Browsing by Author "Quiroga, Teresa"

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    Is my patient a bleeder? A diagnostic framework for mild bleeding disorders
    (AMER SOC HEMATOLOGY, 2012) Quiroga, Teresa; Mezzano, Diego
    Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagnostic problems. Most MBDs are categorized as disorders of primary hemostasis (ie, type 1 VWD and platelet function disorders), but mild or moderate deficiencies of clotting factors and some rare hyperfibrinolytic disorders are also included. These patients have abnormal bleeding from the skin and mucous membranes, menorrhagia, and disproportionate hemorrhages after trauma, invasive procedures, and surgery. This review addresses the main problems that physicians and hemostasis laboratories confront with the diagnosis of these patients, including: discerning normal/appropriate from pathological bleeding, the role and yield of screening tests, the lack of distinctive bleeding pattern among the different diseases, the inherent difficulties in the diagnosis of type 1 VWD and the most common platelet functional disorders, improvements in assays to measure platelet aggregation and secretion, and the evidence that most of the patients with MBDs end up without a definite diagnosis after exhaustive and repeated laboratory testing. Much research is needed to determine the pathogenesis of bleeding in MBD patients. Better standardization of current laboratory assays, progress in the knowledge of fibrinolytic mechanisms and their laboratory evaluation, and new understanding of the factors contributing to platelet-vessel wall interaction, along with the corresponding development of laboratory tools, should improve our capacity to diagnose a greater proportion of patients with MBDs.
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    Mutations in sphingolipid metabolism genes are associated with ADHD
    (2020) Henriquez-Henriquez, Marcela; Acosta, Maria T.; Martinez, Ariel F.; Velez, Jorge, I; Lopera, Francisco; Pineda, David; Palacio, Juan D.; Quiroga, Teresa; Worgall, Tilla S.; Deckelbaum, Richard J.; Mastronardi, Claudio; Molina, Brooke S. G.; Arcos-Burgos, Mauricio; Muenke, Maximilian
    Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75-80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) sample, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa sample, 298 subjects) and 3 (US sample, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes (GALC,CERS6,SMPD1,SMPDL3B,CERS2,FADS3,ELOVL5, andCERK). Successful local replication for associations with variants inGALC,SMPD1, andCERS6was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increasedGALCexpression in the cerebellum.
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    Normal plasma insulin and HOMA values among chilean children and adolescents
    (SOC MEDICA SANTIAGO, 2011) Barja, Salesa; Arnaiz, Pilar; Dominguez, Angelica; Villarroel, Luis; Cassis, Berta; Castillo, Oscar; Salomo, Gianina; Farias, Marcelo; Goycoolea, Manuela; Quiroga, Teresa; Mardones, Francisco
    Background: Plasma insulin and HOMA (homeostasis model assessment) index, used to determine insulin resistance, do not have local standard values for children and adolescents in Chile. Aim: To establish the normal reference intervals for insulin and HOMA in children and adolescents aged 10-15 years, according to sex and puberal maturation. Material and Methods: A cross-sectional study of 2,153 children and adolescents from Puente Alto County was performed, during 2009 and 2010. Anthropoinetry and self-report of puberal maturation were assessed. Fasting glucose (hexoquinase) and insulin blood levels (chemiluminiscence), were determined and HOMA index was calculated. Percentile distributions of these variables were calculated. Results: The reference group included only subjects with normal body mass index and fasting blood glucose (n = 1,192). Girls had higher insulin and HOMA values than boys (12.5 +/- 6.0 and 9.1 +/- 4.9 mu U/mL (p <0.01) and 2.7 +/- 1.4 and 2.1 +/- 1,1 (p <0.01), respectively). Subjects with Tanner land II puberal stages had lower insulin and HOMA mean values than subjects with Tanner III and IV (9.0 +/- 4.3 and 12.5 +/- 6.2 mu U/ml (p < 0.01) and 2.0 +/- 1 and 2.8 +/- 1.4 (p <0.01), respectively). Conclusions: The 90th percentile of insulin and HOMA distributions according to sex and maturation, was selected as the upper cut-off point to identify individuals with insulin resistance. HOMA cutoff point for Tanner I and II boys was 3.2, for Tanner land II girls was 4.1, for Tanner III and IV boys was 4.2 and for Tanner III and IV girls was 5.0. (Rev Med Chile 2011; 139: 1435-1443).