RESUMO
Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5'-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.
Assuntos
Epilepsia , Ácido Valproico , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia/tratamento farmacológico , Epilepsia/genética , Humanos , Polimorfismo de Nucleotídeo Único , Convulsões/tratamento farmacológico , Convulsões/genética , Ácido Valproico/uso terapêuticoRESUMO
PURPOSE: To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. METHODS: Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. RESULTS: A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3-7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6-7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4-55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6-109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan-Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3 Gy) being associated with increased risk of post-re-RT pseudo-progression. CONCLUSION: This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.
Assuntos
Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Glioma/mortalidade , Glioma/radioterapia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/radioterapia , Reirradiação , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Progressão da Doença , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Reirradiação/efeitos adversos , Reirradiação/métodos , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.
Assuntos
Humanos , Criança , Ácido Valproico/uso terapêutico , Epilepsia/genética , Epilepsia/tratamento farmacológico , Convulsões/genética , Convulsões/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Anticonvulsivantes/uso terapêuticoRESUMO
PURPOSE: This study examined the prevalence of Helicobacter pylori (H. pylori) infection in school children from an urban area in Northwest Mexico and attempted to identify the risk factors that predispose children to infection in the community.METHODS: The cross-sectional study was conducted in 1997/98 in the poorest socio-economic sectors of the city of Hermosillo, Sonora, among 178 children aged 9 and 10 years. H. pylori status was determined in children by the accurate and safe non-invasive 13C-urea breath test. Family socio-demographic/socio-economic status and living conditions data were elicited from parents by interview via structured questionnaires and/or direct observation.RESULTS: The overall prevalence rate of H. pylori infection for the children in Hermosillo as determined by this study was 47.1%. The overall prevalence rate of H. pylori infection was not found to be related to either gender (p = 0.531) nor to the two age groups (p = 0.483). It was not related to child's birthplace (p = 0.291) even after controlling for age and gender. However, the overall prevalence of infection was strongly and significantly associated with the parent's birthplace; rural-born mother (p = 0.028) and rural-born father (p = 0.029). There was a noticeable lack of statistical association with the presence of animals at home (p = 0.988) and with direct contact with indoor/outdoor animals for study children (p = 0.099). When all of the explanatory variables that were significant in the bivariate analysis were fitted into a direct logistic regression model, the same strong effect of father's birth place (rural setting), number of siblings (>/=3 per family), type of main water supply (one tap in the yard) and the sharing of bed by the study child were observed as potential risk factors for acquiring the infection.CONCLUSIONS: The findings indicate that high prevalence rate of H. pylori infection observed on study children seems to depend on factors related to poor living conditions, particularly (but not exclusively) number of children, ruralism (rural-born father), the sharing a bed in childhood and type of main water supply (one tap in the yard).
RESUMO
Weight gains occur during normal pregnancy in women with free access to food. Maternal nutrition status prior to conception and during pregnancy is a critical determinant of foetal growth and pregnancy outcomes. These gains reflect changes in the composition of the maternal body as well as changes in the products of conception. There are limited data from the West Indies about maternal nutritional status during pregnancy as well as the factors determining changes in body composition and pregnancy weight gain. We report the results of a prospective study of 342 pregnant Barbadian women conducted between August 1994 and February 1996 which assessed nutritional changes during pregnancy and their impact on glucose metabolism. This report is, however, limited to the changes observed in nutritional indices. At registration, age and parity were strongly analysed demonstrated that change in weight between registration (at a median time of 15 weeks gestation) and 36 weeks gestation and postpartum, were independently and inversely associated with BMI and age. Parity was not found to be independently associated with weight change. Changes in body composition were examined by deriving estimates of fat and lean mass. Estimated fat mass gains were consistent with those reported from well-nourished Western societies, and were mainly determined by initial BMI. We also observed gains in lean mass as a consequence of pregnancy. (AU)
Assuntos
Feminino , Gravidez , Humanos , Gravidez , Glicemia/metabolismo , Índice de Massa Corporal , Paridade , Barbados , Estado NutricionalRESUMO
Two hundred and fifty women were studied to evaluate the effects of maternal growth on glucose and insulin metabolism during the pregnancy. Participants were recruited from the antenatal clinic at the Queen Elizabeth Hospital, Barbados, if they booked by 16 weeks' gestation. Anthropometric indices, including skinfold thickness, weight, height and hip circumference, were measured at recruitment, and participants subjected to a 75-gm oral glucose tolerance test (WHO criteria) at 18 weeks' gestation. Fasting blood samples were collected for plasma lipids, venous plasma glucose (VPG), serum insulin, c-peptide and glycosylated haemoglobin. Samples were taken at 1 and 2 hours post glucose load for VGP (fasting: p=0.003; 1 hour: p=0.008; 2 hour: p=0.026) and fasting insulin levels (p=0.02). High mean hip circumference at booking was associated with raised VPG (fasting:p=0.07; 1 hour: p=0.04; 2hour: p=0.16) and fasting serum insulin (p<0.001). Fat distribution, rather than global obesity per se, may be an important factor influencing glucose and insulin metabolism during pregnancy (AU)