[Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina]. / Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina.

INTRODUCTION: Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. METHODS: The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. RESULTS: BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. CONCLUSION: BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our population. There is a significant correlation between BRAF mutation and lymph-node metastasis.

Introducción: Se ha descrito que alteraciones moleculares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogénesis. Nuestro objetivo fue conocer la frecuencia mutacional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos: Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 muestras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados: La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspondieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la mutación, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los ganglios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión: La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina / Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina

Resumen Introducción : Se ha descrito que alteraciones molecu lares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogé nesis. Nuestro objetivo fue conocer la frecuencia muta cional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos : Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 mues tras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados : La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspon dieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la muta ción, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los gan glios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión : La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Abstract Introduction : Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. Methods : The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. Results : BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. Conclusion : BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our popu lation. There is a significant correlation between BRAF mutation and lymph-node metastasis.

Comparison between two newborn screening strategies for cystic fibrosis in Argentina: IRT/IRT versus IRT/PAP.

BACKGROUND: The benefits of early cystic fibrosis (CF) detection using newborn screening (NBS) has led to widespread use in NBS programs. Since 2002, a two-stage immunoreactive trypsinogen (IRT/IRT) screening strategy has been used as a CFNBS method in all public maternity units in the City of Buenos Aires, Argentina. However, novel screening strategies may be more efficient. The aim of this study is to prospectively compare two CFNBS strategies: IRT/IRT and IRT/PAP (pancreatitis-associated protein). METHODS: A two-year prospective study was performed. IRT was measured in dried blood samples collected 48-72 h after birth. When an IRT value was abnormal, PAP was determined, and a second visit was scheduled to obtain another sample for IRT before 25 days of life. Newborns with a positive CFNBS were referred for a confirmatory sweat test. RESULTS: There were 69,827 births in the City of Buenos Aires during the period studied; 918 (1.31%) had an abnormal IRT. A total of 207 children (22.5%) failed to return for the second IRT, but only two PAP (0.2%) were not performed. IRT/IRT was more likely to lead to a referral for sweat testing than IRT/PAP (odds ratio 2.3 [95% confidence interval 1.8-2.9], p < .001). Sensitivity and specificity were: 80% and 100% and 86.5% and 82.6% for IRT/IRT and IRT/PAP strategies, respectively. CONCLUSION: The IRT/PAP strategy is more sensitive than IRT/IRT and has similar specificity; it avoids a second visit and unnecessary sweat testing, and it reduces loss to follow-up in our population.

Comparación de fórmulas para la estimación del filtrado glomerular: correlación e implicancia clínica / Comparison of formulas for the estimation of glomerular filtration: correlation and clinical implication / Comparação de fórmulas para a estimativa da filtração glomerular: correlação e implicações clínicas

La Enfermedad Renal Crónica (ERC) es un importante problema de salud pública que trae aparejada una gran morbi-mortalidad. Una de las herramientas diagnósticas es la estimación del filtrado glomerular (eFG). Los objetivos de este estudio fueron comparar el eFG según dos ecuaciones: MDRD-4 y CKD-EPI, evaluar su comportamiento en valores clínicamente relevantes y evidenciar Enfermedad Renal Oculta (ERO) según cada una de las fórmulas evaluadas, clasificando a la población estudiada en estadíos de ERC. Se evaluaron 2.526 pacientes con factores de riesgo asociados a ERC. La media de los resultados obtenidos con ambas fórmulas fue: para MDRD-4 84,5 mL/min/1,73 m², y para CKD-EPI 90,9 mL/min/1,73 m². De la relación entre el eFG en sus diversos estadíos y los resultados de creatininemia resultó que 83 pacientes se clasificaron como ERO según MDRD-4, y 23 lo hicieron para CDK-EPI, con lo que se manifestó una subestimación de la eFG utilizando la ecuación MDRD-4. La importancia de este estudio radica en el hallazgo precoz y en la prevención de complicaciones que podrían limitar el bienestar de estos pacientes. La participación de Laboratorios nucleados en red brinda herramientas accesibles y de bajo costo para su asistencia temprana, en busca de seguridad, cuidado y educación del paciente.

Chronic Kidney disease (CKD) is an important public health problem which is associated to an increase in mortality. An important diagnostic tool is the estimated glomerular filtration rate (GFR). The aims of this study were to compare GFR according to two different formulas: MDRD-4 and CKD-EPI, in order to evaluate its performance in clinically relevant values and to display occult chronic kidney disease (OCKD) according to each of the equations reviewed to classify the studied population into different stages of CKD. A total of 2526 patients with CKD-associated risk factors were analyzed. Mean of the results with both formulas were: 84.5 mL/min/1.73 m² for MDRD-4 and 90.9 mL/min/1.73 m² for CKD-EPI. Considering the associations between GFR in each of the stages and the results of blood creatinine, 83 patients were classified as OCKD by MDRD-4 while 23 were classified by MDRD-EPI; showing an underestimation of the GFR when using MDRD-EPI. The importance of this study lies in the early detection of the disease and in preventing the complications that could restrict the patient’s well-being. The support of the networking laboratories brings the appropriate and low cost tools for an early assistance in search of security, care and education forthe patient.

A Doença Renal Crônica (DRC) é um importante problema de saúde pública que traz grande morbimortalidade. Uma das ferramentas de diagnóstico é a estimativa de filtração glomerular (eFG). Os objetivos deste estudo foram comparar eFG de acordo com duas equações: MDRD-4 e CKD-EPI, avaliar seu comportamento em valores clinicamente relevantes e evidenciar Doença Renal Oculta (DRO) de acordo com cada uma das fórmulas avaliadas, classificando a população estudada em estágios de DRC. Foram avaliados 2526 pacientes com fatores de risco associados à DRC. A média dos resultados obtidos com as duas formulações foi: MDRD-4 a 84,5 mL/min /1,73 m², e CKD-EPI 90,9 mL/min/1.73 m². A relação entre o eFG nas suas diversas fases e os resultados de creatininemia mostrou que 83 pacientes foram classificados como ERO segundo MDRD-4, e 23 fizeram para CDK-EPI, demonstrando uma subestimação da eFG usando a equação MDRD-EPI. A importância desse estudo está na detecção precoce e prevenção de complicações que poderiam limitar o bem-estar desses pacientes. A participação de Laboratórios reunidos em uma rede fornece ferramentas acessíveis e de baixo custo para sua assistência precoce, em busca de segurança, cuidado e educação do paciente.

Evaluación de los parámetros de desempeño de un contador hematológico / Evaluation of performance parameters of an automated hematology analyzer / Avaliação dos parâmetros de desempenho de um analisador da hematologia

El primer paso para obtener seguridad en los resultados emitidos por el laboratorio clínico es confirmar que los procedimientos de medida utilizados tienen un desempeño analítico aceptable. Para conseguirlo se verificó el contador hematológico Beckman Coulter LH 750 de acuerdo con las especificaciones del fabricante y con los requisitos de calidad de este laboratorio. Los parámetros de desempeño evaluados, tanto en modo manual como automático, fueron: porcentaje de arrastre, según protocolo CLSI H26-A2, precisión en condiciones de repetibilidad, precisión en condiciones de precisión intermedia y veracidad, según protocolo CLSI EP15-A2 utilizando controles BIO-RAD, intervalo de medición, según protocolo CLSI EP6-A, límite de cuantificación, según protocolo CLSI EP17-A2 e intervalos de referencia, según protocolo CLSI EP28-A3C. Los datos se analizaron mediante LinChecker y GraphPad 5. En los ensayos realizados se cumplió con las especificaciones estipuladas por el fabricante, como así también con el requisito de calidad de este laboratorio que es variabilidad biológica mínima. También se verificaron los intervalos de referencia para individuos adultos. De esta manera, se logró realizar la verificación del contador hematológico, evidenciando que los parámetros analíticos evaluados tienen un desempeño aceptable.

The first step for safety in the results issued by the clinical laboratory is to confirm that all analytical measurement procedures have shown an acceptable analytical performance. A quality performance evaluation of automated hematology analyzer Beckman Coulter LH 750 was performed according to the quality requirements of our laboratory and manufacturer's specifications. The performance parameters evaluated by both manual and automatic mode were: carryover according to CLSI H26-A2 protocol; repeatability, intermediate precision and trueness according to CLSI EP15-A2 protocol and using BIO-RAD controls; linearity according to CLSI EP6-A protocol; quantification limits according to CLSI EP17-A2 protocol; and reference intervals according to CLSI EP28-A3C protocol. Data were analyzed using LinChecker and GraphPad5 programs. The tests performed complied with the requirements stipulated by the manufacturer and the quality requirements of our laboratory like minimal biological variability. Reference intervals for adult individuals were also checked. Consequently, performance evaluation of the automated hematology analyzer showed that the assessed laboratory parameters have acceptable performance.

O primeiro passo para obter segurança nos resultados emitidos pelo laboratório clínico é confirmar que os processos de medição utilizados tenham um desempenho analítico aceitável. Para obtê-los foi verificado o analisador hematológico Beckman Coulter LH 750 de acordo com as especificações do fabricante e os requisitos de qualidade deste laboratório. Os parâmetros de desempenho avaliados, tanto em modo manual quanto automático, foram: percentual de arrastamento, de acordo com o protocolo CLSI H26-A2, em condições de repetitibidade, precisão em condições de precisão intermediária e veracidade, conforme o protocolo CLSI EP15-A2 usando controles Bio-Rad, intervalo de medição segundo o protocolo CLSI EP6-A, limite de quantificação, de acordo com CLSI EP- 17-A2 e intervalos de referência, de acordo com o protocolo CLSI EP28-A3C. Os dados foram analisados através de LinChecker e GraphPad 5. Nos ensaios realizados foram obsevadas as especificações estabelecidas pelo fabricante, bem como a exigência de qualidade deste laboratório que é variabilidade biológica mínima. Os intervalos de referência para indivíduos adultos também foram verificados. Desta forma, foi possível realizar a verificação do analisador hematológico, que demonstra que os parâmetros analíticos avaliados têm um desempenho aceitável.

Improving arylsulfatase activity determination in dried blood spots: Screening and diagnostic approaches for Maroteaux-Lamy syndrome (MPS VI).

BACKGROUND: Mucopolysaccharidosis type VI can be screened by measuring the lysosomal arylsulfatase B (ARSB) residual enzyme activity in dried blood spots (DBS) using synthetic substrates. However, we have found experimental obstacles when determining ARSB activity with the fluorescent method due to the significant quenching effect rendered by DBS components. METHODS: We adapted the methods originally described by Chamoles et al. [1] and Civallero et al. [2] and put forward 2 distinct approaches for ARSB activity quantification from DBS samples by measuring the 4-methylumbelliferone (ß-MU) fluorescence generated from the ARSB 4-methylumbelliferone sulfate (ß-MUS) substrate. RESULTS: We demonstrate the high throughput feasibility of a novel approach for measuring ARSB activities by incorporating tailor-made calibration curves according to each patient's DBS sample quenching properties. The second method is used to calculate ARSB activities by measuring the fluorescence and absorbance parameters in each reaction sample with a single DBS-free calibration curve. CONCLUSIONS: The quantitative correlation between the DBS sample absorbance and its quenching effect can be used to calculate predictive ARSB activities and would serve as an affordable first tier screening test. The method described herein demonstrates the critical importance of adapting the ß-MU calibration curves to each patient's unique DBS sample matrix and its positive impact on the accuracy and reliability of ARSB activity measurements.

Association between vitamin D and Apo B concentrations in Argentinean Indian children.

OBJECTIVE: The objective of the study was to determine the prevalence of vitamin D insufficiency and its association with non-traditional cardiovascular disease (CVD) risk factors such as Apo B in South American Indian school children. METHODS: A cross-sectional study of 355 children (166 Males) aged 9.6±2.3 y was performed. Anthropometric measures, glucose, lipids, insulin, Apo B, Apo A, and vitamin D concentrations were measured. RESULTS: The prevalence of overweight and obesity was 10.7% (38) per CDC. One child (0.3%) had optimal vitamin D concentrations [25(OH)D[>30 ng/ml. Univariate analysis showed significant associations between vitamin D and HDL-C (r=0.12 p<0.05), age (r=-0.11 p<0.05) BMI (r=-0.22 p<0.05), LDL-C (r=-0.22 p<0.01), triglycerides (r=-0.16 p<0.01), non HDL-C (r=-0.21 p<0.01), Apo B (r=-0.23 p<0.01), Apo B/Apo A (r=-0.21 p<0.01), insulin (r=-0.17 p<0.05), and HOMA-IR (r=-0.16 p<0.05). Multiple linear regression analysis showed that female gender and Apo B were significantly associated with vitamin D adjusted for confounding factors (R(2) 0.12). CONCLUSION: Vitamin D deficiency was associated with increased Apo B among Indian children, suggesting that it could be used as a risk marker of CVD.

Estudio de parámetros bioquímicos en jugadores de fútbol de élite / Study of biochemical parameters in elite football players / Estudo de parâmetros bioquímicos em jogadores de futebol de elite

El deporte exige de quienes lo practican una adaptación, entrenamiento y buen estado físico. El objetivo del trabajo fue estudiar en suero/plasma de individuos jugadores de fútbol de élite (n=32) y no entrenados (n=16), los perfiles hematológico, endocrinológico y de química clínica, relacionar los hallazgos bioquímicos con la fisiopatología deportiva y evaluar la probable implicancia clínica de los resultados. De acuerdo con los resultados obtenidos se observó disminución significativa en: hematocrito, hierro, plaquetas y bilirrubina (expansión plasmática fisiológica); magnesio (consumo enzimático); y proteínas y glucemia (incremento del metabolismo energético y recambio proteico). No se detectaron cambios significativos en el perfil endocrinológico (TSH disminuida, mayor eficacia de la hormona) y perfil lipídico (aumento de HDL y disminución de LDL; efecto protector de las lipoproteínas). Se observó un aumento significativo en: calcio (mayor disponibilidad); urea (metabolismo proteico aumentado); y aldolasa y creatinquinasa (lisis fibra muscular entrenada). Se concluye que la creatinquinasa es el marcador de pertenencia al grupo de élite; se debería implementar un valor de referencia diferente para esta población de deportistas ya que el deporte es objeto de estudio del laboratorio bioquímico; y la implementación de los conocimientos científicos en forma práctica y adecuada permite ayudar al profesional médico deportólogo a tomar decisiones oportunas y acertadas.

Estudio de parámetros bioquímicos en jugadores de fútbol de élite / Study of biochemical parameters in elite football players / Estudo de parÔmetros bioquímicos em jogadores de futebol de elite

El deporte exige de quienes lo practican una adaptación, entrenamiento y buen estado físico. El objetivo del trabajo fue estudiar en suero/plasma de individuos jugadores de fútbol de élite (n=32) y no entrenados (n=16), los perfiles hematológico, endocrinológico y de química clínica, relacionar los hallazgos bioquímicos con la fisiopatología deportiva y evaluar la probable implicancia clínica de los resultados. De acuerdo con los resultados obtenidos se observó disminución significativa en: hematocrito, hierro, plaquetas y bilirrubina (expansión plasmática fisiológica); magnesio (consumo enzimático); y proteínas y glucemia (incremento del metabolismo energético y recambio proteico). No se detectaron cambios significativos en el perfil endocrinológico (TSH disminuida, mayor eficacia de la hormona) y perfil lipídico (aumento de HDL y disminución de LDL; efecto protector de las lipoproteínas). Se observó un aumento significativo en: calcio (mayor disponibilidad); urea (metabolismo proteico aumentado); y aldolasa y creatinquinasa (lisis fibra muscular entrenada). Se concluye que la creatinquinasa es el marcador de pertenencia al grupo de élite; se debería implementar un valor de referencia diferente para esta población de deportistas ya que el deporte es objeto de estudio del laboratorio bioquímico; y la implementación de los conocimientos científicos en forma práctica y adecuada permite ayudar al profesional médico deportólogo a tomar decisiones oportunas y acertadas.(AU)

Sports demand from those who practice it, adaptation, training and a good physical condition. The objective of the work was to study in serum/plasma of trained people (elite football players, n=32) and untrained people (n=16) the clinical laboratory, haematological, and endocrinal profiles; 2) to relate the biochemical findings to sports physiopathology; 3) Assess the probable clinical implication of the results obtained. The results detained showe a significant decrease in hematocrit, iron, platelets and bilirrubin (physiological plasma expansion); magnesium (enzymatic consumption); proteins and glycemia (increase in energy metabolism and protein change). Without significant changes in endocrinological profile (decreased TSH, greater hormone efficiency); and lipid profile (increased HDL and decreased LDL; lipoprotein protector effect).Significant increase: calcium (more availability); urea (increased protein metabolism); and aldolase y creatinkinase (lysis of trained muscle fibre). Creatinkinase is the scoreboard of belonging to the elite group. It should be a different reference value for this group. -Thus, sport is object of study at the clinical laboratory; and implementation of the scientific knowledge in a practical and suitable manner enables the health professional to make relevant and right decisions.(AU)

O esporte exige daqueles que o praticam uma adaptaþÒo, treinamento e bom estado físico. O objetivo do trabalho foi estudar em soro/plasma de indivíduos jogadores de futebol de elite (n=32) e nÒo treinados (n=16), os perfis hematológico, endocrinológico e de química clínica, relacionar os achados bioquímicos com a fisiopatologia esportiva, e avaliar as possíveis implicaþ§es clínicas dos resultados. De acordo com os resultados obtidos se observou diminuiþÒo em hematocrito, ferro, plaquetas e bilirrubina (expansÒo do plasma fisiológico), magnésio (consumo enzimático); e proteína e glicemia (aumento do metabolismo energético e recÔmbio proteico). NÒo foram observadas alteraþ§es significativas no perfil endocrinológico (TSH diminuído, maior eficácia do horm¶nio); e perfil lipídico (aumento de HDL e diminuiþÒo de LDL; efeito protetor das lipoproteínas). Observou-se-aumento significativo em: cálcio (maior disponibilidade); ureia (metabolismo proteico aumentado); e aldolase e creatina-quinase (lise fibra muscular treinada). Conclui-se que a creatina-quinase é o marcador de pertenþa ao grupo de elite. Deveria ser implementado um valor de referÛncia diferente para esta populaþÒo de esportistas visto que o esporte é objeto de estudo do laboratório bioquímico; e a implementaþÒo dos conhecimentos científicos em forma prática e adequada permite ajudar o profissional médico esportólogo a tomar decis§es oportunas e certas.(AU)

Estudio de parámetros bioquímicos en jugadores de fútbol de élite / Study of biochemical parameters in elite football players

El deporte exige de quienes lo practican una adaptación, entrenamiento y buen estado físico. El objetivo del trabajo fue estudiar en suero/plasma de individuos jugadores de fútbol de élite (n=32) y no entrenados (n=16), los perfiles hematológico, endocrinológico y de química clínica, relacionar los hallazgos bioquímicos con la fisiopatología deportiva y evaluar la probable implicancia clínica de los resultados. De acuerdo con los resultados obtenidos se observó disminución significativa en: hematocrito, hierro, plaquetas y bilirrubina (expansión plasmática fisiológica); magnesio (consumo enzimático); y proteínas y glucemia (incremento del metabolismo energético y recambio proteico). No se detectaron cambios significativos en el perfil endocrinológico (TSH disminuida, mayor eficacia de la hormona) y perfil lipídico (aumento de HDL y disminución de LDL; efecto protector de las lipoproteínas). Se observó un aumento significativo en: calcio (mayor disponibilidad); urea (metabolismo proteico aumentado); y aldolasa y creatinquinasa (lisis fibra muscular entrenada). Se concluye que la creatinquinasa es el marcador de pertenencia al grupo de élite; se debería implementar un valor de referencia diferente para esta población de deportistas ya que el deporte es objeto de estudio del laboratorio bioquímico; y la implementación de los conocimientos científicos en forma práctica y adecuada permite ayudar al profesional médico deportólogo a tomar decisiones oportunas y acertadas.(AU)

Low vitamin D concentrations among indigenous Argentinean children living at high altitudes.

BACKGROUND: Hypovitaminosis D is an international problem; however, there is little information about its prevalence in apparently healthy Indian children living at high altitudes. OBJECTIVES: To determine (i) the prevalence of hypovitaminosis D and (ii) the association of serum vitamin D with the risk factors for diabetes among Indian Koya children. METHODS: A cross-sectional study of 290 (129 males) school children aged 10.7 ± 2.9 yr was performed. Anthropometric measures, blood pressure (BP), Tanner stages and serum levels of glucose, lipids, and insulin were measured. 25-hydroxyvitamin D [25(OH)D] was measured by radioimmunoassay (Dia Sorin). RESULTS: The prevalence of obesity was 3.4% (10), overweight 3.4% (10), normal weight 79.0% (229), and underweight 14.1 % (41) per CDC reference standards. Concentrations of [25(OH)D] were median 10 (range 8-13 ng/mL); 10 (3.4%) had insufficient vitamin D levels (20 to <30 ng/mL), 136 (46.9%) had deficient levels (10 to <20 ng/mL), 144 (49.7%) had severe deficiency (<10 ng/mL) and none had optimal levels (≥30 ng/mL). There was an inverse significant correlation between [25(OH)D] and age (r = 0.14), body mass index (BMI) (r = 0.16), waist circumference (r = 0.15), systolic BP (r = 0.19), hemoglobin (r = 0.19), glucose (r = 0.22), insulin (r = 0.13), and homeostasis model of assessment-insulin resistance (r = 0.16). Multiple linear regression analysis showed that 25(OH)D concentrations were significantly and inversely associated with glucose concentrations (ß = -0.28; p = 0.02) adjusted for age, BMI, systolic BP, hemoglobin, and insulin. CONCLUSIONS: This study demonstrated a high prevalence of both 25(OH)D deficiency and insufficiency and an inverse association between 25(OH)D and glucose concentration in apparently healthy Koya Indian children. Further research is needed to confirm these findings.

Association of vitamin D with glucose levels in indigenous and mixed population Argentinean boys.

INTRODUCTION: There is little information about low vitamin D concentrations in apparently healthy indigenous children in South America. OBJECTIVES: (a) To compare the prevalence of hypovitaminosis D in SAC (San Antonio de los Cobres) versus BA (Buenos Aires) boys and (b) to determine the association of serum vitamin D concentration with age, gender, and risk factors for diabetes. METHODS: This cross-sectional study compares 129 boys from SAC with a 98% indigenous population, versus 116 boys from BA with a mixed population. Anthropometric measures and serum levels of glucose, lipids, insulin, and 25-hydroxyvitamin D [25(OH)D] were measured in May 2011 and May 2010 (fall season). Optimal, insufficiency, deficiency, and severe deficiency of vitamin D were defined as [25(OH)D[levels ≥75 nmol/L, 50 to <75 nmol/L, 25 to <50 nmol/L, and <25 nmol/L respectively. RESULTS: The mean age was 9.7±2.7 in SAC and 11.3±2.51 years in BA children. Seventeen (13.2%) SAC and 2 (1.7%) BA children were underweight; 99 (76.7%) SAC and 58 (50.0%) BA children were normal weight; 5 (3.9%) SAC and 15 (12.9%) BA children were overweight; and 8 (6.2%) SAC and 41 (35.3%) BA children were obese (p<0.001). Sixty-six (51.2%) SAC and 1 (0.9%) BA children had vitamin D severe deficiency; 58 (45.0%) SAC and 53 (45.7%) BA children had deficiency; 5 (3.9%) SAC and 61 (52.6%) BA had insufficiency; and 0 (0%) SAC and 1 (0.9%) BA children had optimal vitamin D (p<0.001). Therefore, there was a lower prevalence of overweight/obesity and a higher prevalence of vitamin D deficiency in SAC than in BA children. Separate linear regression models showed an inverse association between glucose levels (beta=-0.22; p=0.01) and HOMA=IR (beta=-0.21; p=0.02) with vitamin D levels adjusted for age, z-BMI and community. CONCLUSIONS: There was a higher prevalence of 25(OH)D deficiency in SAC versus BA boys, suggesting that dark skin, high altitudes, or genetic backgrounds could contribute to this problem. In addition, we found an inverse association between [25(OH)D] and glucose concentration in apparently healthy children. Additional longitudinal studies should be done to confirm these findings.

Dyslipidemia without obesity in indigenous Argentinean children living at high altitude.

OBJECTIVES: To compare the prevalence of cardiovascular disease risk factors in Indian children from San Antonio de los Cobres (SAC) and children from Buenos Aires (BA), and to examine body mass index (BMI), waist circumference (WC), and WC/height as predictors of dyslipidemia in both groups. STUDY DESIGN: Data were collected cross-sectionally from BMI, WC, blood pressure, Tanner scale, glucose, lipids, and insulin. Dyslipidemia was defined by the National Cholesterol Education Program and American Heart Association. RESULTS: The mean ages were 10.6 ± 3.0 and 9.5 ± 2.0 years in SAC vs BA children. Of the 330 SAC children, 15 (4.5%) were overweight and 12 (3.6%) obese, and of the 603 BA, 97 (16.1%) were overweight and 82 (13.6%) obese per Centers for Disease Control. There was a significantly higher prevalence of high triglycerides (28.8% vs 3.5%) and low high-density lipoprotein cholesterol (30.0% vs 5.5%) in SAC vs BA children. The areas under the receiver operating characteristic curve in predicting high triglycerides were BMI = 0.55 (95% CI, 0.48-0.62; P = .15) in SAC and BMI = 0.65 (95% CI, 0.52-0.77; P = .02) in BA children. Similar results from the areas under the receiver operating characteristic curve were obtained when low high-density lipoprotein cholesterol was used, indicating that BMI was not a significant predictor for dyslipidemia in SAC children. When BMI was replaced by WC and WC/height, results were similar. CONCLUSIONS: Anthropometric markers were not an acceptable predictor for National Cholesterol Education Program cutoffs for dyslipidemia in SAC children. Longitudinal studies should determine if SAC children are at high risk for cardiovascular diseases because of genetic background.

Lifestyle behaviors and dyslipidemia in Argentinean native versus urban children.

OBJECTIVE: To determine the prevalence and distribution of dyslipidemia among urban children from Buenos Aires (BA) versus Koya Indian from San Antonio de los Cobres (SAC). DESIGN AND METHODS: Anthropometric measures, blood pressure, Tanner stages, glucose, lipids and insulin were measured. Dyslipidemia was defined by the NCEP (the National Cholesterol Education Program standards) and AHA (American Heart Association) criteria. RESULTS: The mean ages were 10.6 ± 3.0 of SAC and 9.5 ± 2.0 years of BA children. Of the 603 BA children, 97 (16.1%) were overweight (OW) and 82 (13.6%) obese (OB), and of 330 SAC, 15 (4.5%) were OW and 12 (3.6%) OB (p < 0.01). Twenty six percent SAC vs 2.5% BA children ate ≥ 5 servings/day of fruits and vegetables (p < 0.001), 30% SAC vs 59% BA children watched TV ≥ 2 h/day(p < 0.001), and 8.2% SAC vs 13.1% BA children skipped breakfast (p < 0.001). In separate linear regression models, we found that SAC children had a 1.8 mmol/L (p < 0.001) higher hemoglobin level, a 0.56 mmol/L higher triglyceride level (p<0.001), a 0.15 mmol/L higher total cholesterol level (p=0.001), a 0.19 mmol/L higher LDL-C level (p < 0.001), and a 0.33 mmol/L lower HDL-C level (p < 0.001) than BA children adjusted for confounding factors. CONCLUSION: Koya children have a higher risk for dyslipidemia in comparison with BA children, even after controlling for lifestyle behaviors, obesity, age, and sex , suggesting that dyslipidemia could be related to their genetic backgrounds.

Association of lipoprotein-associated phospholipase A2 activity with components of the metabolic syndrome in apparently healthy boys.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been proposed as a biomarker of risk of cardiovascular disease (CVD). OBJECTIVE: To determine the association between Lp-PLA(2) activity and BMI, insulin-resistance, components of the metabolic syndrome (MS), and lifestyle behaviors in healthy adolescent boys. METHODS: Data were collected cross-sectionally from 164 adolescents from an amateur rugby club. BMI, blood pressure (BP), Tanner stages, glucose, insulin, lipids, and Lp-PLA(2) activity were measured. Questionnaires for lifestyle behaviors were completed. RESULTS: Approximately 26% of the adolescents were obese and 23% overweight. There was a univariate association between Lp-PLA(2) and BMI (r=0.16;p=0.042), triglycerides (r=0.26;p=0.001), LDL-C (r=0.46;p<0.001), apo B (r=0.55;p<0.001), whereas waist circumference , BP, glucose, HOMA-IR, and HDL-C were not correlated. None of the lifestyle behaviors were significantly correlated with Lp-PLA(2). In order to analyze Lp-PLA(2) association with known CVD risk conditions, adolescents were categorized according to overweight/obesity and to the presence of metabolic syndrome. Conversely, as it was for LDL-C and apo B concentration, Lp-PLA(2) activity was not higher in adolescents with obesity. Multiple regression analysis showed that apo B was significantly associated with Lp-PLA(2) adjusted for age, BMI, triglycerides and LDL-C (R2=0.32). CONCLUSION: Lp-PLA(2) activity was only associated with apo B adjusted for several confounding variables, suggesting that its clinical utility to identify individuals at risk for CVD does not surpass LDL-C and apo B in healthy adolescents. As plaque morphology may change with age, associations of Lp-PLA(2) with CVD may likewise vary with age.

Impact of unhealthy lifestyle behaviors and obesity on cholesteryl ester transfer protein among adolescent males.

BACKGROUND AND AIMS: Cholesteryl ester transfer protein (CETP) has been proposed to be associated with high risk of cardiovascular disease. Increased CETP activity was previously reported in obese adults, although its association with lifestyle behaviors has not been assessed in healthy adolescents. We undertook this study to determine the association between CETP activity and overweight/obesity, insulin resistance markers, components of the metabolic syndrome and lifestyle behaviors in healthy adolescent males. METHODS: Data were collected from 164 adolescents from an amateur rugby club. Body mass index (BMI), blood pressure (BP), Tanner stages, lipids, glucose, insulin and CETP activity were measured. Questionnaires for daily intake of breakfast, sweet drinks, milk, and hours of TV watching were completed. RESULTS: About 26% of the adolescents were obese and 23% overweight. The prevalence of metabolic syndrome was 6.7%. CETP activity was higher in obese than in normal and overweight adolescents (174 ± 35, 141 ± 30, and 149 ± 38%/ml/min, respectively; p <0.001). Univariate correlations showed an inverse association between CETP and HDL-C (r = -0.43; p = 0.018) and positive ones with BMI (r = 0.38; p = 0.007), systolic BP (r = 0.20; p <0.01) triglycerides (r = 0.40; p = 0.001), LDL-C (r = 0.46; p <0.001), TV watching >2 h/day (r = 0.17; p 0.02), and milk intake >3 glasses/day (r = 0.16; p = 0.03). Multivariate analysis showed that triglycerides, LDL-C, HDL-C, TV watching >2 h/day, milk intake >3 glasses/day and BMI were significant independent predictors for CETP (R(2) = 0.41). CONCLUSIONS: Unhealthy lifestyle habits such as TV watching >2 h daily and milk intake higher than three glasses per day and the increase in BMI were shown to be closely associated with high CETP activity in apparently healthy adolescent males. Future longitudinal studies should be performed to confirm these findings.

Comparison of different anthropometric indices for identifying dyslipidemia in school children.

BACKGROUND: Anthropometric indices have been associated with dyslipidemia. OBJECTIVE: To compare the abilities of BMI, waist circumference (WC) and WC/height to identify children's dyslipidemia. METHODS: Students 1261 (639 male) age 9.5±2.1 years. were examined for anthropometry and lipid levels. Triglycerides ≥1.69 mmol/L and high-density lipoprotein cholesterol (HDL-C) <0.91 mmol/L were considered abnormal per American Heart Association. RESULTS: The prevalence of abnormal triglycerides was 4.1% and HDL-C 8.1%. The areas under the receiver operator curves (ROC) were: BMI=0.87, WC=0.83, and WC/height=0.84 in predicting both low HDL-C and high triglycerides. Multiple regression analyses showed that the odds ratios (OR) were highest for WC [6.5], followed by WC/height [5.4], and BMI [4.9], for dyslipidemia. CONCLUSIONS: The results suggest that WC, WC/height, and BMI similarly predicted dyslipidemia, using ROC analyses. However, regression analyses showed that WC followed by WC/height was most predictive of dyslipidemia.

Tall stature without growth hormone: four male patients with aromatase deficiency.

CONTEXT: From preliminary observations, GH-IGF-I seems to be compromised in men with aromatase deficiency. The GH deficiency (GHD) coexists paradoxically with tall stature, raising the question whether or not a true GHD is part of this rare syndrome. OBJECTIVE: To evaluate the GH secretion in aromatase-deficient men, their GH response to the GHRH plus arginine (GHRH-ARG) test was compared with that of normal subjects. The effect of estrogen replacement treatment on the GH-IGF-I axis in aromatase-deficient men was evaluated before and during therapy. DESIGN AND SETTING: A case-control study was conducted. PATIENTS: Four adult men with aromatase deficiency were compared with 12 normal subjects. MAIN OUTCOME MEASURES: We measured the GH response to GHRH-ARG in aromatase-deficient men (at baseline and during estrogen treatment) and in normal subjects. Basal serum IGF-I was measured in both patients and controls. RESULTS: The response of GH to GHRH-ARG was severely impaired in men with aromatase deficiency and resulted in significantly lower (P < 0.001) levels than in normal subjects. Although normal, serum IGF-I levels were also significantly lower (P < 0.001) than in normal subjects. Both GH peak and IGF-I concentrations were not modified by estrogen therapy in men with aromatase deficiency. CONCLUSIONS: In aromatase-deficient men, GH response to potent provocative stimuli is impaired and is not restored by exogenous estrogens. Furthermore, a tall stature may be reached, notwithstanding the coexistence of GHD, if a prolonged time for growth is available due to a delay in bone maturation, and other growth factors different from GH (mainly insulin) promote growth.

Is albuminuria associated with obesity in school children?

BACKGROUND: Different studies in adults have shown that obesity is an independent risk factor for end-stage renal disease. OBJECTIVE: It was to (i) determine the association between albuminuria and age, gender, BMI, waist circumference (WC), and blood pressure (ii) relate albuminuria to gender and age in healthy school children. METHODS: Over 1564 students (806 males) aged 9.35 +/- 2.00 yr from 9 elementary schools in Buenos Aires, were examined between April and September 2005. BMI, WC, blood pressure, urinary albumin excretion and albumin/creatinine ratio (ACR) were determined. RESULTS: Over 220 (14.1%) children were obese (OB), and 300 (19.2%) overweight (OW) using centers for disease control (CDC) norms. Median ACR and urinary albumin levels were higher in normal weight children than in OW/OB children (p < 0.01). Median values for ACR were higher in girls than in boys (p < 0.001). OW/OB proved to be a protective factor against ACR [OR, 0.77 (95% CI 0.64-0.92)], whereas female gender [OR, 2.72 (95% CI 2.13-3.47)] was associated with a higher ACR adjusted for age systolic and diastolic blood pressure in the multiple logistic regression analysis. Therefore, children with OW/OB had 23% lower odds of having ACR >or= III quartile and girls had more than two and half times the risk of having high ACR. CONCLUSIONS: Our results suggest that OW/OB is inversely associated with childhood albuminuria while female gender is positively associated. Whether the results can be explained by the increased physical activity in lean children should be the subject of future investigations. These results suggest that micro-albuminuria in children may not be a useful tool in the early identification of children at risk for future renal and cardiovascular disease (CVD).