19 research outputs found
Pharmacogenetics of dabigatran etexilate interindividual variability
No full textIntroduction Dabigatran etexilate is given in fixed doses without coagulation monitoring for the prevention of blood clots in at risk adults. A high inter-individual variability in blood concentrations of the active metabolite of dabigatran has been reported. ABCB1 and CES1 exert an important effect in the metabolism of dabigatran etexilate and allele variants at these two loci are likely to play a pivotal role. To investigate whether screening for polymorphisms within the ABCB1 and the CES1 genes would explain a portion of the inter-individual variability in blood concentrations of the active metabolite of dabigatran. Material and methods In a cohort of patients who had atrial fibrillation and on anticoagulant prophylaxis with dabigatran etexilate, we investigated whether genotypes at rs4148738 (ABCB1), rs8192935 (CES1), and rs2244613 (CES1) loci would affect plasma dabigatran trough and peak concentrations. Results and discussion Among 92 patients (median age: 72.0 years, range: 52-92) analyzed, no clinical variable or genotype was associated with a significant difference in dabigatran peak concentrations. As for trough concentrations, in addition to creatinine clearance, and sex a significant association with the CES1 SNP rs8192935 (p = 0.023) was detected. The mean adjusted plasma levels were higher among patients with the CC genotype (86.3 ng/dl) than in those carrying the T allele (62.1 ng/dl). No significant effect was found for the ABCB1 SNP rs4148738. The CES1 SNP rs8192935 significantly influenced the dabigatran trough concentrations and carriers of the T allele showed significantly lower concentrations than did carriers of the CC genotype
Factor XI gene variants in factor XI-deficient patients of Southern Italy: identification of a novel mutation and genotype-phenotype relationship
No full textCongenital Factor XI (FXI) deficiency shows a high variability in clinical phenotype. To date, many allele variants have been shown to cause this bleeding disorder. However, the genotype-phenotype relationship is difficult to establish. This report provides insights into this bleeding disorder. Sixteen unrelated Italian index cases with congenital FXI deficiency and their relatives were investigated. After the identification of the deficiency, we obtained DNA from each subject and analyzed the FXI gene using direct sequencing. We identified 5 and 11 individuals with severe and moderate deficiency of FXI activity, respectively. Most patients (8/16) carried mutations in the Apple 2 domain and 4 patients showed c.403G>T (p.Glu135*; type II mutation). Four novel compound heterozygosities were identified. Bleeding symptoms were present in two severely deficient subjects carrying the combinations c.901T>C (p.Phe301Leu)/c.1556G>A (p.Trp519*) and c.943G>A (p.Glu315)/c.1556G>A (p.Trp519*), respectively. Bleeding episodes were also observed in the presence of a moderate deficiency in two individuals heterozygous for c.449C>T (p.Thr150Met) and c.1253G>T (p.Gly418Val), respectively. One novel mutation, c.1682C>A (p.Ala561Asp), was identified as potentially deleterious in an asymptomatic individual. We confirm an unclear prediction of phenotype from mutational data. The FXI levels should be coupled with FXI analysis for a more comprehensive prediction of the bleeding phenotype in FXI deficiency
Clinical Utility of Antithrombotic Prophylaxis in ART Procedures: An Italian Experience
No full textThe usefulness of antithrombotic prophylaxis in management of Assisted Reproductive Technologies (ART) is questionable.We prospectively examined the contribution of an antithrombotic prophylaxis in influencing clinical pregnancy and live-birth in an unselected cohort of women approaching ART.1107 women with fertility problems and a valid indication for ART were recruited. Baseline and follow-up information of obstetric outcomes and antithrombotic treatment were collected.Median follow-up time was 34.5 months (range: 2–143). During the follow-up period, 595 (53.8%) women underwent ART (total 1234 cycles); 202 (33.9%) women achieved a pregnancy for a total of 255 clinical pregnancies. The concomitant use of LMWH and aspirin was significantly associated with a higher rate of clinical pregnancies (p: 0.003, OR: 4.9, 95% CI: 1.7–14.2). The pregnancy rate was also significantly increased by the use of LMWH alone (p: 0.005, OR: 2.6, 95% CI: 1.3–5.0). Carriership of inherited or acquired thrombophilia did not affect clinical outcomes of the ART. The efficacy of antithrombotic treatment was confirmed when the outcome “ live-birth” was considered. Present data suggest a potential benefit of antithrombotic prophylaxis during ART in improving the number of live-births
Obstetric outcomes in pregnant COVID-19 women: the imbalance of von Willebrand factor and ADAMTS13 axis
No full textBackground Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy. Methods We prospectively investigated 90 pregnant women admitted to two tertiary academic hospitals in Italy with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Demographic, clinical information and routine laboratory data were collected at the hospital admission and until discharge. We investigated whether vonWillebrand /ADAMTS13 axis imbalance is a predictor of adverse outcomes. Logistic regression analysis, which controlled for potential confounders, was performed to evaluate the association between laboratory parameters and clinical outcomes. Results Most women (55.6%) were parae, with median gestational age at admission of 39 weeks. At hospital admission, 63.3% were asymptomatic for COVID-19 and 24.4% showed more than one sign or symptom of infection. Nulliparae with group O showed Willebrand / ADA MTS-13 ratios significantly lower than non-O, whereas in multiparae this difference was not observed. Logistic regression showed that ratio von Willebrand to ADAMTS13 was significantly and independently associated with preterm delivery (OR 1.9, 95%CI 1.1-3.5). Conclusion This study shows an imbalance of vonWillebrand /ADAMTS13 axis in pregnant women with COVID-19, leading to a significantly higher and independent risk of preterm delivery. Monitoring these biomarkers might support decision making process to manage and follow-up pregnancies in this setting
Clinical utility of antithrombotic prophylaxis in ART procedures: an Italian experience
No full textBackground: The usefulness of antithrombotic prophylaxis in management of Assisted Reproductive Technologies (ART) is questionable. Objectives: We prospectively examined the contribution of an antithrombotic prophylaxis in influencing clinical pregnancy and live-birth in an unselected cohort of women approaching ART. Patients/Methods: 1107 women with fertility problems and a valid indication for ART were recruited. Baseline and follow-up information of obstetric outcomes and antithrombotic treatment were collected. Results and Conclusions: Median follow-up time was 34.5 months (range: 2-143). During the follow-up period, 595 (53.8%) women underwent ART (total 1234 cycles); 202 (33.9%) women achieved a pregnancy for a total of 255 clinical pregnancies. The concomitant use of LMWH and aspirin was significantly associated with a higher rate of clinical pregnancies (p: 0.003, OR: 4.9, 95% CI: 1.7-14.2). The pregnancy rate was also significantly increased by the use of LMWH alone (p: 0.005, OR: 2.6, 95% CI: 1.3-5.0). Carriership of inherited or acquired thrombophilia did not affect clinical outcomes of the ART. The efficacy of antithrombotic treatment was confirmed when the outcome "live-birth" was considered. Present data suggest a potential benefit of antithrombotic prophylaxis during ART in improving the number of live-births
ICONOGRAFIA E HISTÓRIA NA LITERATURA DE DEREK WALCOTT
No full textConsiderado um autor regional até pouco tempo antes de ganhar o Prêmio Nobel em 1992, com o épico de poesias Omeros, Derek Walcott, autor creole do Caribe Britânico, foi beneficiado pela globalização, após produzir uma obra literário-poética e pictórica significativa do imaginário do século XX, fragmentado por incursões pós-modernas, exigindo leituras para além dos “binarismos” primários de poder (Homi Bhabha). O estudo iconográfico que pretendemos, utilizando como ponto de partida seu livro Omeros e suas pinturas produzidas entre os anos de 1990 e 2006, busca ultrapassar a limitação da pesquisa iconográfica e iconológica, detectada nos últimos anos, por autores como Peter Burke, não só para reexaminar e reavaliar o imaginário de nossa época, como para evidenciar uma espécie de síntese humanística voltada para o diálogo entre os povos, em meio a outras abordagens. O entrecruzamento de fontes orais, pictóricas e literárias, visando a ampliação de perspectivas, tão bem defendido por Michel Vovelle, denota tanto a presença de alguns paradigmas e métodos conflitantes na abordagem da imagem e da linguagem, como justifica a pesquisa diante da escassez de trabalhos históricos nessa área, sugerindo novas análises.
Palavras-chave: Derek Walcott. Poesia. Prosa. Imaginário. Caribe
Resumen
Derek Walkott fue considerado un autor regional hasta obtener el Premio Nobel de Literatura en 1992 con su obra Omeros. El estudio que proponemos pretende trascender la investigación Iconográfica, aunque está apoyado en sus pinturas producidas entre 1990 y 2006. Se trata de contrastar fuentes pictóricas y literárias enfrentando paradigmas y utilizando variados métodos en la búsqueda de uma ampliación de perspectivas de la propia Historia.
Palavras claves: Derek Walkott. Poesía. Prosa. Imaginário. Pintura. Caribe
Abstract
Considered a regional author until he was awarded the Nobel Prize in 1992 for his epic poetry Omero, Derek Walcott, a Creole writer and painter, benefited from globalization after producing a significant literary-poetic and artistic work about the twentieth-century imaginary, fragmented by post-moderns influences, demanding interpretations beyond primary ‘binarisms’ of power (Homi Bhabha). The iconography study that we propose, using as starting-point his book Omero and his paintings produced between 1990 and 2006, attempts to go beyond the iconographic and iconological research of the recent years, conducted by Peter Burke; it aims not only to re-examine and re-evaluate the imaginary’s epoch, but also to give evidence of a kind of humanistic synthesis directed to the dialogue between peoples, among other approaches. The intertwining of oral, pictorial and literary sources, with the aim to increase perspectives, as it has been supported by Michel Vovelle, denotes the presence of some paradigms and conflicting methods with the aim to increase perspectives, conflictive methods in the approach of image and language. The lack of historical studies in this area justifies the proposed research, with the proposal of new analyses.
Keywords: Derek Walcott. Poetry. Prose. Painting. Imaginary. Caribbea
ICONOGRAFIA E HISTÓRIA NA LITERATURA DE DEREK WALCOTT
No full textConsiderado um autor regional até pouco tempo antes de ganhar o Prêmio Nobel em 1992, com o épico de poesias Omeros, Derek Walcott, autor creole do Caribe Britânico, foi beneficiado pela globalização, após produzir uma obra literário-poética e pictórica significativa do imaginário do século XX, fragmentado por incursões pós-modernas, exigindo leituras para além dos “binarismos” primários de poder (Homi Bhabha). O estudo iconográfico que pretendemos, utilizando como ponto de partida seu livro Omeros e suas pinturas produzidas entre os anos de 1990 e 2006, busca ultrapassar a limitação da pesquisa iconográfica e iconológica, detectada nos últimos anos, por autores como Peter Burke, não só para reexaminar e reavaliar o imaginário de nossa época, como para evidenciar uma espécie de síntese humanística voltada para o diálogo entre os povos, em meio a outras abordagens. O entrecruzamento de fontes orais, pictóricas e literárias, visando a ampliação de perspectivas, tão bem defendido por Michel Vovelle, denota tanto a presença de alguns paradigmas e métodos conflitantes na abordagem da imagem e da linguagem, como justifica a pesquisa diante da escassez de trabalhos históricos nessa área, sugerindo novas análises.Palavras-chave: Derek Walcott. Poesia. Prosa. Imaginário. CaribeResumenDerek Walkott fue considerado un autor regional hasta obtener el Premio Nobel de Literatura en 1992 con su obra Omeros. El estudio que proponemos pretende trascender la investigación Iconográfica, aunque está apoyado en sus pinturas producidas entre 1990 y 2006. Se trata de contrastar fuentes pictóricas y literárias enfrentando paradigmas y utilizando variados métodos en la búsqueda de uma ampliación de perspectivas de la propia Historia.Palavras claves: Derek Walkott. Poesía. Prosa. Imaginário. Pintura. CaribeAbstractConsidered a regional author until he was awarded the Nobel Prize in 1992 for his epic poetry Omero, Derek Walcott, a Creole writer and painter, benefited from globalization after producing a significant literary-poetic and artistic work about the twentieth-century imaginary, fragmented by post-moderns influences, demanding interpretations beyond primary ‘binarisms’ of power (Homi Bhabha). The iconography study that we propose, using as starting-point his book Omero and his paintings produced between 1990 and 2006, attempts to go beyond the iconographic and iconological research of the recent years, conducted by Peter Burke; it aims not only to re-examine and re-evaluate the imaginary’s epoch, but also to give evidence of a kind of humanistic synthesis directed to the dialogue between peoples, among other approaches. The intertwining of oral, pictorial and literary sources, with the aim to increase perspectives, as it has been supported by Michel Vovelle, denotes the presence of some paradigms and conflicting methods with the aim to increase perspectives, conflictive methods in the approach of image and language. The lack of historical studies in this area justifies the proposed research, with the proposal of new analyses.Keywords: Derek Walcott. Poetry. Prose. Painting. Imaginary. Caribbea
The figure depicts the entire cohort of women enrolled.
No full text<p>The figure depicts the entire cohort of women enrolled.</p
Cumulative live-birth rate during the follow-up and stratified according to the age, and calculated assuming that women who did not return for ART had the same chance as those who remained in treatment (Optimistic, Panel A) or no chance of a pregnancy resulting in a live-birth (Conservative, Panel B).
No full text<p>In both models, the age-stratified curves in women from 38 to 40 yrs and >40 yrs were significantly different from those of women <35 yrs (p<0.001) and those in women from 35 to 38 yrs (p<0.01 and <0.05, respectively).</p
Main obstetric outcomes of cycles with and without medical treatment.
No full text<p>Main obstetric outcomes of cycles with and without medical treatment.</p
