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Persistent organic pollutants are synthetic chemicals highly resistant to degradation with strong tendency to bioaccumulation. Assessment of human exposure to these compounds is crucial for public health protection, especially during vulnerable periods. The aim of the present cohort study was to evaluate the level of contamination to PCBs, o,p’- and p,p’-DDE, o,p’ and p,p’-DDD, o,p’ and p,p’-DDT and HCB in pregnant women. Hair, amniotic fluid and serum samples were collected and analyzed by HS-SPME-GCMS. The most detected analytes in amniotic fluids were p,p’-DDE, p,p’-DDD, o,p’-DDE and PCB101, in serum p,p’-DDE, HCB and PCB101 and in hair p,p’-DDE, HCB and PCB101. The levels of HCB and PCB101 in amniotic fluids were positively correlated with those in hair. Higher levels of DDDs and DDTs in hair samples and PCB28 in amniotic fluids were observed in smoker pregnant women. Gestation age was inversely proportional with the detected levels of PCB101 in all tested samples.

The present study aims to investigate the expression levels of two critical mammalian target of rapamycin (mTOR) downstream effectors, 4E binding protein 1 (4EBP1) and eukaryotic initiation factor 4E (eIF4E) proteins, in precancerous squamous intraepithelial lesions and cancer of the uterine cervix, and their association with human papilloma virus (HPV) infection status. Uterine cervical biopsies from 73 patients were obtained, including 40 fresh-frozen samples and 42 archival formalin-fixed, paraffin-embedded tissue specimens. Whole protein extracts were analyzed for the expression of 4EBP1 and eIF4E proteins using western blotting. In addition, distribution of 4EBP1 and eIF4E protein expression and 4EBP1 phosphorylation (P-4EBP1) were analyzed by immunohistochemistry in archival tissues and correlated with the degree of dysplasia. The presence of high-risk HPV (HR-HPV) types was assessed by polymerase chain reaction. Using western blot analysis, high expression levels of 4EBP1 and eIF4E were observed in all uterine cervical carcinomas, which significantly correlated with the degree of dysplasia. By immunohistochemistry, overexpression of 4EBP1 and eIF4E was detected in 20 of 21 (95%) and 17 of 21 (81%) samples, respectively, in patients with high-grade dysplasia and carcinomas, compared with 1 of 20 (5%) and 2 of 20 (10%) samples, respectively, in patients with low-grade lesions or normal histology. All 4EBP1-positive cases tested were also positive for P-4EBP1. Furthermore, overexpression of 4EBP1 and eIF4E significantly correlated with the presence of HR-HPV oncogenic types. The present study demonstrated that critical effectors of mTOR signaling, which control protein synthesis initiation, are overexpressed in cervical high-grade dysplasia and cancer, and their levels correlate with oncogenic HPV types. These findings may provide novel targets for investigational therapeutic approaches in patients with cancer of the uterine cervix.

Objective The goal of this study is to evaluate the potential of first trimester (FT) screening in the diagnosis of agenesis of the ductus venosus (ADV) and to study its prevalence in a low-risk population, the associated conditions, and pregnancy outcome. Method Prospective, sequential screening study at two tertiary units with morpho-functional evaluation of the ductus venosus during the first and second trimester screening. We quantified the FT detection rate, prevalence, and associated conditions: umbilical shunting type, concomitant anomalies, and outcome. Results In 6114 consecutive pregnancies, we identified 11 cases of ADV. Ten (91%) were identified during the FT examination. The prevalence was 1 in 556, similar for both centers (1/478 vs. 1/691). Major structural defects and fetal effusions were detected in 8 (73%). twenty two percent had a major chromosomal abnormality. In 3 cases, the anomaly was isolated and had normal outcome, independent of liver by-pass, caliber of the shunt, and NT thickness. Conclusions Agenesis of the ductus venosus can be detected during FT. The early detection of ADV is important given its high association with major abnormalities. © 2014 John Wiley & Sons, Ltd.

The aim of the study was to estimate the risk of pre-term birth in women giving birth in Greece in different age groups. Data about women giving birth in Greece were retrieved from the Hellenic Vital Statistics covering the years from 1999 to 2008. Relative risk using χ(2) contingency tables was estimated among maternal age groups formed. These groups included mothers15 years of age, 15-19, 20-34 (used as a control group) and women34 (35-39, 40-44, 45-49 and ≥ 50) years of age. Relative risk of each age group was compared with mothers 20-34 years of age. A total of 1,069,413 valid births were included in the study and 72,156 of them were pre-term (6.75% of total count). Results exhibit a 'U'-shaped distribution of risk. Higher risk of pre-term birth is noted in the groups of15 years (Pearson χ(2) = 14.964, p0.001, risk = 1.569, CI = 1.249-1.970) and above 34 years of age (Pearson χ(2) = 2991.26, p0.001, risk = 1.572, CI = 1.546-1.597). For older women, a steep rise in the relative risk for pre-term birth was noted beyond the 40-44 years of age group. Finally, of interest is the fact that 'late' pre-terms (34-36 gestational weeks) account for most of the pre-term birth in mothers beyond 34 years of age.

Objective To evaluate the blood flow characteristics of the cervix in normal women and in women with cervical precancerous lesions or cervical cancer. Methods We studied 165 women with three-dimensional power Doppler ultrasound (3D-PDU), of whom 71 had cervical cancer, 61 had precancerous lesions and 33 were healthy controls. The cervix was manually traced in the stored volumes using 15° rotation steps and the following 3D-PDU indices were calculated: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). These indices were compared among the study groups and were also correlated with features of the precancerous lesions group and cancer group. Results The three indices were all statistically significantly higher in the cervical cancer group and precancerous lesions group than in controls (P 0.05). However, VI was significantly higher in patients with Stages IIIB–IV cancer than in patients with less advanced disease (P = 0.045). In the cervical cancer group there was a significant positive correlation between 3D-PDU indices and cervical volume. Conclusion 3D-PDU assessment of the cervix reveals significant differences in all indices studied between women with cervical precancerous lesions or cancer and healthy women. In women with cervical cancer, an advanced stage is associated with higher VI, but 3D-PDU indices are not related to other pathological characteristics. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Angiogenesis consists a fundamental mechanism required for a number of pathophysiological processes, among others tumour growth. It constitutes a dynamic process and a high number of proangiogenic and antiangiogenic molecules have critical roles in regulating angiogenesis. In response to stimuli, such as hypoxia, oxidative stress and acidosis, several proangiogenic factors are released from endothelial, stromal and tumour cells into the microenvironment (Gasparini et al, 2005). Over 30 angiogenic factors have been identified and reported to have important roles in angiogenesis, with the dominant growth factor controlling this process being the vascular endothelial growth factor (VEGF) (Ribatti and Vacca, 2008). Vascular endothelial growth factor is a dimeric polypeptide with molecular weight ranging from 35 to 45 kDa. Vascular endothelial growth factor refers to a family of growth factors, comprising seven different proteins, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and placental growth factor isoforms 1 and 2 (Lyons et al, 2010). Direct actions of VEGF include stimulation of endothelial mitogenesis, promotion of endothelial survival/control of vascular permeability and promotion of cell migration (Zucker et al, 1998; Tam et al, 2006). Moreover, it has been recently proposed that VEGF may have a direct effect on tumour cell growth (Tam et al, 2006).

Aims The objective of this study was to validate four specific International Consultation on Incontinence Questionnaires (ICIQ) modules in the Greek language: (i) the ICIQ-FLUTS long form (ICIQ-FLUTS-LF), (ii) the ICIQ-FLUTS, (iii) the ICIQ-FLUTS-SEX, and (iv) the ICIQ-Vaginal Symptoms Questionnaire (ICIQ-VS), originally validated in English. Methods The English questionnaires were initially translated into Greek, then back-translated into English and final modifications were made after testing the questionnaires on a sample of patients. To validate the translated questionnaires, the following tests were undertaken: Content/face validity, internal consistency (reliability) and stability (test–retest reliability). Results A total of 122 women participated in the study. Eighty-nine presented with pelvic organ prolapse (POP) and/or urinary incontinece (UI) symptoms and 33 attended an outpatient gynecological clinic without POP/UI symptoms. All modules showed excellent content/face validity (missing values 0–2.5%). Cronbach's alpha test for internal consistency showed satisfactory to excellent reliability (0.876 for ICIQ-FLUTS-LF, 0.85 for ICIQ-FLUTS, and 0.83 for ICIQ-VS), with the exception ICIQ-FLUTS-SEX which was 0.69. The test–retest reliability showed moderate to near-perfect agreement (weighted kappa value 0.52–0.99). Conclusions The Greek versions of the ICIQ-FLUTS-LF, ICIQ-FLUTS, and ICIQ-VS questionnaires were successfully validated. Our data showed that the ICIQ FLUTS-SEX questionnaire, as it stands in its current English version, cannot be reliably used to assess sex symptoms in the Greek female population. Neurourol. Urodynam. 31:1141–1144, 2012. © 2012 Wiley Periodicals, Inc.

Please cite this paper as: Papoutsis D, Rodolakis A, Mesogitis S, Sotiropoulou M, Antsaklis A. Regeneration of uterine cervix at 6 months after large loop excision of the transformation zone for cervical intraepithelial neoplasia. BJOG 2012;119:678–684. Objective To sonographically investigate cervical regeneration 6 months after large loop excision of the transformation zone (LLETZ) conisation for cervical intraepithelial neoplasia (CIN) pathology. Design Prospective observational study. Setting University Hospital setting. Population Women having LLETZ conisation for intraepithelial lesions in response to abnormal Papanicolaou smears or colposcopic findings. Methods Cervical dimensions were estimated before conisation and at 6 months with three-dimensional sonography and use of vocal™ software. Cone depth was measured using a ruler before fixation, and cone volume was measured using a volumetric tube and the fluid displacement technique. Cervical regeneration was sonographically estimated. Main outcome measures Correlation of cervical volume regeneration with percentage of initial cervical volume excised and remaining cervical tissue immediately after conisation. Results A cohort of 112 women were initially recruited over a 2-year period and 73 women presented for ultrasound follow up at 6 months. Multivariate linear regression analysis showed that for women matched for age and initial cervical volume, if cervical volume excised was increased by 1% then regeneration of tissue deficit at the cervical crater was reduced by 1.37%. There also seemed to be a cutoff point suggesting that when >14% of initial cervical volume was excised, the tissue deficit at the cervical crater at 6 months was restored by 25% of remaining tissue deficit. Conclusions Cervical regeneration at 6 months after excision is dependent on the percentage of initial cervical volume excised and on the remaining cervical tissue immediately after conisation. The greater the cone and the less cervical tissue remaining, the less the degree of cervical regeneration achieved.

Purpose: To evaluate the use of three-dimensional off-line ultrasonography (3D) as an alternative for examining fetal anatomy and nuchal translucency (NT) in the 1st trimester of pregnancy. Method: A Prospective study of 1007 low risk singleton pregnancies at 11 to 14 weeks of gestation. The gestational age, NT and fetal anatomy (10 anatomic features) were evaluated by off-line three-dimensional (3D) ultrasonography after the standard two-dimensional (2D) examination. The results of the two methods were compared using the 2D as a gold standard. Results: In some of the evaluated parameters the 3D method approximates the conventional 2D results. These parameters are the crown-rump length (CRL), the skull - brain anatomy (96.8%), the spine (89.7%), the upper (91.1%) and lower limbs (87%) and the fetal abdomen (98.5%). Some of the anatomic features revealed statistically significant differences in favor of the 2D examination such as the nasal bone (70.6% with the 3D), the stomach (79.6%) and the urinary bladder (59.6%). The NT was measured with the 3D in 87.5% of cases; although in only 60% values were accurate to the corresponding 2D. Conclusion: The off-line assessment of 3D ultrasound volumes can accurately date gestation and satisfactorily visualize fetal anatomy in about 75% of cases. Yet it seems insufficient for the 1st trimester examination, although with modifications and improvements it might serve a potential screening tool especially for areas with difficult access to advanced prenatal diagnosis.

Background There is increasing interest in the therapeutic potential of human mesenchymal stem cells (hMSCs), especially in diseases such as acute hepatic failure (AHF) that are predominantly caused by a variety of drugs and viruses. In previous studies, a distinct population termed human spindle-shaped MSCs were isolated and expanded from second trimester amniotic fluid (AF-MSCs) and characterised based on their phenotype, pluripotency and differentiation potential. Methods AF-MSCs, hepatic progenitor-like (HPL) cells and hepatocyte-like (HL) cells derived from AF-MSCs were transplanted into CCl 4 -injured NOD/SCID mice with the AHF phenotype in order to evaluate their therapeutic potential. Conditioned medium (CM) derived from AF-MSCs or HPL cells was then delivered intrahepatically in order to determine whether the engraftment of the cells or their secreted molecules are the most important agents for liver repair. Results Both HPL cells and AF-MSCs were incorporated into CCl 4 -injured livers; HPL cell transplantation had a greater therapeutic effect. In contrast, HL cells failed to engraft and contribute to recovery. In addition, HPL-CM was found to be more efficient than CM derived from AF-MSCs in treatment of the liver. Proteome profile analysis of HPL-CM indicated the presence of anti-inflammatory factors such as interleukins IL-10, IL-1ra, IL-13 and IL-27 which may induce liver recovery. Blocking studies of IL-10 secretion from HPL cells confirmed the therapeutic significance of this cytokine in the AHF mouse model. Conclusions Human spindle-shaped AF-MSCs or HPL cells might be valuable tools to induce liver repair and support liver function by cell transplantation. More importantly, the factors they release may also play an important role in cell treatment in diseases of the liver.

Early-stage epithelial ovarian cancer represents a prognostically heterogenous group. We studied prognostic factors in patients treated with adjuvant paclitaxel/carboplatin chemotherapy.Data was extracted from 147 patients with FIGO stage IA/IB, grade 2/3 or stage IC/IIA (any grade) who underwent primary surgery followed by paclitaxel/carboplatin chemotherapy.Median follow-up was 88 months. Ten-year relapse-free (RFS) and disease-specific survival (DSS) were: 81% (95% confidence interval [CI]: 73-89) and 81% (95% CI: 73-89). On multivariate analysis, non serous histology was associated with reduced risk for RFS (0.294, 95% CI: 0.112-0.577, p=0.001) and DSS (0.194, 95% CI: 0.075-0.504, p=0.001), while high-risk category (stage IC/IIA and grade 2/3) with increased risk for RFS (3.989, 95% CI: 1.189-13.389, p=0.009) and DSS (3.989, 95% CI: 1.064-16.386, p=0.038). The combination of histology and grade identified 3 groups with distinctly different 10-year RFS and DSS rates (p0.001): grade 1 (100% and 100%), non-serous grade 2/3 (83% and 86%) and serous grade 2/3 (60% and 60%).Serous histology is an adverse prognostic factor in early-stage ovarian cancer treated with adjuvant paclitaxel/carboplatin. Risk stratification according to histology and grade is a useful discriminator of prognosis and can be used in the design of future studies.

Men with Down syndrome are considered as infertile although the causes of infertility are not known in detail yet. Although this constitutes a general rule there are three confirmed cases of parenting by fathers with Down syndrome. Many investigators have addressed the causes of infertility and their studies indicate that the causes may be hormonal deficits, morphological alterations of the gonads, abnormal spermatogenesis, psychological and social factors related to the mental retardation. It is obvious that the extra chromosome 21 has a detrimental direct and indirect effect on the reproductive capacity of the affected male patient. But the definite cause of the insufficient and inadequate spermatogenesis remains to be discovered.

The purpose of this article is to create the first complete review concerning the role of calprotectin, a calcium- and zinc-binding protein of the S100/calgranulins family, in obstetrics and gynecology. A Medline search was conducted between 6 and 8 June 2009 using the term calprotectin and its synonyms combined with the following ones: calprotectin, obstetrics and gynecology, breast cancer, ovarian cancer, endometrial cancer, cervical cancer, menstrual cycle, pregnancy, fetal implantation, labor, intra-amniotic inflammation, preeclampsia, HELLP syndrome, Rh(-) incompatibility. We found 46 studies which referred to obstetrics and gynecology. We excluded 11 studies which referred to obstetrics and gynecology but did not include enough information about calprotectin, and another two which referred to calprotectin but were not related to subjects of obstetrics and gynecology. Thus, we ended up with 33 studies which contained sufficient information to extract data for this review. All the articles were written in English. It was found that calprotectin is associated with many physiologic and pathologic processes in obstetrics and gynecology, such as: breast cancer, ovarian cancer, endometrial cancer, cervical cancer, cervical and vaginal physiology, menstrual cycle, pregnancy and labor. The role of calprotectin in these conditions is significant. In conclusion, the role of calprotectin seems to be important in several issues of obstetrics and gynecology. For example, calprotectin could be used as a diagnostic, prognostic or metastatic marker in several types of cancer, as a marker of inflammation and as a pharmaceutical target in many conditions. Further studies must be conducted to elucidate this role.

The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach. A 35-year-old pregnant woman with a yolk sac tumor underwent left salpingo-oophorectomy at 25 weeks of gestation. Chemotherapy was deferred to the end of the pregnancy owing to concerns for potential fetal risks. Alpha-feto protein level was used to monitor the underlying disease activity. The patient underwent exploratory laparotomy with cesarean section followed by total hysterectomy, omentectomy, right salpingooophorectomy, pelvic, and para-aortic lymphadenectomies at 32 weeks of gestation. She received four postoperative courses of chemotherapy (cisplatin, etoposide, and peplomycin). Currently, mother and child are doing well 6 months after the last chemotherapy cycle. In a case of yolk sac tumor in the second trimester of pregnancy, radical surgery combined with elective caesarian section followed by chemotherapy could achieve remission and rescue of fetus. However, the treatment needs to be individualized as there is lack of evidence.

Humoral hypercalcemia of malignancy (HHM) is a metabolic phenomenon that is mediated by the paraneoplastic secretion of parathyroid hormone-related peptide (PTHrP). Gynecologic malignant neoplasms complicated by HHM have been reported for organs such as the uterus, cervix, ovary, vulva and the vagina. The purpose of our study was to perform a review of the published cases in the literature and, further, to identify parameters with effect on outcome. Among 34 women with gynecologic neoplasms, 22 suffered from ovarian and 6 from uterine malignancies, while 3 had vulvar and another 3 cervical cancer. Furthermore, clear cell carcinoma was the predominant histology associated with PTH-rP expression. A significant correlation was found between serum calcium and PTH-rP levels. Treatment of hypercalcemia was successful in all cases; pamidronate was utilized in 8 patients. Ovarian cancer patients with severe hypercalcemia and high PTH-rP serum levels had shorter survival compared to their counterparts with mild hypercalcemia or moderately elevated PTH-rP serum levels, but the differences were not statistically significant.

Objective To compare 3-dimentional hysterosonography (3-DHS) and diagnostic hysteroscopy for the evaluation of intrauterine lesions. Methods In this prospective study 124 women with suspected intrauterine abnormality on 2-D ultrasonography or on hysterosalpingography were scheduled to undergo hysteroscopy, 3-DHS, and 3-D power Doppler (3-DPD) examination. However, 3-DHS could not be performed in 3 of the women because of cervical stenosis. The sensitivity and specificity of 3-DHS and 3-DPD were compared with those of hysteroscopy. Results Of the 121 women found to have an intracavitary abnormality, 20 had polyps, 11 had myomas, 2 had Mullerian duct anomalies, and 6 had synechiae on hysteroscopy. There was agreement between hysteroscopy and 3-DHS in 19 of the polyp cases, 11 of the myoma cases, 2 of the Mullerian anomaly cases, and 4 of the synechiae cases. Examination with 3-DHS and 3-DPD reached a sensitivity of 91.9% and specificity of 98.8%, with a positive predictive value of 97.1% and a negative predictive value of 96.5%, respectively. Conclusions Examination with 3-DHS and 3-DPD both allows for accurate assessment of intrauterine abnormalities.

To compare outcomes for fetuses at term in breech presentation during 2 periods when different delivery policies were in effect.Outcomes of the 392 planned vaginal deliveries and 1160 elective cesarean sections (CSs) performed from January 1, 1988, through December 31, 2000, were compared with those of the 24 emergency vaginal deliveries, the 403 planned CSs, and 75 emergency CSs performed from January 1, 2001 through December 31, 2004 at Alexandra Hospital, Athens, Greece.A significant difference was found in rates of low 5-minute Apgar score, birth trauma, serious neonatal morbidity, and admission to the neonatal intensive care unit (0% vs. 1.02% [P=0.004], 1.02% vs. 0% [P=0.004], 3.06% vs. 0.43% [P0.001], and 2.8% vs. 0.43% [P0.001], respectively) between neonates born by planned vaginal delivery and those born by elective CS during the first period. Only a reduction in rates of admission to the neonatal intermediate care unit was found between the first and second periods.Planned CS was found to be safer than planned vaginal delivery for fetuses at term in breech presentation. However, the study did not demonstrate that the change in policy improved neonatal outcome.

Objective To assess the role of maternal demographic characteristics, uterine artery Doppler velocimetry, maternal serum pregnancy-associated plasma protein-A (PAPP-A) and their combination in screening for pre-eclampsia and small-for-gestational age (SGA) fetuses at 11–14 weeks. Methods This was a prospective study of 878 consecutive women presenting for a routine prenatal ultrasound examination at 11–14 weeks. Pulsed wave Doppler was then used to obtain uterine artery flow velocity waveforms and the mean pulsatility index (PI) of the uterine arteries was calculated. Maternal serum samples for PAPP-A were assayed. Along with maternal history, these measurements were compared in their ability to predict adverse outcome, defined as pre-eclampsia and/or SGA and/or placental abruption. Results Mean uterine artery PI ≥ 95th centile and PAPP-A ≤ 10th centile each predicted 23% of the women that developed pre-eclampsia and 43% of cases of placental abruption. For SGA ≤ 5th centile, mean uterine artery PI ≥ 95th centile predicted 23% of cases and PAPP-A ≤ 10th centile predicted 34%. Independent predictors for subsequent development of pre-eclampsia were increased mean uterine artery PI ≥ 95th centile (OR, 2.76; 95% CI, 1.11–6.81) and maternal history of pre-eclampsia/hypertension (OR, 50.54; 95% CI, 10.52–242.73). The predicting factors for SGA ≤ 5th centile were increased mean uterine artery PI ≥ 95th centile (OR, 2.0; 95% CI, 1.07–3.74) and low PAPP-A (OR, 0.43; 95% CI, 0.20–0.93). Increased uterine artery PI was the only independent factor in the prediction of placental abruption (OR, 8.49; 95% CI, 2.78–25.94). The combination of uterine artery PI and maternal history of pre-eclampsia/hypertension was better than was using uterine artery Doppler alone in predicting pre-eclampsia. Similarly, for the prediction of SGA ≤ 5th centile, combining uterine artery Doppler and maternal serum PAPP-A was better than was uterine artery Doppler alone. In both cases, the difference approached statistical significance. Conclusions The combination of maternal history with abnormal uterine artery Doppler and low PAPP-A level at 11–14 weeks achieves better results than does either test alone in the prediction of pre-eclampsia and SGA. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

Oocyte maturation is a complex process involving both the progression of meiotic cycle and the reprogramming of cytoplasmic events. The aim of this study was to investigate the effects of prolactin (PRL) in the in vitro maturation (IVM) of preantral mouse oocytes, in the absence of human chorionic gonadotrophin (hCG). Mouse preantral follicles were collected from female mice without prior hormonal ovarian stimulation and were cultured in the presence of varying concentrations of PRL (20, 100, 200, and 300 ng/mL) for 12 days. A group of in vitro matured oocytes were assessed for polar body (PB) formation, while the rest were fertilized and embryonic development was recorded. The maturation of preantral mouse follicles, as well as their fertilization and cleavage rates, observed when the culture medium was supplemented with middle- and high-range doses of PRL was beneficially affected. This effect was considerably high, although the culture media lacked hCG, a hormone extensively used in modern ovulation induction regiments, as well as in IVM media.

BACKGROUND: Diethylstilboestrol (DES) exposure in-utero has been shown to have negative effects on pregnancy. DES-exposed women are at increased risk of early spontaneous pregnancy loss, ectopic gestation and infertility. DESIGN: ` 34-year old woman with a 6-year history of primary infertility is presented. The patient underwent in vitro fertilization (IVF) treatment without success. To improve the quality of the endometrium following IVF treatment, E2 and progesterone supplementation was added to the usual therapeutic regimen. The pregnancy progressed uneventfully and a normal female was born. CONCLUSIONS: This case indicates that the administration of E2 and progesterone in DES-exposed women might improve endometrium receptivity and consequently pregnancy outcome.

OBJECTIVE A number of hormones and growth factors have been reported to affect the in vitro maturation of oocytes. Their exact effects on follicular growth and oocyte maturation and the mechanisms involved are still unclear. In the present study, we have investigated the effects of Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) on the in vitro maturation of mouse oocytes. DESIGN Immature preovulatory oocytes without cumulus cells (denuded), were obtained from 4- to 8-week old female mice and were cultured in Ham's F-10 medium. GH and IGF-1 were added separately or in combination in gradually increasing concentrations in the culture media, while medium-only containing samples were employed as controls. Oocyte development was assessed daily for three days and maturation was considered to be completed when the first polar body appeared. RESULTS In control samples, 44+/-3% (mean+/-SE) of denuded oocytes formed a polar body. The achieved maturation rate after the addition of either GH or IGF-1 or GH plus IGF-1 was significantly higher than in controls. The highest maturation rates were achieved after the addition of 0.2 microg/ml GH (76%+/-5%), 50 ng/ml IGF-1 (69%+/-5%) and a combination of 0.2 microg/ml GH plus 10 ng/ml IGF-1 (75%+/-5%). CONCLUSIONS The data suggest that GH and IGF-1, alone or in combination, affect mouse oocyte maturation significantly. The lack of a synergistic effect on oocyte cultures when both hormones were added indicates that both hormones act through the same signaling pathway.

Objective To assess the feasibility of examining cardiac and non-cardiac fetal anatomy in a low-risk population in the setting of the routine 11–14-week ultrasound scan. Methods This was a prospective study of 1144 women with viable, singleton pregnancies at 11–14 weeks of gestation. The ultrasound examination was performed transabdominally and transvaginally and fetal anatomy assessment included visualization of the skull, brain, face, spine, four-chamber and three-vessel views of the heart, stomach, abdominal wall, kidneys, bladder and extremities. Results Complete examination of the fetal anatomy was achieved in 48% of the fetuses, whereas non-cardiac anatomy was examined successfully in 86% of the fetuses. The use of the transvaginal approach increased successful examination of the fetal anatomy from 72% to 86% of the fetuses and transvaginal scanning was particularly helpful in examining the face, kidneys and bladder. Non-cardiac anatomy visualization increased from 65% for fetuses with a crown–rump length of 45–54 mm, to 84%, 93% and 96% for fetuses with a crown–rump length of 55–64 mm, 65–74 mm and more than 74 mm, respectively. In the same groups the four-chamber view was seen in 67%, 86%, 93% and 97% of fetuses, and the three-vessel view was seen in 25%, 46%, 58% and 67% of fetuses, respectively. Maternal habitus and crown–rump length were found to be statistically significant contributors to the rate of successful examination of fetal anatomy. Conclusion Examination of fetal anatomy is feasible during the routine 11–14-week scan. The optimal gestational age for examining both cardiac and non-cardiac anatomy is from the beginning of the 12th week to the end of the 13th week of gestation. Access to the transvaginal approach is important for completeness of the examination. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.

In triplet pregnancies, to compare pregnancy outcome of expectant management with that after embryo reduction to twins.Retrospective study of 255 trichorionic triplet pregnancies, of which 185 had embryo reduction to twins (reduced group) and 70 were managed expectantly (non-reduced group).Median birth weight was higher by about 500 g and gestation prolonged by about 3 weeks in the reduced pregnancies compared with the expectantly managed pregnancies (2300 vs. 1760 g; 36 vs. 33 weeks). The rates of preterm delivery were significantly lower in the reduced group (11.17 vs. 36.76% for delivery ator = 32 weeks and 40.58 vs. 83.82% for delivery ator = 35 weeks, reduced vs. non-reduced group). The percentage of infants born with low birth weight was significantly higher in the expectantly managed triplets (10.98 vs. 28.44% for birth weightor = 1500 g and 68.55 vs. 92.89% for birth weightor = 2500 g, reduced vs. non-reduced group). Total fetal loss was significantly higher in the reduced group than in the non-reduced group (15.41 and 4.76%, respectively) and the difference was mainly due to the higher miscarriage rate in the reduced group (8.11 vs. 2.86% in the non-reduced group). With the expected rates of handicap in preterm infants, we would anticipate 0.63% of severely handicapped children due to extreme prematurity in the reduced group and 1.64% in the non-reduced group.In triplet pregnancies, embryo reduction to twins significantly reduces the risk of severe preterm delivery and very low birth weight by about one-third, at the expense of a significant increase in total fetal loss, by about one-quarter. The procedure is likely to reduce the risk of having a severely handicapped child due to extreme prematurity.

The aim of the present study was to assess the fetal and maternal outcome in a cohort of patients with lupus nephritis. Twenty-four pregnancies in 22 women with lupus nephritis occurring between 1991 and 2000 were analysed retrospectively. Lupus nephritis was biopsy proven before pregnancy in all cases. Women were followed from the beginning of pregnancy up to 6 months postpartum. Close fetal-maternal monitoring and frequent laboratory investigations were applied routinely to all patients. All women were prescribed steroid therapy from the beginning of the pregnancy. There were 18 live births, four spontaneous abortions and two stillbirths. Of the 18 live births, 14 were premature and four were term deliveries, representing a 25% fetal loss rate and 58% prematurity rate. There were two fetuses with congenital heart block. We recorded hypertension in 42%, proteinuria in 50% and pre-eclampsia in 25% of our patients. Proteinuria was irreversible in four cases. No maternal deaths or postpartum exacerbation of the disease were recorded in the study period. All renal flares were reversed postpartum. Patients positive for antiphospholipid antibodies had a worse perinatal outcome. Hypertension, proteinuria and antiphospholipid antibodies appear to be associated with adverse perinatal outcome and pregnancy complications. Pregnancy is not contraindicated in women with lupus nephritis, but is associated with significant fetal and maternal risks.

Objective To study the impact of invasive procedures for prenatal diagnosis on multiple pregnancies and compare first-trimester chorionic villus sampling with second-trimester amniocentesis. Design Retrospective study of 347 second-trimester amniocenteses and 69 chorionic villus sampling procedures. Results Miscarriage occurred in 4.18% of women after amniocentesis and 4.54% of women after chorionic villus sampling. In the amniocentesis group the risk of miscarriage was higher in the cases with transplacental entry (4.54%) than in those with transamniotic entry (2.08%). The rates of preterm delivery ≤ 32 weeks and preterm delivery ≤ 35 weeks in the amniocentesis group were 11.8% and 32.4% and in the chorionic villus sampling group 16.66% and 23.8%, respectively. Total fetal loss rate was similar in the amniocentesis group (8.8%) and the chorionic villus sampling group (10.22%). In the 21 cases where selective feticide was carried out the total fetal loss rate was lower in the chorionic villus sampling group (8.3%) than in the amniocentesis group (11.1%), although the difference did not reach statistical significance. Conclusion Chorionic villus sampling appears to be a safe alternative to amniocentesis and should be considered as the method of choice particularly when there is a high risk of an affected fetus necessitating selective feticide. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology

Mesenchymal stem cells (MSCs) are a population of cells harboring in many tissues with the ability to differentiate toward many different lineages. Unraveling the molecular profile of MSCs is of great importance due to the fact that these cells are very often used in preclinical and clinical studies. We have previously reported the expression of insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) an oncofetal mRNA-binding protein-in different stem cell types such as bone marrow (BM)-MSC and umbilical cord blood (UCB)-hematopoietic stem cells. Here, we demonstrate that MSCs of adipose tissue, BM, and UC origin have a differential pattern of IGF2BP1 and ten-eleven-translocate 1/2 (TET1/2) expression that could correlate with their proliferation potential. Upon IGF2BP1 interference, a significant reduction of cell proliferation is observed, accompanied by reduced expression of c-MYC and GLI1 and increased p21. We also present, for the first time, evidence that IGF2BP1 is epigenetically regulated by TET1 and TET2 demethylases. Specifically, we show that TET1 directly binds to the promoter of IGF2BP1 gene and affects the hydroxymethylation status of its promoter. These results indicate that IGF2BP1 and TET1/2 contribute to the stemness of MSCs, at least regarding their proliferative potential.

MicroRNAs (miRNAs) have recently been shown to act as regulatory signals for maintaining stemness and for determining the fate of adult and fetal stem cells, such as human mesenchymal stem cells (hMSCs). hMSCs constitute a population of multipotent stem cells that can be expanded easily in culture and are able to differentiate into many lineages. We have isolated two subpopulations of fetal mesenchymal stem cells (MSCs) from amniotic fluid (AF) known as spindle-shaped (SS) and round-shaped (RS) cells and characterized them on the basis of their phenotypes, pluripotency, proliferation rates, and differentiation potentials. In this study, we analyzed the miRNA profile of MSCs derived from AF, bone marrow (BM), and umbilical cord blood (UCB). We initially identified 67 different miRNAs that were expressed in all three types of MSCs but at different levels, depending on the source. A more detailed analysis revealed that miR-21 was expressed at higher levels in RS-AF-MSCs and BM-MSCs compared with SS-AF-MSCs. We further demonstrated for the first time a direct interaction between miR-21 and the pluripotency marker Sox2. The induction of miR-21 strongly inhibited Sox2 expression in SS-AF-MSCs, resulting in reduced clonogenic and proliferative potential and cell cycle arrest. Strikingly, the opposite effect was observed upon miR-21 inhibition in RS-AF-MSCs and BM-MSCs, which led to an enhanced proliferation rate. Finally, miR-21 induction accelerated osteogenesis and impaired adipogenesis and chondrogenesis in SS-AF-MSCs. Therefore, these findings suggest that miR-21 might specifically function by regulating Sox2 expression in human MSCs and might also act as a key molecule determining MSC proliferation and differentiation.

Objective To evaluate the role of fetal blood sampling for prenatal diagnosis in twin pregnancies. Methods This was a retrospective study of 84 twin pregnancies that had undergone fetal blood sampling between the years 1977 and 2000. These results were compared with those from a similar study on amniocentesis and chorionic villus sampling. Results Miscarriage occurred in 3.6% of cases after fetal blood sampling. The total fetal loss rate was 13.6% and the fetal loss that could be attributed to the procedure was 8.2%. The procedure-related fetal loss rate was dependent on the indication for fetal blood sampling. The rates of preterm delivery at ≤ 32 weeks, preterm delivery at ≤ 35 weeks, perinatal mortality at ≤ 28 weeks, perinatal mortality at > 28 weeks and neonatal mortality were 16.9%, 28.3%, 10.9%, 3.1% and 7.7%, respectively. Conclusion Fetal blood sampling in twin pregnancies carries higher risks for the fetus than do amniocentesis and chorionic villus sampling. However, it remains useful in evaluating the fetal condition in special circumstances such as hydrops and infection. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

The aim of this study is to emphasize on the diagnostic effectiveness of fetal MRI that led to increased utilization in fetal medicine as well as its value in prognosis and decision making in the modern obstetric practice.One hundred five (n = 105) pregnant women were referred for a fetal MRI examination after a high detailed ultrasound examination revealed a fetal abnormality. Fetal MRI was performed using 1, 5 Tesla units, with T1, T2-weighted and diffusion-weighted images. The findings were analyzed in comparison to the previous ultrasound findings, according to the fetal organ affected and the value of the MRI for therapeutic decision making was addressed. A statistical analysis was performed.The fetal MRI provides a more accurate diagnosis compared to ultrasound examination, and when the ultrasound detects fetal anomalies, the MRI can efficiently either confirm or reject the finding, proving its high value for prenatal diagnosis and perinatal and management. The sensitivity, specificity and positive predictive value of fetal MRI as a screening tool approaches 100%.Despite the fact that ultrasound is the method of choice for fetal screening, MRI can add up significantly to the diagnosis and management of congenital abnormalities and the indications for MRI continue to increase as new sequences and shorter acquisition times evolve.

A nulliparous female of 22 years of age was admitted to the emergency department of Alexandra University Hospital because of severe vaginal haemorrhage. She reported to have fallen off a personal w...

Therapy for endometrial, ovarian and cervical cancer in young women can cause sudden onset of intense menopausal symptoms, such as hot flushes, emotional disorders and sexual dysfunction. In order to overcome these unpleasant and sometimes severe symptoms, hormone replacement therapy (HRT) has proven to be very effective. However, its safety remains controversial. We reviewed English literature and examined whether administration of HRT in this specific population is related with more recurrences and worse prognosis. Current scientific data, comprising mainly retrospective studies, suggest that recurrence rates and survival are comparable between HRT users and non-users. However, large randomised trials are missing and definitive conclusions cannot be drawn. Gynaecological cancer survivors using HRT, although they seem to have little if any risk for recurrence, should be correctly informed about the lack of strong evidence.

A 39-year-old Caucasian nulligravid woman presented to our Department of Obstetrics and Gynaecology for investigation of infertility. Her medical history was unremarkable apart from a mild hypothyr...

Aims The objective of this study was to validate four specific International Consultation on Incontinence Questionnaires (ICIQ) modules in the Greek language: (i) the ICIQ-FLUTS long form (ICIQ-FLUTS-LF), (ii) the ICIQ-FLUTS, (iii) the ICIQ-FLUTS-SEX, and (iv) the ICIQ-Vaginal Symptoms Questionnaire (ICIQ-VS), originally validated in English. Methods The English questionnaires were initially translated into Greek, then back-translated into English and final modifications were made after testing the questionnaires on a sample of patients. To validate the translated questionnaires, the following tests were undertaken: Content/face validity, internal consistency (reliability) and stability (testretest reliability). Results A total of 122 women participated in the study. Eighty-nine presented with pelvic organ prolapse (POP) and/or urinary incontinece (UI) symptoms and 33 attended an outpatient gynecological clinic without POP/UI symptoms. All modules showed excellent content/face validity (missing values 02.5%). Cronbach’s alpha test for internal consistency showed satisfactory to excellent reliability (0.876 for ICIQ-FLUTS-LF, 0.85 for ICIQ-FLUTS, and 0.83 for ICIQ-VS), with the exception ICIQ-FLUTS-SEX which was 0.69. The testretest reliability showed moderate to near-perfect agreement (weighted kappa value 0.520.99). Conclusions The Greek versions of the ICIQ-FLUTS-LF, ICIQ-FLUTS, and ICIQ-VS questionnaires were successfully validated. Our data showed that the ICIQ FLUTS-SEX questionnaire, as it stands in its current English version, cannot be reliably used to assess sex symptoms in the Greek female population. Neurourol. Urodynam. 31:11411144, 2012. (c) 2012 Wiley Periodicals, Inc.

Study Objective The purpose of this study was the recording of physical activity and sedentary habits of adolescents with polycystic ovarian syndrome (PCOS). Methods We performed a structured interview to assess the level of physical activity and sedentary habits of girls with PCOS. We used a group of healthy adolescents as controls. All girls had their age, height, weight, hip and waist circumference measured and their BMI calculated. Results 81 girls (35 with PCOS and 46 controls) participated in the study. Girls with PCOS engaged in physical activities less than controls. Even when they did, the frequency and intensity of exercise was less. Also, girls with PCOS were less likely to be aware of the positive effects of exercise on their health. Girls in both groups were sedentary in excess of the 4 hours per day limit, which has been linked with obesity. Conclusion Healthy teenagers were involved in a sporting activity more often and more frequently than the PCOS group. Athletic and sedentary habits of adolescents with PCOS may interact with other factors leading to obesity.

The objective of this study was to validate four specific International Consultation on Incontinence Questionnaires (ICIQ) modules in the Greek language: (i) the ICIQ-FLUTS long form (ICIQ-FLUTS-LF), (ii) the ICIQ-FLUTS, (iii) the ICIQ-FLUTS-SEX, and (iv) the ICIQ-Vaginal Symptoms Questionnaire (ICIQ-VS), originally validated in English.The English questionnaires were initially translated into Greek, then back-translated into English and final modifications were made after testing the questionnaires on a sample of patients. To validate the translated questionnaires, the following tests were undertaken: Content/face validity, internal consistency (reliability) and stability (test-retest reliability).A total of 122 women participated in the study. Eighty-nine presented with pelvic organ prolapse (POP) and/or urinary incontinence (UI) symptoms and 33 attended an outpatient gynecological clinic without POP/UI symptoms. All modules showed excellent content/face validity (missing values 0-2.5%). Cronbach's alpha test for internal consistency showed satisfactory to excellent reliability (0.876 for ICIQ-FLUTS-LF, 0.85 for ICIQ-FLUTS, and 0.83 for ICIQ-VS), with the exception ICIQ-FLUTS-SEX which was 0.69. The test-retest reliability showed moderate to near-perfect agreement (weighted kappa value 0.52-0.99).The Greek versions of the ICIQ-FLUTS-LF, ICIQ-FLUTS, and ICIQ-VS questionnaires were successfully validated. Our data showed that the ICIQ FLUTS-SEX questionnaire, as it stands in its current English version, cannot be reliably used to assess sex symptoms in the Greek female population.

Aim Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied. Patients and methods Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC–IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas. Results Median overall survival (OS) was 49 months for type I versus 45 for type II (p = 0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p = 0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information. Conclusion The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel.

Mesenchymal stem cells (MSCs) are a very important adult stem cell population with a multitude of potential applications in regenerative medicine. The thorough characterization of the bone marrow MSC (BM-MSC) population derived from the BALB/c species was essential, considering the significance of the murine model amongst animal models. In the present study, we examined the effect of gender, age, and in vitro culture on the basic properties (proliferation, differentiation, and immunosuppressive potential) of BM-MSCs. We found a decline in the progenitor frequencies from the BM of adult mice, lower MSC frequencies in all female donors, and an increase in the BM-MSC proliferation rate upon in vitro propagation. We also examined BM-MSCs for the expression of the 3 major embryonic stem cell transcription factors, Oct3/4, Sox-2, and Nanog, as well as 2 mRNA binding proteins, coding region determinant binding protein/insulin-like growth factor 2 mRNA binding protein 1 (Crd-bp/Imp1) and Deleted in azoospermia-like (Dazl), which are expressed in primitive stem cells, umbilical cord blood-hematopoietic stem cells and amniotic fluid stem cells, respectively. Further, it has been reported that these 2 genes are critical for embryonic development. In this study, therefore, we report, for the first time, the expression of Crd-bp/Imp1 and Dazl in BM-MSCs. Dazl, Oct3/4, and Sox2 were detected in relatively low levels in contrast to Crd-bp/Imp1, its major target c-Myc, as well as Nanog, which were expressed redundantly, irrespective of sex, donor age, or in vitro passaging. These findings could further support the extrinsic theory of aging of the MSC population and the potential implication of embryonic genes in adult stem cell physiology.

Surgical termination of pregnancy is of high risk for the woman's health and safe medical ways are required. The use of prostaglandins may substantially reduce this risk. The efficacy and safety of misoprostol as a medication for the termination of the second trimester pregnancies were studied. During a 15-month period ninety-eight healthy pregnant women (13-24 weeks) wishing to terminate their pregnancy due to medical reasons participated voluntarily in this study. Misoprostol was administered 400 microg per os and 400 microg vaginally. Dose was repeated every 6 hours until adequate contractions and cervical ripening were achieved. Outcome measures included successful termination rates, mean expulsion time and side effects of the medication. The efficacy of the method was as high as 91.8% (90/98 cases 95%, CI 86-97%). Mean expulsion time was 10.2 h (range 3-23.4 h) for primigravida and 9.2 h (range 2.5-22.2 h) for multigravida. In 9 cases (9.2%) placenta remnants and in 8 (8.2%) placenta retention were found. Most common side effect was shivering in 17.3% of cases, vomiting and nausea (10.2%), headache and dizziness (7.1%), abdominal pain (79.6%), while diarrhea was noticed in 4.1%. The high efficacy and low incidence of side effects make misoprostol a useful alternative method for medical termination of second trimester pregnancies.

The broad acceptance of prenatal diagnosis of various genetic diseases leads to an ever-increasing number of parturients with twin gestations undergoing selective feticide of an affected fetus. In most of the cases, delayed diagnosis leads to second trimester reduction. The aim of the present study was to investigate whether this procedure can be performed in the second trimester with results comparable to those obtained when it is performed in the first trimester. There was a 5.6% miscarriage rate in the group reduced in the first trimester (n=18, Group A) and an 8.3% miscarriage rate in the group reduced in the second trimester (n=48, Group B). The mean weight of neonates in the first group was 2780 g, and in the second group 2620 g. The mean gestational age at delivery was 36.7 weeks for Group A and 35.1 weeks for Group B. No significant differences were observed for any two-paired values considered. There was no perinatal mortality in either group. We therefore conclude that selective feticide of an affected fetus is as safe in the second trimester as it is in the first. Copyright © 2001 John Wiley & Sons, Ltd.

Human mesenchymal progenitor cells (MPCs) are considered to be of great promise for use in tissue repair and regenerative medicine. MPCs represent multipotent adherent cells, able to give rise to multiple mesenchymal lineages such as osteoblasts, adipocytes or chondrocytes. Recently, we identified and characterized human second trimester amniotic fluid (AF) as a novel source of MPCs. Herein, we found that early colonies of AF-MPCs consisted of two morphologically distinct adherent cell types, termed as spindle-shaped (SS) and round-shaped (RS). A detailed analysis of these two populations showed that SS-AF-MPCs expressed CD90 antigen in a higher level and exhibited a greater proliferation and differentiation potential. To characterize better the molecular identity of these two populations, we have generated a comparative proteomic map of SS-AF-MPCs and RS-AF-MPCs, identifying 25 differentially expressed proteins and 10 proteins uniquely expressed in RS-AF-MPCs. Furthermore, SS-AF-MPCs exhibited significantly higher migration ability on extracellular matrices, such as fibronectin and laminin in vitro, compared to RS-AF-MPCs and thus we further evaluated SS-AF-MPCs for potential use as therapeutic tools in vivo. Therefore, we tested whether GFP-lentiviral transduced SS-AF-MPCs retained their stem cell identity, proliferation and differentiation potential. GFP-SS-AF-MPCs were then successfully delivered into immunosuppressed mice, distributed in different tissues and survived longterm in vivo. In summary, these results demonstrated that AF-MPCs consisted of at least two different MPC populations. In addition, SS-AF-MPCs, isolated based on their colony morphology and CD90 expression, represented the only MPC population that can be expanded easily in culture and used as an efficient tool for future in vivo therapeutic applications.

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti-CD3 and IL-2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4-hr 51 Cr-release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose-dependent manner. Protein expression studies demonstrated that CD3 1 T cells express VEGFR-2 on their surface upon activation. Experiments with anti-VEGFR-2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR-2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2. Angiogenesis is a fundamental process required for a number of pathophysiological processes, including cancer growth. The dynamic process of angiogenesis is highly regulated by a number of proangiogenic and antiangiogenic molecules. In

The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked recessive genetic disorder (Lowe et al. 1952). A hallmark of the syndrome is the prenatal development of congenital cataract. Additi...

A 15-year-old girl presented with mild to moderate hirsutism and among other investigations, had an ultrasound scan of her pelvis in order to rule out the presence of polycystic ovaries. During exa...

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans, the major proteoglycans in the extracellular matrix and cell surfaces. Traditionally, heparanase activity was implicated in cellular invasion associated with angiogenesis, inflammation, and cancer metastasis. More recently, heparanase up-regulation was documented in an increasing number of primary human tumors. Ιn this study, we sought to investigate the expression of heparanase messenger RNA (mRNA) in normal cervical tissue and intraepithelial cervical lesion and its clinicopathologic importance in invasive cervical cancer. Gene expression of heparanase was assessed by quantitative real-time reverse transcriptase polymerase chain reaction in 28 normal cervical, 26 intraepithelial neoplastic, and 48 cervical cancer tissue samples. Heparanase mRNA expression was different between the 3 groups and lower in normal cervical specimens in relationship with intraepithelial cervical lesions and invasive cervical cancer tissue samples (P= 0.048). Gradually increasing expression of heparanase was evident as the cells progressed from low-grade to high-grade squamous intraepithelial lesions (P= 0.002). In invasive cervical cancer cases, there was a direct correlation between heparanase expression and tumor size (P= 0.002). In cases treated with radical hysterectomy and pelvic lymphadenectomy, the heparanase mRNA expression was significantly higher in tumors exhibiting lymph vascular space invasion (P= 0.044) and in cases with big tumor size (P= 0.005). In our study, we did not find any significant correlation between disease-free and overall survival rates and expression of heparanase (P= 0.396 andP= 0.712, respectively). The results of this study suggest that the gene expression of heparanase in cervical cancer enhances growth, invasion, and angiogenesis of the tumor and may have therapeutic applications.

Corifollitropin alfa is being developed by Schering-Plough Corp as an injectable, long-acting follicle-stimulating hormone (FSH) agonist for the treatment of infertility. A single dose of corifollitropin alfa could initiate and sustain multifollicular growth in patients undergoing controlled ovarian stimulation, such as during in vitro fertilization or intracytoplasmic sperm injection. The agent comprises an alpha-subunit, which is identical to that of FSH, and a beta-subunit, which is produced by the fusion of the C-terminal peptide from the beta-subunit of chorionic gonadotropin to the beta-subunit of FSH. Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing. The drug was well tolerated and does not appear to be associated with any serious adverse events or the formation of antibodies. The initial results from a large, phase III, double-blind clinical trial indicated that the ongoing pregnancy rate achieved with corifollitropin alfa treatment was high and similar to the rate established with daily treatment of recombinant FSH. The number of oocytes retrieved following the administration of corifollitropin alfa was slightly higher compared with the number observed with daily recombinant FSH treatment. Thus, corifollitropin alfa has the potential to serve as a viable fertility agent and to gain a place in the infertility market.

Henoch-Schonlein purpura (HSP) is a hypersensitivity vasculitis. This is a case report of HSP during pregnancy and a review of the literature in this rare pregnant disease. We present a case of a 32-year-old woman with HSP. Treatment with low-dose oral corticosteroids was administered leading to a beneficial outcome for the fetus and the mother. Henoch-Schonlein purpura is the most common connective tissue disorder of children. It is rarely reported in adults. Only 16 cases of HSP during pregnancy have been described in the literature worldwide, and this is the 17th reported case.

The aim of the study was to determine the incidence and outcome of cervical intraepithelial neoplasia (CIN) in Greek young women. A retrospective analysis was conducted of women aged 16 - 20 years with a histological diagnosis of CIN during the years 1999-2005. Management was individualised for each case. The rates of regression, persistence and progression were measured. A total of 80 adolescents were identified. Some 54 patients (67.5%) had CIN1 and 26 (32.5%) had CIN2/3. Regression of the CIN1 lesions expressed as negative cytological or histological follow-up was observed in 74% and 93% of the patients at 12 and 24 months, respectively. The majority of adolescents (92%) with CIN2/3 underwent conisation and in 79% of them, histology of the specimen confirmed the initial diagnosis. CIN1 lesions will most likely regress over a 2-year period following diagnosis in women aged 16 - 20 years. Nevertheless, close monitoring is mandatory, as 10 - 15% of these lesions will either persist or progress to high-grade CIN. Management for adolescents with high-grade CIN lesions should be individualised according to a variety of parameters and adjusted to the patients' safety.

Human oocyte maturation is a long process during which nuclear maturation occurs resulting in germinal vesicle breakdown (transition from prophase I to metaphase II) and extrusion of the first polar body. During oocyte maturation, in parallel with nuclear maturation, a number of events take place in the oocyte cytoplasm that assist fertilization and early embryonic development. So far several attempts have been made to mature human oocytes in vitro. The main patient group to which in vitro maturation (IVM) has been applied is polycystic ovarian syndrome. In a concise review we present the techniques used for the IVM of oocytes and the role of hormones and growth factors in IVM and subsequent fertilization and early embryonic development.

Objectives Tumor infiltrating lymphocytes (TILs) and T regulatory cells (Tregs) have been associated with prognosis in ovarian cancer, but their prognostic significance in ascites has not been studied. We performed a prospective study of T lymphocytes isolated from ascites from patients with ovarian carcinoma and we compared them with the respective populations in blood and tumors. Methods Mononuclear cells from ascites ( n =71) and blood were isolated by Ficoll, while tumor lymphocytes ( n =20) were obtained upon mechanical dissociation. Phenotypic analysis was performed with flow cytometry. Ascites from 10 patients with cirrhosis was used as control. Results Tregs containing CD4 + CD25 + cells, NK-T containing CD3 + CD56 + cells and CD69 and HLADR expression of CD4 and CD8 lymphocytes were significantly increased in tumor ascites compared to blood and control ascites. A selective accumulation of these populations in the ascites of cancer patients, was suggested by the significantly higher ascites/blood (A/B) ratios in cancer patients but not controls. Cancer cell content in ascites was correlated with CD4 + CD25 + , CD4 + CD69 + , CD4 + HLADR + and CD8 + CD69 + cells. There was no correlation of lymphocyte populations between ascites and samples from peritoneal metastases. Higher tumor grade was associated with increased A/B CD4 + CD25 + ratio and reduced CD3 + CD56 + cells, while platinum resistance was associated with reduced A/B CD3 + CD56 + ratio. Conclusions There are significant differences of CD3 + CD56 + and CD25 + CD4 + lymphocytes and increase in lymphocyte activation between blood, ascites and peritoneal metastases from patients with ovarian cancer. The selective accumulation of CD3 + CD56 + population in ascites may be a predictive factor for platinum resistance.