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Santiago de Compostela, Spain

Xu H.,University of Montreal | Perez-Cuevas R.,Instituto Mexicano del Seguro Sosial | Xiong X.,Tulane University | Reyes H.,National Institute of Public Health | And 23 more authors.
American Journal of Obstetrics and Gynecology

Objective: We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women. Study Design: In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions. Results: Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes. Conclusion: Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes. © 2010 Mosby, Inc. All rights reserved. Source

Fernandez-Rodriguez E.,University of Santiago de Compostela | Barreiro J.,University of Santiago de Compostela | Marazuela M.,Autonomous University of Madrid | Pereiro I.,CHUS | And 6 more authors.

Objectives: To investigate the prevalence of pituitary stalk dysgenesis (PSD) in adult hypopituitary patients by describing the chronology of hormone deficiencies and their potential correlation with traumatic delivery, mutations in genes required for pituitary development and function and pituitary stalk visibility on MRI. Design: Retrospective and prospective study involving 231 hypopituitary patients, including 26 diagnosed with PSD. Clinical, biochemical and radiological studies were reviewed. Molecular analyses of HESX1, LHX4,PROP1 and POU1F1 genes were performed prospectively. Results: PSD was present in 11.2% of hypopituitary patients. PSD was diagnosed before 14 years of age in 46.2% of cases, between 14 and 18 years of age in 23%, and in adulthood in 30.8%. Perinatal complications or gene mutations were present in 26.9 and 4.3% of patients, respectively. At first assessment, 92.3% of patients had growth hormone (GH) deficiency. 26.9% presented as combined pituitary deficiencies and 7.6% as panhypopituitarism. Hormone deficiencies were progressive during follow-up in 84.6%. 96% progressed to multiple deficiencies and 46% to panhypopituitarism. No significant association was found between hormonal dysfunction and previous perinatal damage or breech delivery (p = 0.17), PROP1 mutations (p = 0.26) or pituitary stalk visibility on MRI (p = 0.52). No mutations in POU1F1, HESX1 and LHX-4 genes were detected. Conclusion: In this study, PSD prevalence in adult hypopituitary patients was 11.2%. Typical clinical presentation includes isolated or combined pituitary hormone deficiencies during the pediatric age, which usually progress to combined or complete hypopituitarism in adulthood. Phenotype is highly variable depending on hormone profile and age at onset. Copyright © 2011 S. Karger AG. Source

Lamas M.J.,Complejo Hospitalario Universitario Of Santiago | Duran G.,Complejo Hospitalario Universitario Of Santiago | Balboa E.,Molecular Medicine Unit | Bernardez B.,Complejo Hospitalario Universitario Of Santiago | And 7 more authors.

Aim: Polymorphisms in the metabolism, detoxification or DNA repair pathways have been proposed as potential predictors of response to 5-fluorouracil and oxaliplatin. We have studied the predictive value of a set of germline genetic polymorphisms in metastatic colorectal cancer patients treated with mFolfox-6. Materials & methods: A total of 72 patients, comprising 50 men (69.4%) and 22 women (30.6%), were included after the signing of an informed consent form. Median age was 65.5 years (range: 32-80). All participants received mFolfox-6. DNA was extracted from peripheral blood samples and genotyped by direct sequencing, SnapShot®Â and multiplex PCR techniques. Eight polymorphisms within six genes were investigated: TS 5́Ấ-UTR (variable number tandem repeat + G/C), TS 3́-UTR (TS1494del6); MTHFR C677T and A1298C; GSTP1 I105V; ERCC1 C118T; XPD Lys751Gln and XRCC1 Arg399Gln. Association was evaluated by univariate analysis, and Cox regression and Kaplan-"Meier assessed survival. The local ethics committee approved the pharmacogenetic study protocol and all subjects signed an informed consent before participating in the study. Results: The sample was in Hardy-"Weinberg equilibrium. Only XPD Lys751Gln was found to be significantly associated with a favorable progression-free survival (PFS). Median PFS for XPD Lys751Gln patients (n = 33) was 16 months (95% CI: 9.2-"22.7), 10 months (95% CI: 6.1-"13.9) for Gln/Gln (n = 11) and 8 months (95% CI: 5.8-"10.2) for Lys/Lys (n = 28), p = 0.019. The increased risk of progression was: 1.93 (95% CI: 1.13-"13.30; p = 0.017) for Lys/Lys and 2.1 (95% CI: 1.01-"4.22; p = 0.047) for Gln/Gln. Patients with one or two Val alleles of GSTP1 tended to a lower risk of progression compared with Ile/Ile homozygotes, p = 0.067. When XPD Lys751Gln and GSTP1 were analyzed jointly, patients who carried one or two favorable genotypes, XPD Lys751Gln and Val, had a longer median PFS: 11 months (95% CI: 7.4-"14.6) compared with six (95% CI: 4.6-7.4) with unfavorable genotypes, p < 0.001. Conclusion: In metastatic colorectal cancer patients treated with mFolfox-6, the combination of haplotype XPD Lys751Gln-GSTP1 105Val seems to predict the risk of progression. © 2011 Future Medicine Ltd. Source

Damaj L.,Neurology Service | Lupien-Meilleur A.,CHU Ste Justine | Lortie A.,Neurology Service | Riou E.,CHUS | And 5 more authors.
European Journal of Human Genetics

CACNA1A loss-of-function mutations classically present as episodic ataxia type 2 (EA2), with brief episodes of ataxia and nystagmus, or with progressive spinocerebellar ataxia (SCA6). A minority of patients carrying CACNA1A mutations develops epilepsy. Non-motor symptoms associated with these mutations are often overlooked. In this study, we report 16 affected individuals from four unrelated families presenting with a spectrum of cognitive impairment including intellectual deficiency, executive dysfunction, ADHD and/or autism, as well as childhood-onset epileptic encephalopathy with refractory absence epilepsy, febrile seizures, downbeat nystagmus and episodic ataxia. Sequencing revealed one CACNA1A gene deletion, two deleterious CACNA1A point mutations including one known stop-gain and one new frameshift variant and a new splice-site variant. This report illustrates the phenotypic heterogeneity of CACNA1A loss-of-function mutations and stresses the cognitive and epileptic manifestations caused by the loss of Ca V 2.1 channels function, presumably affecting cerebellar, cortical and limbic networks. © 2015 Macmillan Publishers Limited. Source

Anton Aparicio L.M.,UDC | Anton Aparicio L.M.,Oncology Group | Medina Villaamil V.,Oncology Group | Aparicio Gallego G.,Oncology Group | And 9 more authors.
Cancer Genomics and Proteomics

Background: Mutations in signalling pathways essential for embryonic development often lead to tumourigenesis, as is also true for Notch. The aim of this study was to assess the relationship between Notch1 to -4 and their ligands with anatomopathological features of the patients with renal cell carcinoma (RCC). Materials and Methods: This study investigated the pattern of protein expression in RCC specimens using tissue microarray technology. A total of 80 paraffin-embedded RCC samples were retrospectively analysed together with ACHN and A.704 cell lines. Results: Notch1 showed significant positive correlation with chromophobe RCC, no broken capsule, Furhman grade I and when the number of nodes involved was small [(N=1); p=0.039, 0.016, 0.037 and 0.001, respectively)]. Notch3 showed higher expression when the tumour was located in the right kidney (p=0.048). Conclusion: Notch1 may be useful in the future as a biomarker for the differential diagnosis of different RCC histological subtypes. Notch1 to -3 may also have potential use as a strong prognostic factor. Source

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