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George Creatsas - Top 30 Publications

Assessment of bone metabolism and biomechanical properties of the femur, following treatment with anastrozole and letrozole in an experimental model of menopause.

The aim of the present study was to investigate the impact of anastrozole and letrozole supplementation following surgically induced menopause on bone metabolism and biomechanical properties. A total of 45 Wistar rats underwent ovariectomy and were then randomly allocated to receive no treatment, anastrozole or letrozole. At 2 and 4 months following the initiation of the present study, the serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined, and the animals were sacrificed at the end of the 4-month period to assess the biomechanical properties of the femoral bones. The applied force and the deflection of the central section were recorded during the test. Taking advantage of these quantities, the fracture force, the stiffness of the bone and the energy absorbed until fracture were determined. At 2 months following the initiation of the experimental protocol, the mean OPG levels were significantly increased in the control group compared with the anastrozole-treated group (P<0.01). Similarly, RANKL levels were significantly increased in the control rats compared with the anastrozole-treated animals (P<0.001) and animals that received letrozole (P<0.05). Notably, these trends were not observed at the end of the experiment (4 months). A biomechanical study of the femoral bones revealed significantly decreased stiffness among animals that received anastrozole (P<0.05) and letrozole (P<0.01) compared with their control counterparts. The results of the present study indicate that treatment with anastrozole and letrozole significantly increases the levels of OPG and RANKL in bone, an effect that appears to be directly associated with the biomechanical properties of bones.

Polymorphisms of Platelet Glycoprotein Receptors and Cell Adhesion Molecules in Fetuses with Fetal Growth Restriction and Their Mothers As Detected with Pyrosequencing.

Vascular thrombotic tendency may lead to fetal growth restriction (FGR). Altered platelet function and genetic heterogeneity may play a role in this procedure. We investigated whether maternal or fetal genotypic frequencies of genes polymorphisms for certain platelet receptor and cell adhesion molecules are altered in FGR.

mTOR downstream effectors, 4EBP1 and eIF4E, are overexpressed and associated with HPV status in precancerous lesions and carcinomas of the uterine cervix.

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.

Chlamydia trachomatis infection and Vγ9Vδ2 Τ cells in women with recurrent spontaneous abortions.

Vγ9Vδ2 T cells (γ9δ2) are involved in antibacterial immune responses. The aim of this study was to look for associations between peripheral blood (PB) γ9δ2 T cells and cervix/vaginal Chlamydia trachomatis (Ct) infection in women with recurrent spontaneous abortions (RSA).

Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome.

Primary amenorrhea, oligomenorrhea and secondary amenorrhea are diagnosed commonly during adolescence. Weight aberrations are associated with menstrual disorders. Autoimmune thyroiditis is frequent during adolescence. In this study, the commonest clinical and hormonal characteristics of amenorrhea or oligomenorrhea during adolescence were investigated.

The impact of Anastrazole and Letrozole on the metabolic profile in an experimental animal model.

Anastrazole and Letrozole are used as endocrine therapy for breast cancer patients. Previous studies suggested a possible association with metabolic and liver adverse effects. Their results are conflicting. Fifty-five 4-week-old female Wistar rats were allocated in 4 groups 1) ovariectomy control (OC), 2) ovariectomy-Anastrazole (OA) 3) ovariectomy -Letrozole (OL), 4) control. Serum glucose, cholesterol, triglycerides, HDL-c and LDL-c were measured at baseline, 2 and 4 months. At the end, the animals' liver were dissected for pathology. At 4 months, total cholesterol differed among the OC and OL groups (p = 0.15) and the control and OL groups (p = 0.12). LDL-C differed between the control and OC groups (p = 0.015) as well as between the control and OA (p =0 .015) and OL groups (p = 0.002). OC group triglycerides, differed from those of the OL group (p =0 .002) and the control group (p = 0.007). The OA also significantly differed from the OL (p = 0.50). Liver pathology analysis revealed differences among groups with favored mild steatosis and ballooning. Anastrazole and Letrozole seem to negatively influence the lipid profile in our experimental model. This information should be taken in caution by medical oncologists when addressing patients with altered lipid metabolism.

Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives.

Diabetes mellitus, the prevalence of which has increased dramatically worldwide, may put patients at a higher risk of cancer. The aim of our study is the clarification of the possible mechanisms linking diabetes mellitus and gynecological cancer and their epidemiological relationship.

Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins.

Callo: The first known case of ambiguous genitalia to be surgically repaired in the history of Medicine, described by Diodorus Siculus.

Dehydroepiandrosterone administration before IVF in poor responders: a prospective cohort study.

The use of dehydroepiandrosterone (DHEA) may improve ovarian stimulation outcomes in women of advanced reproductive age and could reduce embryo aneuploidy. In this prospective study, 48 women diagnosed with poor ovarian response received DHEA supplementation for at least 12 weeks. These women were compared with a group of poor responders (n = 113) who did not receive supplementation. During the study period, patients taking day 2 FSH and oestradiol were measured monthly before and after treatment. Stimulation characteristics, stimulation outcome and clinical outcome (clinical pregnancy and live birth rates) were reported. Evaluation of anti-Müllerian hormone (AMH) was carried out before initiation of treatment and immediately before the subsequent stimulation. Supplementation with DHEA for at least 12 weeks resulted in a modest, but statistically significant, increase in AMH levels and decrease in baseline FSH (P < 0.001 and P = 0.007, respectively). Administration of DHEA had no effect on any of the stimulation parameters nor was there any difference in clinical pregnancy rates and live birth rates between the two groups. Supplementation with DHEA significantly affects women with poor prognosis undergoing ovarian stimulation for IVF. Patients should be counselled about the uncertain effectiveness, potential side-effects and cost of this treatment.

Oocyte and embryo vitrification in the IVF laboratory: a comprehensive review.

Vitrification is an excellent tool in the IVF laboratory, enabling options and offering flexibility in assisted reproduction. The technology of cryopreservation has been underway since the early 20th century. The advent of vitrification has advanced the expectations in routine clinical practice in the IVF laboratory presenting impressive results both in post-thaw survival, and in clinical pregnancy rates, as well as significantly enhancing clinical results on preimplantation genetic diagnosis (PGD). Contradicting opinions have been published recently on the limitations and potential that vitrification has in the laboratory, as well as on the optimal approach to employ vitrification in IVF. This review aims to present a comprehensive analysis of the practical aspects of vitrification including concerns and options regarding its use on oocytes and embryos while comparing it with the traditional "slow-freezing" cryopreservation technique.

Neonatal birth waist is positively predicted by second trimester maternal active ghrelin, a pro-appetite hormone, and negatively associated with third trimester maternal leptin, a pro-satiety hormone.

In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energy intake for the mother and for the fetus. The role of maternal appetite-related peptides and their possible association with neonatal energy stores and glucose metabolism have not been investigated as yet. The aim was to investigate, during pregnancy, the association of fasting maternal appetite-related hormones levels [ghrelin (active), GLP1 (active), total PYY and leptin] with neonatal waist, percent total body fat and insulin levels at birth.

Experiencing sexuality in youth living in Greece: contraceptive practices, risk taking, and psychosocial status.

To assess initiation of sexual activity and contraception methods used among Greek adolescents. To determine the association of adolescents' emotional and behavioral status with their sexual activity.

Effect of a low dose combined oral contraceptive pill on the hormonal profile and cycle outcome following COS with a GnRH antagonist protocol in women over 35 years old.

This prospective study examines if pre-treatment with two different doses of an oral contraceptive pill (OCP) modifies significantly the hormonal profile and/or the IVF/ICSI outcome following COS with a GnRH antagonist protocol. Infertile patients were allocated to receive either OCP containing 0.03 mg of ethinylestradiol and 3 mg of drospirenone, or OCP containing 0.02 mg of ethinylestradiol and 3 mg of drospirenone prior to initiation of controlled ovarian stimulation (COS) with recombinant gonadotropins on a variable multi-dose antagonist protocol (Ganirelix), while the control group underwent COS without OCP pretreatment. Lower dose OCP was associated with recovery of FSH on day 3 instead of day 5, but the synchronization of the follicular cohort, the number of retrieved oocytes and the clinical pregnancy rate were similar to higher dose OCP.

The effect of hormone therapy on biochemical and ultrasound parameters associated with atherosclerosis in 46,XY DSD individuals with female phenotype.

The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2 mg 17β-estradiol/1 mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC), LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow-mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT raised HDL (35.4 mg/dl versus 40.1 mg/dl, p = 0.019) while lowering TG (166 mg/dl versus 109 mg/dl, p = 0.026) and AIP (0.24 versus 0.04, p = 0.007). No changes were noted in TC and LDL (215.7 mg/dl versus 192.25 mg/dl and 87.46 mg/dl versus 76.35 mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05 ng/ml versus 2.20 ng/ml, p = 0.002) and E-selectin (73.98 ng/ml versus 56.73 ng/ml, p = 0.004). No change was observed in Thrombomodulin and vWf (11.76 ng/ml versus 13.90 ng/ml and 80.75% versus 79.55%, respectively). FMD improved significantly (5.4% versus 8.15%, p = 0.003), while only carotid bulb IMT decreased significantly (0.65 mm versus 0.60 mm, p = 0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.

Application of Creatsas vaginoplasty after radical surgical treatment of sarcoma botryoides.

Sarcoma botryoides of the female genital tract is a rare malignancy. For many years, treatment consisted of radical procedures involving removal of the vagina, cervix, and uterus. Reconstructive surgery is essential for these patients, in order to achieve vaginal penetrative sexual intercourse.

Gynecological care in young women: a high-risk period of life.

Adolescence has been described as period of life when emotions are heightened and regulatory controls are reduced, and this can result in an escalation in risk-taking. Importantly for younger females, risk behaviors associated with the onset of sexual activity, and alcohol and substance abuse may coincide with pathologies such as polycystic ovary syndrome (PCOS) and abnormal uterine bleeding, an iron-deficient diet (vegetarian or vegan) and a negative body image leading to eating disorders. Girls transitioning through adolescence face a number of specific emotional and physical issues related to the onset of menarche and regular menstrual cycles. Menstruation combined with these risk behaviors and pathologies, and the rapid growth and development that is taking place, often results in numerous unwanted effects including iron deficiency. A low iron level is the most common cause of anemia in adolescent girls and can be detrimental to mood and cognition as well as physical well-being. In this article we review the impact of menarche, poor nutrition and some of the risk behaviors and pathologies that predispose females to challenges associated with adolescence, including anemia. We also examine factors that need to be taken into consideration during the initial, and follow-up, consultations with young women. Finally, we present some of the latest advice regarding nutrition and oral iron supplementation, particularly extended-release ferrous sulfate with mucoproteose, with a view to minimizing the development and risks of anemia in this vulnerable population.

First trimester maternal BMI is a positive predictor of cord blood c-peptide levels while maternal visfatin levels is a negative predictor of birth weight.

The role of first trimester maternal body mass index (BMI) and adipocytokines in cord blood c-peptide and birth weight in pregnancy was investigated.

Role of coagulation factor XII in unexplained recurrent abortions in the Greek population.

To investigate the prevalence and clinical significance of congenital factor XII (FXII) deficiency in the South-European Caucasian (Greek) population in a cohort of women with recurrent spontaneous abortions (RSAs).

Greece's birth rates and the economic crisis.

Primary amenorrhea in adolescent girls: normal coitus or not? Always take a look in the physician's office.

Primary care physicians are frequently faced with the challenge of evaluating primary amenorrhea in adolescent girls. Approximately 15% of these women have abnormal genital examination, with Müllerian agenesis being the second most frequent cause. We report two cases of adolescents with Müllerian agenesis that presented to a tertiary adolescent medicine center with primary amenorrhea and the very rare sexual phenomenon of urethral coitus. The aim of this report is to emphasize the importance of performing a genital examination in girls who present with amenorrhea in the primary care setting, even if 'normal' vaginal sexual activity is assumed.

The effect of Soranus of Ephesus (98-138) on the work of midwives.

In the Roman period, midwives continued to play an important role in female health care primarily in the attendance of women birth. In the second century AD, midwives' education received a significant boost thanks to the distinguished physician Soranus of Ephesus.

HPV infection: immunological aspects and their utility in future therapy.

High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, and alterations in the microenvironment of the lesion. Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans cells fail to present the antigens efficiently, tumor-associated macrophages aggregate resulting in an unsuccessful immune response by the host. HPV products also downregulate the expression of microenvironment components which are necessary for natural-killer cells response and antigen presentation to cytotoxic cells. Additionally HPV promotes T-helper cell 2 (Th2) and T-regulatory cell phenotypes and reduces Th1 phenotype, leading to suppression of cellular immunity and lesion progression to cancer. Humoral response after natural infection is inefficient, and neutralizing antibodies are not adequate in many women. Utilizing this knowledge, new endeavors, such as therapeutic vaccination, aim to stimulate cellular immune response against the virus and alter the milieu of the lesion.

Continuous versus cyclic use of oral contraceptives after surgery for symptomatic endometriosis: a prospective cohort study.

To evaluate the efficacy of continuous oral contraceptive (OC) use versus the usual cyclic fashion in the recurrence of endometriosis-related symptoms after surgery.

Pulsatile interleukin-6 leads CRH secretion and is associated with myometrial contractility during the active phase of term human labor.

Our objective was to investigate IL-6 and CRH secretion during the active phase of human labor and to define their potential involvement in myometrial contractility.

Bakri balloon tamponade for the management of postpartum hemorrhage.

Osteoprotegerin as a marker of atherosclerosis in diabetic patients.

Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients.

PON1-108 TT and PON1-192 RR genotypes are more frequently encountered in Greek PCOS than non-PCOS women, and are associated with hyperandrogenaemia.

To investigate the frequencies of three paraoxonase (PON)1 polymorphisms in Greek polycystic ovary syndrome (PCOS) and non-PCOS women, and their genotypes association with hyperandrogenaemia and insulin resistance.

Cabergoline as treatment of ovarian hyperstimulation syndrome: a review.

One of the most serious complications of assisted reproduction techniques is ovarian hyperstimulation syndrome (OHSS). OHSS not only increases morbidity and mortality in IFV cycles, but also causes significant other problems, as cancelled in vitro fertilization (IVF) cycles, prolonged hospitalization, causing emotional and sociofinancial consequences. Several treatments for OHSS have been proposed and among these Cabergoline (Cb2). Despite the above-mentioned beneficial effect, Cb2 has not been widely used in everyday's clinical practice. With our study, we try to review all studies with strong evidence examining Cb2 use for OHSS prevention.

Study of carbohydrate metabolism indices and adipocytokine profile and their relationship with androgens in polycystic ovary syndrome after menopause.

Hyperandrogenism, insulin resistance, and altered adipocytokine levels characterize polycystic ovary syndrome (PCOS) women of reproductive age. Hyperandrogenism persists in postmenopausal PCOS women. In the latter, this study aimed at investigating carbohydrate metabolism, adipocytokines, androgens, and their relationships.