HT than the secondary HT group (44.6% vs. 21.2%, P = 0.01). In the primary HT group, BMI z-score at the last follow-up had a significant decrease in the controlled HT than the uncontrolled HT group (-0.39 vs. 0.01, P = 0.032). Primary HT was negatively associated with uncontrolled HT by ABPM. In addition, ABPM showed greater sensitivity (77.8% vs. 55.8%) and negative predictive value (80.9% vs. 70.8%) to predict LVH than those of office BP measurement. CONCLUSION: Only one-third of patients achieved the BP goal by ABPM and most were in the primary HT group. Weight reduction is an important measure of BP control in patients with primary HT to attenuate the risk of LVH.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Hipertensão , Humanos , Monitorização Ambulatorial da Pressão Arterial/métodos , Masculino , Feminino , Hipertensão/diagnóstico , Criança , Adolescente , Pré-Escolar , Pressão Sanguínea , Estudos Retrospectivos , Anti-Hipertensivos/uso terapêutico
2.
Viruses ; 15(11)2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-38005890

RESUMO

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4-12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (p = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = -0.553, p = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (p = 0.03 and p = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.


Assuntos
Infecções por Citomegalovirus , Transplante de Fígado , Humanos , Criança , Citomegalovirus , Transplante de Fígado/efeitos adversos , Linfócitos T CD8-Positivos , Linfócitos T CD4-Positivos , Transplantados
3.
Pediatr Infect Dis J ; 42(1): e26-e31, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476533

RESUMO

BACKGROUND: Pediatric patients with systemic lupus erythematosus (SLE) are at increased infectious risk caused by underlying immunologic dysregulation and immunosuppressive therapy. Hepatitis B virus (HBV) could be reactivated during the immunosuppressive treatment in patients with past HBV infections. Information on immunogenicity after hepatitis B (HB) immunization and reimmunization are still scarce. METHODS: SLE patients 5-18 years of age who had completed a primary HB immunization were enrolled. Anti-HBs levels at enrollment and after each vaccine dose were determined. Patients with anti-HBs levels < 10 mIU/mL were administered 1 booster dose. After 1 booster dose, patients with negative anti-HBs levels were administered 2 more booster doses. RESULTS: Ninety-three SLE patients were enrolled. The prevalence of seroprotection assessed by anti-HBs > 10 mIU/mL after completion of a primary HB immunization was 25.8% (95% CI: 17.2-34.4). Lupus nephritis was associated with unprotective anti-HBs levels [odds ratio (OR): 4.341; 95% CI: 1.044-18.040]. The anti-HBs seroconversion was 72.3% (95% CI: 61.5-83.0) after 1 booster dose and increased up to 93.4% (95% CI: 86.9-98.4) after 3 booster doses. SLE Disease Activity Index-2000 score ≥ 4 (OR: 4.625; 95% CI: 1.45-14.80) was significantly associated with nonseroconversion after the first booster dose. Hypocomplementemia before the first and second booster doses (OR: 27; 95% CI: 1.26-578.35) was significantly associated with nonseroconversion after 3 booster doses. CONCLUSIONS: All pediatric SLE patients should be evaluated for HBV serological status before immunosuppressive treatment. SLE patients with SLE Disease Activity Index-2000 score > 4 should need 3 booster doses if their anti-HBs level was < 10 mIU/mL.


Assuntos
Vacinas contra Hepatite B , Lúpus Eritematoso Sistêmico , Humanos , Criança
4.
Glob Pediatr Health ; 9: 2333794X221142415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36544505

RESUMO

Children with severe acute kidney injury (AKI) have had a high mortality rate despite the use of advanced renal replacement therapy (RRT). This study aims to determine the clinical outcomes and the predictors of survival in pediatric AKI requiring RRT in Thailand. All patients aged 1 month to 18 years with AKI requiring RRT in the Department of Pediatrics, Ramathibodi Hospital from January 1st, 2010 to December 31st, 2019 were enrolled. Clinical and laboratory data were obtained through a medical record review. There were 92 patients with a 45% survival rate. Five factors associated with mortality included multi-organ dysfunction syndrome, presence of sepsis, high pediatric risk of mortality III, use of nephrotoxic drugs, and use of vasopressors. By multivariate analysis, the presence of sepsis and the use of nephrotoxic drugs were independently associated with mortality. Patients with fluid overload ≥10% was associated with poor survival.

5.
PLoS One ; 17(2): e0263536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35130317

RESUMO

OBJECTIVE: Juvenile-onset systemic lupus erythematosus (JSLE) is a complex and heterogeneous immune-mediated disease. Cellular components have crucial roles in disease phenotypes and outcomes. We aimed to determine the associations of lymphocyte subsets with clinical manifestations and long-term outcomes in JSLE patients. METHODS: A cohort of 60 JSLE patients provided blood samples during active disease, of whom 34 provided further samples during inactive disease. In a longitudinal study, blood samples were obtained from 49 of the JSLE patients at 0, 3, and 6 months. The healthy control (HC) group consisted of 42 age-matched children. Lymphocyte subsets were analyzed by flow cytometry. RESULTS: The percentages of CD4+ T, γδ T, and NK cells were significantly decreased in JSLE patients compared with HC, while the percentages of CD8+ T, NKT, and CD19+ B cells were significantly increased. The percentage of regulatory T cells (Tregs) was significantly lower in JSLE patients with lupus nephritis (LN) than in non-LN JSLE patients and HC. The patients were stratified into high and low groups by the median frequency of each lymphocyte subset. The γδ T cells high group and NK cells high group were significantly related to mucosal ulcer. The CD4+ T cells high group was significantly associated with arthritis, and the NKT cells high group was substantially linked with autoimmune hemolytic anemia. The CD8+ T cells low group was mainly related to vasculitis, and the Tregs low group was significantly associated with LN. The percentage of Tregs was significantly increased at 6 months of follow-up, and the LN JSLE group had a lower Treg percentage than the non-LN JSLE group. Predictors of remission on therapy were high Tregs, high absolute lymphocyte count, direct Coombs test positivity, and LN absence at enrollment. CONCLUSION: JSLE patients exhibited altered lymphocyte subsets, which were strongly associated with clinical phenotypes and long-term outcomes.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Subpopulações de Linfócitos/patologia , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/patologia , Contagem de Linfócitos , Masculino , Fenótipo , Prognóstico , Índice de Gravidade de Doença , Tailândia/epidemiologia
6.
Front Cardiovasc Med ; 9: 1026606, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36712271

RESUMO

Background: Waist-to-height-ratio (WHtR) has been proposed as another indicator for cardiometabolic risk factors including hypertension. Normally, hypertension can be diagnosed in the office setting by detecting high blood pressure for three occasions. However, patients with high office blood pressure may not exhibit high blood pressure outside the office. Ambulatory blood pressure monitoring (ABPM) is a procedure to measure blood pressure over 24-h. Sustained hypertension is characterized as hypertension detected by both office measurement and ABPM. This study aimed to evaluate the performance of WHtR in the diagnosis of sustained hypertension in patients with high office blood pressure. Materials and methods: Demographic data, height, body weight, body mass index (BMI), and waist circumference were retrospectively reviewed in children and adolescents who underwent ABPM due to persistently high office blood pressure. Patients were separated into two groups: a sustained hypertension group and a normal ABPM group. BMI was adjusted to z-score using the WHO Anthroplus software. WHtR was calculated by the formula: waist circumference (cm)/height (m). The performances of different parameters were analyzed using the receiver operating characteristic (ROC) curve and multivariate logistic regression. Results: Sixty patients (63% male) with a mean age of 12.9 ± 3.7 years had persistently high office blood pressure. Twenty-nine (48.3%) had high ambulatory blood pressure parameters so-called "sustained hypertension." The sustained hypertension group had a higher mean BMI z-score (2.32 vs. 1.31, p = 0.01) and a higher mean WHtR (57.7 vs. 49.2 cm/m, p < 0.001) than those of the normal ABPM group. For the diagnosis of sustained hypertension, the ROC analysis revealed that WHtR had a greater area under the ROC curve (AUC) than that of BMI z-score (0.772 vs. 0.723). WHtR remained associated with sustained hypertension (OR 1.2, 95% CI 1.022-1.408, p = 0.026) after adjusting for age, gender, and BMI z-score. Conclusions: Apart from being a more user-friendly metric, WHtR tended to outperform BMI z-score in predicting sustained hypertension in children and adolescents with persistently high office blood pressure.

7.
Paediatr Int Child Health ; 40(2): 124-128, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31809660

RESUMO

Background: In dengue infection, knowing time to platelet recovery is essential for optimal management.Aims: To determine a predictor for platelet recovery in patients with dengue infection.Methods: Platelet count and immature platelet fraction (IPF) from daily blood samples of patients with dengue infection during hospitalisation and 1-4 weeks after discharge were retrospectively analysed. The levels of patients' IPF were compared with normal controls recruited from healthy children with normal platelet counts.Results: A total of 244 EDTA blood samples were collected daily from 64 patients (45 males) with dengue infection (36 dengue fever, 28 dengue haemorrhagic fever) during hospitalisation and after discharge from the hospital. They did not receive any platelet concentrate transfusion. The median IPF among normal children was 3.6% with a 95 percentile of 9.9%. In dengue patients, an IPF of ≥10.0% after defervescence was associated with a subsequent platelet count of ≥60 × 109/L within 72 hours.Conclusion: In patients with dengue infection, IPF ≥10.0% after defervescence is a predictor of subsequent platelet recovery to a haemostatic level ≥60 × 109/L within 72 hours.


Assuntos
Plaquetas/fisiologia , Dengue/sangue , Adolescente , Criança , Feminino , Humanos , Masculino , Contagem de Plaquetas , Fatores de Tempo
8.
Pediatr Infect Dis J ; 39(3): 184-187, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31725549

RESUMO

BACKGROUND: The study aimed to develop dengue severity score to assess severe manifestations among hospitalized patients with dengue infection. METHOD: Children and adolescents with serologically confirmed dengue infection admitted at Ramathibodi Hospital from 2004 to 2018 and treated by an expert multidisciplinary team were recruited. Medical records were retrospectively reviewed and 14 items, related to clinical parameters and managements during hospitalization, were obtained daily as dengue severity score. RESULTS: A total of 191 patients with a mean age of 10.7 years from 2004 to 2013 were recruited. They were classified as dengue fever (35), dengue hemorrhagic fever (DHF) I (53), II (50), III (37) and IV (16). The analysis of 593 daily records revealed the range of daily severity score among patients with DHF grades III (10-20) and IV (31-47) were significantly higher than those of other groups (dengue fever, 5-13; DHF I, 2-10; DHF II, 6-11) with P-values of 0.0001. Using a validity test, a total daily score of ≥12 was an assessment tool for dengue shock syndrome with sensitivity, 86% and specificity, 84%. An additional 51 hospitalized patients with DHF grades II, III and IV with similar ages from 2014 to 2018 were recruited. The number of patients with severe manifestations, having daily score of ≥12, was significantly higher than those without severe manifestations starting from Day -3 to Day +1 of illness. CONCLUSIONS: Daily dengue severity score of ≥12 was an accurate assessment tool for severe manifestations.


Assuntos
Vírus da Dengue , Dengue/diagnóstico , Adolescente , Criança , Pré-Escolar , Dengue/mortalidade , Dengue/virologia , Feminino , Hospitalização , Humanos , Masculino , Prognóstico , Índice de Gravidade de Doença , Avaliação de Sintomas , Fatores de Tempo
9.
Pediatr Transplant ; 23(6): e13499, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31157501

RESUMO

BACKGROUND: Adequate BP control in RT recipients should not rely only by normal office BP but also on normal 24-hour BP. This study aims to assess adequacy of BP control by ABPM and to assess ABPM parameters associated with LVMI in pediatric RT recipients. MATERIALS AND METHODS: Patients aged 5-20 years who have been followed after RT were enrolled. Demographic data and BP assessed by office and ABPM were collected. Echocardiography was performed to detect LVMI. RESULTS: Thirty RT recipients (18 males) with median age of 15 years (IQR 13-18.5) were included. Among 23 patients who were taking antihypertensive drugs, uncontrolled hypertension was detected in 34.8% and 78.3% by office BP measurement and ABPM, respectively. Thus, the difference in prevalence of uncontrolled hypertension observed by ABPM versus office BP was 43.5%. Those seven patients who were not taking antihypertensive drugs because of normal office BP, four patients (57.1%) had masked hypertension and one patient had elevated BP. Fifteen patients have progression of LVH after RT. Multivariate analysis revealed that age (OR 1.369, 95%CI 0.985-1.904, P-value = 0.062) had a trend to be associated with progression of LVH. Moreover, nighttime systolic BP z-score was significantly correlated with LVMI (r = 0.551, P-value = 0.002). CONCLUSION: The difference in prevalence of uncontrolled hypertension uncovered by ABPM was 43.5%. Nighttime SBP z-score was significantly correlated with LVMI.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Falência Renal Crônica/cirurgia , Transplante de Rim , Adolescente , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Determinação da Pressão Arterial , Criança , Pré-Escolar , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Hipertensão Mascarada/complicações , Prevalência , Adulto Jovem
10.
J Biomed Sci ; 25(1): 64, 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30149800

RESUMO

BACKGROUND: B cells play an essential role during dengue viral infection. While a major expansion of antibody secreting cells (ASCs) was observed, the importance of these increased frequencies of ASCs remains unclear. The alteration of B cell subsets may result from the expression of tissue specific homing molecules leading to their mobilization and distribution to different target organs during acute dengue viral infection. METHODS: In this study, whole blood samples were obtained from thirty pediatric dengue-infected patients and ten healthy children and then stained with fluorochrome-conjugated monoclonal antibodies against CD3, CD14, CD19, CD20, CD21, CD27, CD38, CD45, CD138 and homing molecules of interest before analyzed by polychromatic flow cytometry. B cell subsets were characterized throughout acute infection period. RESULTS: Data shows that there were no detectable differences in frequencies of resting, activated and tissue memory cells, whereas the frequency of ASCs was significantly increased and associated with the lower frequency of naïve cells. These results were found from patients with both dengue fever and dengue hemorrhagic fever, suggesting that such change or alteration of B cells was not associated with disease severity. Moreover, several homing molecules (e.g., CXCR3 and CCR2) were found in ASCs, indicating that ASCs may distribute to inflamed tissues and various organs. CONCLUSIONS: Findings from this study provide insight into B cell subset distribution. Furthermore, organ mobilization according to homing molecule expression on different B cell subsets during the course of dengue viral infection also suggests they are distributed to inflamed tissues and various organs.


Assuntos
Subpopulações de Linfócitos B/virologia , Dengue/diagnóstico , Dengue/genética , Expressão Gênica , Plasmócitos/virologia , Doença Aguda/classificação , Adolescente , Infecções Assintomáticas/classificação , Criança , Pré-Escolar , Vírus da Dengue/fisiologia , Feminino , Marcadores Genéticos , Humanos , Masculino , Adulto Jovem
11.
PLoS Negl Trop Dis ; 12(2): e0006202, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29447178

RESUMO

Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.


Assuntos
Povo Asiático/genética , Vírus da Dengue/genética , Dengue/genética , Genoma Viral/genética , Estudo de Associação Genômica Ampla , Dengue Grave/genética , Adolescente , Adulto , Sudeste Asiático , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas de Transporte/genética , Linhagem Celular , Núcleo Celular/virologia , Pré-Escolar , Estudos de Coortes , Dengue/virologia , Feminino , Expressão Gênica , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Proteínas do Tecido Nervoso/genética , Razão de Chances , Proteína Fosfatase 2/genética , Proteínas Repressoras/genética , Sorogrupo , Dengue Grave/etnologia , Sulfotransferases , Tailândia , Fosfolipases Tipo C/genética , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética , Adulto Jovem
12.
Immunology ; 153(4): 455-465, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29105052

RESUMO

Dengue virus (DENV) infection is considered one of the most important mosquito-borne diseases. It causes a spectrum of illness that could be due to qualitative and/or quantitative difference(s) of the natural killer (NK) cell responses during acute DENV infection. This view prompted us to perform a detailed phenotypic comparative characterization of NK cell subsets from DENV-infected patients with dengue fever (DF), patients with dengue haemorrhagic fever (DHF) and healthy controls. The activation/differentiation molecules, CD69 and CD57 and a variety of tissue homing molecules were analysed on the CD56hi CD16- and CD56lo CD16+ NK cells. Although there was no increase in the frequency of the total NK cells during DENV infection compared with the healthy individuals, there was a significant increase in the frequency of the CD56hi CD16- subset and the frequency of CD69 expression by both NK cell subsets during the febrile phase of infection. We also found an increase in the frequencies of cells expressing CD69 and CD57 in the CD56lo CD16+ subset compared with those in the CD56hi CD16- subset. Moreover, although the CD56lo CD16+ subset contained a high frequency of cells expressing skin-homing markers, the CD56hi CD16- subset contained a high frequency of cells expressing bone marrow and lymph node trafficking markers. Interestingly, no differences of these NK cell subsets were noted in samples from patients with DF versus those with DHF. These findings suggest that activation and differentiation and the patterns of tissue homing molecules of the two major NK cell subsets are different and that these might play a critical role in the immune response against acute DENV infection.


Assuntos
Antígenos CD/imunologia , Dengue/imunologia , Células Matadoras Naturais/imunologia , Doença Aguda , Adolescente , Anticorpos Monoclonais/imunologia , Biomarcadores , Criança , Pré-Escolar , Dengue/sangue , Vírus da Dengue/imunologia , Feminino , Humanos , Masculino , Adulto Jovem
15.
Clin Exp Rheumatol ; 35(2): 344-500, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28229822

RESUMO

OBJECTIVES: To evaluate cardiac structure and function in paediatric SLE patients without clinical evidence of cardiovascular disease in active and inactive diseases. METHODS: Patients aged ≤20 years who fulfilled the diagnostic criteria of active SLE underwent transthoracic echocardiography to evaluate cardiac structure and function, and were then followed up echocardiographically every 3-4 months until SLE disease was inactive. Patients with heart failure, myocarditis, pericarditis, endocarditis, coronary artery disease, or abnormal structural heart disease were excluded. RESULTS: Twenty-six active SLE patients, mean age 13.2±3.3 years, of whom 20 were female (77%), were enrolled. Most patients had cardiac abnormalities especially LV global dysfunction assessed by left ventricular myocardial performance index (LV MPI). LV MPI by conventional method, by tissue Doppler imaging (TDI) at medial and lateral mitral valve annulus were significantly decreased when compared to LV MPI in patients with inactive disease (0.44±0.14 vs. 0.30±0.05, 0.52±0.09 vs. 0.36±0.04, and 0.51±0.09 vs. 0.35±0.05, p<0.001). Using receiver operating characteristic, LV MPI cut-off at 0.37, 0.40, and 0.40 by conventional, medial TDI, lateral TDI had sensitivity and specificity of 90% and 84%, 90% and 96%, 90% and100%, respectively. CONCLUSIONS: Left ventricular global dysfunction was found to be common in paediatric patients with active SLE. LV MPI by TDI might be useful to diagnose active SLE in paediatric patients.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Contração Miocárdica , Miocardite/etiologia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Adolescente , Fatores Etários , Área Sob a Curva , Doenças Assintomáticas , Criança , Ecocardiografia Doppler , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Miocardite/diagnóstico por imagem , Miocardite/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Recuperação de Função Fisiológica , Indução de Remissão , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
16.
J Infect Dis ; 212(12): 2011-20, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26063222

RESUMO

Dengue is a mosquito-borne viral disease that afflicts millions of individuals worldwide every year. Infection by any of the 4 dengue virus (DENV) serotypes can result in a spectrum of disease severity. We investigated the impact of variants of interferon-regulated innate immunity genes with a potent antiviral effect on the outcome of DENV infection. We compared the effect of OAS gene family variants on 2 DENV serotypes in cell culture. While both OAS1-p42 and p46 showed antiviral activity against DENV-2, only OAS1-p42 presented anti-DENV-1 activity. Conversely, whereas both OAS3_S381 and R381 variants were able to block DENV-1 infection, the anti-DENV-2 activity observed for OAS3_S381 was largely lost for the R381 variant. By means of an allelic association study of a cohort of 740 patients with dengue, we found a protective effect of OAS3_R381 against shock (odds ratio [OR], 0.37; P < .001). This effect was due to DENV-2 infections (OR, 0.13; P = .007) but was absent for DENV-1, in accordance with the serotype-dependent OAS3 activity found in the functional study. Severe dengue has long been associated with a cytokine storm of unclear origin. This work identifies an early innate immunity process that could lead to the immune overreaction observed in severe dengue and could be triggered by a specific host genotype-pathogen genotype interaction.


Assuntos
2',5'-Oligoadenilato Sintetase/genética , Vírus da Dengue/imunologia , Dengue/patologia , Predisposição Genética para Doença , 2',5'-Oligoadenilato Sintetase/metabolismo , Adolescente , Adulto , Células Cultivadas , Criança , Pré-Escolar , Dengue/genética , Dengue/imunologia , Feminino , Estudos de Associação Genética , Humanos , Lactente , Masculino , Adulto Jovem
17.
Int J Vasc Med ; 2015: 917143, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25722892

RESUMO

The vascular leakage was shown by the increment of hematocrit (Hct), dengue viral infected monocyte, monocyte status, and cytokines production in patients infected with dengue virus. Dengue viral antigens were demonstrated in monocytes (CD14+) from peripheral blood mononuclear cells. The increased levels of Hct, interleukin- (IL-) 10, and tumor necrosis factor-alpha (TNF-α) were detected in dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) patients as compared with other febrile illnesses (OFIs). The highest levels of Hct and IL-10 were detected in DSS patients as compared with other groups (P < 0.05) especially on one day before and after defervescence. The unstimulated and lipopolysaccharide- (LPS-) stimulated monocytes from DSS patients showed the significantly decreased of intracellular IL-1ß and TNF-α. In addition, the lowest level of mean fluorescence intensity (MFI) of CD11b expression on monocytes surface in DSS patients was also demonstrated. Furthermore, the negative correlations between IL-10 levels and intracellular IL-1ß and MFI of CD11b expression in unstimulated and LPS-stimulated monocytes were also detected. Nevertheless, not only were the relationships between the prominent IL-10 and the suppression of intracellular monocyte secretion, namely, IL-1ß, TNF-α, demonstrated but also the effect of vascular leakage was observed.

18.
Paediatr Int Child Health ; 33(2): 97-101, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23925283

RESUMO

BACKGROUND: A single nucleotide polymorphism located at the promoter -308A of tumour necrosis factor-alpha (TNF-α) gene may affect transcription and increase cytokine production, leading to the severe manifestation of dengue virus infection. AIM: To study the association of the TNF-α -308A allele and the severity of patients with dengue infection. METHODS: 112 patients suspected of having dengue infection and 106 normal controls were enrolled in the study. Mean (SD) age was 10.4 (3.6) years. In all, 19 and 82 patients were diagnosed with dengue fever (DF) and dengue haemorrhagic fever (DHF), respectively, while 11 were diagnosed with other febrile illnesses (OFIs). They were tested for the polymorphisms at the promoter -308 position of the TNF-α gene and their TNF-α levels were measured. RESULTS: In the patients with dengue infection (14/202, 6.9%) with OFIs (1/22, 4.5%) and in normal controls (17/212, 8.0%), the frequency of the TNF-α -308A allele was not significantly different. Moreover, no statistically significant difference was found in patients with various clinical manifestations of dengue infection involving DF (5.3%, 2/38), DHF grade I (5.0%, 2/40), DHF grade II (9.5%, 4/42), DHF grade III (2.5%, 1/40) and DHF grade IV (11.9%, 5/42). However, patients with dengue infection and significant bleeding manifestations, apart from petechiae and ecchymosis, tended to have a higher frequency of the TNF-α -308A allele (11.8%, 9/76) than those without significant bleeding manifestations (5/126, 4.0%) (P = 0.056). The levels of TNF-α were additionally measured in 67 patients but the results failed to demonstrate a functional effect in the transcriptional rate of the TNF-α -308A allele. CONCLUSION: In patients with dengue infection there is an association between the TNF-α -308A allele and the risk of bleeding. The test may be used as one of the predictors of the severity of dengue infection.


Assuntos
Dengue/complicações , Dengue/genética , Predisposição Genética para Doença , Hemorragia/epidemiologia , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adolescente , Criança , Pré-Escolar , Feminino , Frequência do Gene , Humanos , Masculino , Medição de Risco
20.
Pediatr Transplant ; 17(2): 112-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23442099

RESUMO

As universal coverage for pediatric kidney transplantation (KT) was introduced in Thailand in 2008, the number of recipients has been increasing. We evaluated predictive factors for graft failure to understand how to improve clinical outcomes in these children. Using data obtained from the National Transplant registry, we assessed the risk of graft failure using the Kaplan-Meier method and Cox proportional hazards regression. Altogether, 201 recipients aged <21 yr at the time of KT were studied. Living donors (LD) were significantly older than deceased donor (DD). Mean cold ischemia time of DD was 17 h. The mean donor glomerular filtration rate (GFR) was 84.0 mL/min/1.73 m(2) . Induction immunosuppressive therapy was administered more frequently in DD than in LDKT. Delayed graft function (DGF) occurred in 36 transplants. Over 719 person years of follow-up, 42 graft failures occurred. Graft survival at one, three, and five yr post-transplant were 95%, 88% and 76%, respectively. Two factors independently predicted graft failure in multivariate analysis. The hazard ratios for graft failure in patients with DGF and in patients with donor GFR of ≤30 mL/min/1.73 m(2) were 2.5 and 9.7, respectively. Pediatric recipients should receive the first priority for allografts from young DD with a good GFR, and DGF should be meticulously prevented.


Assuntos
Função Retardada do Enxerto/etiologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim , Adolescente , Adulto , Criança , Pré-Escolar , Função Retardada do Enxerto/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Transplante de Rim/métodos , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Tailândia , Doadores de Tecidos/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
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