Publications by Year: 2012

2012
Wieringa G, Zerah S, Jansen R, Simundic A-M, Queralto J, Solnica B, Gruson D, Tomberg K, Riittinen L, Baum H, et al. The EC4 European syllabus for post-graduate training in clinical chemistry and laboratory medicine: Version 4-2012. Clinical Chemistry and Laboratory Medicine. 2012;50(8):1317 - 1328.Abstract
Laboratory medicine's practitioners across the European community include medical, scientific and pharmacy trained specialists whose contributions to health and healthcare is in the application of diagnostic tests for screening and early detection of disease, differential diagnosis, monitoring, management and treatment of patients, and their prognostic assessment. In submitting a revised common syllabus for post-graduate education and training across the 27 member states an expectation is set for harmonised, high quality, safe practice. In this regard an extended 'Core knowledge, skills and competencies' division embracing all laboratory medicine disciplines is described. For the first time the syllabus identifies the competencies required to meet clinical leadership demands for defining, directing and assuring the efficiency and effectiveness of laboratory services as well as expectations in translating knowledge and skills into ability to practice. In a 'Specialist knowledge' division, the expectations from the individual disciplines of Clinical Chemistry/Immunology, Haematology/Blood Transfusion, Microbiology/Virology, Genetics and In Vitro Fertilisation are described. Beyond providing a common platform of knowledge, skills and competency, the syllabus supports the aims of the European Commission in providing safeguards to increasing professional mobility across European borders at a time when demand for highly qualified professionals is increasing and the labour force is declining. It continues to act as a guide for the formulation of national programmes supplemented by the needs of individual country priorities. © 2012 by Walter de Gruyter • Berlin • Boston.
Sioulas VD, Politi E, Rizos D, Augoulea A, Kyroudi A, Sergentanis TN, Panoulis C, Aravantinos L, Creatsa M, Lambrinoudaki I. Does hormone therapy, tibolone or raloxifene modify VEGF expression in cervical epithelial cells?. Climacteric. 2012;15(2):181 - 185.Abstract
Aim Vascular endothelial growth factor (VEGF) seems to be a critical molecule in cervical carcinogenesis. We aimed to investigate the possible associations between hormonal factors and VEGF expression in cervical epithelial cells from postmenopausal women. Method A total of 105 healthy postmenopausal women (aged 4568 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived from current users of 17β-estradiol 1 mg + norethisterone acetate 0.5 mg (n = 28), tibolone 2.5 mg (n = 23), raloxifene HCl 60 mg (n = 21) and women not receiving treatment (n = 33). VEGF immunostaining was evaluated in squamous, glandular and metaplastic cells, using a semiquantitative method (rating scale: 03). Results Concerning endogenous hormones, higher Δ4-androstenedione levels were associated with more intense VEGF immunostaining in glandular (p = 0.041) and metaplastic cells (p = 0.004). Hormone therapy and raloxifene did not induce any changes in VEGF immunoreactivity in the examined cells. In contrast, tibolone administration was accompanied by diminished VEGF presence in metaplastic cells (p = 0.016 vs. controls). Conclusion Our findings may in part reflect the molecular processes contributing to the safe profile of hormone therapy, tibolone and raloxifene in cervical carcinogenesis. © 2012 International Menopause Society.
Creatsa M, Armeni E, Stamatelopoulos K, Rizos D, Georgiopoulos G, Kazani M, Alexandrou A, Dendrinos S, Augoulea A, Papamichael C, et al. Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women. Metabolism: Clinical and Experimental. 2012;61(2):193 - 201.Abstract
Although increasing evidence supports an association between endogenous sex hormones and cardiovascular disease, the results still remain controversial. This study aims to examine the association between endogenous sex hormones and indices of vascular function and structure. Serum follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulfate (DHEAS), and Δ4-androstenedione were measured in 120 healthy postmenopausal women aged 41 to 60 years. Possible associations with surrogate markers of subclinical atherosclerosis, arterial stiffness, and endothelial function were investigated. Indices of arterial structure included carotid and femoral intima-media thickness and atheromatous plaques presence. Indices of arterial function included flow-mediated dilation of the brachial artery, carotid-femoral pulse wave velocity (PWV), and augmentation index. Total testosterone and free androgen index (FAI) were the most important predictors of common carotid artery intima-media thickness (β = 0.376 and β = 0.236, P <.001 and P =.014, respectively). Similarly, FAI was the only significant independent predictor of PWV (β = 0.254, P =.027) after adjusting for age, smoking, body mass index, homeostasis model assessment of insulin resistance, and blood lipids. Free estrogen index showed a positive association with PWV, independently of age, smoking, and body mass index, but not of homeostasis model assessment of insulin resistance and blood lipids. Age-adjusted levels of DHEAS exhibited a significant independent negative association with measures of augmentation index. Follicle-stimulating hormone, luteinizing hormone, estradiol, sex hormone-binding globulin, and Δ4-androstenedione were not associated with any of the vascular parameters independently of traditional cardiovascular risk factors. Higher serum testosterone and FAI are associated with subclinical atherosclerosis in healthy recently menopausal women. This association is independent of traditional cardiovascular risk factors or insulin resistance. On the contrary, serum DHEAS exhibits a negative association with arterial stiffness. © 2012 Elsevier Inc. All rights reserved.
Markatou M, Theodoraki K, Rizos D, Fassoulaki A. Targeting perioperative hemoglobin in major abdominal surgery. Journal of Anesthesia and Clinical Research. 2012;3(2).Abstract
Background: Perioperative transfusion optimization may result in blood saving and minimization of complications associated with blood transfusions. The study aimed to compare units transfused, cytokines and patient outcome in a restrictive versus a liberal transfusion strategy. Materials and methods: We conducted a randomized-controlled study, in a single center, from December 2004 to May 2007. Of the 75 patients scheduled for major abdominal surgery and assessed for eligibility, 58 were randomized and 52 completed the study. Preoperatively, patients were randomly assigned to the Hb 7.7 g dL-1 (restrictive) or to the Hb 9.9 g dL-1 (liberal) group to receive blood transfusion intraoperatively and postoperatively if hemoglobin was below 7.7 g dL-1 or Hb 9.9 g dL-1 respectively. The follow-up for hemoglobin and intervention lasted five days, for cytokine measurements three days and for complications till discharge from the hospital. Units of red blood cells (RBC) per patient and the incidence of transfused patients in each group were the main outcome measure. Results: Median RBC transfused (units/patient) was 0 [interquartile range 0,2] in the restrictive versus 1 [0,3] in the liberal group (p=0.013), and the percentage of patients transfused 36% versus 70% respectively (p=0.027). Postoperative IL-10 levels were higher in the liberal transfusion group 24 h postoperatively (p<0.05). Pooled peak postoperative IL-10 levels correlated with the overall number of units of blood transfused (r2 = 0.38, p = 0.032) as well as with the overall mean duration of storage of blood transfused (in days) (r2 = 0.52, p = 0.007). Complications or time to discharge from hospital did not differ between the groups. Conclusion: In major abdominal surgery, restrictive transfusion decreases RBC requirements and IL-10 levels. The association between IL-10 and transfusion variables indicates that IL-10 may play a role in transfusionassociated immunomodulation. © 2012 Markatou M, et al.
Rizos D, Eleftheriades M, Batakis E, Rizou M, Haliassos A, Hassiakos D, Botsis D. Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby. Journal of Maternal-Fetal and Neonatal Medicine. 2012;25(8):1311 - 1315.Abstract
Objective: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. Methods: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. Results: Mean (±SD) concentrations of ADMA (μmol/L) in uncomplicated l pregnancies were: 0.51 ± 0.14; 0.52 ± 0.13; 0.58 ± 0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40 ± 0.10, p = 0.005 1st trim; 0.42 ± 0.10, p = 0.007 2nd trim; 0.45 ± 0.10, p = 0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58 ± 0.10; 0.63 ± 0.14; 0.68 ± 0.11), the difference was statistically significant only in the 2nd trimester (p = 0.02). Conclusions: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia. © 2012 Informa UK, Ltd.
Lambrinoudaki I, Augoulea A, Armeni E, Rizos D, Alexandrou A, Creatsa M, Kazani M, Georgiopoulos G, Livada A, Exarchakou A, et al. Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women. Climacteric. 2012;15(4):350 - 357.Abstract
Objective:s To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. Methods: One hundred and ten postmenopausal women aged 4555 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intimamedia thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. Results: Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. Conclusions: Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention. © 2012 International Menopause Society.
Kalampokas E, Vrachnis N, Samoli E, Rizos D, Iliodromiti Z, Sifakis S, Kalampokas T, Vitoratos N, Creatsas G, Botsis D. Association of adiponectin and placental growth factor in amniotic fluid with second trimester fetal growth. In Vivo. 2012;26(2):327 - 333.Abstract
Background: We investigated the associations between second trimester amniotic fluid (AF) levels of human adiponectin and placental growth factor (PLGF) in small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) fetuses. Materials and Methods: Adiponectin and PLGF levels were determined by enzyme immunoassay in AF of 21 SGA, 13 LGA and 44 AGA fetuses between 15-22 weeks of gestation, derived from pregnant women who underwent amniocentesis. Results: Adiponectin and PLGF levels were detectable in AF. Median (25th-75th percentile) adiponectin levels were 16.1 (10.9-32.3) ng/ml in SGA, 19.5 (15.1-30.9) ng/ml in AGA, and 18.2 (14.7-30.8) ng/ml in LGA fetuses. Median (25th-75th percentile) PLGF levels were 24.2 (19.9-34.9) pg/nl in SGA, 26.4 (20.9-33.8) pg/ml in AGA and 33.5 (21.8-40.4) pg/ml in LGA fetuses. The differences were not statistically significant. Nevertheless, indication of differentiation of levels existed when SGA and LGA fetuses in the extremes of distribution were considered. Specifically, very severely SGA fetuses (≤2.5th percentile) tended to have high levels of adiponectin and reduced levels of PLGF in AF. Conclusion: This is the first study presenting adiponectin and PLGF concentrations in early second trimester amniotic fluid in AGA, SGA and LGA fetuses. The altered concentrations of adiponectin and PLGF in very severely SGA fetuses possibly result from the growth-promoting effect of these factors through the metabolic route and the vascular integrity of the placenta, respectively.
Makris K, Rizos D, Kafkas N, Haliassos A. Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine. Clinical Chemistry and Laboratory Medicine. 2012;50(9):1519 - 1532.Abstract
Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein of the lipocalin superfamily. This protein is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL has recently generated great interest as an early biomarker of renal injury. However, like many other endogenous biomarkers it is not produced by just one cell type and it exists in more than one molecular form. As recent research has shown different pathological conditions may involved in the production of this molecule. This review summarizes the current knowledge about the biology of NGAL and examines the role of this molecule of acute renal injury as well as in other pathologic conditions like neoplasia, anemia, pregnancy, cardiovascular disease chronic kidney disease and in cardiorenal syndrome. Commercial and research immunoassays are used to measure NGAL in both plasma and urine but these assays are not standardized. The existence of different molecular forms of NGAL and their expression at various disease states further complicates the interpretation of the results. Pre analytical issues and biological variation are also not fully elucidated. © 2012 by Walter de Gruyter. Berlin. Boston.
Lambrinoudaki I, Armeni E, Rizos D, Georgiopoulos G, Kazani M, Alexandrou A, Deligeoroglou E, Livada A, Psychas C, Creatsa M, et al. High normal thyroid-stimulating hormone is associated with arterial stiffness in healthy postmenopausal women. Journal of Hypertension. 2012;30(3):592 - 599.Abstract
Objective: Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. Methods: The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4-4.5 μIU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima-media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Results: Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 μIU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 μIU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 μIU/ml were the only significant predictors of PWV (TSH, β-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Conclusion: Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.