Evaluation of Fanconi anaemia genes FANCA, FANCC and FANCL in cervical cancer susceptibility

Objective

Disrupting the function of any of the 13 Fanconi anaemia (FA) genes causes a DNA repair deficiency disorder, with patients being susceptible to a number of cancer types. Variation in the family of FA genes has been suggested to affect risk of cervical cancer. The current study evaluates the influence of three genes in the FA pathway on cervical cancer risk in Swedish women.

Methods

TagSNPs in FANCA, FANCC and FANCL were selected using the Tagger algorithm in Haploview. A total of 81 tagSNPs were genotyped in 782 cases (CIN3 or ICC) and 775 controls using the Illumina GoldenGate Assay and statistically analyzed for association with cervical cancer.

Results

72 SNPs were successfully genotyped in > 98% of the samples. Nominal associations were detected for FANCA rs11649196 (p = 0.05) and rs4128763 in FANCC (p = 0.02). The associations did not withstand correction for multiple testing.

Conclusions

The current study does not support that genetic variation in FANCA, FANCC or FANCL genes affects susceptibility to cervical cancer in the Swedish population.     

Pre-eclampsia is associated with elevated CXCL12 levels in placental syncytiotrophoblasts and maternal blood

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.     

Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility

Objective

Endometriosis has been considered an epigenetic disease. Single nucleotide polymorphisms (SNPs) located in genes encoding enzymes of the folate and choline metabolism may affect DNA methyltransferase activity.

Study design

We studied 16 SNPs in 12 folate and choline metabolism genes, including BHMT (rs7356530 and rs3733890), BHMT2 (rs625879), CBS (844ins68), CHDH (rs893363 and rs2289205), CHKA (rs7928739), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394), PCYT1A (rs712012 and rs7639752), PEMT (rs4244593 and rs4646406) and TCN (rs1801198) in one hundred and sixty-three infertile women with minimal endometriosis and one hundred and fifty fertile women.

Results

There were no significant differences between genotype and allele frequencies of these gene variants in infertile women with endometriosis (n = 163) and controls (n = 150). The lowest, but not statistically significant, p values of the trend test were observed for the CBS 844ins68 and MTR rs1805087 (p_trend = 0.0527 and p_trend = 0.0771, respectively) polymorphisms. However, the exhaustive multifactor dimensionality reduction analysis revealed an epistatic interaction between rs1801133 of MTHFR and rs4244593 of PEMT in endometriosis-associated infertility (p = 0.0240).

Conclusions

Our results showed moderate evidence for the contribution of SNPs located in genes encoding folate and choline metabolism enzymes to infertility in women with endometriosis.     

The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications

Objectives

To prospectively evaluate the safety of metformin administration during pregnancy in a group of PCOS patients by assessing its effect on the prevalence of gestational complications and neonatal outcome.

Study design

Our prospective, single centre study included 98 pregnant women with PCOS treated with metformin throughout pregnancy and 110 normal pregnant controls. All PCOS patients were hyperinsulinemic and received metformin (1700-3000 mg/day) before conception and until 37 weeks’ gestation.

Results

Metformin treatment in the pregnant PCOS patients resulted in significant decrease in miscarriage rate (9.1% vs 20%; p < 0.05), gestational diabetes (0 vs 13%; p < 0.005), and gestational hypertension (0 vs 11%; p < 0.005) and a non-significant decrease in pre-eclampsia (0 vs 3%; p = .24), compared to the control group. Mean neonatal Apgar score, weight and length were comparable between the two groups.

Conclusions

Continuing metformin therapy throughout pregnancy resulted in significant reduction in pregnancy complications with concomitant improved neonatal outcome, with no serious deleterious side effects.     

Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker of cardiac filling pressures in pre-eclampsia

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.     

Upregulation of the CD40-CD40 ligand system in pre-eclampsia

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.     

Association between urotensin II gene polymorphism and pre-eclampsia

Objective

To investigate the association of a specific polymorphism (S89N) in exon 3 of the urotensin II (UTS2) gene in pre-eclampsia.

Study design

One hundred and forty-two subjects, 85 with a diagnosis of pre-eclampsia/eclampsia (group I) and 57 healthy pregnant subjects as a control group (group II), who had been admitted between January 2006 and December 2007, were included. All the subjects were tested for G to A transition in codon 266 in the urotensin II gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The distributions of genotypes and allele frequencies were compared between the groups.

Results

Demographics such as age, gestational age, gravidity, abortion and parity were similar in both groups (p > 0.05). No statistically significant differences were observed between the groups concerning genotype distribution and allele frequency (p = 0.305, p = 0.326, respectively). The observed genotype counts did not deviate significantly from those expected according to the Hardy-Weinberg equilibrium (HWE).

Conclusion

The results of this study suggest that UTS2 single gene (S89N) polymorphism is not associated with pre-eclampsia. Further studies are needed to investigate the prevalence of other single nucleotide gene polymorphisms in pre-eclampsia.     

Maternal circulating osteoprotegerin and soluble RANKL in pre-eclamptic women

Objective

To evaluate alterations in the concentrations of osteoprotegerin (OPG), RANKL and the OPG/RANKL ratio in pre-eclamptic women during the puerperium.

Study design

This cross-sectional study was performed in the maternity ward of Aretaieio Hospital in Athens, Greece. Fifteen pregnant women with severe pre-eclampsia and 15 matched controls with premature rupture of the membranes were recruited. Fasting blood samples were obtained antepartum, immediately after diagnosing pre-eclampsia (median: 32nd gestational week), and during the 3rd-6th day postpartum, to estimate levels of circulating OPG and RANKL as well as the OPG/RANKL ratio. The anthropometric parameters evaluated included body mass index and blood pressure.

Results

Mean circulating OPG levels decreased significantly in both groups in the postpartum period (controls: 43.7 ± 19.1 ng/ml vs 22.9 ± 9.1 ng/ml, p = 0.008; pre-eclamptic group: 72.3 ± 49.9 vs 49.7 ± 40.9 ng/ml, p = 0.002). The antepartum OPG/RANKL ratio was elevated in hypertensive pregnancies (2.41 ± 1.72) compared to normotensive pregnancies (1.45 ± 0.63), but the difference did not reach statistical significance (p = 0.1). The OPG/RANKL ratio decreased in the control group (0.76 ± 0.30, NS) following delivery, while it remained unchanged in the pre-eclamptic women (1.63 ± 1.40, p = 0.13). Consequently, the postpartum OPG/RANKL ratio was significantly higher in the pre-eclamptic women compared to control women (1.63 ± 1.40 vs 0.76 ± 0.30, p = 0.01). Levels of RANKL demonstrated no significant alterations during puerperium in both cases.

Conclusion

Pregnancies complicated with pre-eclampsia exhibit higher OPG levels and OPG/RANKL ratios, compared to control pregnancies, which might be compatible with lower bone turnover. The significance of this finding with respect to bone metabolism remains to be elucidated in larger studies.     

Impact of seroconversion and antichlamydial treatment on the rate of pre-eclampsia among Egyptian primigravidae

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.     

Predictors of resolution of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma in premenopausal women treated with progestin therapy

Objective

To identify clinical and pathologic predictors of response to progestin treatment in premenopausal women with complex atypical hyperplasia (CAH) and Grade 1 endometrial adenocarcinoma (Grade 1 EA).

Methods

Forty premenopausal patients with Grade 1 EA or CAH who underwent progestin therapy for a minimum of 8 weeks were retrospectively identified. Patient characteristics and histopathologic features of pretreatment and first follow-up endometrial specimens were evaluated as predictors of resolution, defined as absence of hyperplasia or carcinoma.

Results

Kaplan-Meier analysis indicated 63% resolution at 18 months of follow-up. Multivariate classification analysis showed that resolution rates were higher in individuals with a low pre-treatment qualitative abnormal architecture score and a BMI < 35 (Standardized Resolution Ratio (SRR) = 1.48, p = 0.03). The diagnosis of benign endometrium or simple hyperplasia on the first follow-up specimen was highly predictive of resolution (SRR = 2.25, p = 0.002). Resolution rates were lower among subjects with a high pre-treatment qualitative abnormal architecture score (SRR = 0.37, p < 0.03) and lowest in subjects whose first follow-up specimen showed persistent complexity, atypia, or carcinoma with adjacent stromal decidualization (SRR = 0.24, p = 0.002).

Conclusions

Clinical and pathologic parameters can predict response to progestin therapy in premenopausal women with CAH and Grade 1 EA. A low likelihood of resolution is predicted by an unfavorable pre-treatment architectural score and lack of pathological response in the first specimen, despite adjacent stromal decidualization.     

A model for prediction of parametrial involvement and feasibility of less radical resection of parametrium in patients with FIGO stage IB1 cervical cancer

Objective

The objective of this study was to evaluate the potential risk factors associated with parametrial invasion and to identify preoperatively a subgroup of patients at low risk for parametrial involvement who could be appropriate candidates for less radical surgery in FIGO stage IB1 cervical cancer.

Methods

We retrospectively reviewed the medical records of 317 FIGO stage IB1 cervical cancer patients undergoing class III radical hysterectomy and bilateral pelvic lymphadenectomy. Clinocopathologic factors associated with parametrial invasion were analyzed and the risk criteria predicting parametrial involvement were calculated using a logistic regression model.

Results

Of 317 patients, 17 patients (5.4%) had parametrial involvement. Tumor size > 3 cm (OR, 3.80; [95% CI, 1.19-12.06]; p = 0.02) and pelvic lymph node metastasis (OR, 3.02; [95% CI, 1.04-8.79]; p = 0.04) were independent pathologic factors for parametrial invasion on multivariate analysis. Significant preoperative factors associated with parametrial involvement were tumor size > 3 cm (OR, 4.29; [95% CI, 1.43-12.89]; p < 0.01) and serum SCC Ag level > 1.40 ng/mL (OR, 3.27; [95% CI, 1.11-9.69]; p = 0.03). We identified 185 low-risk (tumor size ≤ 3 cm and SCC ≤ 1.4 ng/mL) and 132 high-risk (tumor size > 3 cm and/or SCC > 1.4 ng/mL) patients. The rates of parametrial involvement in low- and high-risk patients were 1.1% and 11.4%, respectively (p < 0.01).

Conclusions

In this dataset, a model using tumor size and SCC Ag level is highly predictive of parametrial involvement in patients with stage IB1 cervical cancer and may identify candidates for less radical parametrial resection.     

Increment of absolute neutrophil count in the third trimester and increased risk of small-for-gestational-age birth: Hirakata Risk Associated with Pregnancy Assessment Research (HIRAPAR)

Objective

Velocity vector imaging (VVI) is widely used to quantify cardiac mechanical deformation. This study sought to determine whether VVI could be used to evaluate the stiffness of maternal peripheral arteries in women with pre-eclampsia.

Study design

Twenty-four women with pre-eclampsia and 34 normotensive pregnant women were recruited. Longitudinal and circumferential peak velocity, strain and strain rate of the right common carotid artery (CCA) were measured. All measurements were averaged from three consecutive cardiac cycles and expressed as mean ± standard deviation.

Results

Longitudinal velocity, strain and strain rate of the anterior and posterior walls of the CCA were significantly lower in women with pregnancy-induced hypertension compared with normotensive pregnant women [velocity: 0.22 ± 0.09 cm/s vs 0.29 ± 0.09 cm/s (p < 0.01) and 0.24 ± 0.10 cm/s vs 0.34 ± 0.13 cm/s (p < 0.01); strain: 8.50 ± 4.92% vs 12.2 ± 6.21% (p < 0.01) and 10.11 ± 5.02% vs 14.21 ± 6.48% (p < 0.05); strain rate: 1.62 ± 1.14 s^-1 vs 2.24 ± 1.13 s^-1 (p < 0.05) and 1.91 ± 0.99 s^-1 vs 2.45 ± 0.97 s^-1 (p < 0.05)]. Similar results were also found for circumferential velocity, strain and strain rate of the anterior and posterior walls, and the interior and exterior lateral walls of the CCA.

Conclusions

Stiffness of the maternal CCA was significantly greater in women with pre-eclampsia compared with normotensive pregnant women. VVI may have potential for quantitative assessment of vascular mechanical deformation in the clinical setting.     

Plasma and placental nitric oxide levels in women with and without pre-eclampsia living at different altitudes

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.     

Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study

Purpose

Efflux transporters of the ATP-binding cassette (ABC) family are major determinants of chemoresistance in tumor cells. This study examined associations between functional variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes in patients with epithelial ovarian/primary peritoneal cancer (EOC/PPC) following platinum and taxane-based chemotherapy.

Methods

Sequenom iPLEXTMGOLD Assay and MALDI-TOF platform were used to genotype the non-synonymous G2677T/A (rs2032582; encoding Ala893Ser/Thr) and synonymous C3435T (rs1045642; encoding Ile1145Ile) variants in ABCB1, the non-synonymous G1249A variant in ABCC2 (rs2273697; encoding Val417Ile), and the non-synonymous C421A variant in ABCG2 (rs2231142; encoding Q141K, Gln141Lys) in normal DNA from up to 511 women in Gynecologic Oncology Group (GOG) phase III trials, GOG-172 or GOG-182. Progression-free survival (PFS) and overall survival (OS) were analyzed in relation to genetic polymorphisms using Kaplan-Meier and Cox proportional hazards model.

Results

The C421A variant (CA + AA versus CC) in ABCG2 was associated with a 6-month longer median PFS (22.7 versus 16.8 months, p = 0.041). In multivariate analysis, patients with variant genotypes were at a reduced risk of disease progression (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.59-0.96, p = 0.022). The association between C421A and OS was not statistically significant (HR = 0.88, 95% CI = 0.67-1.15, p = 0.356). None of the other variants measured in either ABCB1 or ABCC2 was associated with PFS or OS.

Conclusion

The C421A variant in ABCG2, previously shown to be associated with enhanced protein degradation and drug sensitivity, was associated with longer PFS in advanced stage EOC/PPC patents treated with platinum + taxane-based chemotherapy. This finding requires further validation.     

Uterosacral-cardinal ligament stretching prior to vaginal hysterectomy increases uterine descent: a novel technique

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.     

ERCC1 (excision repair cross-complementation group 1) expression as a predictor for response of neoadjuvant chemotherapy for FIGO stage 2B uterine cervix cancer

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.     

Single-port versus conventional laparoscopic salpingectomy in tubal pregnancy: a comparison of surgical outcomes

Objective

To compare the surgical outcomes of single-port laparoscopic salpingectomy (SPLS) and conventional laparoscopic salpingectomy for the surgical treatment of tubal pregnancy.

Study design

From January to June 2009, patients with tubal pregnancy were assigned to two surgical groups: SPLS and conventional laparoscopic salpingectomy. Surgical outcomes, including operative time, postoperative haemoglobin drop, hospital stay and complications, were compared prospectively. For SPLS, a novel multichannel port was made using a wound retractor and a surgical glove.

Results

In total, 60 patients were enrolled in the study (30 in the SPLS group and 30 in the conventional group). All operations were completed successfully. No significant difference was observed between the two groups in terms of mean operative time (52.6 ± 16.1 min vs 46.8 ± 16.2 min; p = 0.174), mean difference between pre- and postoperative haemoglobin (1.7 ± 0.8 g/dl vs 1.8 ± 1.0 g/dl; p = 0.636), or mean postoperative hospital stay (2.4 ± 0.5 days vs 2.4 ± 0.9 days; p = 1.000). No complications were encountered in either group, and there was no conversion to conventional laparoscopy in the SPLS group.

Conclusion

SPLS has comparable surgical outcomes to conventional laparoscopic salpingectomy for the surgical treatment of tubal pregnancy in terms of operative time, hospital stay and complication rates. However, further studies are needed to evaluate the merits expected of single-port laparoscopic surgery, such as cosmetic advantage and decreased pain in patients.     

Is testing for aspirin response worthwhile in high-risk pregnancy?

Objective

To explore the clinical impact of aspirin dosage adjustment in pregnant women at high risk of hypertensive disorders.

Study design

In this retrospective observational study including women with pre-existing hypertension, pre-gestational diabetes or previous placental-mediated complications, we compared the rates of pre-eclampsia, early-onset and severe pre-eclampsia between women who used 81 mg of aspirin (ASA) throughout pregnancy without platelet function analyser (PFA-100^®) monitoring (“group ASA no PFA”) and those in whom the aspirin dosage was adjusted according to PFA-100^® results (“group ASA and PFA”).

Results

270 women were included in the analyses, 111 in group ASA and PFA and 159 in group ASA no PFA. Aspirin was started before 13 weeks in 71.7% of women in group ASA no PFA and in 79.3% of those in group ASA and PFA. PFA-100^® monitoring was associated with a lower rate of pre-eclampsia (15.3% vs. 30.8%; aOR 0.36, 95%CI 0.19-0.67) and severe pre-eclampsia (3.6% vs. 15.1%; aOR 0.22, 95% CI 0.07-0.66), after adjustment for various risk factors for pre-eclampsia. The rate of early-onset pre-eclampsia was not statistically different between the two groups (7.2% vs. 13.2%; aOR 0.42, 95%CI 0.17-1.04). The rate of pre-eclampsia was higher in women who needed an increase in aspirin dosage (11/43, 25.6%) than in those who did not (6/68, 8.8%, p = 0.03).

Conclusion

Our results suggest that a strategy involving platelet function testing and individualized dosing is effective in preventing pre-eclampsia in high risk women. PFA testing should not be considered as standard practice, however, until prospective controlled randomized trials have confirmed these observations.     

Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat's claw) extract

Objective

The aim of this study was to analyze the macroscopic and histological changes that occur in experimental endometriosis after treatment with Uncaria tomentosa.

Study design

Experimental endometriosis was induced in twenty-five female Wistar rats. After three weeks, 24 animals developed grade III experimental endometriosis and were divided into two groups. Group “U” received U. tomentosa extract orally (32 mg/day), and group “C” (control group) received a 0.9% sodium chloride solution orally (1 ml/100 g of body weight/day). Both groups were treated with gavage for 14 days. At the surgical intervention and after the animal was euthanized, the implant volume was calculated with the following formula: [4π (length/2) × (width/2) × (height/2)/3]. The autotransplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. The Mann-Whitney test was used for the independent samples, and the Wilcoxon test analyzed the related samples, with a significance level of 5%.

Results

The difference between the initial average volumes of the autotransplants was not significant between the groups (p = 0.18). However, the final average volumes were significantly different between the groups (p = 0.001). There was a significant increase (p = 0.01) between the initial and final average volumes in the control group, and treatment with the U. tomentosa caused a marked reduction in the growth over time (p = 0.009). Histologically, in the experimental group (n = 10) six rats had a well-preserved epithelial layer, three had mildly preserved epithelium, and one had poorly preserved epithelium. The epithelial layer occasionally presented sporadic epithelial cells. The control group (n = 12) presented seven cases (58.3%) of well-preserved epithelial cells and five cases (41.7%) of mildly preserved epithelial cells.

Conclusions

Cat's claw extract appears to be a promising alternative for treating endometriosis.