Kamil Biringer

Fibronectin, plasminogen activator inhibitor type 1 (PAI-1) and uterine artery Doppler velocimetry as markers of preeclampsia

Objective: The purpose of this study was to examine plasma levels of fibronectin and plasminogen inhibitor type 1 (PAI-1), and alterations in uterine artery (UtA) waveforms throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy. Material and methods: Blood samples were collected from 102 healthy, nulliparous women between the 24th and 26th gestational week. Preeclampsia developed in 13 patients; 89 normotensive control subjects were matched from the same cohort. Plasma samples were assayed for fibronectin and PAI-1 by enzyme-linked immunosorbent assay. Color pulsed Doppler examinations of UtA were performed after blood sampling. Trends were compared between two groups. Results: Maternal plasma fibronectin and PAI-1 levels and average PI, RI and S/D ratios of patients with preeclampsia were significantly higher (p < 0.05). The best cut-off values for predicting preeclampsia of fibronectin, PAI-1, PI, RI, S/D ratio based on ROC curve analysis were 290 mg/ml, 77.3 ng/ml, 1,0615, 0.605 and 2,59 respectively. The areas under the curve equal to 0.705, 0.753, 0.689, 0.695 and 0.699 for fibronectin, PAI-1 and uterine artery Doppler PI, RI, S/D ratio were determined for the prediction of preeclampsia. Conclusions: Fibronectin, PAI-1 and UtA Doppler are potentially useful predictors of preeclampsia. Maternal plasma PAI-1 combinated with fibronectin had the highest predictive values in our study.

Platelet aggregation abnormalities in patients with fetal losses: the GP6 gene polymorphism.

OBJECTIVE To evaluate the GP6 gene polymorphism in patients with sticky platelet syndrome (SPS) and fetal loss. DESIGN Genetic association study. SETTING Perinatal center. PATIENT(S) Twenty-seven patients with SPS, manifested as fetal loss, and 42 control subjects without SPS and no history of fetal loss and thrombosis. INTERVENTION(S) SPS was diagnosed by platelet aggregometry (PACKS-4 aggregometer; Helena Laboratories). Seven single-nucleotide polymorphisms (SNPs) of the GP6 gene were evaluated. MAIN OUTCOME MEASURE(S) Occurrence of SNPs of the GP6 gene in SPS patients versus control subjects. RESULT(S) We found a higher occurrence of three SNPs of the GP6 gene in SPS patients versus control subjects (rs1671153: 0.204 vs. 0.048, odds ratio [OR] 5.116, 95% confidence interval [CI] 1.536-17.03; rs1654419: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619; rs1613662: 0.204 vs. 0.071, OR 3.326, 95% CI 1.149-9.619). The haplotype analysis showed a significantly higher occurrence of two haplotypes (CTGAG in haplotype 5: 0.185 vs. 0.059, OR 3.568, 95% CI 1.142-11.14; and CGATAG in haplotype 6: 0.204 vs. 0.048, OR 4.961, 95% CI 1.488-16.53). CONCLUSION(S) Our results, especially the higher occurrence of haplotypes CTGAG and CGATAG in SPS patients, support the idea that GP6 gene polymorphism may be associated with platelet hyperaggregability, a possible cause of fetal loss.

Different models of inheritance in selected genes in patients with sticky platelet syndrome and fetal loss.

INTRODUCTION The aim of this study was to evaluate the genetic variability of selected single nucleotide polymorphisms (SNPs) within GAS6 and PEAR1 genes and explore the association between selected SNPs and risk for fetal loss in women with sticky platelet syndrome (SPS). MATERIALS AND METHODS We examined 23 female patients with SPS and history of spontaneous abortion, and 42 healthy women who served as controls. The diagnosis of SPS was established by light transmission aggregometry according to methods and criteria developed by Mammen et al. We also assessed four SNPs within the GAS6 gene (rs7400002, rs1803628, rs8191974, rs9550270) and two SNPs within PEAR1 gene (rs12041331, rs12566888). RESULTS We identified two SNPs within PEAR1 gene (rs12041331, rs12566888) and one SNP within GAS6 gene (rs9550270) that have higher occurrence in SPS patients with history of abortion. An increased risk for abortion was observed in carriers of the rs7400002 within GAS6 gene. Conversely, we found that the T allele of PEAR1 c. -9-4663G > T polymorphism appears to be protective for fetal loss. CONCLUSION Our results support the idea that genetic variability of GAS6 and PEAR1 genes may be associated with platelet hyperaggregability. The study also suggests a possible polygenic type of SPS heredity.

Delayed delivery following unusual flare-up pelvic abscess after in vitro fertilization and embryo transfer

OBJECTIVE To report a case of delayed delivery of twins following pelvic abscess that required laparotomy after uncomplicated IVF-ET. DESIGN Case report. SETTING Department of Perinatology. PATIENT(S) A 32-year-old nulliparous woman after IVF-ET. INTERVENTION(S) In vitro fertilization and ET, laparotomy, observation in the hospital. MAIN OUTCOME MEASURE(S) Delayed delivery following pelvic abscess that required laparotomy after uncomplicated IVF-ET. RESULT(S) After a successful delayed delivery, the patient and her infant were discharged home. CONCLUSION(S) Pelvic abscess rarely complicates pregnancy. It cannot be excluded in women after IVF-ET. This report confirms the necessity to develop a comprehensive approach for continuation of complicated multiple pregnancies.

Genetic variations of the GP6 regulatory region in patients with sticky platelet syndrome and miscarriage.

Introduction: Thrombophilia increases the risk of venous thrombosis during pregnancy and may predispose to gestational vascular complications. Objective: The aim of this study is to evaluate the variability of GP6 regulatory regions in a group of patients with platelet hyperaggregability manifested as miscarriage compared with control subjects. Methods: We examined 27 female patients with platelet hyperaggregability and history of spontaneous abortion and 42 healthy women. Platelet hyperaggregability was established by light transmission aggregometry. We also assessed eight SNPs within the GP6 gene. Results: We found a higher occurrence of three SNPs in patients with platelet hyperaggregability and history of miscarriage (rs1671152, rs1654433, rs1671215). The haplotype analysis showed a significant higher occurrence of two haplotypes (ACGG, CCGT). Conclusions: Our results support the idea that genetic variability of GP6 regulatory regions can be associated with platelet hyperaggregability – a possible cause of miscarriage.

Arteriovenous malformation of vein of Galen as a rare non-hypoxic cause of changes in fetal heart rate pattern during labor

The aim of this case report is to describe a rare non‐hypoxic cause of pathological changes in fetal heart rate pattern during labor, and to determine management, including a description of important prenatal aspects when pathologic cardiotocographic recording is performed during labor. A fetus with rare arteriovenous malformation of the vein of Galen, which represents less than 1% of all intracranial arteriovenous malformations, was monitored by intrapartum external cardiotocography in the 37 + 5 gestational week. The baby was born by cesarean section because of signs of imminent intrauterine hypoxia on cardiotocography. However, metabolic acidosis was not confirmed in umbilical cord blood sampling. Despite intensive neonatal care management, the newborn died 31 h after delivery because of progressive cardiac decompensation, hypotension and multi‐organ failure. Precise diagnosis of the abovementioned pathology, a pre‐labor plan for delivery and postnatal prognosis assessment can significantly contribute to the avoidance of a misdiagnosis of fetal hypoxia and unnecessary operative delivery with marked medico‐legal consequences.

Activity of coagulation factor XI in patients with spontaneous miscarriage: The presence of risk alleles

Abstract The aim of this study was to compare the activity of coagulation factor XI (FXI) between patients with spontaneous miscarriage versus control group with no history of miscarriage and thrombosis, and then we evaluated the occurrence of risk alleles in the relation to miscarriage. FXI activity was determined using a coagulometer (Sysmex, CA 1500, Japan). Single nucleotide polymorphisms (SNPs) of F11 and CYP4V2 genes were evaluated. We examined 55 patients versus 31 control subjects. We found significantly higher activity of FXI (p = 0.04) in patients versus control subjects. The occurrence of two SNPs (rs2289252 and rs2036914) of the F11 gene and SNP (rs13146272) of CYP4V2 gene was not significantly different between both groups. Increased activity of FXI may be a potential risk factor for miscarriage. High activity of FXI diagnosed in women with history of miscarriage is not probably caused by the presence of studied SNPs.

Sensitivity of airway cough-related afferents is influenced by female sex hormones

Chronic hypersensitivity cough syndrome affects mainly postmenopausal women; however, the pathogenesis of cough hypersensitivity in this demographic is not entirely understood. The role of sex hormones in cough has never been studied in detail; however, sex hormones seem to play an important role in the lung health of women. Our study was aimed to analyse the effect of female sex hormones (oestrogen - E2 and progesterone - Pg) on cough sensitivity measured by inhalation of capsaicin in follicular and luteal phases of menstrual cycle, characterized by significantly different concentrations of sex hormones. These data were compared with a matched group of women taking oral contraceptives. Cough sensitivity to capsaicin increased in luteal phase in subjects with normal menstrual cycle, and this functional change was not present in group with contraceptive pills. The cough sensitivity correlates with the Pg/E2 ratio, and relative lack of oestrogen in luteal phase is associated with higher cough sensitivity to capsaicin.

Bilateral ovarian angiosarcoma arising from the mature cystic teratomas – A case report and review of the literature

Highlights • We present the first case of bilateral ovarian angiosarcoma arising from the mature teratomas.• Due to widespread disease, we performed limited surgical procedure consisting of bilateral adnexectomy and omentectomy.• This work summarizes the current knowledge in the diagnosis and treatment of angiosarcomas arising in the mature teratomas.• Promising results are expected from the trials devoted to antiangiogenic strategies in treatment of aggressive sarcomas.

GP6 Haplotype of Missense Variants is Associated with Sticky Platelet Syndrome Manifested by Fetal Loss.

Disequilibrium of hemostasis is central to the pathogenesis of all thromboses, and platelets are essential for primary hemostasis. The platelet membrane glycoprotein receptor is involved in the clot formation in blood; therefore, the changes in related genes could impair platelet aggregation in patients with sticky platelet syndrome (SPS). Patients with SPS who experienced fetal loss were shown to harbor a risk haplotype at GP6 locus. The aim of the study was to examine the genetic linkage of this selected risk haplotype with single nucleotide variations (SNVs) in the coding sequence of the GP6 gene in order to identify possible functional SNVs in association with SPS and fetal loss. A total of 37 patients with SPS manifested fetal loss, and 42 healthy controls were enrolled in the study. The SPS was diagnosed with platelet aggregometry. The SNVs were determined by dideoxy sequencing and high-resolution melting analysis. The missense variations were detected in patients with risk haplotype only. The association analysis showed association of the minor alleles with the SPS manifested by fetal loss as follows—rs1671152 (odds ratio [OR]: 4.667, 95% confidence interval [CI]: 1.462-14.89, P = .006), rs2304167 (OR: 5.085, 95% CI: 1.605-16.10, P = .003), and rs1654416 (OR: 5.085, 95% CI: 1.605-16.10, P = .003). Using the Expectation-Maximization (EM) algorithm, the estimated minor haplotype with predicted protein residue PEAN was significantly associated with the given phenotype (OR: 4.746, 95% CI: 1.486-15.15, P = .005). We have shown that haplotype PEAN associated with SPS and manifested by fetal loss and suggest that the mechanism involved in the action of GPVI has significant effect on GPVI-mediated signal transduction through Syk-phosphorylation.