FAM19A4 methylation analysis in self-samples compared with cervical scrapes for detecting cervical (pre)cancer in HPV-positive women

Background:High-risk human papillomavirus (hrHPV)-positive women require triage to identify those with cervical high-grade intraepithelial neoplasia and cancer (≥CIN3 (cervical intraepithelial neoplasia grade 3)). FAM19A4 methylation analysis, which detects advanced CIN and cancer, is applicable to different sample types. However, studies comparing the performance of FAM19A4 methylation analysis in hrHPV-positive self-samples and paired physician-taken scrapes are lacking.Methods:We compared the performance of FAM19A4 methylation analysis (and/or HPV16/18 genotyping) in self-samples and paired physician-taken scrapes for ≥CIN3 detection in hrHPV-positive women (n=450,18-66 years).Results:Overall FAM19A4 methylation levels betw

Effects of transdermal and oral postmenopausal hormone therapy on vascular function a randomized placebo-controlled study in healthy postmenopausal women

To compare the effect of transdermal and oral estrogen therapy, the latter with or without the addition of gestodene, on plasma concentrations of markers of endothelial function and on ultrasonographic parameters of vascular function in healthy postmenopausal women.In a 15-month, randomized, double-blind, placebo-controlled study, 152 healthy hysterectomized postmenopausal women received daily doses of placebo (n = 49), 50 microg of transdermal 17ss-estradiol (tE2, n = 33), 1 mg of oral E2 (oE2, n = 37), or 1 mg of oral estradiol combined with 25 microg of gestodene (oE2+ G, n = 33) for 13 cycles of 28 days, followed by four washout cycles with placebo in each group. At baseline and in cycles 4, 13, and 17, we measured plasma levels of endothelial markers and ultrasonographic markers of vascular function (pulsatility index [PI] and, at baseline and cycle 13, arterial stiffness).Compared with placebo, we found reductions in soluble vascular cell adhesion molecule (oE2, P <0.01; oE2+ G, P <0.001), sE-selectin (oE2 + G, P <0.05), von Willebrand factor (tE2, P <0.05), and divergent effects in PI and stiffness parameters in the carotid artery. We found no effect on PI in the retinal and femoral arteries, or on stiffness parameters in the femoral and brachial artery.Oral hormone therapy reduced plasma levels of adhesion molecules, whereas transdermal estrogen therapy reduced von Willebrand factor. Effects on ultrasonographic parameters of vascular function in the carotid artery were inconclusive

Methylation profiles of endometrioid and serous endometrial cancers.

Item does not contain fulltextPromoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC

Oxygen and carbon stable isotope records of marine vertebrates from the type Maastrichtian, The Netherlands and northeast Belgium (Late Cretaceous)

Stable isotope analysis of marine skeletal carbonates is an important tool for palaeoenvironmental reconstructions. However, in Mesozoic sedimentary sequences, diagenetic alteration often overprints the original skeletal carbonate isotope values. Yet, even if carbonate diagenesis did occur in such sequences, the original oxygen isotope values can still be preserved in enamel or bone phosphate of vertebrate fossils. Here are analysed the isotope compositions of tooth enamel structural carbonate and phosphate of various late Maastrichtian and early Palaeocene shark and ray taxa, as well as carapace bone of a late Maastrichtian marine turtle, Allopleuron hofmanni, from the type area of the Maastrichtian Stage in the southeast Netherlands and northeast Belgium. No correlation is observed between

Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: a randomized placebo-controlled study.

Item does not contain fulltextOBJECTIVE: This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease. STUDY DESIGN: In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n=49), transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13. RESULTS: No significant changes versus baseline and placebo were found in the tE(2) group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%, P=.01). In the oE(2) group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, -5.4% (P<.05); factor VII, -7.3% (P<.05); thrombin-antithrombin III complexes, -13.3% (P<.05); tissue-type plasminogen activator (t-PA), -17.3% (P<.001); and PAI-1, -54.3% (P<.001). In the oE(2)+G group, respective changes were factor VII, -17.6% (P<.001); t-PA, -14.5% (P=.01); PAI-1, -36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant changes were observed in prothrombin fragment 1+2 and plasmin-alpha(2)-antiplasmin complexes. CONCLUSION: Low-dose oral estradiol therapy was associated with an increase in fibrinolysis and small decreases in procoagulant variables. Transdermal therapy had minor effects.7 p