RESUMO
Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely CYP3A4, CYP3A5, MDR1 and POR genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations. Using TaqMan® probes, we determined the allelic frequency of seven variants in CYP3A4, CYP3A5, MDR1 and POR in 139 Chilean renal transplant recipients, of which 89 were treated with CsA and 50 with TAC. We tested associations between variants and trough and/or 2-hour concentrations, normalized by dose (C0/D and C2/D) at specific time points post-transplant. We found that CYP3A5*3/*3 carriers required lower doses of TAC. In TAC treated patients, most CYP3A5*3/*3 carriers presented higher C0/D and a high proportion of patients with C0 levels outside the therapeutic range relative to other genotypes. These results reinforce the value of considering CYP3A5 genotypes alongside therapeutic drug monitoring for TAC treated Chilean kidney recipients.
RESUMO
For better management of patients with febrile neutropenia, our study investigated the epidemiologic, microbiologic, and clinical characteristics of adult inpatients with febrile neutropenia and their mortality-associated factors. To this end, we carried out a prospective, observational, multicenter study in 28 Argentinian hospitals between 2007 and 2012. We included 515 episodes of febrile neutropenia from 346 patients, median age 49 years. Neutropenia followed chemotherapy in 77% of cases, half of the cases due to hematological malignancies. Most episodes were classified as high-risk according to MASCC criteria, and 53.6% of patients were already hospitalized at the onset of febrile neutropenia. Bloodstream infections were detected in 14% episodes; whereas an infectious source of fever was identified in 80% of cases. Mortality rate achieved to 14.95%. The binary regression analysis showed that persistence of fever at day 7, or neutropenia at day 14, dehydration and tachycardia at the onset of febrile neutropenia as well as prior infections were significantly associated with mortality. In addition to expanding our current knowledge on the features of adult patients with febrile neutropenia, present findings provide useful information for better management of them in Argentina, given the appropriate representativeness of centers participating in the study.
Assuntos
Neutropenia Febril/epidemiologia , Neutropenia Febril/microbiologia , Neutropenia Febril/mortalidade , Adulto , Antibacterianos/uso terapêutico , Argentina/epidemiologia , Feminino , Febre/complicações , Neoplasias Hematológicas/complicações , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
Se revisan las características clínicas, ECG, Radiológicas y EcoCG de 12 lactantes con Cardiomiopatia dilatada (CD), con un promedio de edad de 9 meses y en un seguimiento desde 1 a 42 meses. El 83% de los pacientes tuvo insuficiencia cardiaca congestiva, soplo sistólico mitral 66%, y el 92% infección respiratoria. El 16% tuvo secuela neurológica por embolía sistémica. Todos tenían alteraciones de la repolarización en el ECG, 75% signos de HVI, 50% crecimiento AI. Un 16% presentó arritmias o bloqueos A-V de primer grado, y en un paciente (8%) se encontró una imagen de pseudoinfarto de pared diafragmática. La radiología mostró Cardiomegalia en el 100%, con relación C/T media de 0,68; en el 66% de los casos había signos sugerentes de hipertensión venocapilar pulmonar. El EcoCG Modo M mostró dilatación VId (x:47,4 mm), disminución de la fracción de acortamiento (FA) (x:13,2%), y aumento de la relación de intervalos sistólicos de aorta (x:0,5). Durante el seguimiento, un 25% ha fallecido, y los que sobreviven aunque han mostrado una mejoría clínica, radiológica y ECG, siguen presentando dilatación VI (x:51.0 mm) y disminución de FA (x:14,4%) en el EcoCG de control. Se concluye que la CD es una patología de mal pronóstico y que el EcoCG es un bueno procedimiento para su diagnóstico, y seguimiento en nuestro medio