Is there any relation between IL-6 gene −174 G>C polymorphism and postmenopausal osteoporosis?

Objective

IL-6 gene single nucleotide polymorphisms (SNPs) have been reported to have a protective effect against bone resorption. We aimed to investigate the association between bone mineral density and IL-6 promoter region −174 G>C SNP.

Study design

This study included 356 postmenopausal Turkish women, of whom 201 were osteoporotic (lumbar spine T score < −2.5 SD) and 155 non-osteoporotic (lumbar spine T score > −1.5 SD). Bone mineral density (BMD) measures were obtained using dual-energy X-ray absorptiometry. SNP of the IL-6 gene (−174 G>C) was examined by polymerase chain reaction-restriction fragment length polymorphism.

Results

The frequencies of the variant C allele (24% vs. 30%, p = 0.074) and mutant CC genotype (12% vs. 20%, p = 0.094) were higher in non-osteoporotic women. Lumbar spine and total hip BMD values were lowest among women with the G/G genotype, intermediate in the heterozygotes, and highest in women with the C/C genotype. The GG (p = 0.022) and GC (p = 0.037) genotypes were covariates which approached statistical significance in the regression model fitting of BMD.

Conclusion

IL-6 promoter region SNP showed an association with BMD in this postmenopausal Turkish population and these data suggest that the wild GG genotype influences the phenotype.     

Association of IL-18 genotype with impaired glucose regulation in Korean women with polycystic ovary syndrome

Objective

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age. The pro-inflammatory cytokine, interleukin (IL)-18, is associated with metabolic syndrome, and elevated serum IL-18 levels are related to obesity and insulin resistance in PCOS patients. However, the role of IL-18 in the PCOS remains unclear. So we examined whether or not two functional polymorphisms in the IL-18 gene, −137G > C and +183A > G, are associated with PCOS itself or glucose intolerance in Korean women with PCOS.

Study design

The IL-18 genotypes of 126 women with PCOS and 113 controls were determined and their serum levels of lipid and hormone profiles measured. The insulin resistance index was calculated from the glucose and insulin concentrations obtained by oral glucose tolerance tests.

Results

There were no statistically significant differences in the distribution of −137 G > C polymorphisms among the women classified according to presence or absence of PCOS and obesity. However, the −137G/G allele was more frequent in the PCOS + impaired glucose regulation (IGR) group than PCOS + normal glucose tolerance group (X² = 7.637, p_Bonf = 0.022). The PCOS group with only the −137G allele had a significantly increased risk of IGR compared to the PCOS group with the −137C allele (92 vs. 8%, odds ratio = 6.325, 95% confidence interval = 1.403–28.519). In the PCOS patients, the mean fasting and 2-h post-prandial plasma glucose level of patients with only the −137G allele was significantly higher than those of the patients with the −137C allele (88.87 ± 9.49 vs. 84.37 ± 6.19, p = 0.002 and 120.07 ± 34.53 vs. 107.54 ± 27.13, p = 0.038). Only one woman was heterozygous for the +183A > G polymorphism and the other 224 subjects were homozygous for the polymorphism (A/A).

Conclusion

The IL-18 −137G allele could play a role in the predisposition to glucose intolerance in Korean women with PCOS, and the +183G allele of IL-18 is not associated with the Korean population.     

Serum C-reactive protein in the differential diagnosis of ovarian masses

Objective

A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer.

Study design

In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n = 44, epithelial ovarian cancer [EOC]: n = 198) ovarian masses. Results were correlated to clinical data.

Results

Median (25th, 75th percentiles) serum CRP in patients with benign ovarian tumors, with ovarian tumors of LMP, and with EOC were 0.5 (0.5, 0.6) mg/dL, 0.5 (0.5, 0.9) mg/dL, and 1.36 (0.5, 4.9) mg/dL, respectively (p < 0.001). In the subgroup of patients with EOC, serum CRP significantly correlated with FIGO stage (p < 0.001), residual tumor mass (p < 0.001), and patients’ age (p = 0.04), but not with tumor grade (p = 0.2) and histologic type (p = 0.4). In univariable and multivariable models including serum CRP, serum CA 125, and patients’ age, serum CRP independently predicted the presence of malignant ovarian masses (p < 0.0001; Odds Ratio [OR] 5.3, 95% Confidence Interval [CI] 3.8–7.4). Serum CRP had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying malignant ovarian masses of 49.8%, 84.1%, 57.1%, and 79.8%, respectively.

Conclusion

Serum CRP is associated with the presence of malignant ovarian tumors independent of serum CA 125 and patients’ age and can therefore be used as additional diagnostic marker in the differential diagnosis of ovarian masses.     

Severely decreased activity of placental dimethylarginine dimethylaminohydrolase in pre-eclampsia

Objectives

Asymmetric dimethylarginine (ADMA) is a key regulator of nitric oxide production. Elevations of ADMA have previously been associated with endothelial dysfunction in pre-eclamptic women. ADMA is degraded mainly by dimethylarginine dimethylaminohydrolase (DDAH), which is also expressed in placental tissue. Therefore, we measured placental DDAH expression and activity in pre-eclampsia and normal pregnancies in order to determine whether impairment of this enzyme in the pre-eclamptic placenta could contribute to elevations of ADMA levels in these women.

Study design

ADMA plasma levels were measured by LC–MS/MS in 18 pre-eclamptic patients and 28 controls. Placental DDAH activity was determined by measuring the degradation of [²H₆]-labeled ADMA in tissue homogenates from placental biopsies in 15 women with pre-eclampsia and 16 controls. Placental mRNA expression of DDAH 1, DDAH 2, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and protein-arginine methyltransferase 1 (PRMT1) was determined in tissue biopsies by RT-PCR.

Results

Placental DDAH activity was almost undetectable in pre-eclampsia, and it was significantly higher in controls. ADMA plasma levels were higher in pre-eclampsia as compared to normal pregnancies (0.51 ± 0.15 μmol/l vs. 0.42 ± 0.07 μmol/l; p = 0.005), and the difference between maternal and fetal ADMA levels (feto-maternal ADMA gradient) was lower in pre-eclampsia (0.63 ± 0.20 μmol/l vs. 0.80 ± 0.18 μmol/l; p = 0.02). Furthermore, mRNA expression levels of DDAH 2 were significantly lower in pre-eclamptic women (p = 0.04), while PRMT1 expression levels were the same. In pre-eclampsia, we found only weak correlations between maternal ADMA levels and DDAH 1 (r = −0.41; p = 0.22) and DDAH 2 expressions (r = −0.45; p = 0.17) but a slightly stronger correlation between DDAH 2 expression and feto-maternal ADMA gradient (r = 0.60; p = 0.07).

Conclusion

Decreased DDAH activity in the pre-eclamptic placenta might contribute to elevated ADMA levels in these patients.     

Relationship of serum adipocyte-derived proteins with insulin sensitivity and reproductive features in pre-pubertal and pubertal daughters of polycystic ovary syndrome women

Objective

To evaluate in a cross-sectional study adiponectin and leptin levels in prepubertal and pubertal daughters of women with PCOS and their relationship to insulin sensitivity and reproductive features.

Study design

We studied 92 daughters of PCOS women (PCOSd) and 76 daughters of control women (Cd) matched by age and body mass index SD scores and distributed according to breast Tanner stage: prepuberty (Tanner 1), early puberty (Tanner 2–3) or late puberty (Tanner 4–5). In all girls an oral glucose tolerance test was performed. Leptin, adiponectin, sex steroids, SHBG, glucose, insulin and lipid profile were determined. Leptin–adiponectin ratio, free androgen index and insulin sensitivity (HOMA-IR and ISI composite) were then calculated.

Results

Prepubertal PCOSd showed lower serum adiponectin compared to Cd (p = 0.028), whereas during puberty no differences were observed between the groups. Leptin concentrations were similar in both groups in all Tanner stages. In addition, in PCOSd during early puberty, adiponectin showed a negative correlation with testosterone and leptin showed a negative correlation with ISI composite, which were independent of BMI SDS (r = −0.39; p = 0.02 and r = −0.42; p = 0.01).

Conclusion

These observations suggest that during the prepubertal period PCOSd exhibit abnormal adiponectin levels, independently of BMI. Moreover, leptin and adiponectin may be related to metabolic and reproductive abnormalities observed in PCOSd during the early stages of sexual development.     

Susceptibility of red blood cell lipids to in vitro oxidation and antioxidant status in preeclampsia

Objective

To investigate susceptibility of red blood cell (RBC) lipids to oxidation and antioxidant status in preeclampsia.

Study design

Twenty-one women with mild preeclampsia, 21 women with severe preeclampsia, and 20 healthy pregnant women were included in this cross-sectional study. Susceptibility of RBC to oxidative stress was determined by measuring RBC-malondialdehyde levels after incubation with hydrogen peroxide. Vitamins E and C, total carotenoids and erythrocyte superoxide dismutase and glutathione peroxidase (GPx) activities and serum total antioxidant capacity (TAC) were determined spectrophotometrically. One-way analysis of variance and correlation analysis were used for statistical analyses.

Results

Compared with the normal pregnant women, susceptibility of RBC to oxidation was enhanced in the mild (p < 0.05) and severe (p < 0.01) preeclampsia groups, TAC was lower in the mild (p < 0.01) and severe (p < 0.001) preeclampsia groups. Vitamin C level was decreased in severe preeclampsia and total carotene level was decreased in mild and severe preeclampsia groups (p < 0.05). GPx activity was also decreased in the mild (p < 0.01) and severe (p < 0.05) preeclampsia groups.

Conclusion

The results of the present study supported the oxidative stress hypothesis of preeclampsia and it is possible that RBC play a role in the pathophysiology of the disease.     

Pre-operative systemic inflammatory response markers in predicting lymph node metastasis in endometrioid endometrial adenocarcinoma

Objectives

To evaluate the correlation of pre-operative systemic inflammatory response (SIR) markers with lymph node (LN) metastasis compared with serum CA-125 in endometrioid endometrial adenocarcinoma.

Study design

Retrospective review of 319 patients who were pathologically proven to have endometrioid endometrial adenocarcinoma after staging operations. Serum CA-125 and pre-operative SIR markers [neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), albumin, platelets and fibrinogen] were assessed. Receiver operating characteristic (ROC) curves were plotted for each SIR marker and serum CA-125.

Results

NLR, PLR and serum CA-125 were higher in the LN-positive group compared with the LN-negative group (p = 0.003, 0.012 and 0.025, respectively). Serum albumin was significantly lower in the LN-positive group compared with the LN-negative group (p < 0.001). ROC curves demonstrated the best cut-off values for NLR (≥1.97), PLR (≥9.14), albumin (≤4.15 g/dl) and serum CA-125 (≥32.50 U/ml) for pre-operative diagnosis of LN metastasis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of serum CA-125 were 63.3%, 87.6%, 37.3%, 95.4% and 85.1%, respectively. No pre-operative SIR markers were superior to serum CA-125 in terms of sensitivity, specificity, PPV, NPV or accuracy, with the exception of the slightly higher sensitivity of PLR (64.5%).

Conclusions

Pre-operative SIR markers do not appear to be more effective in predicting LN metastasis than serum CA-125 in endometrioid endometrial adenocarcinoma.     

Vascular endothelial growth factor −2578 A/C, −460 T/C and +405 G/C polymorphisms in polycystic ovary syndrome

Objective

Vascular endothelial growth factor (VEGF) may be involved in the physiological regulation of ovarian angiogenesis and pathogenesis of polycystic ovary syndrome (PCOS). VEGF −2578 A/C, −460 T/C and +405 G/C single nucleotide polymorphisms (SNPs) are known to be related to VEGF production.

Study design

In order to investigate the possible association between VEGF gene and PCOS susceptibility, we analyzed genotype and allele distributions of above mentioned SNPs in 137 patients with PCOS and 155 healthy women. Differences in genotype distributions and allele frequencies in the cases and controls were compared for statistical significance using the χ²-test. Haplotype frequencies were estimated using a contingency χ²-test. Mann–Whitney U test was used for the statistics of the clinical and biochemical parameters.

Results

No significant association between PCOS and the variant alleles of VEGF −2578 (OR: 0.91, 95% CI = 0.65–1.26), −460 (OR: 0.78, 95% CI = 0.56–1.08), and +405 (OR: 1.25, 95% CI = 0.81–1.93) was observed. However, haplotype analysis demonstrated that the frequency of CTG haplotype, was higher among PCOS compared with controls (p = 0.019) and that there is a strong linkage disequilibrium (D′ = 0.873, r² = 0.752) between −2578 and −460 polymorphisms.

Conclusions

These preliminary results suggest that the −2578, −460 and +405 SNPs of VEGF gene are not significant risk factors for PCOS development alone. However, because of the high VEGF producer CTG haplotype was more frequent among the PCOS, we suppose that investigated polymorphisms – interacting with other genetic and environmental factors – could play a role in the development of PCOS.     

Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11-13 weeks' gestation in pregnancies delivering small for gestational age neonates

Objective

To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 at 11–13 weeks’ gestation in the prediction of small-for-gestational age (SGA) neonates.

Study design

Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls.

Results

In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4–93.4 ng/mL vs 94.9, IQR 56.7–131.2 ng/mL, p = 0.002) and IGFBP-1 (58.2, IGR 39.8–84.9 ng/mL vs 81.4, IGR 57.3–105.5 ng/mL, p = 0.002) but not IGFBP-3 (54.5, IGR 45.6–61.5 ng/mL vs 55.4, IGR 47.4–64.9 ng/mL, p = 0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA.

Conclusion

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.     

First-trimester maternal serum metastin, placental growth factor and chitotriosidase levels in pre-eclampsia

Objective

To investigate whether the serum levels of metastin and PIGF and chitotriosidase activity early in pregnancy differ in women who develop pre-eclampsia from those who remain normotensive.

Study design

A retrospective case–control study of prospectively collected data. Thirty healthy pregnant women and 31 women with pre-eclampsia were included in the study. Serum samples were collected at 11–14 weeks and stored at −70 °C. Levels of metastin, PIGF and chitotriosidase activity were measured in serum from pregnant women with subsequent development of pre-eclampsia and matched controls.

Results

Mean maternal serum metastin (1554 ± 385 pmol/L vs 1995 ± 375 pmol/L, p < 0.001) and PIGF (111.9 ± 7.0 pg/mL vs 124.9 ± 13.5 pg/mL, p < 0.001) levels were significantly lower and chitotriosidase activity was significantly higher (681.6 ± 248.3 nmol/mL/h vs 527.7 ± 223.1 nmol/mL/h, p < 0.01) in women who subsequently developed pre-eclampsia than in those who remained normotensive. The areas under the curve equal to 0.797, 0.831 and 0.681 (p < 0.001, p < 0.001 and p < 0.01) for metastin, PIGF, and chitotriosidase respectively were determined for the prediction of pre-eclampsia.

Conclusions

Metastin and PIGF levels and chitotriosidase activity are altered in the first trimester serum of women destined to become pre-eclamptic, reflecting placental dysfunction. Metastin, like PIGF, may have a potential to be used as a first-trimester biomarker of pre-eclampsia.     

Erythropoietin and erythropoietin receptor expression in normal and disturbed pregnancy

Objective

Erythropoietin (Epo) is known to regulate the number of circulating erythrocytes. Epo receptor (Epo-R) expression is limited to few organs including the uterus. We investigated differences in Epo and Epo-R expression in normal and disturbed first trimester human pregnancy.

Study design

Placental tissue was obtained from normal human pregnancy, abortion and hydatidiform mole during the first trimester of pregnancy. Epo and Epo-R expression was investigated by Immunohistochemistry and real time PCR (TaqMan^®). The intensity and distribution patterns of Epo and Epo-R expression were evaluated by using a semi-quantitative method (immunoreactive score) as previously described.

Results

Epo-R expression was upregulated in the villous trophoblast (VT) of abortive tissue (p = 0.002) as compared to normal pregnancy. This was further confirmed on mRNA level. With regard to mole pregnancy, Epo-R expression was also significantly increased in the VT (p < 0.001). In extravillous trophoblasts (EVT), only Epo, not Epo-R expression was significantly increased in abortive tissue (p = 0.006) as well as in hydatidiform mole (p = 0.041) in comparison to normal pregnancy. Identification of EVT as Epo-and Epo-R-positive cells was obtained by double immunofluorescence with CK7 and Epo/ Epo-R double staining. Both mole pregnancy and abortion were accompanied by an upregulation of Epo (p = 0.041; p = 0.018) and Epo-R expression (p = 0.007; p = 0.015) in decidual tissue as compared to normal pregnancy.

Conclusion

Within our study we were able to demonstrate increased expression of Epo and Epo-R in abortive tissue and hydatidiform mole. Whether upregulation of Epo and Epo-R is secondary to placental hypoxia as part of the abortion process or a risk factor of its own, needs to be further investigated.     

Carbon dioxide pneumoperitoneum induces systemic oxidative stress: a clinical study

Objective

To investigate the effect of carbon dioxide pneumoperitoneum on systemic oxidative stress by using serum oxidative stress markers (ischemia modified albumin (IMA), malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI)) and to compare their effectiveness at clinically accepted safe intra-abdominal pressure levels (<12 mmHg).

Study design

A total of 33 consecutive patients who had a unilateral ovarian cyst were enrolled for this prospective clinical study. All women underwent a laparoscopic ovarian cystectomy procedure. Venous blood was collected from patients preoperatively, 10 min after induction of anesthesia and 30 min after insufflation. Preoperative, 10_min, and 30_min serum IMA, MDA, TOS, OSI and TAS levels were compared.

Results

The mean age was 29.3 ± 6.4 and the range of operation time was 45–80 min. The mean serum IMA levels showed a significant increase 30 min later from CO₂ insufflation (p < 0.05). Significant alterations were not observed in serum MDA, TOS, OSI or TAS levels.

Conclusions

Laparoscopic surgery causes systemic ischemia and this ischemic effect can be revealed by measuring serum ischemia modified albumin. IMA is more sensitive than MDA, TOS, OSI and TAS in early detection of systemic oxidative stress.     

The impact of plasma fibrinogen levels on patients with vulvar cancer

Objective

To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters.

Study design

In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients’ survival.

Results

Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p = 0.001), lymph node involvement (pN0 vs. pN1, p = 0.04), and histological grade (G1 vs. G2 vs. G3, p = 0.03), but not with patients’ age (≤70 years vs. >70 years, p = 0.6). In a multivariate survival analysis, tumor stage (p = 0.006/p = 0.02) and lymph node involvement (p < 0.001/p < 0.001), but neither histological grade (p = 0.2/p = 0.9) nor plasma fibrinogen levels (p = 0.6/p = 0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (≤70 years vs. >70 years) was associated with overall survival (p = 0.03) but not with disease-free survival (p = 0.1).

Conclusion

Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in patients with vulvar cancer.     

Feasibility of same-day discharge after laparoscopic surgery in gynecologic oncology

Objective

The purpose of this study is to evaluate whether same-day discharge after laparoscopic gynecologic oncology surgery is feasible and determines factors associated with admission.

Methods

This retrospective cohort study included all patients consented for laparoscopy by two gynecologic oncologists at a tertiary care academic teaching hospital between January 2006 and June 2009. Procedures included those not typically discharged same-day, such as total laparoscopic simple or radical hysterectomies or radical trachelectomy +/− salpingo-oophorectomy +/− pelvic and para-aortic lymph node dissection +/− omentectomy. Those discharged same-day were compared to those admitted. Multivariate logistic regression analysis was done to determine factors associated with admission.

Results

Three hundred three patients were included. 6.9% were converted to laparotomy. One hundred forty-seven (48.5%) had same-day discharge (median stay 295 minutes). Among outpatients, 7 (4.8%) were readmitted within three weeks of surgery. Three patients (2%) could have avoided the ER or hospital admission had they been originally admitted postoperatively. No patients with same-day discharge had a major acute postoperative complication. Factors associated with admission include age (OR 1.76 for age 70 years vs 50 years, p = 0.001), surgeon (OR 6.91, p < 0.0001), conversion to laparotomy (p < 0.0001), radical hysterectomy (OR 3.43, p = 0.002), length of surgery (OR 2.94 for 4 hours vs 2 hours, p < 0.0001), and surgery start time after 1 PM (OR 3.77, p = 0.0001).

Conclusion

Same-day discharge for laparoscopic gynecologic oncology surgery is feasible, with low morbidity and few readmissions within three weeks of surgery. Successful same-day discharge can increase by refining patient selection and operating room scheduling.     

Markers of visceral obesity and cardiovascular risk in patients with polycystic ovarian syndrome

Background

Polycystic ovarian syndrome (PCOS) is one of most common endocrine disturbances in women of reproductive age. Besides its well known effects on reproductive health, it is also linked to increased cardiovascular risk in later life.

Objectives

The aim of this study was to investigate the link between some anthropometric indices of visceral obesity and surrogate markers of cardiovascular risk according to the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society consensus.

Study design

The study included 36 normal weight (BMI < 25 kg/m²) and 19 obese PCOS subjects (BMI ≥ 30 kg/m²), aged between 18 and 40 years. Different anthropometric markers were compared as predictors for an adverse cardiometabolic profile and composite cardiovascular risk factors as defined by the AE-PCOS consensus.

Results

Both waist-to-stature ratio (WSR) (area under the curve 0.75, p = 0.002) and waist circumference (WC) (area under the curve 0.77, p = 0.001) but not waist-to-hip ratio (WHR) (area under the curve 0.62, p = 0.143) were shown to be good markers of increased cardiovascular risk, insulin resistance and dislipidemia in PCOS patients. The cut-off point for WSR of 0.50 is useful and the cut-off of 80 cm for WC is more appropriate than 88 cm in detecting cardiovascular risk in PCOS patients. Androgen levels and immunoreactive insulin during an oral glucose tolerance test had lower power for predicting increased cardiovascular risk than WC and WSR.

Conclusion

The study indicates that WSR and WC are better associated with composite cardiovascular risk factors as defined by the AE-PCOS consensus than WHR, and that the commonly used cut-off for WSR of 0.5 is useful for detecting cardiovascular risk in PCOS patients.     

Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer

Objectives

Viruses and tumour cells may regulate the expression of HLA molecules on the cell surface to escape immune system surveillance. Absence of classical HLA class I molecules may impair the action of specific cytotoxic cells, whereas non-classical HLA class I molecules may regulate innate and adaptive immune cells. We assess here the possible associations between classical/non-classical class I HLA and p16^INK4a molecule expression in cervical biopsies of women infected with HPV, stratified according to grade of the lesion and HPV type.

Study design

Cervical biopsies (N = 74) presenting cervical intraepithelial neoplasia grade 1 (CIN1) (n = 31), CIN2–3 (n = 19), and invasive cancer (n = 14) were evaluated alongside 10 normal cervical specimens.

Results

HLA-A/B/C/G staining was observed in the early stages of HPV infection. A significant association was detected between HLA-A/B/C staining and HPV16/18 infection (OR = 0.12, 95%CI: 0.0163–0.7899; p = 0.04). HLA-E expression increased with the progression of the lesion (χ²-test for trend = 4.01; p = 0.05), and a significant association was found between HLA-E staining and HPV16/18 infection (OR = 11.25, 95%CI: 2.324–54.465; p = 0.003). Irrespective of the grade of the lesion, HLA-A/B/C staining and p16^INK4a presented a good concordance (Kappa: 0.67).

Conclusions

HLA-E overexpression seemed to be associated with invasive cancer and HPV16/18 infection.     

Effectiveness of local anaesthetics with and without vasoconstrictors for perineal repair during spontaneous delivery: double-blind randomised controlled trial

Objective

to investigate the use of local anaesthetics, in the presence or absence of vasoconstrictors, for perineal repair during spontaneous delivery.

Design

double-blind, randomised-controlled trial.

Setting

a birth centre, in the city of Sao Paulo, Brazil.

Participants

from June to December 2004, a total of 96 women were allocated into three groups (first-degree perineal lacerations, second-degree perineal lacerations or episiotomy), and treated with local anaesthesia (1% lidocaine or 1% lidocaine with epinephrine) (n=16 per treatment per group).

Interventions

an initial local infiltration of the anaesthetic solution was given so that episiotomy could be carried out (5 ml) and to suture spontaneous lacerations (1 ml), followed by repeated doses (1 ml) until pain was completely inhibited.

Measurements and findings

the main outcome measurement was the volume of anaesthetic used during episiotomy and perineal suture. Our data suggest that the concomitant use of the vasoconstrictor resulted in a significantly lower average volume used in the treatment of first-degree (1 ml, 95% confidence interval (CI) 0.4–1.6) and second-degree (3.7 ml, 95% CI 1.6–5.8) lacerations (p=0.002 and 0.001, respectively). A 0.3 ml (95% CI 1.5–2.1) average decrease in anaesthetic volume was observed with episiotomy (p=0.724). The maximum volume of anaesthetic used with and without vasoconstrictor was 1–2 ml in 95% and 3–4 ml in 50% of first-degree lacerations, respectively, and 1–6 ml in 88% and 7–15 ml in 81% of second-degree lacerations, respectively. For episiotomy, the maximum dose was 15 ml, regardless of anaesthetic solution used.

Key conclusions

our data confirm the hypothesis that the use of anaesthetics in conjunction with vasoconstrictors is more effective than anaesthetics alone in the repair of perineal lacerations, but not for episiotomy.     

Urbanization and the likelihood of a cesarean section

Objective

This study examines the association between the likelihood of cesarean section (CS) and the degree of urbanization in Taiwan, exploring possible explanations for the difference.

Study design

The database used in this study was the Taiwan 2004 National Health Insurance Research Database. A total of 200,207 singleton deliveries fulfilled our criteria and were included in our study. The urbanization level of cities/towns where parturients resided at the time of delivery was stratified into seven categories. A multilevel logistic regression model was applied to examine the relative likelihood of CS by urbanization level after adjusting for parturient, physician and hospital characteristics.

Results

There was an upward trend in the CS rate with advancing urbanization level; the CS rates for urbanization level 1 (most urbanized) through 7 (least urbanized) were 33.7, 32.3, 30.4, 30.2 29.7, 29.5, and 28.6%, respectively. Compared with participants living at the highest urbanization level, the adjusted odds of a CS were 0.91 (95% CI = 0.85–0.98, p = 0.014), 0.84 (95% CI = 0.78–0.91, p < 0.001), 0.83 (95% CI = 0.68–0.88, p < 0.001), 0.79 (95% CI = 0.72–0.86, p < 0.001), and 0.70 (95% CI = 0.62–0.80, p < 0.001) times, respectively, for those living in cities/towns ranked from the third highest to the lowest levels of urbanization.

Conclusions

We conclude that higher urbanization levels were associated with higher odds of CS. Highly urbanized communities could therefore be targeted for policy intervention aimed at reducing the unnecessary CS rate.     

Twin pregnancies in Cardiff and Vale of Glamorgan over four decades: natural twinning is on the increase

Objective

To assess trends in twinning over four decades using a population-based registry.

Design

Ecological study to conduct trend analysis of twin pregnancies in a geographically defined area over 40 years.

Setting

All pregnancies in the Cardiff and Vale of Glamorgan area of South Wales from 1965 to 2004, as recorded in the Cardiff Birth Survey (CBS) database.

Methods

Trends of the incidence of all twin pregnancies (≥18 weeks of gestation) were calculated in 5-year increments, beginning with 1965–1969 and ending in 2000–2004. Natural twinning rates could only be calculated for the terminal five time periods (i.e., 1980–1984, 1985–1989, 1990–1994, 1995–1999, and 2000–2004), when information regarding non-spontaneous (iatrogenic) twinning was first collected in the database. All results were adjusted for maternal age.

Results

The total twinning rate was 13.1 per 1000 pregnancies in the 1st time period (1965–1969). Subsequently, there was a gradual reduction in twinning, reaching a nadir of 10.3 per 1000 for the time period 1980–1985 (Z = 3.15, P value < 0.001). This was followed by a gradual increase in twinning, reaching a maximum of 15.7 per 1000 for both 1995–1999 and 2000–2004 (Z = −5.18, P value < 0.0001). After exclusion of the cases of iatrogenic pregnancies, the natural twinning rate showed a continuous and gradual increase from 10 per 1000 spontaneous pregnancies in 1980–1984 to 13.3 per 1000 in 2000–2004 (Z = −5.08, P value < 0.0001).

Conclusion

The data showed a gradual, continuous increase in natural twinning rates over the last two decades. Such an increase cannot be attributed to the rise in maternal age alone.     

Effect of delayed umbilical cord clamping on blood gas analysis

Objective

To ascertain if there are differences in umbilical cord blood gas analysis between immediate and delayed cord clamping.

Study design

In a prospective observational study on 60 vaginally delivered healthy term newborns, we sampled umbilical cord blood immediately after delivery and at the time umbilical cord pulsation spontaneously ceased.

Results

There were significant decreases in pH, oxygen saturation (sO₂), glycemia, oxygen content (ctO₂), bicarbonate (HCO₃⁻) and base excess (BE). Lactate and PCO₂$P_{{\text{CO}}_2}$ increased. Delayed cord clamping pH correlated with immediate cord clamping pH, PO₂$P_{{\text{O}}_2}$, ctHb, sO₂ and time (r² = 0.77, p < 0.000). Delayed cord clamping lactate was associated with immediate cord clamping lactate and time (r² = 0.83, p < 0.000). Delayed BE was associated with previous pH, lactate, glycemia, ctHb and time (r² = 0.83, p < 0.000).

Conclusions

Delayed cord clamping alters acid–base parameters and lactate values compared to immediate cord clamping. Those variations depend mainly on time, prior pH and lactate.