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1.

Objective

Recently it has been proposed that tightly regulated levels of endogenous cannabinoids play a fundamental role in early placental development. The aim of this study was to investigate associations of three single-nucleotide polymorphisms (SNPs) in the cannabinoid 1 receptor (CNR1) gene (rs1049353, rs12720071 and rs806368) and their inferred haplotypes with pre-eclampsia, a severe pregnancy-associated condition characterized by abnormal development and remodeling of spiral decidual arteries.

Study design

The case-control study comprised a total of 115 pre-eclamptic women and 145 healthy pregnant controls, all originating from the Central-European Czech population. Using PCR-based methods, we tested rs1049353, rs12720071 and rs806368 in the CNR1 gene and haplotypes were constructed.

Results

Statistically significant difference in genotype distributions of rs806368 (pg < 10−3) was observed when comparing the cases and the controls; the cases presenting with significantly lower proportion of CC homozygotes. In multivariate modeling, the rs806368 served as a predictor for pre-eclampsia development (β = 0.15; p = 0.04). Haplotype analysis revealed presence of four common haplotypes; the CAA haplotype being less frequent in pre-eclamptic cases compared to the controls (p < 0.008). Analysis of regression models confirmed the independent prediction role of AAC haplotype for pre-eclampsia onset (β = −0.18; p = 0.03).

Conclusion

This is the first study focusing on the relationship between SNPs in the CNR1 gene and pre-eclampsia risk. Although limited by a relatively small sample size, the study indicates that rs806368 in the CNR1 gene may act as a susceptibility marker for pre-eclampsia in humans.  相似文献   

2.

Objective

To evaluate if amino-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels reflect intracardiac filling pressures in pre-eclamptic patients.

Study design

In a cross-sectional study we investigated 22 untreated critically ill pre-eclamptic women between 22 and 34 weeks gestation. All patients underwent intra-arterial blood pressure and central hemodynamic measurements and NT-proBNP was determined in stored plasma. Baseline characteristics, plasma NT-proBNP concentrations and relevant laboratory variables were investigated for correlations with hemodynamic values using Spearman's rank correlation test.

Results

No significant correlations were demonstrated between NT-proBNP concentrations and variables associated with the severity of the pre-eclampsia. We found significant positive correlations between NT-proBNP and diastolic pulmonary pressure (r = 0.59; p = 0.005) and pulmonary capillary wedge pressure (PCWP) (r = 0.51; p = 0.015). Multiple linear regression analysis showed that the association between NT-proBNP and PCWP was not affected by creatinine level.

Conclusion

NT-proBNP is a biomarker of left ventricular cardiac filling pressures in untreated pre-eclamptic patients.  相似文献   

3.

Objectives

Placental derived vasculogenic/angiogenic substances in maternal blood are dysregulated in pre-eclampsia. We hypothesized that CXCL12, a chemokine with vasculogenic actions, is amongst such molecules.

Study design

CXCL12, CXCL16, CXCR4, and CXCR6 immunolocalization in placental tissue was analyzed in pre-eclampsia (n = 8) in comparison to controls (n = 8). CXCL12, measured by ELISA in blood, in women diagnosed with pre-eclampsia (n = 14) and prior to the development of pre-eclampsia (at 20 weeks’ gestation, n = 20) was compared with CXCL12 concentrations in gestation-matched, healthy control subjects (n = 34).

Results

In placental tissue, syncytiotrophoblast staining for CXCL12 was increased in pre-eclampsia. Maternal serum CXCL12 was increased in pre-eclampsia [2000 (SD 402) vs 1484 (SD 261) pg/ml, P = 0.01] but not in plasma obtained at 20 weeks of gestation prior to the onset of pre-eclampsia [1183 (SD 336) vs 1036 (SD 144) pg/ml, P = 0.09].

Conclusion

Our data suggest that the syncytiotrophoblast contributes to a pre-eclampsia-associated increase in CXCL12 levels in maternal blood. These findings support the hypothesis that an imbalance of angiogenic factors contributes to the pathogenesis of pre-eclampsia.  相似文献   

4.

Objective

To investigate the nitric oxide (NO) levels in the plasma and the placentas of pregnant women with pre-eclampsia and women without pre-eclampsia, and to determine the effect of high or low altitude of residence.

Methods

NO was determined by chemoluminescence and group comparisons were performed.

Results

Women with pre-eclampsia (n = 63) had higher plasma NO levels (38.6 ± 17.44 vs 30.6 ± 12.44 µmol/L, P = 0.004) and higher placental NO levels (38.5 ± 17.0 vs 24.3 ± 7.16 ng/mg protein, P < 0.05) compared with women without pre-eclampsia. A similar trend was found when comparisons were made according to altitude of residence. NO levels were significantly higher in the plasma of pre-eclamptic women living at sea level (41.11 ±18.78 vs 28.96 ± 9.57 µmol/L, P = 0.003), and in the placentas of women living at high altitude (39.51 ± 16.98 vs 21.91 ± 6.64 ng/mg protein, P < 0.0001).

Conclusion

Women with pre-eclampsia had higher plasma and placental NO levels and the differences were associated with altitude of residence.  相似文献   

5.

Objective

To investigate the CD40-CD40 ligand (CD40L) system in women with pre-eclampsia.

Methods

Expression of CD40 on monocytes and expression of CD40 and CD40L on platelets were determined by whole blood flow cytometry in 23 women with pre-eclampsia and in 23 normotensive pregnant women. Serum levels of soluble CD40L in both groups of women were measured by enzyme-linked immunosorbent assay.

Results

There was a significantly higher expression of CD40 and CD40L on platelets and CD40 on monocytes in the women with pre-eclampsia compared with normotensive pregnant women (P < 0.001 for all comparisons). The serum concentration of soluble CD40L was significantly higher in women with pre-eclampsia compared with normotensive pregnant women (P = 0.012).

Conclusion

Pre-eclampsia is associated with activation of the CD40-CD40L system. The activation of this system may contribute to the development or maintenance of the proinflammatory and prothrombotic responses, increased cytokine production, and endothelial cell dysfunction found in pre-eclampsia.  相似文献   

6.

Objective

We examined the association between recurrent versus isolated pre-eclampsia and feto-infant morbidity outcomes.

Study design

This is a population-based retrospective study on Florida hospital discharge data linked to the birth cohort files from 1998 through 2007. The study population comprised women with singleton first and second births who experienced pre-eclampsia in both pregnancies, and a comparison group consisting of women who were normotensive during their first pregnancy but developed pre-eclampsia in their second pregnancy. Feto-infant morbidities (low birth weight, very low birth weight, preterm, very preterm and small for gestational age) were the outcome of interest. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between recurrent pre-eclampsia and feto-infant morbidity outcomes were obtained from logistic regression models.

Result

Women who experienced recurrent pre-eclampsia were at elevated risk for low birth weight, very low birth weight, preterm and very preterm. The risk was most pronounced for preterm infants (OR = 1.58 CL = 1.42-1.76). Subgroup analysis demonstrated that infants born to black mothers with recurrent pre-eclampsia experienced the most elevated risk across all the racial/ethnic subgroups and this was most pronounced for very low birth weight and very preterm with a more than three-fold increase in risk (OR = 3.77, 95% CI = 2.77-5.13 and OR = 3.66, 95% CI = 2.66-5.03, respectively) as compared to the referent category (white mothers who were normotensive in first pregnancy but developed pre-eclampsia in their second pregnancy).

Conclusion

Pre-eclampsia is very severe when it recurs and black women are affected more than white or Hispanic women.  相似文献   

7.

Objective

To evaluate the effect of antichlamydial treatment and Chlamydia pneumoniae seroconversion on the incidence of pre-eclampsia among Egyptian primigravidae.

Methods

The present prospective study included 600 healthy normotensive primigravidae who attended an outpatient clinic at 10-16 weeks of pregnancy. A single venous blood sample was collected to test for C. pneumonia-specific immunoglobulin G (IgG) antibodies using an enzyme-linked immunosorbent assay. Seropositive women were randomly allocated to receive or not receive antichlamydial treatment before 20 weeks of pregnancy. Seronegative participants had another test at delivery for the presence of C. pneumonia-specific IgG to determine seroconversion. All participants were followed up for up to 8 weeks postpartum and observed for the development of pre-eclampsia.

Results

The rate of pre-eclampsia among seropositive participants differed significantly depending on whether the women received treatment or not (6.5% and 19.1%, respectively; P = 0.014). No statistically significant difference in the rate of pre-eclampsia was detected between seronegative participants who underwent seroconversion and those who did not.

Conclusion

The present results indirectly support the hypothesis that infectious agents (in particular C. pneumoniae) have a role in the development of pre-eclampsia. The findings also indicate that antichlamydial treatment might help to reduce the incidence of pre-eclampsia.  相似文献   

8.

Objective

Ovarian cancer is most frequently diagnosed at a late stage with a poor prognosis. No markers for early diagnosis have been established. Aberrantly methylated DNA appears as a promising molecular cancer marker. The aim of this study was to analyze the methylation status of the proapoptotic cancer related gene death-associated protein kinase (DAPK) in ovarian cancer patients, healthy controls and in patients suffering from a benign proliferative disease such as uterine leiomyoma.

Methods

Methylation-specific PCR (MSP) was used to detect DAPK methylation in primary tumor tissue and serum of both ovarian cancer (n = 32) and uterine leiomyoma patients (n = 17 primary tissue, n = 30 serum). Serum samples from healthy women served as controls (n = 20). MSP results were confirmed by restriction digest and sequencing analyses of cloned PCR products.

Results

DAPK methylation was detected in 50% and 35.3% of primary tissue and 56% and 23.8% of serum samples from ovarian cancer and leiomyoma patients, respectively. However, the association of methylation frequencies in tissue and serum was low (kappa = −0.053). Sequencing experiments revealed fully methylated MSP products in sera of both ovarian cancer and leiomyoma patients. In contrast sera from control patients showed only partially methylated DAPK sequences.

Conclusion

DAPK hypermethylation was neither specific for the tissue of origin nor for cancer. The high prevalence of leiomyoma compromises the utility of this gene as a serum marker for early ovarian cancer detection. These data emphasize the necessity to co-analyze controls presenting with non-cancer proliferative disease in the quest for molecular cancer markers.  相似文献   

9.

Objective

To assess whether supplementation with Coenzyme Q10 (CoQ10) during pregnancy reduces the risk of pre-eclampsia.

Methods

Women at increased risk of pre-eclampsia were enrolled in a randomized, double-blind, placebo-controlled trial. Women were assigned to receive 200 mg of CoQ10 or placebo daily from 20 weeks of pregnancy until delivery. The primary outcome was rate of pre-eclampsia. Statistical analyses were by intention-to-treat.

Results

Of the 235 women enrolled in the trial, 118 were randomized to receive CoQ10 and 117 received a placebo. A total of 197 (83.8%) women were followed-up. The overall rate of pre-eclampsia was 20% (n = 47). Thirty women (25.6%) in the placebo group developed pre-eclampsia compared with 17 women (14.4%) in the CoQ10 group, and this reduction was significant (P = 0.035) (relative risk [RR] 0.56; 95% confidence interval [CI], 0.33-0.96).

Conclusion

Supplementation with CoQ10 reduces the risk of developing pre-eclampsia in women at risk for the condition.  相似文献   

10.

Objective

To evaluate the feasibility of laparoscopic hysterectomy for uteri weighing more than 1000 g.

Study design

A retrospective study was conducted in a tertiary center of laparoscopic surgery including 38 women submitted to hysterectomy for uteri weighing more than 1000 g. Patients submitted to open hysterectomy were compared to those submitted to laparoscopic hysterectomy. The primary statistical endpoint was the complication rate. Secondary endpoints were operating time, estimated blood loss, length of hospital stay, and conversion to laparotomy.

Results

The patients’ mean age was 49.4 years and mean BMI was 25.2 kg/m2. The surgical intent was laparoscopic hysterectomy in 23 patients (60.5%) and laparotomy in 15 patients (39.5%). Conversion to open surgery was required in 4 patients (17.4%) due to inaccessibility of the pelvis at the beginning of surgery (n = 2), technical difficulties during surgery (n = 1), and intraoperative bleeding (n = 1). One patient in the laparotomy group had an intraoperative ureteral injury. Despite longer operative time (130 vs. 80 min, p = 0.002), laparoscopic surgery was associated with reduced length of hospital stay (3 vs. 6 days, p < 0.001). Intraoperative bleeding was evaluated by the difference of pre- and post-operative hemoglobin and was equivalent in both groups (2.2 vs. 1.6 g/dL; p = 0.84). There was a tendency for more postoperative complications in the laparotomic group (33.4% vs. 8.7%; p = 0.05).

Conclusion

Laparoscopic hysterectomy is feasible for selected patients with uteri weighing more than 1000 g.  相似文献   

11.

Objective

To evaluate the efficacy and biological effects of the gemcitabine/tanespimycin combination in patients with advanced ovarian and peritoneal cancer. To assess the effect of tanespimycin on tumor cells, levels of the chaperone proteins HSP90 and HSP70 were examined in peripheral blood mononuclear cells (PBMC) and paired tumor biopsy lysates.

Methods

Two-cohort phase II clinical trial. Patients were grouped according to prior gemcitabine therapy. All participants received tanespimycin 154 mg/m2 on days 1 and 9 of cycle 1 and days 2 and 9 of subsequent cycles. Patients also received gemcitabine 750 mg/m2 on day 8 of the first treatment cycle and days 1 and 8 of subsequent cycles.

Results

The tanespimycin/gemcitabine combination induced a partial response in 1 gemcitabine naïve patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine naïve and 4 gemcitabine resistant). The most common toxicities were hematologic (anemia and neutropenia) as well as nausea and vomiting. Immunoblotting demonstrated limited upregulation of HSP70 but little or no change in levels of most client proteins in PBMC and paired tumor samples.

Conclusions

Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures.  相似文献   

12.

Objective

Adequate maternal, intervillous and fetal blood flow are all necessary for fetal well-being. Compromise to any part of this exchange would be detrimental to pregnancy outcome. Pre-eclampsia is associated with reduced maternal spiral artery flow, resulting in reduced placental perfusion. This in turn creates an ischaemic environment, which may predispose to morphological changes in placental villi. This pilot study sought to assess whether there were morphological alterations in the fetal component of the placenta which could be detrimental to exchange and therefore pregnancy outcome.

Study design

This study utilized morphometric image analysis to examine some features of the fetal component of the placenta in normotensive (NT) and pre-eclamptic (PE) groups. The features examined included: density of placental villi (expressed as percentage of field area occupied by placental tissue); stem vessel carrying capacity (expressed as percentage of stem villus area occupied by vessel lumina); the thickness of the stem arterial walls relative to artery size (expressed as percentage of artery area occupied by arterial wall) and the extent of fibrosis associated with villi (expressed as percentage of field area occupied by fibrosis).

Results

There were significant differences between NT and PE placentae in density of placental villus arrangement NT: 51.89 ± 6.19, PE: 64.78 ± 6.93 (P < 0.001); carrying capacity of stem villi NT: 17.20 ± 11.78, PE: 8.67 ± 8.51 (P < 0.001); relative thickness of stem villi arterial walls NT: 74.08 ± 12.92, PE: 86.85 ± 10.55 (P < 0.001); and extent of fibrosis NT: 0.727 ± 0.310, PE: 1.582 ± 0.707 (P < 0.001).

Conclusion

These significant differences between normotensive and pre-eclamptic placentae suggest possible fetal maladaptations in response to the intervillous ischaemia, compounding the existing maternal compromise to materno-fetal exchange. Further investigations would, however, be necessary in order to make more conclusive deductions.  相似文献   

13.

Objective

To investigates the effect of sphingosine-1-phosphate (S1P) supplementation on follicular integrity and apoptosis in vitrified-warmed mouse ovarian grafts.

Study design

Ovaries from 4-week-aged ICR mice were vitrified using a vitrification solution with or without 2 μM S1P. After warming, follicular normality was assessed by histological analysis and TUNEL assay. A part of ovaries vitrified with or without 2 μM S1P was transplanted, and 2 weeks later, gross and microscopic follicular morphology was assessed.

Results

During vitrification and warming, inclusion of 2 μM S1P into the vitrification solution significantly raised the rate of morphologically intact follicles compared to controls (36.6% vs. 30.8%, p = 0.047). This protective effect was profound especially in primordial follicles (45.5% vs. 34.6%, p = 0.034). After transplantation of vitrified-warmed ovaries, the morphological integrity of primordial follicles was superior in the S1P-treated group (55.0% vs. 39.4%, p = 0.035). The rates of non-apoptotic follicles (TUNEL-negative) were similar in the two groups in either non-transplanted or transplanted ovaries.

Conclusion

Inclusion of S1P in the vitrification solution during transplantation of vitrified-warmed ovary had a beneficial effect on preservation of the primordial follicular pool.  相似文献   

14.

Objective

Platinum-based neoadjuvant chemotherapy for locally advanced cervical cancer has some benefits for patients responding to chemotherapy. However, no validated clinical or biologic predictor of response to this chemotherapy has been identified to date.

Methods

We employ immunohistochemical analysis to determine the expression patterns of the excision repair cross-complementation group1 (ERCC1) protein in pre-treatment cervical biopsy tissue. In total, 43 stage IIB patients had been enrolled in a previous etoposide and cisplatin neoadjuvant phase II clinical trial, allowing comparison of the effects of cisplatin-based neoadjuvant chemotherapy on response in relation to ERCC1 expression.

Results

Among the 43 patients studied, 34 (79.1%) were positive and 9 (20.9%) were negative for ERCC1. Response to chemotherapy (according to RECIST criteria) was observed in all patients with negative ERCC1 expression. In logistic regression analysis, ERCC1 negativity continued to be an independent predictor for responsiveness to neoadjuvant chemotherapy (p = 0.021). Among the pretreatment factors, low ERCC1 expression was a significant prognostic factor of disease-free survival in multivariate analysis (p = 0.046).

Conclusions

The ERCC1 expression patterns in pretreatment specimens may thus facilitate the prediction of responses to cisplatin-based NAC. We propose that patients expressing low levels of ERCC1 derive the most benefit from cisplatin-based NAC.  相似文献   

15.

Objective

The finding that ischemia-modified albumin (IMA) is increased in pre-eclamptic pregnancy suggests a role for IMA as a potential biomarker for abnormal placental development related to miscarriage. This study was undertaken to evaluate IMA levels in women with recurrent pregnancy loss (RPL).

Study design

This case-control study was performed between March 2008 and September 2009, at the Department of Obstetrics and Gynecology of Meram School of Medicine. Serum IMA and albumin concentrations were assessed in 43 women with a history of two or more unexplained first trimester miscarriages (group 1), and 42 healthy pregnant women (group 2) in the first trimester. IMA, adjusted IMA and albumin concentrations were compared between the groups. Statistical analysis was performed using Student's t-test and Mann-Whitney U test.

Results

IMA and adjusted IMA levels were significantly higher in women with RPL (1.11 + 0.08 and 1.09 + 0.09, respectively) compared to women in group 2 (0.88 + 0.10 and 0.88 + 0.11, respectively). Albumin levels in group 1 were significantly lower compared with group 2. There was a negative correlation between IMAand albumin levels in each group.

Conclusion

Maternal IMA levels appear to be elevated in women with early RPL. This finding may suggest that an abnormally high hypoxic intrauterine environment may be associated with abnormal placental development that contributes to early miscarriage.  相似文献   

16.
17.

Objective

The objective of this study was to determine the incidence of invasive cancer in ovarian masses diagnosed as borderline tumor (BT) at the time of frozen section.

Methods

We performed a retrospective review of all patients diagnosed with ovarian BT on frozen section (FS) at our institution between 2000 and 2010. Clinical and pathologic data were extracted. Univariate and multivariate analyses were performed using standard two-sided statistical tests.

Results

A total of 120 patients were identified, of which 104 (86.7%) had BT on frozen section that was confirmed on final pathology. In 15 (12.5%) patients, BT was diagnosed on FS but was reclassified as invasive cancer on final pathology. One patient (0.8%) had BT on FS but benign pathology on final diagnosis. Histologies included serous in 79 (65.8%), seromucinous in 13 (10.8%), mucinous in 21 (17.5), endometrioid in 5 (4.2%), and clear cell in 2 (1.7%) patients. Reclassification of pathologic diagnosis was related to histologic subtype, but only for endometrioid and clear cell tumors (P < 0.001). The rate of invasive cancer for serous micropapillary tumors on frozen section was 42.8% compared with 2.8% for serous non-micropapillary tumors (P < 0.001). Tumor size > 8 cm was associated with a 22.4% incidence of invasive cancer on final pathology compared to 3.2% in tumors ≤ 8 cm (P = 0.004).

Conclusion

Comprehensive surgical staging can be considered in BT > 8 cm in diameter, as well as those with micropapillary serous, endometrioid, and clear cell histology diagnosed at the time of frozen section analysis.  相似文献   

18.

Objective

To look for associations between pregnancy outcomes and prepregnancy body mass index and gestational weight gain among Han women from Shenyang province, China.

Method

A total of 2586 women were distributed across 4 prepregnancy categories according to the Chinese classification of body mass index, and to 4 end-of-pregnancy categories according to median weekly gestational weight gain.

Results

The risks for gestational hypertension, pre-eclampsia, gestational diabetes, and preterm premature rupture of membranes were higher for those who were overweight or obese before becoming pregnant (< 0.05). Moreover, a gestational weight gain of 0.50 kg per week or greater was associated with a higher risk for gestational hypertension, preterm premature rupture of membranes, and fetal macrosomia (< 0.05). Women in the highest quartile for weight gain (≥ 0.59 kg per week) were at higher risk for pre-eclampsia (< 0.05).

Conclusion

A high prepregnancy body mass index and excessive gestational weight gain were associated with increased risks for adverse pregnancy outcomes.  相似文献   

19.

Objective

To examine the effect of uterosacral-cardinal ligament complex stretching prior to vaginal hysterectomy on uterine descent.

Study design

A prospective trial of 25 consecutive women undergoing vaginal hysterectomy. Pre-operative, apical, anterior and posterior wall POP-Q measurements were recorded for each patient before and after uterosacral-cardinal ligament complex stretching during general anesthesia.

Results

Uterosacral-cardinal ligament complex stretching yielded a significant increase in mean stage of uterine and anterior wall descent (2.6 ± 0.6 vs. 3.2 ± 0.6 cm, p < 0.001, and 2.5 ± 0.8 vs. 2.9 ± 0.8 cm, respectively, p < 0.004). There was no significant change in posterior wall prolapse measurements (1.3 ± 0.7 vs. 1.4 ± 0.8 cm, p = 0.05).

Conclusion

Uterosacral-cardinal ligament complex stretching prior to vaginal hysterectomy increase uterine descent.  相似文献   

20.

Objective

To determine if a wide genital hiatus is a risk factor for recurrence of anterior vaginal wall prolapse following anterior vaginal repair.

Methods

A retrospective cohort study was performed on patients who had undergone an anterior vaginal wall repair. Patients were placed into 1 of 2 groups: wide genital hiatus (≥ 5 cm) or normal genital hiatus (< 5 cm). The wide genital hiatus group (= 35) was compared with the normal genital hiatus group (= 30) for surgical failure.

Results

There were no significant differences between the 2 groups in demographic data, additional operative procedures, or apical suspensions. The rate of postoperative anterior vaginal wall prolapse was greater in patients with a wide genital hiatus compared with those with a normal genital hiatus (34.3% vs 10% respectively; odds ratio 4.7 [95% confidence interval, 1.0-24.1]; = 0.02).

Conclusion

The rate of recurrent anterior vaginal wall prolapse is higher in patients with a wide genital hiatus.  相似文献   

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