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INTRODUCTION: Due to its high specificity and sensitivity, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is the gold standard method for immunosuppressant quantification in therapeutic drug monitoring. In this context, dried blood spots (DBS) have become a promising strategy as a sample collection procedure. Although the advantages of DBS over venipuncture are well known, this approach has limitations that strongly influence the acceptance of analytical results. Among them, the most important is hematocrit (Ht). The easiest way of overcoming this problem is by analyzing complete spots. In this strategy, called dried matrix on paper discs (DMPD), blood is volumetrically applied on pre-punched discs. OBJECTIVES: To validate an LC-MS/MS method for the quantification of tacrolimus, sirolimus, everolimus and cyclosporin A using DMPD. METHODS: The procedure was validated according to international guidelines using a commercial kit. The following performance parameters were evaluated: selectivity, carryover, linearity, accuracy, precision, lower limit of quantitation, relative recovery, commutability and stability. In addition, a method comparison study was performed to evaluate the clinical influence of Ht on the results. RESULTS: All performance parameters were within acceptance criteria and, hence, it was determined that the validated method is fit for the intended purpose. Likewise, calculated bias values on medical decision levels showed that there was no clinical influence of Ht on the results. CONCLUSION: Unlike other similar methodologies that have been published, here, a simple method has been fully validated. This is the first LC-MS/MS methodology adapting a commercial kit to use DMPD as a sampling strategy.
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UNLABELLED: Several ChimeriVax-Dengue (CYD)-based vaccination strategies were investigated as potential alternatives to vaccination with tetravalent CYD vaccine (CYD-TDV) in this phase IIa trial conducted in 2008-9 in 150 healthy adults. Participants were randomized and vaccinated on D0 and D105 (± 15 days). One group received bivalent CYD vaccine against serotypes 1 and 3 (CYD-1;3) on day 0 and CYD-2;4 on day 105 (± 15 days). Two groups received an injection at each timepoint of a tetravalent blend of CYD-1;3;4 and a VERO cell derived, live attenuated vaccine against serotype 2 (VDV-2), or the reference CYD-TDV. A fourth group received Japanese encephalitis (JE) vaccine on days -14, -7 and 0, followed by CYD-TDV on day 105. Viraemia was infrequent in all groups. CYD-4 viraemia was most frequent after tetravalent vaccination, while CYD-3 viraemia was most frequent after the first bivalent vaccination. Immunogenicity as assessed by 50% plaque reduction neutralisation test on D28 was comparable after the first injection of either tetravalent vaccine, and increased after the second injection, particularly with the blended CYD-1;3;4/ VDV-2 vaccine. In the bivalent vaccine group, immune response against serotype 3 was highest and the second injection elicited a low immune response against CYD 2 and 4. Immune responses after the first injection of CYD-TDV in the JE-primed group were in general higher than after the first injection in the other groups. All tested regimens were well tolerated without marked differences between groups. Bivalent vaccination showed no advantage in terms of immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: NCT00740155.
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Anticorpos Antivirais/sangue , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Viremia/sangue , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Dengue/prevenção & controle , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/uso terapêutico , Feminino , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Vacinas contra Encefalite Japonesa/efeitos adversos , Vacinas contra Encefalite Japonesa/imunologia , Vacinas contra Encefalite Japonesa/uso terapêutico , Masculino , México , Testes de Neutralização , Vacinação , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Viremia/imunologia , Vacinas contra o Vírus do Nilo Ocidental/efeitos adversos , Vacinas contra o Vírus do Nilo Ocidental/imunologia , Vacinas contra o Vírus do Nilo Ocidental/uso terapêutico , Adulto JovemRESUMO
Prenatal lead exposure is a health hazard that may cause cognitive development impairments and other adverse effects in children. We conducted a cross sectional study analyzing cord blood lead levels (CBLL) of newborns and their relationship with maternal determinants of lead exposure. Mothers answered a questionnaire about socio-demographic, lifestyle habits and environmental characteristics. We used Mann-Whitney's test to compare CBLL geometrical means (GM) corresponding to the presence or absence of each lead exposure determinant, and Chi square test to study the relationship between CBLL and maternal lead exposure determinants. A total of 159 newborns participated in the study. CBLL GM was 2.1 µg/dL; and 25% of the participants had a measurable CBLL (LOQ=3.3 µg/dl). Although the participants had several determinants of lead exposure, we only found a significant relationship with inside household determinants, such as presence of lead piping (p=0.026), unplastered walls (p=0.046) and peeling paint (p=0.048). Our results show that CBLL GM was similar to that reported in several studies conducted around the world. However, 25% of the participants might have some degree of risk for lead poisoning.
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Poluentes Ambientais/sangue , Chumbo/sangue , Exposição Materna/estatística & dados numéricos , Adulto , Argentina/epidemiologia , Feminino , Maternidades , Habitação/estatística & dados numéricos , Humanos , Recém-Nascido , Intoxicação por Chumbo/epidemiologia , Masculino , GravidezRESUMO
Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8-13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-h. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-h, there were statistically significant (p<0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-h and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8-13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted.