Insulin resistance and endothelial function in children and adolescents

Aims

Insulin resistance (IR) impairs cellular response to insulin due to a dysfunction in glucose metabolism, associated with an increased cardiovascular risk. The aim of our study was to investigate the relationship among homeostasis model assessment index (HOMA index), endothelial function and vascular morphology in order to better stratify cardiovascular risk in children and adolescents.

Methods

A total of 150 children and adolescents (55 pre-pubertal, mean age 10.4 ± 3.1 years) were enrolled. Anthropometric [body mass index (BMI), waist circumference (WC)], laboratory [blood lipids, inflammatory markers, insulinemia, glycemia], HOMA index and ultrasound parameters [flow-mediated dilatation (FMD), common carotid intima–media thickness (cIMT) and antero-posterior diameter of infra-renal abdominal aorta (APAO)] were assessed.

Results

cIMT was positively related to age (r = 0.274, p < 0.01), BMI (r = 0.318, p < 0.01), WC (r = 0.315, p < 0.01) and triglycerides (r = 0.230, p < 0.01). APAO measurements showed a linear positive correlation with age (r = 0.435, p < 0.01), BMI (r = 0.505, p < 0.01), WC (r = 0.487, p < 0.01), triglycerides (r = 0.280, p < 0.01), C-reactive protein (r = 0.209, p < 0.05), fasting insulin (r = 0.378, p < 0.01) and HOMA index (r = 0.345, p < 0.01). FMD was inversely related to age (r = − 0.251, p < 0.01), rough BMI (r = − 0.318, p < 0.01), WC (r = − 0.340, p < 0.01), fasting insulin (r = − 0.281, p < 0.01) and HOMA index (r = − 0.282, p < 0.01). Multiple regression analysis found no influence of HOMA index on APAO and cIMT. HOMA index was an independent predictor for brachial artery FMD worsening after the statistical adjustment.

Conclusion

HOMA index increase induced a worsening in endothelial function since childhood.     

Inflammatory parameters associated with systemic reactogenicity following vaccination with adjuvanted hepatitis B vaccines in humans

Background

Adjuvants like AS01_B increase the immunogenicity of vaccines and generally cause increased transient reactogenicity compared with Alum. A phase II randomized trial was conducted to characterize the response to AS01_B and Alum adjuvanted vaccines. A post-hoc analysis was performed to examine the associations between reactogenicity and innate immune parameters.

Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab')2 fragments of an anti-carcinoembryonic antigen monoclonal antibody: a multicenter study

F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody F023C5, determined to be more suitable than intact IgG and Fab fragments for immunoscintigraphy, were labeled with 131I or conjugated to DTPA for instant 111In-labeling, and administered i.v. (2-3 mCi/0.5 mg) to 509 patients in 11 nuclear medicine departments: 284 patients had gastrointestinal adenocarcinomas, 204 had nongastrointestinal adenocarcinomas and 21 were control; serum CEA was elevated in 169 patients, normal in 115, and not determined in 225. The following results were obtained: (a) no adverse reactions; (b) tumor imaging in 324 patients (in particular, in 81.5% CEA-seropositive and in 69.0% CEA-seronegative patients); (c) no significant difference in sensitivity among the results of the 11 departments; (d) no significant difference in overall sensitivity between 131I-and 111In-labeled immunoradiopharmaceuticals; (e) the fraction of documented lesions imaged was 73.3% in CEA-seropositive and 53.7% in CEA-seronegative patients; (f) the detection of liver metastases was hampered, particularly when using the 111In-labeled reagent, by nonspecific radioactivity uptake; (g) the major cause of negative immunoscintigraphy results was a lack of CEA in tumor lesions, as documented by immunohistochemistry; (h) lesion size is also important since the sensitivity was 64% for lesions up to 2 cm in diameter and 84% for larger lesions; (i) many "unexpected" radiolocalizations were recorded. Most were identified as occult tumor lesions. In 35 patients, this finding contributed to the early detection of tumor recurrences.     

Genospecies of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks from the Autonomous Province of Trento, Italy

Sequences of the variable intergenic spacer region 5S (rrfA) 23S (rrlB) rRNA were used to identify Borrelia genospecies present in Ixodes ricinus nymphs collected from the Lamar Lakes area of the Province of Trento, Italy (overall prevalence=6.3%). Four genospecies were identified, one for the first time in this Province (B. valaisiana), and three which have been noted previously (B. afzelii, B. garinii, and B. burgdorferi s.s.). In order to compare the genetic variability of these genospecies in Trento with that at a European level, our 21 sequences (15 new haplotypes) and all appropriate European Borrelia sequences registered in GenBank (up to the end of 2004) were subjected to a phylogenetic analysis (for a total of 73 sequences and 43 haplotypes). Clusters of sequences representing the five main European genospecies (afzelii, garinii, burgdorferi s.s., valaisiana, lusitaniae) are well-supported. At least two other groups of haplotypes (genospecies) are suggested by our analysis; moreover, divergent evolution may be occurring in several genospecies. The maximum uncorrected pairwise differences between sequences within genospecies ranges from 1.5% (B. burgdorferi s.s.), to 2.3% (B. garinii and B. valaisiana) to 4.7% (B. afzelii), and are not correlated with geographical distribution. Within the Province of Trento, these values for the same genospecies are 1.5%, 2.3%, 0.9%, 1.9%, respectively. These high mutation rates within genospecies suggest that the sequencing of haplotypes should continue if we are to fully understand and monitor the evolution and epidemiology of Borrelia.     

Score test for age at onset genetic linkage analysis in selected sibling pairs

A new score statistic is derived, which uses information from registries (age‐specific incidences) and family studies (sib–sib marginal correlation) to weight affected sibling pairs according to their age at onset. Age at onset of sibling pairs is modelled by a gamma frailty model. From this model we derive a bivariate survival function, which depends on the marginal survival and on the marginal correlation. The score statistic for linkage is a classical nonparametric linkage (NPL) statistic where the identical by descent sharing is weighted by a particular function of the age at onset data. Since the statistic is based on survival models, it can also be applied to discordant and healthy sibling pairs. Simulation studies show that the proposed method is robust and more powerful than standard NPL methods. As illustration we apply the new score statistic to data from a breast cancer study. Copyright © 2009 John Wiley & Sons, Ltd.     

Supplementation with fiber-rich multimixtures yields a higher dietary concentration and apparent absorption of minerals in rats

Multimixtures (MMs) are dietary supplements prepared with low-cost ingredients and food by-products that are widely used in various countries to counteract malnutrition. Although MMs have a high content of minerals, they also contain high levels of dietary fiber and associated compounds, which might bind minerals and impair their absorption. In this study, we investigated the hypothesis that the increased dietary fiber content of MMs would impair gastrointestinal mineral absorption due to the metal-binding capacity of dietary fiber. Thus, the objective of the present study was to feed growing rats with a basal diet, representative of a nutritionally deficient diet, alone or supplemented with a low dietary fiber level MM, intermediate dietary fiber level MM, or high dietary fiber level MM (HF) to evaluate the apparent absorption of calcium, phosphorus, magnesium, manganese, and copper. The relative apparent calcium absorption was slightly decreased by the HF addition, with no change in the absolute apparent absorption. The absolute apparent absorption of phosphorus and magnesium was increased by the intermediate dietary fiber level MM and HF additions, whereas the manganese absorption was increased only by the HF addition. The apparent absorption of copper was not affected by the MM supplementation. The increased apparent absorption of minerals was always related to the increase in the mineral dietary concentration triggered by the MM. Thus, we concluded that the increased dietary fiber levels in the MMs increased the mineral levels, and MMs with intermediate and high fiber levels may be used to improve the mineral balance of poor diets.     

Successful Treatment of Severe Iatrogenic Calcinosis Cutis with Intravenous Sodium Thiosulfate in a Child Affected by T-Acute Lymphoblastic Leukemia

Abstract:   Sodium thiosulfate has been successfully used to treat calcyphilaxis in adults and children, but its effect on iatrogenic calcinosis cutis secondary to extravasation of calcium solutions is less known. We describe a 5-year-old boy with acute lymphoblastic leukemia who developed severe calcinosis cutis in the right forearm and hand, and in the left leg and foot after extravasation of calcium gluconate during treatment for tumor-lysis-syndrome-related hypocalcaemia. Surgical debridement, local wound care, hyperbaric oxygen therapy, and sodium thiosulfate infusion achieved a complete healing of all lesions in an eight-month period with a short discontinuation of chemotherapy. No functional or sensitive impairment remained.     

The BCTRIMS expanded consensus on treatment of multiple sclerosis: II. The evidences for the use of glucocorticoids and immunomodulatory treatments

Multiple sclerosis is an inflammatory disease in which immunological mechanisms play an important role in causing demyelinating lesions in the central nervous system. A number of drugs acting in different stages of these mechanisms have been tested for its treatment. This paper analyses the most important clinical trials with glucocorticoids and immunomodulatory treatments, including human immunoglobulin, using the classes of evidences and types of recommendations as have been defined and widely accepted by the international scientific community. It aims to provide sufficient information to support the BCTRIMS Expanded Consensus on Treatment of MS.     

Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling

We evaluated in an open-label, randomized, controlled, pilot trial if the re-emergence of previously selected resistant strains, harbouring M184V mutation, could be modulated by the use of different drug associations as components of the new antiretroviral regimens. In addition, we assessed the clinical relevance of this mutation on the management of heavily pretreated HIV-infected patients. The primary end-point of the study was the reselection of M184V mutation. Secondary end-points were the variation over time of HIV RNA plasma levels and CD4 cell counts and the progression of HIV disease. The primary population for efficacy analysis was the intention-to-treat exposed population. After a run-in phase consisting in a new treatment regimen excluding either lamivudine (3TC) or abacavir (ABC) so as to clear the previously documented M184V mutation, 18 patients with an HIV RNA plasma level greater than 10000 copies/ml were randomized to receive an antiretroviral drug regimen (at least three drugs) including either ABC or the association of ABC+3TC. All patients were naive to ABC. The M184V mutation reappeared in 1/9 patients in the ABC group and in 8/9 patients in the ABC+3TC group (P<0.003, 95% CI: 0.5-1). In the ABC group we observed a rapid decrement of viral load that was maintained throughout all the study period (P<0.05). On the contrary, in the ABC+3TC group, after a transient decrement at 2 months, a progressive increment towards baseline values was observed. The proportion of patients with a viral load reduction of at least 0.5 logs at 12 months was significantly higher in the ABC group: 8/9 patients vs 3/9 (P=0.05, 95% CI: 0.2-0.92). Similarly, from an immunological point-of-view, the increase at all time points (since randomization) in CD4 cell count was statistically significant in the ABC group (P<0.01), while no difference was observed in the ABC+3TC group. The possibility of a successful use of ABC in salvage regimens opens alternative therapeutic options for heavily pretreated patients with previously documented M184V mutation. Further studies should clarify whether this is true for other drugs of the nucleoside analogues class.