Newborn LpL (Ser447Stop, Asn291Ser) genotypes and the interaction with maternal genotypes influence the risk for different types of preeclampsia: modulating effect on lipid profile and pregnancy outcome.

AIM: To establish that newborn Ser447Stop and Asn291Ser may have interactive effects with maternal genotypes on the plasma lipoprotein levels, risk of preeclampsia as well as on the prognosis of preeclampsia. MATERIALS AND METHODS: Seventy preeclamptic women and 94 normotensive pregnant women, and their newborns were genotyped using PCR-RFLP methods. RESULTS: The risk of mild and severe preeclampsia was 4 (p = 0.004) and 5.18 (p = 0.001), respectively, if both the mother and newborn were carriers of the Ser447/Ser477 genotype. If both the mother and newborn were carriers of the Asn291Ser variant, the risk to develop severe preeclampsia was 6.07 (p = 0.03). Women with mild and severe preeclampsia had higher TG (p < 0.001; p < 0.001) and LDL-C levels (p = 0.008; p < 0.001) if both the mother and newborn were carriers of the Ser447/Ser447 genotype. Women with severe preeclampsia had significantly higher TG (p = 0.03) and LDL-C levels (p = 0.037) if both the mother and newborn were carriers of Asn291Ser. Newborn/maternal LpL interaction had no statistically significant influence on pregnancy outcome. CONCLUSIONS: The newborn/maternal LpL interaction influences the severity of preeclampsia and modulates the lipid profile particularly in severe preeclampsia.

Role of serum concentration of VEGFR1 and TIMP2 on clinical outcome in primary cervical cancer: results of a companion protocol of the randomized, NOGGO-AGO phase III adjuvant trial of simultaneous cisplatin-based radiochemotherapy vs. carboplatin and paclitaxel containing sequential radiotherapy.

OBJECTIVE: Aim of the present study was to analyze the expression-profile of IGF1, IGFBP3, sICAM1, sVCAM1, MMP2, MMP9, TIMP2, VEGFA, VEGFD, VEGFC and VEGFR1 in patients with high-risk FIGO-stage Ib-IIb cervical cancer. METHODS: Serum from 68 cervical cancer patients treated within a phase-III-trial with either simultaneous cisplatin radiochemotherapy or sequential systemic carboplatin and paclitaxel followed by percutaneous irradiation was analyzed by ELISA. Both target expression and correlation with important clinicopathological factors were analyzed following standard statistic procedures. RESULTS: All 68 patients underwent a primary radical hysterectomy with pelvic and/or paraaortic lymphadenectomy. 85.3% of the extirpated tumors had clear surgical margins (R0). Increased levels of VEGFR1, TIMP2 and MMP2 were significantly associated with positive surgical margins (p=0.004, p=0.018 and p=0.004, respectively). High concentration of MMP2 and TIMP2 correlated additionally with an advanced age at time of diagnosis (p=0.001 and p=0.007, respectively). For the cut-off value of 100 pg/ml, an increased VEGFR1 was significantly associated with poor overall (OS) and progression-free (PFS) survival (p=0.017 and p=0.015, respectively). A TIMP2 concentration of lower than 90 ng/ml was significantly associated with poorer OS and PFS (p=0.009 and p=0.043, respectively). In the multivariate analysis, TIMP2 expression in serum was the only independent prognostic factor for OS (p=0.032, HR=6.51, 95% CI=1.17-36.01). CONCLUSIONS: Expression-profile of specific biomarkers associated with tumor invasion, cell migration and angiogenesis seems to be of prognostic value for both OS and PFS in patients undergoing surgery due to primary cervical cancer. Further analyses are warranted to allow an implementation of such markers into clinical practice.

The effect of the D1-C785T polymorphism in the type 1 iodothyronine deiodinase gene on the circulating thyroid hormone levels in Romanian women with preeclampsia. Association with the degree of severity and pregnancy outcome of preeclampsia.

AIM: To investigate the biochemical and genetic thyroid status in women with preeclampsia by the determination of serum FT3 and FT4 levels in association with D1-C785T genotypes. METHODS: We genotyped using PCR-RFLP methods 50 women with preeclampsia and 50 normotensive pregnant women. RESULTS: FT3 levels (pg/ml, 2.63 ± 0.56 vs. 2.91 ± 1.41) were low, and FT4 levels (ng/dl, 1.11 ± 0.3 vs. 0.88 ± 0.14) were high in women with preeclampsia compared to normal pregnant women. The association with severe preeclampsia was stronger for the homozygous T/T genotype (OR 6.57, p = 0.029). Women with preeclampsia with the D1-T785 mutated allele had lower FT3 levels (pg/ml, 2.31 ± 0.81 vs. 3.04 ± 0.39, p < 0.001), higher FT4 levels (ng/dl, 1.32 ± 0.87 vs. 0.84 ± 0.24, p = 0.009) than women with preeclampsia with the D1-C/C genotype. Significant decrease in serum FT3 levels in positive women with severe preeclampsia compared to women negative for this genetic variation (pg/ml, 1.59 ± 0.74 vs. 2.77 ± 0.23, p = 0.003) was observed. Women with severe preeclampsia, positive for the mutated T785 allele, delivered at a significantly lower gestational age (31.75 ± 3.69 vs. 38.66 ± 3.21 weeks, p = 0.035) neonates with a lower birth weight (1861.11 ± 869.9 vs. 3500 ± 424.26 g, p = 0.023) compared to women negative for the same allele. CONCLUSIONS: Thyroid hormone levels and the D1-C785T polymorphism, alone or in combination, correlate with the severity of preeclampsia. The D1-C785T polymorphism influences the outcome of pregnancy in severe preeclampsia.

Correlation between the TSHRc-Asp727Glu polymorphism and plasma thyroid stimulating hormone levels in Romanian preeclamptic women.

AIM: To analyze the influence of thyroid stimulating hormone (TSH) levels and/or the Asp727Glu polymorphism on the severity and perinatal outcome of preeclampsia. METHODS: Forty-nine women with preeclampsia and 58 normal pregnant women were genotyped for the TSHRc-Asp727Glu polymorphism using PCR-RFLP methods. The plasma TSH levels were measured by ELISA method. RESULTS: Fourteen (77.78%) women of 18 pregnant women with abnormal TSH levels had preeclampsia compared to 35 (39.33%) of 89 pregnant women with normal TSH levels who had preeclampsia (OR 5.4, p = 0.003). The mean TSH levels were 2.13 ± 1.44 µU/ml, 2.47 ± 2.03 µU/ml and 4.27 ± 2.75 µU/ml in women with pregnancy induced hypertension (PIH), mild and severe preeclampsia, respectively. OR for PIH and mild preeclampsia was 1.08 (p = 1) and 9.45 (p = 0.06), respectively, in association with the Asp/Asp genotype. All women with severe preeclampsia had the Asp/Asp genotype. The risk for preeclampsia in association with TSH > 4 µU/ml and Asp/Asp genotype is 20.8 (p < 0.01). Preeclamptic women with TSH levels > 4 µU/ml and the Asp/Asp genotype delivered earlier (weeks, 34.92 ± 4.33 vs. 36.6 ± 3.21, p = 0.3) neonates with lower birth weight (grams, 2361.54 ± 1155.81 vs. 3000 ± 1072.38, p = 0.3) than preeclamptic women with TSH levels  < 4 µU/ml and the Asp/Glu genotype. CONCLUSIONS: Higher TSH levels and/or the TSHRc-Asp727Glu polymorphism represent risk factors for preeclampsia and could be correlated with the severity of preeclampsia.

[Current trends in the treatment of ectopic pregnancy]. / Tendinte actuale în tratamentul sarcinii extrauterine.

Ectopic pregnancy represents even nowadays a problem with a major impact upon women reproductive health, with an incidence that is still growing. Modern diagnosis methods have allowed the disappearance of the mortality, but there are persisting significant tubal dysfunctions. The present clinical study has analyzed the evolutions of the diagnosis and treatment methods upon 238 cases of extrauterine pregnancy hospitalized in the Ist Clinic of Obstetrics and Gynecology Cluj-Napoca between years 2000 and 2006. The use of the new biochemical markers and the transvaginal ultrasound examination have allowed the diagnosis of extrauterine pregnancy in an early stage, with an increased percent of uncomplicated cases raising from 55.8% to 74%. Also the percent of laparoscopic approach has grown from 23.5 to 58.6%. The radical procedure, salpingectomy was predominantly used. The laparoscopic approach has been as successful as the laparotomy and no complications have been reported. The mean hospitalization period after laparoscopy has been significantly shorter than after laparotomy (p<0.05). These results confirm the medical and economical advantages of the laparoscopic approach and recommend laparoscopy as the election method in the management of ectopic pregnancy.

The influence of maternal epidural analgesia upon intrapartum fetal oxygenation.

OBJECTIVE: The use of maternal epidural analgesia in labor may be associated with non-reassuring fetal heart rate (FHR) patterns. We aimed to assess changes in fetal oxygen saturation (FSpO(2)) during epidural analgesia in labor. METHODS: This was a prospective observational study. Twenty healthy parturients were enrolled following the inclusion criteria. Informed consent was obtained. Mode of delivery, use of oxytocin, maternal blood pressure, umbilical cord blood analysis, Apgar score, and neonatal outcomes were evaluated. Ropivacaine at a low concentration of 0.1% (1 mg/mL) co-administered with an opioid (fentanyl 2.5 microg/mL) was used. The values of fetal oxygen saturation were registered continuously 10 minutes before the administration of the analgesic drug and during the following 30 minutes after administration. Pulse oximetry was used simultaneously with cardiotocography (CTG). RESULTS: The average value for fetal oxygen saturation before the analgesic drug administration was 44.3 +/- 8.8%; during the first 10 minutes following administration it was 41.3 +/- 7.2% (p = 0.25) and during the following 20 minutes it was 43.05% +/- 6.9% (p = 0.63). There was no direct relationship between non-reassuring CTG pattern appearance and FSpO(2) <30% (RR = 1.11, 95% CI 0.76-1.64). No significant correlation was found between FSpO(2) values within the first 30 minutes of epidural analgesia and neonatal acidotic status (pH or=30%.