RESUMO
BACKGROUND: Tamoxifen metabolism is translated into four genetic phenotypes (GP): genetic poor metabolizer (gPM); genetic intermediate metabolizer (gIM); genetic normal metabolizer (gNM); and genetic ultra-rapid metabolizer (gUM). Although CYP2D6 is involved in tamoxifen biotransformation, its association with tamoxifen side effects (TSE) is limited. Therefore, we evaluated CYP2D6 GP and clinical variables as potential predictors of TSE in Mexican Mestizo patients. METHODS: This cross-sectional study evaluated CYP2D6 GP, clinical data, and self-reported TSE in 71 women. Potential predictors were tested in uni- and multivariable models. RESULTS: Hot flashes (57.75%), arthralgia (45.07%), headache (43.66%), and cramps (39.44%) were the most frequent TSE. Three GP were identified: gPM (2.8%); gNM (93.0%); and gUM (4.2%). In the univariate analysis, none of the GP was predictive of TSE. However, the uni- and multivariable models showed contraceptive use and chemotherapy treatment prior to tamoxifen therapy to be predictive. Two alleles were identified for the first time at unusually high frequencies: CYP2D6*34 (13.2%); and *39 (14.7%). CONCLUSIONS: Our findings indicate that CYP2D6 GP were not significantly predictive of TSE, though two clinical descriptors were. The present results are a valuable contribution to pharmacogenetic characterization of Mexican Mestizo populations who, like other Latin-American groups, are poorly represented in the literature.
RESUMO
To date, several methods for the quantification of tamoxifen and its metabolites have been developed, most of which employ liquid chromatography tandem-mass spectrometry (LC-MS/MS). These methods are highly sensitive and reproducible, but are also time-consuming and require expensive equipment; one of their main disadvantages is matrix ionization effects. A more viable option, particularly in developing countries, is high-performance liquid chromatography coupled with UV or fluorescence detection. We developed and validated a method for simultaneous quantification of tamoxifen, endoxifen and 4-hydroxytamoxifen based on high-performance liquid chromatography with fluorescence detection in a reverse-phase column. The method is rapid (16 min plus 5 min of column re-equilibrium), accurate (80-100%) and precise (0.23-6.00%), and does not require any additional irradiation process. Sample pretreatment consists of protein precipitation with acetonitrile under alkaline conditions, employing only 200 µL plasma. The validated method's wide range allowed quantification of steady-state levels in patients under standard tamoxifen treatment (20 mg/day). This assay is ready for application in clinical studies and routine quantification of tamoxifen, endoxifen and 4-hydroxytamoxifen in healthcare institutions.
Assuntos
Antineoplásicos Hormonais/sangue , Neoplasias da Mama/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Fluorescência/métodos , Tamoxifeno/sangue , Antineoplásicos Hormonais/química , Antineoplásicos Hormonais/uso terapêutico , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Tamoxifeno/análogos & derivados , Tamoxifeno/química , Tamoxifeno/uso terapêuticoRESUMO
AIM: To describe delay intervals, their impact on clinical stage and initiation of first oncologic treatment, and evaluate associated factors in breast cancer patients in Yucatan, Mexico, a low-density population region. PATIENTS & METHODS: A retrospective analysis was done of 92 medical records, and bivariate and multivariate models applied to identify associations between healthcare delay and several factors. RESULTS: System delay accounted for most of the delay (median: 86 days; 61% of delay). Socioeconomic status and delivery to tertiary-care hospital predicted delay. Clinical stage determined initiation of first oncologic treatment. CONCLUSION: Delay in treatment was largely due to system delay. Only a few variables explained this delay. Clinical stage had the strongest effect on initiation of first oncologic treatment.
Assuntos
Neoplasias da Mama/epidemiologia , Diagnóstico Tardio , Atenção à Saúde , Tempo para o Tratamento , Adulto , Algoritmos , Neoplasias da Mama/diagnóstico , Comorbidade , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Vigilância da População , Estudos Retrospectivos , Classe Social , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Supracondylar humerus fractures are common in children between 5-7 years of age and more frequent in the males, 90-95% of these fractures are in extension mechanism, the urgency of immediate attention is to prevent complications and sequelae. OBJECTIVE: To establish the clinical and epidemiological profile of supracondylar humerus fractures, in a General Regional Hospital from the Instituto Mexicano del Seguro Social in Yucatan Mexico, during 2011-2013. MATERIAL AND METHODS: A cross-sectional study. Strength association was measured by odds ratios and statistical significance with chi(2) test, p value was considered in < 0.05 RESULTS: 56 cases were analyzed, the mean age was 2.6 ± 5.33 years, the mechanism of injury was falling over at home, male gender is associated with extent injure mechanism (OR 5.6, 95% CI 1.0-30.1, p = 0.03), we observed that at most time elapsed between injury and medical means more hospital days (r = 0.40; p = 0.002), surgical treatment was established in 44 cases (78.6%), 18 (40.9%) with closed technique and placement of cloves and 26 (59.1%) with open reduction, in 100% cross configuration was used, ten complications were reported. CONCLUSIONS: Supracondylar humerus fractures are a common injury in children, males are more likely to be injured by extension, and the speed in medical treatment is an important issue.