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Charalambos Siristatidis - Top 30 Publications

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.

Zooming in on the definition of 'recurrent implantation failure'.

Reproducibility study of fetal 3-D volumetry in the first trimester: effect of fetal size and rotational angle of VOCAL software.

Intra- and inter-observer reproducibility of fetal volume measurement by 3-D ultrasound scan (using VOCAL [Virtual Organ Computer-Aided Analysis] software) in 27 fetuses at 7 to 13 wk was studied. For intra-observer variability, the mean difference (MD) and 95% limits of agreement (95% LOA) at 12°, 18° and 30° were MD(12) = 0.097, 95% LOA(12) = -0.87 to +1.06; MD(18) = 0.07, 95% LOA(18) = -1.31 to +1.45; and MD(30) = -0.07, 95% LOA(30) = -1.55 to +1.41. The standard deviation of the differences (SD(DIF)) increased with crown-rump length at 12° (p = 0.0016), 18° (p = 0.0011) and 30° (p = 0.02). For inter-observer variability, MD(12) = 0.15, 95% LOA(12) = -1.65 to +1.95; MD(18) = 0.042, 95% LOA(18) = -1.79 to +1.87; and MD(30) = 0.19, 95% LOA(30) = -1.24 to +1.62. SDDIF increased with crown-rump length at 18° (p = 0.0084) and 30° (p = 0.0073). The accuracy of fetal volume measurement was not influenced by rotational angle or fetal size. Precision deteriorated for wider rotational angles and larger fetuses.

Fetal volume at 11-14 gestational weeks: reference ranges and association with first trimester biochemical and biophysical markers.

To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11-14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters.

Monocyte function in the fetus and the preterm neonate: immaturity combined with functional impairment.

It is well known that the innate immunity system, involving the contribution of monocytes and macrophages, may dysfunction in fetuses and preterm neonates. Monocytes are capable of differentiating into dendritic cells (DCs) or into mucosal macrophages during certain infections and of producing inflammatory mediators such as TNF- α (tumor necrosis factor-alpha), nitric oxide, and reactive oxygen species. Fetuses as well as neonates are prone to infections as a result of a defective mechanism within the above mononuclear system. Monocyte function in fetuses and preterm neonates depends on the phagocytic and oxidative capacity of macrophages and their antigen-adhesion ability. Functional rather than anatomical impairment is probably the underlying cause, while a defective production of cytokines, such as TNF-α , IL-6 (Interleukin 6), IL-1β (Interleukin 1 beta), and G-CSF (Granulocyte Colony-Stimulating Factor), has also been involved. The insufficient production of the above inflammatory mediators and the phenomenon of endotoxin intolerance, which latter occurs during entry of any antigen into the premature neonate, place preterm neonates at higher risk for infections. Existing research data are herein presented which, however, are deficient and fragmental, this accounting for the fact that the precise pathophysiology of these disturbances is not yet fully clarified.

Acute lung injury in preterm fetuses and neonates: mechanisms and molecular pathways.

Acute lung injury (ALI) results in high morbidity and mortality among preterm neonates and efforts have therefore been devoted to both antenatal and postnatal prevention of the disease. ALI is the result of an inflammatory response which is triggered by a variety of different mechanisms. It mostly affects the fetal lung and, in particular, causes damage to the integrity of the lung's alveolar-capillary unit while weakening its cellular linings. Chemotactic activity and inflammatory products, such as proinflammatory cytokines TNF-α, IL-1, IL-6, IL-11, VEGF,TGF-α and TGF-β, provoke serious damage to the capillary endothelium and the alveolar epithelium, resulting in hyaline membrane formation and leakage of protein-rich edema fluid into the alveoli. Chorioamnionitis plays a major part in triggering fetal lung inflammation, while mechanical ventilation, the application of which is frequently necessary in preterm neonates, also causes ALI by inducing proinflammatory cytokines. Many different ventilation-strategies have been developed in order to reduce potential lung injury. Furthermore, tissue injury may occur as a result of injurious oxygen by-products (Reactive Oxygen Species, ROS), secondary to hyperoxia. Knowledge of the inflammatory pathways that connect intra-amniotic inflammation and ALI can lead to the formulation of novel interventional procedures. Future research should concentrate on the pathophysiology of ALI in preterm neonates and οn possible pharmaceutical interventions targeting prevention and/or resolution of ALI.

Impact of maternal diabetes on epigenetic modifications leading to diseases in the offspring.

Gestational diabetes, occurring during the hyperglycemic period of pregnancy in maternal life, is a pathologic state that increases the incidence of complications in both mother and fetus. Offspring thus exposed to an adverse fetal and early postnatal environment may manifest increased susceptibility to a number of chronic diseases later in life. Compelling evidence for the role of epigenetic transmission in these complications has come from comparison of siblings born before and after the development of maternal diabetes, exposure to this intrauterine diabetic environment being shown to cause alterations in fetal growth patterns which predispose these infants to developing overweight and obesity later in life. Diabetes of the offspring is also mainly the consequence of exposure to the diabetic intrauterine environment, in addition to genetic susceptibility. Since obesity and diabetes are known to increase the risk of cardiovascular disease, cardiovascular sequelae in the offspring of diabetic mothers are virtually inevitable. Research data also suggest that exposure to a diabetic intrauterine environment during pregnancy is associated with an increase in dyslipidemia, subclinical vascular inflammation, and endothelial dysfunction processes in the offspring, all of which are linked with development of cardiovascular disease later in life. The main underlying mechanisms involve persistent hyperglycemia hyperinsulinemia and leptin resistance.

Review: Impact of mediators present in amniotic fluid on preterm labour.

Preterm birth continues to be one of the most important issues in current obstetric medicine, being the single largest cause of perinatal morbidity and mortality. The signals that initiate preterm and term labour remain a mystery. Intrauterine inflammation with the secretion of cytokines is one of the accepted explanations for the mechanism of initiation of preterm labour. This review discusses the current understanding of the molecular mechanisms for the initiation of preterm labour, focusing chiefly on the role of intra-amniotic fluid mediators, whether endogenous or infection-induced, in the regulation of inflammatory response pathways associated with spontaneous preterm labour. Prostaglandins (PGs) are considered to be one of the key mediators of preterm labour, with the concentration of biologically active PGs in the amniotic fluid, particularly PGE(2) and PGF(2α), being significantly higher in women with preterm labour. Cytokines, such as interleukins and tumour necrosis factor alpha, additionally play a dominant role in preterm labour, particularly in association with infection. Elevated amniotic fluid concentrations of extracellular matrix mediators, including metalloproteases, are also implicated in the process of foetal membrane rupture in preterm labour. Allelic variations in the main amniotic fluid mediators may be the key to understanding the disparity in the rates of preterm birth between different ethnic populations. We also discuss the role of other potential mediators such as cell-adhesion molecules, nitric oxide and novel biomarkers found in the amniotic fluid.

Interval routine appendectomy following conservative treatment of acute appendicitis: Is it really needed.

Conservative management of acute appendicitis (AA) is gradually being adopted as a valuable therapeutic choice in the treatment of selected patients with AA. This approach is based on the results of many recent studies indicating that it is a valuable and effective alternative to routine emergency appendectomy. Existing data do not support routine interval appendectomy following successful conservative management of AA; indeed, the risk of recurrence is low. Moreover, recurrences usually exhibit a milder clinical course compared to the first episode of AA. The role of routine interval appendectomy is also questioned recently, even in patients with AA complicated by plastron or localized abscess formation. Surgical judgment is required to avoid misdiagnosis when selecting a conservative approach in patients with a presumed "appendiceal" mass.

Role of adipokines and other inflammatory mediators in gestational diabetes mellitus and previous gestational diabetes mellitus.

Previous Gestational Diabetes Mellitus (pGDM) is a common condition and has been associated with future development of Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MS) in women affected. The pathogenesis and risk factors implicated in the development of these conditions later in the lives of women with pGDM are not as yet fully understood. Research has recently focused on a group of substances produced mainly by adipose tissue called adipokines, this group including, among others, adiponectin, leptin, Retinol-Binding Protein-4 (RBP-4), and resistin. These substances as well as other inflammatory mediators (CRP, IL-6, PAI-1, TNF-α) seem to play an important role in glucose tolerance and insulin sensitivity dysregulation in women with pGDM. We summarize the data available on the role of these molecules.

Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction.

Gonadotrophin-releasing hormone agonists (GnRHa) are used in assisted reproduction technology (ART) cycles to prevent a luteinizing hormone surge. Various protocols have been described in the literature, such as long protocols (continuous and stop or reduce dose, long luteal, or long follicular protocol); short protocols and ultrashort protocols.

Aspirin for in vitro fertilisation.

Aspirin is used to improve the outcome in women undergoing in vitro fertilisation despite inconsistent evidence of its efficacy. The most appropriate time to commence aspirin therapy and the length of treatment required are also still to be determined. This is an update of the review first published in 2007.

Office hysteroscopy: current trends and potential applications: a critical review.

Office hysteroscopy is an excellent method of identifying and treating intracavitary uterine lesions. It has become easy to learn and perform; as an aid of modern technological applications, it is safe, accurate, provides immediate results under direct visualisation, and offers the additional benefit of histological confirmation and the discomfort of patients is minimal. We applied an extended literature search to explore the special features and details of the technique itself, as it evolved since it first appeared 30 years back. Our initial goal was to examine potential changes/improvements of the modality, in terms of the instrumentation used and the technique itself, the indications of use, its incorporation in daily practice, and patients' and clinicians' acceptability.

In vitro maturation in sub fertile women with polycystic ovarian syndrome undergoing assisted reproduction.

Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of reproductive age and 20% of women presenting with sub-fertility. A significant proportion of these women will ultimately need assisted reproductive techniques (ART). In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome. A potentially useful intervention for women with PCOS-related infertility involves earlier retrieval of immature oocytes followed by in vitro maturation (IVM).

Wavelet analysis and neural networks for intrapartum fetal monitoring. Can we long for a new technique? Is it doable?

Unexplained infertility: does it really exist? Does it matter?

Unexplained infertility (UI) refers to a diagnosis made in couples in whom standard investigations including semen analysis, tests of ovulation and tubal patency are normal. It has been suggested that the term UI is unsustainable, as conditions such as endometriosis, tubal infertility, premature ovarian ageing and immunological infertility tend to be misdiagnosed as UI. In this debate, we present the view that, although scientifically unsatisfying, the diagnosis of UI is sustainable from a clinical and practical perspective. Given our present treatment options, further investigations leading to a more 'accurate' diagnosis is unlikely to change our management in these cases. Scientific curiosity must take second place to a more pragmatic approach, which takes into account the clinical and financial costs of making a more 'accurate' diagnosis.

Continuous combined replacement therapy in postmenopausal women: effect on plasma lipoproteins, bone mass and the endometrium.

The purpose of this study was to examine the effects of Hormone Replacement Therapy (HRT) on plasma lipoprotein levels, bone mass and the endometrium.

Immunological factors and their role in the genesis and development of endometriosis.

The article presents an overview of immunological factors and their role in the genesis and development of endometriosis, with emphasis on inflammatory cytokines and growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women with retrograde menstruation suffer the disease. Development of endometriosis seems to be a complex process, facilitated by several factors, including quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies, upregulated during development of endometriosis, seem useful in the development of a non-surgical diagnostic tool. In this review work, the immune role in endometriosis is examined through the role of immunological factors in the genesis and development of the disease. Furthermore, it could be concluded that, although endometriosis can be treated using hormonal suppression, there is a need today for non-hormonal drugs, probably to modulate immune function, in order to confront the disease and alleviate pain or infertility without inhibition of ovulation.

Fetal pulse oximetry and wavelet analysis of the fetal heart rate in the evaluation of abnormal cardiotocography tracings.

Previous studies indicate that the addition of wavelet analysis of the fetal pulse oximetry tracings (FSPO2) and fetal heart rate (FHR) variability to cardiotocography (CTG), for intrapartum fetal monitoring, provides useful information on the fetal response to hypoxia. We applied the new procedure in non-reassuring CTG patterns, in which cesarean section was performed, and tested its accuracy in the diagnosis of the intrapartum fetal compromise.

Hormonal alterations in gum disease leading to preterm labor.

Alterations in Doppler velocimetry indices of the umbilical artery during fetal hypoxia in labor, in relation to cardiotocography and fetal pulse oximetry findings.

The aim was to investigate fetal peripheral blood flow using external cardiotocography (CTG), Doppler velocimetry, and pulse oximetry (PO) in normal labor compared with those complicated by hypoxia.

Thyroid hormone resistance and enlargement of the sella turcica during pregnancy.

A 26-year-old pregnant woman was admitted to our institution running her 30 weeks of gestation. The patient had a past history of total thyroidectomy cause of a thyroid papillary carcinoma and presented with increased supraphysiological TSH levels under 250 microg T4, while slightly hyperthyroid, from the clinical point of view. Partial resistance to thyroid replacement therapy or TSH-secreting tumour was evoked. Pituitary MRI revealed a pituitary enlargement without excluding a pituitary adenoma. To avoid further stress on pituitary a caesarean section was performed at 38 weeks of gestation. MRI 7 months later was normal, while the patient remained under high doses of T4 replacement therapy and TSH was found at the upper limits of normalcy, while T3, T4 and FTI were above normalcy.

Evaluation of fetal intrapartum hypoxia by middle cerebral and umbilical artery Doppler velocimetry with simultaneous cardiotocography and pulse oximetry.

To investigate fetal circulation at different stages of hypoxia during labor, and to study blood flow alterations in the brain and peripheral tissues, through simultaneous use of three non-invasive techniques.

The clinical significance of Doppler findings in fetal middle cerebral artery during labor.

(1) To investigate fetal intracranial circulation, relative to peripheral blood flow, during labor with abnormal cardiotocographic (CTG) patterns, using three non-invasive methods. (2) To determine the utility of monitoring middle cerebral artery (MCA) Doppler during labor.

Intrapartum surveillance of IUGR fetuses with cardiotocography and fetal pulse oximetry.

To investigate the efficacy and safety of intrapartum fetal pulse oximetry, as a predictor of metabolic acidosis at birth of fetuses with intrauterine growth retardation (IUGR).