We have prospectively assessed the influence of GHR and VDR gene polymorphisms on the response to rhGH therapy in Venezuelan children with growth hormone deficiency (GHD, n= 28) and Turner syndrome (TS, n= 25). Clinical data during rhGH treatment were compared in GH and TS patients with different genotypes. PCR amplifications were performed to obtain the genotype frequencies of the polymorphisms. Clinical data at the start of treatment and rhGH doses were indistinguishable among patients with GHD or TS with different GHR or VDR genotypes. After the first two years of rhGH treatment, clinical data in both GHD and TS patients were not different according GHR or VDR genotypes. In addition, there was no significant difference among the subjects when both these genotypes were combined. Gene polymorphisms in low penetrance genes do not contribute to the rhGH therapy response in patients with GHD and TS. KEY WORDS

BackgroundIt is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients.MethodsThis was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n =  93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n =  34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined.ResultsSeventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm.ConclusionsThe parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals.

Background/Aims: Significant endothelial dysfunction as determined by lower flow-mediated vasodilation of the brachial artery was recently reported by us in growth hormone-deficient (GHD) adolescents. The circulating concentrations of markers of vascular endothelial cell and platelet activation and their relationship to inflammatory markers have not been previously evaluated in this group of patients. Objective: To assess the relationship between circulating levels of high-sensitivity C-reactive protein (CRP) and soluble markers of vascular endothelial cell activation in GHD adolescents. Design/Methods: Twenty-eight GHD children on GH treatment with a chronological age of 15.7 ± 2.6 years and 16 untreated GHD adolescents with a chronological age of 16.6 ± 3.3 years were studied. Concentrations of CRP, as an inflammatory marker, were measured in all patients and the association between CRP and the fasting soluble markers of vascular endothelial cell activation intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin levels was evaluated. Sixteen healthy adolescents with a mean chronological age of 15.1 ± 2.2 years served as controls. Results: CRP and P-selectin levels were significantly higher in untreated GHD adolescents than in treated GHD subjects or in healthy controls (p < 0.02), while VCAM-1 concentrations were increased in both untreated and treated GHD adolescents when compared to controls (p < 0.007). E-selectin and ICAM-1 levels were similar in all three groups. CRP was found to be associated with BMI (r: 0.62; p < 0.001), P-selectin (r: 0.43; p < 0.01), E-selectin (r: 0.27; p < 0.03), ICAM-1 (r: 0.23; p < 0.05) and VCAM-1 (r: 0.40; p < 0.001) concentrations in untreated GHD adolescents and with P-selectin (r: 0.88; p < 0.001) and E-selectin (r: 0.29; p < 0.01) in treated GHD subjects. A weak inverse association was observed in a subgroup of patients between brachial artery endothelium-dependent dilation and P-selectin (r: –0.56; p < 0.07). Conclusions: Low-grade inflammation as manifested by increased circulating levels of CRP seems to be associated with the early activation of vascular endothelial cells in GHD adolescents

Objectives. To investigate whether lifestyle-only intervention in obese children who maintain or lose a modest amount of weight redistributes parameters of body composition and reverses metabolic abnormalities. Study Design. Clinical, anthropometric, and metabolic parameters were assessed in 111 overweight or obese children (CA of 11.3 ± 2.8 years; 63 females and 48 males), during 8 months of lifestyle intervention. Patients maintained or lost weight (1–5%) (group A; n: 72) or gained weight (group B). Results. Group A patients presented with a decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) ( and , resp.), BMI (), z-score BMI (), waist circumference (), fat mass (), LDL-C (), Tg/HDL-C ratio (), fasting and postprandial insulin (), and HOMA (), while HDL-C () and QUICKI increased (). Conversely, group B patients had an increase in BMI (), waist circumference (), SBP (), and in QUICKI (), while fat mass (), fasting insulin (), and HOMA () decreased. Lean mass, DBP, lipid concentrations, fasting and postprandial glucose, postprandial insulin, and ultrasensitive C-reactive protein (CRP) remained stable. Conclusions. Obese children who maintain or lose a modest amount of weight following lifestyle-only intervention tend to redistribute their body fat, decrease blood pressure and lipid levels, and to improve parameters of insulin sensitivity.

Even when IDUs use their own syringes, the common use of drug preparation materials can expose them to blood-borne pathogens. Notwithstanding the accumulated evidence about the riskiness of drug preparation practices (DPPs), the factors that lead IDUs to engage in DPPs have remained understudied. We conducted 80 semi-structured interviews to elicit salient beliefs about engaging in low-risk DPPs. Data were content analyzed for consequences, normative influences, and barriers. For the most part respondents described positive consequences of engaging in low-risk DPPs. The majority of respondents mentioned IDU peers as a major source of pressure to engage in high-risk DPPs. Lack of access to clean materials and the need to carry materials on oneself were the most salient barriers elicited. The results suggest that preventive interventions need to address the preference for re-using filters, help develop skills to fend off pressures from peers, and increase the accessibility of materials in ways that do not require IDUs to carry additional items.