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.

[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.

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.

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.

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).

Chromogranin A as a biochemical marker for the management of neuroendocrine tumors: a multicenter study developed in Argentina.

Elevated circulating levels of chromogranin A (CgA) are found in the neuroendocrine tumors (NETs), but diagnostic usefulness of this marker is still debatable. To assess the role of CgA for the identification and follow up of gastroenteropancreatic neuroendocrine tumors (GEP-NET), a multicenter prospective longitudinal study has been carried out in Argentina. CgA was measured by RIA in 119 histologically proven GEP-NET patients and in 39 healthy controls. A cutoff value of 2.8 nmol/L was established from a receiver-operating characteristic (ROC) curve, as discriminating between controls and patients with active disease (specificity 100% and sensitivity 92.3%). CgA levels were higher in functioning than in no functioning tumors (median 55 nmol/L vs 5 nmol/L, p < 0.05). Metastases were present in 83 patients and their CgA levels were significantly higher than levels in the 36 patients without metastases (median 44 nmol/L vs 64 nmol/L, p < 0.0001). CgA levels are strongly correlated with tumor metastatic spread. Sensitivity differed between patients with localized disease (median 6 nmol/L), extensive disease (median 22 nmol/L) and very extensive disease (median 44 nmol/L) (p < 0.001). In conclusion, due to its high sensitivity and specificity, CgA is useful in a newly discovered GEP-NET especially when no abnormal hormone secretion can be demonstrated. CgA levels were significantly higher in functioning tumors than in non-functioning tumors and increased with metastatic spread. If serial evaluation of CgA levels is sufficient for the detection of tumor growth changes remains to be prospectively demonstrated.

Association between school children's overweight and maternal obesity and perception of their children's weight status.

AIM: To determine the association between overweight children and a) other components of the mothers' metabolic syndrome, such as body mass index (BMI), waist circumference (WC), HDL-cholesterol, triglycerides, glucose, HOMA-IR, blood pressure (BP), and age; and b) the mothers' perception of their children's overweight. METHODS: Six hundred and twenty children (297 M) aged 9 +/- 2 years and their mothers aged 37.7 +/- 7 years were examined between April and August 2006. BMI, BP, fasting glucose and lipids and children's Tanner stage were determined. Questionnaires were filled in about the mothers' perceptions of their children's eating habits and of their children's shape. RESULTS: Ninety-five (17.4%) of the children were obese (> 95th percentile), 108 (15.3%) overweight (> 85th percentile) and 418 (67.3%) normal. One hundred and twelve (18%) of the mothers were obese and 183 (29.5%) overweight. Mean values for measures in mothers differed between normal vs overweight/obese children: z-BMI (-0.19 vs 0.42), triglycerides (84 vs 105 mg/dl), cholesterol (147 vs 157 mg/dl), glucose (78 vs 82 mg/dl) and insulin resistance (HOMA-IR 1.34 vs 1.72). There were significant differences in the proportion with distorted perception of shape (2.2% vs 47.5%) and eating habits (11.2% vs 37%) between mothers of normal versus overweight/ obese children. Logistic regression analysis using BMI > or = 85th percentile as the dependent variable showed that the mothers' perceptions of their children's shape (OR: 18.84; 95% CI: 5.0-69.6), eating habits (OR: 3.82; 95% CI: 1.5-9.5) and mothers' BMI (OR: 2.1; 95% CI: 1.3-3.4) were associated with children's overweight. CONCLUSIONS: There was an association between mothers' distorted perception of their children's shape and eating habits and mothers' obesity and their children's overweight. This observation provides clues for obesity prevention programs.

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.

Skeletal effects of long-term estrogen and testosterone replacement treatment in a man with congenital aromatase deficiency: evidences of a priming effect of estrogen for sex steroids action on bone.

The relative contribution of each sex steroid (i.e. estrogen and androgen) on bone in men and the relationships among sex steroids and changes in BMD and bone strength are still unknown. A defective BMD of bone tissue is constantly present in men with aromatase deficiency. This study evaluates the effects of different regimens of treatment with sex steroids over 7.3 years follow-up on BMD in an adult man affected by aromatase deficiency and by a concomitant mild hypogonadism, as previously described. The aim of the study is to provide additional data on the relative roles of androgens and estrogens in male bone metabolism. The effects of testosterone (T) treatment alone and estrogen (tE(2)) treatment alone as well as the effects of the combined treatment with testosterone and estradiol (T plus tE(2)) on areal BMD (aBMD) at dual-energy X-ray absorptiometry (DXA) and the effects of T plus tE(2) on volumetric BMD (vBMD), particular at cortical site, measured by peripheral quantitative computed tomography (pQCT), are investigated. Hormones and markers of bone turnover were monitored during all phases of the study. Treatment with tE(2) normalized serum estradiol, but only the combined treatment with T plus tE(2) normalized both serum estradiol and testosterone. Markers of bone turnover reached a pattern close to normality during T plus tE(2). The aBMD was little modified by T, but increased more during tE(2). T plus tE(2) resulted in a further increase in both aBMD at DXA and vBMD at pQCT. Cortical thickness increased during T plus tE(2) both in radius and tibia. Only the combined treatment led to optimal parameters of aBMD suggesting that testosterone needs estrogens as a permissive factor for a direct androgen anabolic action on bone in men.

Waist circumference identifies primary school children with metabolic syndrome abnormalities.

OBJECTIVE: This study was designed to assess whether waist circumference can predict metabolic syndrome abnormalities in primary schoolchildren. RESEARCH DESIGN AND METHODS: Of 5,103 children (2,526 males) 4-13 years old who underwent anthropometric measurements, 530 had more extensive testing. Body mass index (BMI), waist circumference, and blood pressure were determined in all subjects. The subgroup had Tanner stage, glucose, lipid profile, and insulin assays. The BMI of the 5,103 children was used to calculate our z scores. To determine which marker was a better predictor for metabolic syndrome, a receiver operating characteristic (ROC) curve was generated for BMI and waist circumference, with metabolic syndrome as the dichotomous variable. RESULTS: Over 530 children (8.7 +/- 2.4 years) 6% (n = 32) were obese (BMI >95(th) percentile; z BMI = 2.55), 13.6% (n = 72) were overweight (OW) (85(th) < BMI < 95(th) percentile; z BMI = 1.45), and 80.4% (n = 426) were non-OW (BMI <85(th) percentile; z BMI = - 0.14). Fifty-eight percent [95% confidence interval (CI) 53, 6], 22.8% (95% CI 19, 27), 15.5% (95% CI 12, 19), and 4.1% (95% CI 2, 6) were Tanner stage I, II, III, and IV, respectively. Metabolic syndrome was present in 9.4% overall, 6% of the non-OW, 22.2% of the OW, and 31% in the obese group (P < 0.01). The differences between ROC areas were not significant (0.009) (95% CI -0.035 to 0.053; P = 0.679) for BMI and waist circumference. The optimal threshold for waist circumference percentile was 71.3 with a sensitivity and specificity of 58.9 (95% CI 48.4, 68.9) and 63.1 (95% CI 58.4, 67.7), respectively. CONCLUSIONS: Waist circumference and BMI predict metabolic syndrome abnormalities in children. Waist circumference > or =75(th) percentile could be the optimal threshold to predict metabolic syndrome in children.

Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback.

BACKGROUND: In men, the feedback of gonadotropins is regulated by estrogens that come from the aromatization of testosterone, but the relative contribution to the inhibition of LH and FSH secretion by the amount of locally produced estrogens within the hypothalamus and/or the pituitary, and the amount of circulating estrogens still remains unknown. OBJECTIVE: In order to evaluate the effect of regulation induced by estradiol on the hypothalamic-pituitary-gonadal (HPG) axis, we studied the pulsatility of LH and FSH in two aromatase-deficient men (called subject 1 and subject 2), in which the production rate of estrogen (both local and circulating) is completely, or at least severely, impaired. DESIGN: FSH and LH were evaluated in terms of their pulsated secretion and as GnRH-stimulated secretion in two phases: phase 1, before estrogen treatment; and phase 2, during estrogen treatment with 25 microg transdermal estradiol twice weekly. METHODS: Blood samples were taken during phase 1 and phase 2 at 0800 h for basal measurements of LH, FSH, inhibin B, testosterone, and estradiol. The analysis of the pulsatility of LH and FSH was performed by sampling every 10 min for 8 h in the two phases. Gonadotropin response to GnRH-stimulation test was studied by serial standard sampling after 100 microg GnRH i.v. bolus in phases 1 and 2. RESULTS: Estrogen treatment led to a significant reduction in both LH-pulsated frequency (7.5 +/- 0.7 in phase 1, 4.5 +/- 0.7 in phase 2) and amplitudes (3.5 +/- 0.006 in phase 1, 1.9 +/- 0.4 in phase 2) of peaks, whereas FSH showed only a conspicuous reduction in serum levels and a trend towards the reduction of the amplitudes of its peaks without modification of the frequency of the pulses. Both testosterone and gonadotropins decreased during phase 2, whereas estradiol reached the normal range in both subjects. Transdermal estradiol treatment significantly lowered the peaks of both serum LH and FSH after GnRH as well as the incremental area under the curve after GnRH administration in both subjects. Basal serum inhibin B levels were slightly higher before transdermal estradiol treatment (phase 1) than during estrogen treatment (phase 2) in both subjects. CONCLUSIONS: The administration of estrogen to aromatase-deficient men discloses the effects of circulating estrogens on LH secretion, exerted both at pituitary level, as shown by the decrease of basal and GnRH-stimulated secretion of LH and the LH pulsed amplitude, and at hypothalamic level as shown by the reduction of the frequency of LH pulses. The present study, coupling the outcomes of basal, GnRH-stimulated and the pulsatile evaluation of LH and FSH secretion in two aromatase-deficient men, demonstrates that circulating estrogens play an inhibitory role in LH secretion by acting on the hypothalamus and the pituitary gland of men. The discrepancy among testosterone levels, the arrest of spermatogenesis and a slightly inappropriate respective increase of serum FSH (lower than expected) suggests a possible role of estrogens in the priming and the maturation of HPG axis in men, an event that has never occurred in these two subjects as a consequence of chronic estrogen deprivation.

Sex steroids and sexual desire in a man with a novel mutation of aromatase gene and hypogonadism.

Sexual behavior was investigated by a sexological interview in a man with aromatase deficiency and hypogonadism. The study was performed at the end of a long testosterone treatment, during transdermal estradiol treatment and during estradiol and testosterone associated treatment. Sexual behavior did not show abnormalities. As assessed by a sexological interview and by a sexological questionnaire gender-identity was male, sexual orientation was heterosexual and libido was normal. Sexual function was limited to masturbation and was seemingly unaffected by testosterone or estradiol alone; only the associated treatment induced a great increase in libido and in frequency of masturbation and sexual fantasies when both testosterone and estradiol reached the range of normality. Sexual behavior is mainly under the control of cognitive functions in men, but sex steroids may modulate some aspects of male sexuality. Our findings suggest that in men estrogens could play a role in sexual activity.

Can waist circumference identify children with the metabolic syndrome?

OBJECTIVE: To determine in children the association between waist circumference (WC) and insulin resistance determined by homeostasis modeling (HOMA-IR) and proinsulinemia and components of the metabolic syndrome, including lipid profile and blood pressure (BP). METHODS: Eighty-four students (40 boys) aged 6 to 13 years and matched for sex and age underwent anthropometric measurements; 40 were obese; 28, overweight; and 16, nonobese. Body mass index (BMI), WC, BP, and Tanner stage were determined. An oral glucose tolerance test, lipid profile, and insulin and proinsulin assays were performed. Children were classified as nonobese (BMI < 85th percentile), overweight (BMI, 85th-94th percentile), and obese (BMI > or = 95th percentile). RESULTS: There was univariate association (P < .01) between WC and height (r = 0.73), BMI (r = 0.96), Tanner stage (r = 0.67), age (r = 0.56), systolic BP (r = 0.64), diastolic BP (r = 0.61), high-density lipoprotein cholesterol level (r = 0.45), triglyceride level (r = 0.28), proinsulin level (r = 0.59), and HOMA-IR (r = 0.59). Multiple linear regression analysis using HOMA-IR as the dependent variable showed that WC (beta coefficient = 0.050 [95% confidence interval, 0.028 to 0.073]; P = .001) and systolic BP (beta coefficient = 0.033 [95% confidence interval, 0.004 to 0.062]; P = .004) were significant independent predictors for insulin resistance adjusted for diastolic BP, height, BMI, acanthosis nigricans, and high-density lipoprotein cholesterol level. CONCLUSION: Waist circumference is a predictor of insulin resistance syndrome in children and adolescents and could be included in clinical practice as a simple tool to help identify children at risk.

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.

Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate, and estradiol treatment.

We present the fourth case of an adult man (29 yr old) affected by aromatase deficiency resulting from a novel homozygous inactivating mutation of the CYP19 (P450(arom)) gene. At first observation, continuing linear growth, eunuchoid body proportions, diffuse bone pain, and bilateral cryptorchidism were observed. The patient presented also a complex dysmetabolic syndrome characterized by insulin resistance, diabetes mellitus type 2, acanthosis nigricans, liver steatohepatitis, and signs of precocious atherogenesis. The analysis of the effects induced by the successive treatment with high doses of testosterone, alendronate, and estradiol allows further insight into the roles of androgens and estrogens on several metabolic functions. High doses of testosterone treatment resulted in a severe imbalance in the estradiol to testosterone ratio together with the occurrence of insulin resistance and diabetes mellitus type 2. Estrogen treatment resulted in an improvement of acanthosis nigricans, insulin resistance, and liver steatohepatitis, coupled with a better glycemic control and the disappearance of two carotid plaques. Furthermore, the study confirms previous data concerning the key role of estrogens on male bone maturation, at least in part, and regulation of gonadotropin secretion. The biopsy of the testis showed a pattern of total germ cell depletion that might be due to the concomitant presence of bilateral cryptorchidism. Thus, a possible role of estrogen in male reproductive function is suggested but without revealing a direct cause-effect relationship. Data from this case provide new insights into the role of estrogens in glucose, lipid, and liver metabolism in men. This new case of aromatase deficiency confirms previous data on bone maturation and mineralization, and it reveals a high risk for the precocious development of cardiovascular disease in young aromatase-deficient men.

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.

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.

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.

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.