© 2016 Elsevier Ireland Ltd. Background and aims: We aimed to assess the prognostic value of free androgen index (FAI) and its change over time in arterial stiffness progression, endothelial function and hypertension in postmenopausal women. Methods: Postmenopausal women (n = 180) without clinically overt cardiovascular disease or diabetes were consecutively recruited and followed for a median of 29 months. The main outcome measures were changes over time in endothelial function (FMD), reflected waves, localized and systemic (PWV) arterial stiffness and hypertension. Results: Increased baseline FAI was significantly associated with new onset hypertension (OR for each SD, 2.71, 95% CI 1.14-6.41, p = 0.024), deterioration of pulse wave velocity (PWV) (0.414 m/s per SD), flow-mediated dilation (FMD) (-0.42% per SD), systolic (2.5 mmHg per SD) and pulse pressure progression (2.3 mmHg per SD, p < 0.05 for all). Baseline FAI remained an independent predictor of changes in PWV (p = 0.006), FMD (p = 0.02), peripheral pulse pressure (p = 0.028), transition to new onset hypertension (p = 0.001) and higher BP category (p = 0.012), after adjustment for age, changes in systolic blood pressure, traditional risk factors, vasoactive medication or total testosterone. Baseline FAI improved reclassification for the risk of transition into higher BP category (NRI = 47.5 ± 20.3%, p = 0.02) and abnormal PWV (NRI = 53.4 ± 23.2%, p = 0.021). Similarly, in a subgroup of patients with measured FAI at follow-up, its changes over time predicted changes in PWV, peripheral pulse pressure and hypertension status (p < 0.05 for all). Conclusions: In apparently healthy postmenopausal women, FAI could be a novel biomarker superior to total testosterone for accelerated vascular aging and hypertension status.

© Athens Medical Society. In March 2013, the Health Procurement Committee of the Greek Ministry of Health appointed a committee consisting of laboratory scientists to compile a list of laboratory tests performed on biological fluids, cells and tissues. This committee compiled a list entitled Catalog of Uniform Nomenclature and Coding of Laboratory Tests (CUNCLT), using as its basis the list of reagents of the European Diagnostics Manufacturers Association (EDMA). The CUNCLT refers to the nomenclature of the laboratory tests and does not include all the materials (reagents, consumables, solutions, calibrators, controls, equipment, etc.) and software that may be necessary for performing the tests. The CUNCLT categorizes the laboratory tests that are performed on biological fluids, cells and tissues into eight main categories, each including subcategories of the 1st and 2nd levels. The eight main categories of the CUNCLT, namely Clinical Chemistry- Biochemistry, Immunochemistry, Hematology, Microbiology (cultures), Infectious Immunology, Molecular Biology and Genetics, Pathology-Cytology, Immunology, generally correspond to the categories of clinical laboratories that operate in public hospitals. The CUNCLT includes a total of 2,403 tests and according to its creation rationale, it is imperative that this list is regularly updated. CUNCLT is an important effort at the recording and classification of the laboratory tests carried out in clinical laboratories on biological fluids, cells and tissues. This list could be the basis for introducing the coding of laboratory tests in the laboratory information systems of public hospitals, for matching with the codes of laboratory tests prescribed by the National Organization for Health Care Services (EOPYY) and for specifications for the purchase of the reagents for laboratory testing.

© 2014 by The North American Menopause Society. Objective This study aims to evaluate the potential effects of renal function variations on vascular structure before the development of hypertension. Methods This pilot study included 141 postmenopausal women without evidence of renal dysfunction or hypertension. Markers of renal function and levels of glomerular filtration rate (GFR) - using standard calculations (GFR based on levels of creatinine [GFR epi ]) and newer creatinine and/or cystatin calculations (GFR based on levels of creatinine and cystatin [GFR cr cystatin ] and GFR based on levels of cystatin [GFR cystatin ]) - were associated with hemodynamic parameters and markers of vascular structure (intima-media thickness [IMT] and presence of atheromatous plaques in carotid and femoral arteries). Results Levels of GFR epi, GFR cr cystatin, and GFR cystatin exhibited a significant negative correlation with femoral artery IMT, whereas levels of GFR epi correlated significantly with mean carotid bulb (CB) IMT. Multivariate analysis showed that CB-IMT was predicted by GFR epi levels and age (β-coefficient = -0.212, P = 0.020), whereas femoral artery IMT was predicted by GFR epi levels (β-coefficient = -0.293, P = 0.001). GFR epi levels lower than the 25th percentile were associated with higher CB-IMT (P = 0.009), femoral artery IMT (P = 0.001), and combined IMT (P = 0.035) compared with higher GFR epi levels. Moreover, GFR epi levels greater than the 25th percentile were associated with lower odds for the presence of atherosclerotic plaques at the CB and carotid arteries combined (CB: odds ratio, 0.146; P = 0.006; combined: odds ratio, 0.249; P = 0.043) compared with lower GFR epi levels. Conclusions A mild decrease in renal function within normal limits of GFR is independently associated with the presence of subclinical atherosclerosis in a sample of apparently healthy young postmenopausal women. Assessment of GFR using creatinine (vs cystatin C) levels is a more sensitive marker of its association with IMT and atherosclerotic plaques in this postmenopausal population.

© 2015 International Menopause Society. Objectives We aimed to evaluate the association between circulating androgens and the presence of psychological symptoms in a sample of healthy middle-aged women. Methods Psychological and depressive symptoms were evaluated in a total of 207 postmenopausal women, using the Symptom Checklist-90-R (SCL-90R) and the Zung Depression Scale, respectively. We investigated the associations between the SCL-90R and Zung Scale scores, and anthropometric, lifestyle parameters, as well as serum levels of androgens. Results The free androgen index was positively associated with scores of depression (b-coefficient ± standard error (SE) = 0.2 ± 0.2, p = 0.040), anxiety (b-coefficient ± SE = 0.2 ± 0.2, p = 0.028), anger/aggressiveness (b-coefficient ± SE = 0.3 ± 0.2, p = 0.026), psychotism (b-coefficient ± SE = 0.3 ± 0.1, p = 0.013) as well as with the global index of the SCL-90R scale (b-coefficient ± SE = 0.2 ± 0.1, p = 0.036), while sex hormone binding globulin was negatively associated with depression (b-coefficient ± SE = -0.2 ± 0.0, p = 0.046) and psychotism (b-coefficient ± SE = -0.2 ± 0.0, p = 0.047). These associations were independent of vasomotor symptomatology, smoking and hormone therapy intake and were more pronounced in younger (≤ 5.5 years) compared to older postmenopausal women. Levels of dehydroepiandrosterone sulfate were positively associated with interpersonal sensitivity (b-coefficient ± SE = 0.3 ± 0.3, p = 0.042), psychotism (b-coefficient ± SE = 0.4 ± 0.2, p = 0.007) and the global index (b-coefficient ± SE = 0.3 ± 0.2, p = 0.040) in women < 5.5 years postmenopausal. No significant associations were observed between the Zung or Greene Scale scores and levels of androgens. Conclusion Higher androgenicity was positively associated with symptoms of anxiety and depression in postmenopausal women. These associations were stronger in women closer to the menopausal transition, a finding which may suggest that menopause rather than aging may mediate the association of androgens with mood disorders.

© 2015 European Society of Endocrinology. Objective: We aimed to evaluate the association between thyroid hormones and indices of obesity in a sample of euthyroid postmenopausal women. Design: Cross-sectional study. Methods: Serum levels of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) as well as BMI and waist:hip ratio (WHR) were evaluated in 194 healthy euthyroid postmenopausal women. Ultrasonography was used to assess abdominal fat layers (subcutaneous fat (SF), preperitoneal fat (PF), and SF:PF ratio). Indices of adiposity were defined as high vs low depending on the median value of the assessed parameters. Results: After multivariate adjustment for traditional risk factors, lower FT4 levels and a higher FT3:FT4 ratio predicted higher SF mass (FT4, Exp(β)=0.035, P=0.020 and FT3:FT4, Exp(β)=2.374, P=0.018), whereas higher FT3 predicted higher PF mass (Exp(β)=2.815, P=0.032). Women with FT3:FT4 above the highest quartile had a significantly higher SF mass as compared to women in the lowest quartile (1.81±0.62 cm vs 1.54∓0.46 cm, P=0.027). BMI had a positive independent association with TSH (Exp(β)=1.829, P=0.018). Finally, FT3 was significantly associated with SF mass among women with higher BMI (FT3, β=0.259, P=0.040) and women with higher WHR (β=0.309, P=0.020) but not among women with lower BMI or WHR values. Conclusion: Thyroid hormone levels, and in particular FT3, were independently associated with SF and PF in euthyroid postmenopausal women, and this association was mainly evident in women with higher BMIs. On the other hand, among traditional indices of adiposity, only TSH was positively associated with BMI. Larger prospective studies are needed to evaluate the significance of the present findings.

Copyright © 2015 Informa Healthcare USA, Inc. Purpose/Aim: To evaluate the association between the Bsm1 vitamin D receptor polymorphism and the calcium-vitamin D-parathormone axis following bariatric surgery. Materials and Methods: This cross-sectional study included 86 morbidly obese patients, who underwent either gastric bypass or sleeve gastrectomy, with a mean follow-up of four years. Calcium metabolism indices and bone turnover markers were assessed according to the presence of secondary hyperparathyroidism and the Bsm1 vitamin D receptor genotypes. Results: Secondary hyperparathyroidism (42.2% of sample) was associated with lower levels of 25hydroxyvitamin D and elevated markers of bone turnover. In subjects without secondary hyperparathyroidism, presence of the unfavorable B allele resulted in higher levels of parathormone (Bb and BB vs. bb genotype: 50.3 ± 8.2 pg/dl vs. 44.4 ± 10.7 pg/dl, p = .011, adjusted for weight loss, baseline body mass index, 25hydroxyvitamin D, surgical procedure, and duration after surgery). In the whole sample, patients bearing the unfavorable B allele exhibited lower weight loss, a parameter that was negatively associated with markers of bone resorption. Conclusions: Secondary hyperparathyroidism is highly prevalent after bariatric surgery. Bsm1 vitamin D receptor polymorphism may have an effect in early stages of calcium metabolism imbalance, while no association is detected in patients who have already developed secondary hyperparathyroidism. Moreover, vitamin D receptor polymorphism is associated with post-surgery weight loss, a process related to bone turnover.

© 2015 Andreas Alexandrou et al. Objective. Nutritional deficiencies are common after bariatric surgery. We aimed to assess the prevalence and possible predictors of secondary hyperparathyroidism (SHPT) in bariatric patients. Methods. A total of 95 patients who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were assessed after a median of 3 years after surgery. Anthropometric/demographic and weight-loss parameters were compared according to the presence of SHPT, independently for men/premenopausal women and postmenopausal women. Results. SHPT was highly prevalent (men/premenopausal women, 52.1%; postmenopausal women, 31.9%). Among men/premenopausal women, multivariate analysis indicated that SHPT was predicted by (a) 25-hydroxyvitamin D levels (Exp(B) = 0.869, P-value = 0.037), independently of age, sex, smoking; (b) calcium (Exp(B) = 0.159, P-value = 0.033) and smoking, independently of age and sex; (c) magnesium (Exp(B) = 0.026, P-value = 0.046) and smoking, independently of age and sex. Among postmenopausal women, SHPT was predicted by menopausal age independently of age, smoking, and levels of 25-hydroxyvitamin D or calcium. The development of SHPT was not associated with the type of surgery. Conclusions. RYGB and SG exhibited similar effects regarding the regulation of the hypothalamus-pituitary-parathyroid axis after surgery. Vitamin D status and menopausal age appear to determine SHPT on the long term. SHPT should be sought and vigorously treated with calcium and vitamin D supplementation.

Objective Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. Methods One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. Results In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. Conclusions Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms. © 2014 International Menopause Society.

© 2014 Informa UK Ltd. All rights reserved. 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 2mg 17β-estradiol/1mg 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 (35.4mg/dl versus 40.1mg/dl, p=0.019) while lowering TG (166mg/dl versus 109mg/dl, p=0.026) and AIP (0.24 versus 0.04, p=0.007). No changes were noted in TC and LDL (215.7mg/dl versus 192.25mg/dl and 87.46mg/dl versus 76.35mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05ng/ml versus 2.20ng/ml, p=0.002) and E-selectin (73.98ng/ml versus 56.73ng/ml, p=0.004). No change was observed in Thrombomodulin and vWf (11.76ng/ml versus 13.90ng/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 (0.65mm versus 0.60mm, p=0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.

Blood transfusion is associated with well-known risks. We investigated the difference between a restrictive versus a liberal transfusion strategy on the immune response, as expressed by the production of inflammatory mediators, in patients subjected to major abdominal surgery procedures. Fifty-eight patients undergoing major abdominal surgery were randomized preoperatively to either a restrictive transfusion protocol or a liberal transfusion protocol (with transfusion if hemoglobin dropped below 7.7 g dL-1 or 9.9 g dL -1, respectively). In a subgroup of 20 patients randomly selected from the original allocation groups, blood was sampled for measurement of IL-6, IL-10, and TNFα. Postoperative levels of IL-10 were higher in the liberal transfusion group on the first postoperative day (49.82 ± 29.07 vs. 15.83 ± 13.22 pg mL-1, P < 0.05). Peak postoperative IL-10 levels correlated with the units of blood transfused as well as the mean duration of storage and the storage time of the oldest unit transfused (r 2 = 0.38, P = 0.032, r2 = 0.52, P = 0.007, and r 2 = 0.68, P < 0.001, respectively). IL-10 levels were elevated in patients with a more liberal red blood cell transfusion strategy. The strength of the association between anti-inflammatory IL-10 and transfusion variables indicates that IL-10 may be an important factor in transfusion-associated immunomodulation. This trial is registered under ClinicalTrials.gov Identifier: NCT02020525. © 2014 Kassiani Theodoraki et al.

Background: The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), and MMP-9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA). Methods: Neutrophil gelatinase-associated lipocalin, MMP-9, and MMP-9/NGAL were determined in the first, second, and third trimesters in 33 normal pregnancies, 12 pregnancies complicated by preeclampsia, and 14 pregnancies that delivered a SGA neonate. Results: Median NGAL concentration (ng/mL) in normal pregnancies increased significantly from 12.8 in the first trimester to 25.9 in the second trimester (p=0,002) and 48.0 (p<0.0001) in the third trimester. In preeclamptic pregnancies, NGAL was significantly higher, compared with normal pregnancies, in the first (30.9; p=0.006) and second (44.6; p=0.015) trimesters. MMP-9 and MMP-9/NGAL complex concentrations in preeclamptic pregnancies did not differ significantly from normal pregnancies in either trimester. Pregnancies with an SGA infant did not have different marker concentrations in either trimester, compared with normal pregnancies. Conclusion: Maternal serum NGAL, MMP-9, and MMP-9/NGAL complex concentrations tend to increase during pregnancy in normal and preeclamptic pregnancies. NGAL was significantly elevated in the first and second trimesters, in pregnancies that later developed preeclampsia. © 2014 John Wiley & Sons, Ltd.

Purpose; Hepatic resection is the mainstay of the curative treatment of primary hepatic tumors, with constantly improving short and long term results. Radiofrequency ablation (RFA)-assisted liver resection is a relatively new method of transection of the liver parenchyma with favorable intra- and perioperative results. The aim of this study was to investigate the oncological efficacy (long term overall survival/OS and disease free survival/DFS) and to confirm the favorable short term morbidity and mortality. Methods: Between May 2004 and January 2007, 28 patients underwent 32 resections with removal of 50 hepatocellular carcinoma (HCC) lesions. The technique of parenchymal transection has been described previously as RFA-assisted liver resection. Results: Thirty-day morbidity and mortality were 42.8 and 0%, respectively. Blood transfusion was necessary for 28.5% of the patients. The median hospital stay was 16.5 days (range 5-34). The 1- and 3-year OS were 92.9 and 65.7%, respectively. The 1- and 3-year DFS were 62.3 and 54.6% respectively. No patient developed metastatic disease or local recurrence at the margin site. Twelve patients (42.9%) developed in-the-liver recurrence away from the resection area. Conclusion: RFA-assisted liver resection is a safe and oncologically efficacious method for the surgical treatment of HCC with results comparable to other surgical techniques.

Objective To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. Methods In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). Results The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. Conclusion While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women. © 2013 International Menopause Society.

Objective: The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. Methods: This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima - media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Results: Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Conclusion: Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Background Early treatment of breast cancer patients with loco-regional relapse or contralateral disease has been shown to improve survival. There is no current consensus on the optimal follow-up strategy. This study estimates the risk of isolated contralateral relapse (CR) after breast cancer surgery and its change over time, together with the efficacy of clinical examination, self-examination and mammography in the detection of CR. Methods Data from patients treated for early breast cancer at Guy's Hospital between 1990 and 1997 were collected and those with isolated contralateral recurrences were analysed. Life table analysis was performed and CR, CR-free and cumulative CR rates were calculated. Correlations were evaluated using Pearson's correlation coefficient. Results One thousand one hundred and forty-three women were included in the study and 23 patients had isolated CR. The median probability of CR was a constant 0.24% per year. Only one recurrence was found clinically at follow up, while the majority was detected through mammography and self-palpation. Conclusions The risk of CR is low and constant with time. Contralateral mammography is useful and can detect the vast majority of contralateral recurrences. These findings may have practical implications especially on the planning of postmastectomy follow up. Linked Comment: Fentiman. Int J Clin Pract 2013; 67: 1071-2. © 2013 John Wiley & Sons Ltd.

We aimed to determine the second-trimester amniotic fluid (AF) levels of soluble Fas (sFas) and Fas-ligand (FasL) and investigate their association with fetal growth. Therefore, sFas and FasL levels were measured by enzyme immunoassay in the AF of 21 small for gestational age (SGA), 13 large for gestational age (LGA), and 44 appropriate for gestational age (AGA) fetuses of pregnant women who underwent amniocentesis at between 15 and 22 weeks gestation. Our study results showed that sFas and FasL levels were detectable in AF. sFAS median (25th-75th centile) levels were 3.8 (2.8-4.6). ng/ml in SGA, 3.6 (3.1-4.5). ng/ml in AGA, and 4.0 (3.1-4.4). ng/ml in LGA. FasL median (25th-75th centile) levels were 26.0 (20.3-32.7). pg/ml in SGA, 22.7 (18.4-28.5). pg/ml in AGA, and 21.5 (15.8-30.9). pg/ml in LGA. The differences were not statistically significant. Nevertheless, statistically significant differentiation of FasL levels existed when SGA fetuses in the extremes of distribution (≤5th, ≤2.5th centile) were considered. This is the first study presenting sFas and FasL concentrations in early second-trimester amniotic fluid in AGA, SGA, and LGA fetuses. We found indications that severe and very severe SGA fetuses (≤5th and ≤2.5th centile) have high levels of FasL in the amniotic fluid. This finding probably reflects the increased rate of apoptosis that is assumed to exist in cases of extreme growth restriction. © 2013 Elsevier Ireland Ltd.

Vitamin D receptor's (VDR) genotypes have been associated both with the development of bone disease and the pathogenesis of multiple sclerosis (MS). We aimed to evaluate the association between the presence of Bsm1 restriction fragment length polymorphism of VDR and bone loss in ambulatory patients with MS. This cross-sectional study included 82 adult patients with relapsing-remitting MS. Fasting blood samples were obtained for biochemical-hormonal assessment and genotyping. Bone mineral density (BMD) was assessed at the lumbar spine (LS) and the femoral neck (FN), using dual energy X-ray absorptiometry. Possible associations between VDR's genotypes and BMD levels as well as biochemical and hormonal indices were evaluated. Among premenopausal women and men, carriers of the B allele exhibited higher BMD and Z score at the FN and a trend toward higher BMD at the LS, compared to patients with the bb genotype, after adjusting for age, BMI, sex, EDSS scoring, interferon administration, duration of MS and total steroids intake. Among postmenopausal women, the presence of the B allele was not associated with BMD or T score at any site, whereas carriers of the B allele exhibited higher levels of calcium (p value 0.008, univariate). No other significant differences were exhibited between levels of electrolytes, parathormone, 25-hydroxyvitamin D 3 and the genotype of VDR, in any of the groups. VDR's Bsm1 polymorphism is associated with a mild effect on BMD in younger patients with MS. Larger studies are necessary to corroborate these findings. © 2012 Springer-Verlag Italia.

Objective To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia. Study design In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy. Results In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p = 0.035) and in the 3rd trimester (202; 109-284) (p = 0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p = 0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%. Conclusions Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia. © 2013 Elsevier Ireland Ltd © 2013 Published by Elsevier Ireland Ltd. All rights reserved.

Aim: To assess the prevalence of climacteric symptoms and their association with demographic, life-style and hormonal parameters in Greek peri-and recently postmenopausal women. Methods: 1025 Greek women who were either perimenopausal or within their first 5 postmenopausal years participated in this cross-sectional observational study. Menopausal symptoms were assessed by the Greene Climacteric Scale and were tested for associations with demographic, anthropometric, life-style and hormonal parameters. Results: 29.8% Of the women reported moderate to severe menopausal symptoms. More specifically, 39.2% reported vasomotor, 21.3% psychological, 6.3% psychosomatic and 34.5% sexual symptoms. Years since menopause (r = 0.13, p < 0.01), waist circumference (r = 0.11, p < 0.05) as well as serum FSH, LH and estradiol (r = 0.15, r = 0.118, r =-0.157; p < 0.01) correlated with the intensity of menopausal symptoms. In the multivariate analysis years since menopause and serum estradiol were the only significant predictors of menopausal symptoms (b =-0.158 and b =-0.198, p < 0.001, respectively), explaining though only 4.8% of the variance. Conclusion: One out of three Greek women has moderate to severe climacteric symptoms during the menopause transition or the first postmenopausal years. This frequency is comparable to other White populations. Menopausal age and endogenous estrogens are significant predictors of climacteric symptoms. © 2013 Informa UK, Ltd.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In Greece, there is no officially organized training in clinical chemistry for scientists. The Greek Society of Clinical Chemistry-Clinical Biochemistry (GSCC-CB), following the encouragement of the EC4/RC decided to organize a voluntary Register for specialists in clinical chemistry. The following criteria for registration were defined: 1) University degree in Chemistry, Biochemistry, Biology, Medicine, Pharmacy or other relevant subject. 2) A total of 9 years of university studies and postgraduate specialization in clinical chemistry-clinical biochemistry. 3) A minimum of 4 years of postgraduate specialization in clinical chemistry-clinical biochemistry on the job. 4) The candidate must be practicing clinical chemistry-clinical biochemistry in a laboratory in a medical environment in Greece. The postgraduate specialization in clinical chemistry-clinical biochemistry includes the laboratory training and the theoretical education. The laboratory training is organized by the GSCC-CB according to the Professional Training Dossier. The theoretical education was organized in a series of 18 "Seminars" which was the content of the "Educational program" of the GSCC-CB. Successful completion of the Educational program leads to a Certificate of Competence. The Greek Register has gained equivalence with the EC4 Register and it has 218 members, more than 80 of whom are European clinical chemists. © 2011 by Walter de Gruyter.

Context: Ovarian and adrenal hyperandrogenism characterize premenopausal women with polycystic ovary syndrome (PCOS). Androgens decline with age in healthy and PCOS women. Objective: The objective of the study was to investigate hyperandrogenism in PCOS after menopause. Design: This was a case-control, cross-sectional study. Setting: The study was conducted at a university hospital endocrinology unit. Patients: Twenty postmenopausal women with PCOS and 20 age- and body mass index-matched controls participated in the study. Interventions: Serum cortisol, 17-hydroxyprogesterone (17-OHP), Δ4- androstenedione (Δ4A), dehydroepiandrosterone sulfate (DHEAS), total testosterone (T), and free androgen index (FAI) levels were measured at baseline, after ACTH stimulation, and after 3-d dexamethasone suppression. The ACTH and cortisol levels were measured during the CRH test. Main Outcome Measures: Androgen profile at baseline, after ACTH stimulation, and 3-d dexamethasone suppression tests were the main outcome measures. Results: Postmenopausal PCOS women had higher 17-OHP, Δ4A, DHEAS, total T, FAI (P < 0.05) and lower SHBG (P<0.05) baseline levels than control women. ACTH and cortisol responses during the CRH test were similar in the two groups. After ACTH stimulation, Δ4A, DHEAS, and total T levels were equally increased in both groups. After dexamethasone suppression, LH levels did not change in either group; 17-OHP-, Δ4A-, and FAI-suppressed levels remained higher in PCOS than in control women (P < 0.05), whereas total T and DHEAS levels were suppressed to similar values in both groups. Conclusions: In postmenopausal PCOS women, ACTH and cortisol responses to CRH are normal. Androgen levels at baseline are higher in PCOS than control women and remain increased after ACTH stimulation. The dexamethasone suppression results in postmenopausal PCOS women suggest that DHEAS and total T are partially of adrenal origin. Although the ovarian contribution was not fully assessed, increased Δ4A production suggests that the ovary also contributes to hyperandrogenism in postmenopausal PCOS women. In conclusion, postmenopausal PCOS women are exposed to higher adrenal and ovarian androgen levels than non-PCOS women. Copyright © 2011 by The Endocrine Society.

Aim.?Postpartum mood disturbances are common among Greek women, with postpartum depression (PPD) being as high as 19%. This study aimed to investigate whether sex steroid hormone levels affect the incidence of postpartum mood disturbances. Materials and methods.?Fifty-seven women were evaluated for postpartum mood disturbances using the Postpartum Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the 1st and 6th week. Serum estradiol, progesterone and testosterone concentrations were measured upon admission for delivery and daily until the fourth postpartum day. We then studied the association between hormone levels and the scores in the two psychometric scales. Results.?Testosterone was the only hormone that was marginally associated with psychometric scoring in simple regression analysis. (Postpartum Blues during days 14: b = 4.291, 95% C.I. -0.796 to 9.377 and p-value = 0.096). Women with lower testosterone drops had higher scores in Postpartum Blues Questionnaire. This association, however, lost statistical significance in the multivariable analysis after adjusting for pregnancy duration. In multiple regression analysis, only pregnancy duration had the most constant adverse effect on psychometric scores: The shorter the duration of pregnancy, the higher the scores for Postpartum Blues. (r = -0.39, p < 0.01). Conclusions.?Our findings do not indicate an association between the occurrence of postpartum mood disorders and sex steroid hormone levels. Preterm labour may be associated with a higher risk of postpartum mood disturbances. © 2010 Informa UK Ltd.

Objective: To evaluate alterations in the concentrations of osteoprotegerin (OPG), RANKL and the OPG/RANKL ratio in pre-eclamptic women during the puerperium. Study design: This cross-sectional study was performed in the maternity ward of Aretaieio Hospital in Athens, Greece. Fifteen pregnant women with severe pre-eclampsia and 15 matched controls with premature rupture of the membranes were recruited. Fasting blood samples were obtained antepartum, immediately after diagnosing pre-eclampsia (median: 32nd gestational week), and during the 3rd-6th day postpartum, to estimate levels of circulating OPG and RANKL as well as the OPG/RANKL ratio. The anthropometric parameters evaluated included body mass index and blood pressure. Results: Mean circulating OPG levels decreased significantly in both groups in the postpartum period (controls: 43.7 ± 19.1 ng/ml vs 22.9 ± 9.1 ng/ml, p = 0.008; pre-eclamptic group: 72.3 ± 49.9 vs 49.7 ± 40.9 ng/ml, p = 0.002). The antepartum OPG/RANKL ratio was elevated in hypertensive pregnancies (2.41 ± 1.72) compared to normotensive pregnancies (1.45 ± 0.63), but the difference did not reach statistical significance (p = 0.1). The OPG/RANKL ratio decreased in the control group (0.76 ± 0.30, NS) following delivery, while it remained unchanged in the pre-eclamptic women (1.63 ± 1.40, p = 0.13). Consequently, the postpartum OPG/RANKL ratio was significantly higher in the pre-eclamptic women compared to control women (1.63 ± 1.40 vs 0.76 ± 0.30, p = 0.01). Levels of RANKL demonstrated no significant alterations during puerperium in both cases. Conclusion: Pregnancies complicated with pre-eclampsia exhibit higher OPG levels and OPG/RANKL ratios, compared to control pregnancies, which might be compatible with lower bone turnover. The significance of this finding with respect to bone metabolism remains to be elucidated in larger studies. © 2010 Elsevier Ireland Ltd.

In Greece, there is no officially organized training in clinical chemistry for scientists. The Greek Society of Clinical Chemistry-Clinical Biochemistry decided to organize an intensive educational program of 18 seminars on clinical chemistry content as it is described in the EC4 Syllabus. The duration of each seminar was about 6 hours and consisted of 6 to 9 lectures. At the end of each seminar there was a voluntary written examination, comprised of 24 multiple choice questions. Successful completion of the Educational program was leading to a Certificate of Competence. Two cycles of the 18 seminars were performed: 1st cycle from October 2003 to December 2005 and 2nd cycle from March 2005 to October 2007. One hundred eighty nine colleagues was the mean attendance per seminar for the seminars of the 1st cycle and 38 colleagues for the seminars of the 2nd cycle. The mean participation to the examination for each seminar was almost 80% for the 1st cycle and 68% for the 2nd cycle. More than 80% of the participants performed Good or Very good in the examination in both cycles. It is estimated that more than 40% of the scientists who practice Clinical Chemistry in Greece, participated to this educational activity. This program is now provided as an e-learning application, and it is open for all scientists who want to follow the discipline of clinical chemistry.

The aim of our study was to evaluate the effect of BMI on the change in circulating sex hormone in postmenopausal women during 6 months of oral continuous combined low-dose hormone therapy (HT). Fifty postmenopausal women were allocated to receive daily one tablet containing combination of 17Β-estradiol (1mg)/norethindrone acetate (0.5mg) for 6 months. Serum levels of follicle-stimulating hormone (FSH), estradiol, total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), free estrogen index (FEI), Δ4-androstendione (Δ4A), and dehydroepiandrosterone sulfate were assessed at baseline and at the end of 6 months. Mean absolute values and percent changes from baseline were compared between lean and overweight women. Mean FSH decreased and mean 17Β-estradiol increased significantly in both groups (FSH lean: 82.3 26.7 decreased to 45.0±17.0mIU/ml, P = 0.0001; FSH overweight: 85.5±22.1 decreased to 52.3±23.8mIU/ml, P = 0.003; P between groups = 0.661; E2 lean: 23.24±12.55 increased to 53.62±28.29pg/ml, P = 0.006; E2 overweight: 24.17±10.88 increased to 68.36± 53.99pg/ml, P = 0.0001; P between groups = 0.619). Lean individuals had statistically significant higher increments of FAI and specifically FEI compared to overweight (FEI lean; 0.14±0.09 increased to 0.29±0.14, P = 0.009; overweight 0.23±0.18 increased to 0.52±0.40, P = 0.126; P between groups = 0.034). Although BMI does not affect total 17Β-estradiol changes, free sex steroid concentrations increase more steeply in lean compared to overweight women receiving oral low-dose HT. © 2011 The Obesity Society.

Background and Objectives Follow up for breast cancer patients aims at the timely detection of loco-regional recurrences and contralateral breast cancers (LRR). This study investigates the annual risk of LRR after breast conserving treatment (BCT) and the potential value of mammographic surveillance and/or routine clinical examination. Methods Data on 650 women who underwent BCT were obtained and LRR was divided into parenchymal and non-parenchymal. LRR-free and cumulative LRR-free rates were calculated. In patients where recurrence was diagnosed at a routine clinic visit and had negative mammography ("clinical detection only" group) were also separately examined. Results Median follow up was 115 months, range 9-196. Seventy-three patients had parenchymal and 16 nodal recurrence. The median probability of LRR was 1.4% and of parenchymal LRR was 1.32% per year, remaining constant for up to 168 months. The 16 patients in the "clinical detection only" group relapsed mainly during the first 2 years (annual risk 0.77% and 0.80%, respectively). Conclusions This study shows that the risk of parenchymal LRR remains constant for at least 14 years and is significant enough to warrant routine long-term follow up mammography. Routine clinical examination contributes significantly to the detection of LRR only for the first 2 years. © 2011 Wiley-Liss, Inc.

Abdominal aortic aneurysm (AAA) progression and disease resistance are related to transmural degenerative processes and an inflammatory infiltration (INF). Diabetes is associated with low prevalence and growth rate of AAA. We sought to characterize INF in established AAA (INFAAA), in diabetic patients. From 89 male patients aged 52 to 83 years, aneurysm specimens obtained at open asymptomatic nonruptured AAA repair were graded for INF and immunostained using antibodies against T-lymphocytes (CD3) and macrophages (CD68). Diabetic patients had an odds ratio (OR) 3.8, 95% confidence interval ([CI] 1.14-12.96), P =.03, of experiencing above-median INFAAA. These associations were affected by serum glucose (SG) levels (OR 3.6, 95% CI [0.72-18.77]; P =.1). Macrophage subpopulations higher in diabetic patients (1.44 ± 0.78 versus 0.98 ± 0.76; P =.02) were correlated with SG (r =.21, P =.044). Abdominal aortic aneurysms in diabetic patients are associated with higher INF. Macrophage densities are correlated with SG. © The Author(s) 2010.

Background: Postpartum mood disturbances are very common with postpartum blues being as high as 44.5% among Greek women. This study aimed to investigate whether thyroid function within the normal range affects the incidence of postpartum mood disturbances. Methods: In a cross-sectional study in the maternity ward of Aretaieion Hospital, 57 Greek women were evaluated for postpartum mood swings by the Maternity Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the first and sixth week postpartum. Serum Free T4, Free T3 and TSH concentrations as well as thyroglobulin and thyroid peroxidase antibodies were measured on admission for delivery and daily until the fourth postpartum day. We examined the association between hormone and antibody levels, and scores in the two scales evaluating postpartum mood disturbances. Results: Prepartum serum FT3 and FT4 correlated negatively with blues scores in the first week postpartum (blues on day 4: with FT3, rho = - 0.44, p ≤ 0.01; with FT4 rho = - 0.36, p ≤ 0.01). Women with lower FT3 and FT4 levels belonged to the high scoring group (high scoring group: FT3 = 1.22 pg/ml, FT4 = 0.66 ng/dl; low scoring group: FT3 = 1.64 pg/ml, FT4 = 0.73 ng/dl). Serum FT3 showed a negative independent correlation with postpartum blues scores in the first postpartum days. No association was found between thyroid antibody levels and mood scores. Conclusion: Our findings indicate an association between the occurrence of postpartum mood disorders and antenatal thyroid function. Within normal limits, lower levels of serum FT3 and FT4 are associated with increased incidence of mood disturbances in the first postpartum week. © 2009 Elsevier B.V. All rights reserved.

One hundred healthy postmenopausal women were randomly assigned to receive 17β-E2 1 mg/drospirenone 2 mg or 17β-E2 1 mg/norethisterone acetate 0.5 mg for 6 months, and circulating soluble Fas, soluble Fas ligand, and cytochrome c were measured at baseline and at 6 months in 87 women who completed the study. Although cytochrome c levels were undetectable, circulating soluble Fas/soluble Fas ligand ratio decreased in both groups, suggesting a decrease in ligand-mediated apoptosis. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous Guides to the Register have been published, one in 1997 and another in 2003. The third version of the Guide is presented in this article and is based on the experience gained and development of the profession since the last revision. Registration is valid for 5 years and the procedure and criteria for re-registration are presented as an Appendix at the end of the article. © 2010 by Walter de Gruyter, Berlin, New York.

Objective Autoimmune thyroiditis and overt or subclinical hypothyroidism have been associated with increased prevalence of cardiovascular disease (CVD). Design Cross-sectional investigation of the association between gene polymorphisms related to CVD with thyroid function and autoimmunity. Patients In total 84 healthy postmenopausal women aged 49-69 years. Measurements FT3, FT4, anti-TPO and anti-TG were assessed in the sera of participants. The following polymorphisms were assessed from peripheral lymphocyte DNA: Apolipoprotein E E2/E3/E4, paraoxonase 1 A/B, Glycoprotein IIIa leu33pro, MTHFR ala222val, ApoBarg3500gln, plasminogen activator inhibitor 1 4G/5G, cholesterol 7-α hydroxylase A204C and cholesterol ester transfer protein B1/B2. Results A statistically significant correlation was found between Apolipoprotein E and paraoxonase1 polymorphisms and serum thyroid hormones: carriers of the E2 or E4 allele of the ApoE gene had lower levels of FT4 (P = 0·0005) than women with the E3/E3 genotype. Carriers of the B allele of paraoxonase 1 gene had lower levels of FT3 compared to women with the wild-type genotype (P = 0·047). A statistically significant positive association (P = 0·049) was also observed between anti-TG antibodies and the presence of the E2 allele of the Apolipoprotein E gene. Conclusions Polymorphisms of apolipoprotein E and paraoxonase 1 are associated with different levels of thyroid hormone and anti-Tg antibody levels in the study population in this pilot study. The mechanism underlying this association remains to be elucidated. © 2009 Blackwell Publishing Ltd.

Hyperprolactinemia has been associated with endothelial dysfunction and an adverse cardiovascular risk profile, possibly as a result of the vasoconstrictive properties of prolactin. In this cross-sectional study, we examined the hypothesis that prolactin contributes to the increased cardiovascular risk occurring in early menopause by studying apparently healthy women without hyperprolactinemia. Prolactin serum levels were measured by immunoassay in 76 women aged 54.4±4.9 years in menopause for 4.9±2.8 years, and possible correlations with traditional cardiovascular risk factors and surrogate markers of preclinical atherosclerosis, arterial stiffening, and endothelial and microcirculatory function were examined. Positive correlations between prolactin serum levels and arterial blood pressure, but no other traditional risk factors, were found. Prolactin also correlated with central aortic systolic (r=0.337; P=0.002) and diastolic (r=0.272; P=0.012) blood pressures and pulse wave velocity (r=0.264; P=0.02), a marker of aortic stiffness, but not with endothelial or microcirculatory function or carotid intima-media thickness. By multivariate regression analysis, prolactin levels determined, independent of traditional risk factors, both blood pressures and aortic stiffness. Notably, prolactin correlated with European Society of Cardiology HeartScore (r=0.364; P=0.002), a composite index that predicts 10-year cardiovascular mortality. Prolactin levels >8.0 ng/mL had 100% sensitivity to predict a high peripheral blood pressure. Prolactin may play a role in accelerated arteriosclerosis in early menopause by affecting central/peripheral blood pressure and arterial stiffness. In contrast, no correlation was observed with other risk factors or surrogate markers of atherosclerosis. Prospective studies to assess whether prolactin is an additional hormone increasing cardiovascular risk are warranted. © 2009 American Heart Association, Inc.

Background: Neutrophil gelatinase-associated lipocalin (NGAL), an iron-transporting protein rapidly accumulating in the kidney tubules and urine after nephrotoxic and ischemic insults, has been put forward as an early, sensitive, non-invasive biomarker for acute kidney injury (AKI). The aim of this study was to evaluate urinary NGAL levels as a predictor of early AKI (first 5 days after injury) in multi-trauma patients. Methods: We studied multi-trauma adult patients admitted to the intensive care unit of a trauma hospital. Exclusion criteria were a) known cardiac or chronic kidney disease, and b) initial evaluation after more than 24 h had elapsed from injury. Urinary NGAL was measured using an ELISA technique upon admission and at 24 and 48 h. Presence of AKI was defined by the risk injury failure loss and end-stage kidney classification (RIFLE) criteria. Data are reported as median and interquartile range. Results: A total of 31 patients (25 male, 6 female) were studied. NGAL levels at admission were significantly higher among patients who subsequently developed AKI [155.5 (50.5-205.9) ng/mL vs. 8.0 (5.7-17.7) ng/mL, p=0.0000] and these higher levels persisted over the following 2 days. On the basis of receiver-operating characteristic analysis both NGAL and serum creatinine baseline measurements could predict AKI [area under the curve (95% confidence interval) 0.977 (0.823-0.980) and 0.789 (0.556-0.906), respectively], but the area under the curve for NGAL was significantly larger (p=0.024). A cut-off point >25 ng/mL for NGAL had a sensitivity of 0.91 and specificity of 0.95 in predicting AKI. Conclusions: Urinary NGAL can be used from the 1st day of injury as a reliable predictor of early AKI in multi-trauma patients. © 2009 by Walter de Gruyter.

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 10 years, more than 2000 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Federation of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). A Code of Conduct was adopted in 2003 and a revised and updated version, taking account particularly of the guidelines of the Conseil Européen des Professions Libérales (CEPLIS) of which EFCC is a member, is presented in this article. The revised version was approved by the EC4 Register Commission and by the EFCC Executive Board in Paris on 6 November, 2008. © 2009 by Walter de Gruyter Berlin New York.

Objective: Modulating effects of genetic and environmental risk factors on severity of human abdominal aortic aneurysm (AAA) tissue inflammation remain unclear. We investigated the influence of total plasma homocysteine (tHcy) and traditional atherosclerotic risk factors (ARF) on degree of AAA tissue inflammation. Methods: Aneurysm specimens were obtained from 89 male patients aged 52 to 83 years, underwent asymptomatic not ruptured AAA (mean diameter 5.5 cm) open repair and graded for degree of histologic inflammation. Multivariate analysis was used to determine the association of tHcy and ARF, with degree of inflammation. Results: Current cigarette smoking, odds ratio (OR) 4.4, 95% confidence interval 1.3 to 15.2, P =.01 and no other ARF, neither tHcy levels OR 0.9 (0.9-1.02), P =.2 were associated with high-grade tissue inflammation. Conclusion: These results provide evidence against a major effect of tHcy levels on AAA tissue inflammation, while current cigarette smoking is a significant modulating factor.

Background: Cytokines are significant mediators of the immune response to surgery and also play a role in parturition. The aim of the study was to investigate the impact of the anesthetic technique for cesarean section on plasma levels of cytokines IL-6 and TNF-α. Methods: Thirty-five parturients scheduled for elective cesarean section were randomly assigned to general (n = 18) or neuraxial (n = 17) anesthesia. The general anesthesia group received thiopental 4 mg/kg, succinylcholine 1-1.5 mg/kg and 1% end-tidal concentration of sevoflurane in nitrous oxide and 50% oxygen. The neuraxial anesthesia group received intrathecal 0.5% levobupivacaine 1.8-2.2 mL and epidural fentanyl 1 μg/kg. Blood samples were taken for IL-6 and TNF-α immediately after positioning the parturient on the operating table, after uterine incision and before the umbilical cord clamping and 24 h after surgery (T1, T2 and T3 respectively). Results: The two groups did not differ in IL-6 (P = 0.15) or TNF-α (P = 0.73) serum concentrations at any time point. In the general and neuraxial anesthesia groups, IL-6 serum concentrations were significantly higher in the third blood sample, T3 (12.2 ± 5.0 and 15.2 ± 4.3 pg/mL), than in T1 (0.41 ± 0.38 and 0.29 ± 0.10 pg/mL) and T2 (0.37 ± 0.47 and 0.24 ± 0.05) respectively (P < 0.001). Within each group, serum TNF-α concentrations did not differ significantly over time (P = 0.44). Conclusions: Under the present study design anesthetic technique did not affect IL-6 or TNF-α concentrations in parturients undergoing elective cesarean section. Serum IL-6 levels increased 24 h postoperatively independently of anesthetic technique. © 2008 Elsevier Ltd. All rights reserved.

The study was aimed to find out the prevalence of non-classical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (21-OHdef) among Greek women with hirsutism and polycystic ovary syndrome (PCOS) and to compare the results of ACTH stimulated 17-hydroxyprogesterone 60 min (17-OHP60) values, with human leukocyte antigens (HLA) phenotypes, in any patient diagnosed as having NC-CAH. One hundred and seven women with hirsutism and PCOS were included in the study. All were presented at the Reproductive Endocrinology Outpatient Clinic with hirsutism and PCOS. After ACTH stimulation test, 10 women were diagnosed as having NC-CAH because of high 17-OHP60 values ≥36 nmol/l, and 97 as having PCOS. Ten (10.3%) of the 97 women presented hormonal findings compatible with adrenal hyper-response due to ACTH testing, because of hyperstimulated 17-OHP60 values ≥21 nmol/l and <32 nmol/l. The HLA typing of 10 patients with NC-CAH revealed the phenotypes B14, DR1, B35, B7 and B44 which present positively genetic linkage disequilibrium with 21-OHdef, as reported in the literature. In conclusion: In Greek women with hirsutism and PCOS we have found that: a. The prevalence of NC-CAH among these women is relatively high and reaches at 10%. b. The HLA phenotypes B14, DR1, B35, B7 and B44 were found in high frequency in these NC-CAH patients. c. Adrenal NC-CAH due to 21-OHdef as well as adrenal hyperactivity, revealed after ACTH testing, constitutes an important reason of hirsutism and PCOS in these Greek women and both reach a rate of 20%.

Aims: To correlate the values of MBG to HbA1c in Greek patients with Type 2 diabetes and/or metabolic syndrome. Methods: We followed up 140 Greek adult patients: 92 patients with Type 2 diabetes treated with insulin or oral glucose-lowering medication, and 48 patients with newly diagnosed Type 2 diabetes or metabolic syndrome not receiving any treatment. MBG was calculated for each patient from self-measurements of blood glucose using a portable glucometer, made six times a day (before eating and 2 h after a meal), three times a week for 1 month. HbA1c was determined by HPLC at 0 and 12 weeks. Results: HbA1c at 0 (x) and 12 weeks (y) correlated strongly (y = 0.790x + 1.115, r = 0.92), confirming that the patient's glycaemic status remained stable during the whole period of follow-up. Linear regression was performed on MBG values; HbA1c at 12 weeks, sex, age, body mass index (BMI) and patient status (Type 2 diabetes treated or not) were used as independent variables. None of the independent variables reached statistical significance in the model, with the exception of HbA1c at 12 weeks. The final model was: MBG (mg/dl) = (34.74 × HbA1c) - 79.21, r = 0.93; or MBG (mmol/l) = 1.91 × HbA1c - 4.36, r = 0.93. Conclusions: Our results establish for the first time a strong correlation between MBG and HbA1c in Type 2 diabetic patients and support the idea of expressing HbA1c results as MBG. This will help patients to gain a clearer interpretation of the result, with less confusion. This simplification will allow every person with diabetes using home glucose-monitoring to understand his or her own target level. © 2008 The Authors.

Proteins that are expressed by both malignant and healthy fetal tissues are recognized as oncofetal. These antigens are associated with cell proliferation and differentiation and are produced in high concentrations in pregnancy and malignancy. Their biological role in malignancy is the suppression of the host's immune system, while in pregnancy they affect the maternal immune response, generating maternal tolerance toward the embryo. This review describes the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), squamous cell carcinoma antigen (SCC), cancer antigen 15-3 (CA 15-3), mucin-like carcinoma-associated antigen (MCA), tissue polypeptide-specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), and prostate-specific antigen (PSA) in maternal serum (MS), umbilical cord serum (UC), and amniotic fluid (AF) and outlines their roles in the assessment of pregnancy and malignancy. All antigens studied, except CA 15-3, are oncofetal. The presence of considerable concentrations of AFP, hCG, CEA, CA125, SCC, MCA, TPS, CA 19-9, and PSA in AF during pregnancy may be attributed to their involvement in biological functions associated with fetal development, differentiation, and maturation. MS CEA, CA 15-3, and CA 19-9, in contrast to all the others, are not influenced significantly by pregnancy and thus remain reliable tumor markers in monitoring malignancy in pregnant patients. Copyright © 2007 Informa Healthcare.

Objective: To evaluate the cytokine concentration patterns during the first 5 days of life by measuring serum concentrations of type-1 cytokines, like interleukin-2 (IL-2) and interferon-γ (IFN-γ) and type-2 cytokines, like IL-4, as well as the receptors of IL-2 (sIL-2R) and IL-4 (sIL-4R) during the early neonatal period. Subjects and methods: Forty-two healthy term neonates were included in the study. Cytokine concentrations were measured in umbilical cord, in the 1st and 5th day after birth and compared with those in serum of 30 healthy adults. Results: IL-2 concentrations presented a decrease trend from umbilical cord to 5th day, while sIL-2R showed a significant elevation from umbilical cord to 5th day after birth. IL-4 concentrations did not differ significantly among umbilical cord, the 1st and the 5th day, while the sIL-4R showed the highest values in the 1st day after birth. Both IL-4 and sIL-4R concentrations in neonatal samples were elevated compared to adults. IFN-γ concentrations increased significantly from umbilical cord to 5th day of life. Conclusion: Our findings indicate a dysregulation among IL-2, IL-4 and IFN-γ concentrations during the 1st day after birth, favoring a more precocious expression of IL-2 and IL-4 against IFN-γ that seems to be ameliorated in the end of the 1st week of life. © 2006 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to assess the association of endogenous sex steroids with bone mineral density (BMD) in healthy postmenopausal women not on hormone therapy. A total of 884 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Parameters assessed were follicle-stimulating hormone, luteinizing hormone, estradiol, total testosterone, sex hormone-binding globulin, free estrogen index (FEI), free androgen index (FAI), Δ4-androstendione (Δ4A), dehydroepiandrosterone sulfate (DHEAS), bone alkaline posphatase, and bone mineral density at the lumbar spine (L-BMD) and femoral neck (N-BMD). Estradiol and FEI associated positively with both L-BMD and N-BMD (r = 0.21-0.47, P < 0.01). These associations remained significant after adjustment for age, years since menopause, and body mass index. FAI correlated positively with both L-BMD and N-BMD (r = 0.18 and 0.33, respectively; P < 0.01). At the multivariate analysis, however, FAI remained the significant determinant only for N-BMD. Δ4A associated positively with N-BMD (r = 0.27, P = 0.001), whereas DHEAS showed no association with BMD at either site. Thus, endogenous steroids are significant determinants of postmenopausal BMD. Endogenous estradiol may be more important for lumbar spine BMD, whereas endogenous androgens are associated mainly with femoral neck BMD. © Springer-Verlag Tokyo 2006.

OBJECTIVE: The determinants of serum homocysteine in healthy postmenopausal women remain uncertain. The aim of this study was the assessment of the association of endogenous sex steroids with serum homocysteine levels in healthy postmenopausal women not on hormone therapy. DESIGN: 484 postmenopausal women aged 43-69 years were studied in a cross-sectional design. Parameters assessed were serum FSH, estradiol, total testosterone, SHBG, Free Androgen Index, delta4-Androstendione, Dehydroepiandrosterone sulphate, and homocysteine. RESULTS: Serum FSH correlated positively (r=0.23, p=0.01), while serum estradiol correlated negatively (r=-0.25, p=0.03) with circulating Hcy. This association remained statistically significant after adjustment for age, years since menopause, and BMI. Serum estradiol decreased, while FSH increased linearly with increasing homocysteine quartiles (p=0.04 and p=0.02, respectively). None of the serum androgens assessed correlated with circulating homocysteine. CONCLUSIONS: Endogenous estrogens and not androgens are related to serum homocysteine values in postmenopausal women. Whether this association has clinical implications remains to be clarified.

Background. Lipoprotein(a), Lp(a), has been recognized as an atherogenic and thrombogenic lipoprotein in the general population and in hemodialysis (HD) patients. In addition, fibrinogen and fibronectin may promote atherothrombosis. The aim of this study was to investigate any possible relationship between Lp(a) and thrombogenic coagulation proteins in non-diabetic HD patients. Patients and Methods. Serum Lp(a) and plasma fibrinogen, plasminogen, and fibronectin levels were measured pre-HD in 60 uremic patients (30 male, 30 female) aged 58.6 ± 8.0 years who had been receiving HD treatment for 61.3 ± 50.7 months. The control group comprised 20 age- and sex-matched healthy subjects. All patients were receiving erythropoietin treatment. Results. The mean serum Lp(a) (33.88 ± 34.12 mg/dL) and plasma fibrinogen (329.45 ± 80.62 mg/dL) levels were significantly higher in the HD patients compared with those in the controls (16.70 ± 10.36 and 254.00 ± 43.34 mg/dL, respectively; p < .05 and p < .001, respectively). Plasminogen levels did not differ between the HD patients (11.64 ± 3.22 mg/dL) and the control group (10.67 ± 1.41 mg/dL, p>.05). Fibronectin levels were slightly increased in the HD patients (33.96 ± 5.49 mg/dL) versus in the control group (30.9 ± 5.80 mg/dL, p < .05). There was a significant positive correlation between Lp(a) and fibrinogen levels (r = 0.305, p < .02), as well as between Lp(a) and fibronectin levels (r = 0.360, p < .01). Moreover, there was a significant positive correlation between fibrinogen and fibronectin levels (r = 0.587, p < .0001). Conclusions. According to our results, in non-diabetic HD patients, abnormal serum Lp(a) levels significantly correlated with abnormal levels of fibrinogen and fibronectin. There is a concern that the relationship between these atherogenic and thrombogenic acute-phase proteins may contribute to the increased incidence of atherosclerotic cardiovascular disease in this patient population.

The EC4 Syllabus for Postgraduate Training is the basis for the European Register of Specialists in Clinical Chemistry and Laboratory Medicine. The syllabus: • Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); • Indicates the level of content of national training programmes to obtain adequate knowledge and experience; • Is approved by all EU societies for clinical chemistry and laboratory medicine. The syllabus is not primarily meant to be a training guide, but on the basis of the overview given (common minimal programme), national societies should formulate programmes that indicate where knowledge and experience is needed. The main points of this programme are: • Knowledge in biochemistry, haematology, immunology, etc.; • Pre-analytical conditions; • Evaluation of results; • Interpretations (post-analytical phase); • Laboratory management; and • Quality insurance management. The aim of this version of the syllabus is to be in accordance with the Directive of Professional Qualifications published on 30 September 2005. To prepare the common platforms planned in this directive, the disciplines are divided into four categories: • General chemistry, encompassing biochemistry, endocrinology, chemical (humoral), immunology, toxicology, and therapeutic drug monitoring; • Haematology, covering cells, transfusion serology, coagulation, and cellular immunology; • Microbiology, involving bacteriology, virology, parasitology, and mycology; • Genetics and IVF. © 2006 by Walter de Gruyter.

Objective: To assess the association between endogenous sex hormones and risk factors for atherosclerosis in healthy postmenopausal women. Design: Cross-sectional study in a university menopause clinic. Methods: Serum sex hormones and lipid-lipoprotein profile, arterial pressure, homocysteine and insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-111), were assessed in 598 healthy postmenopausal women not on hormone therapy. Results: Compared with women in the lowest testosterone quartile (Q), women in the highest testosterone quartile had higher total cholesterol (Q1: 225.2±41.3 vs Q4: 246.2±38.4 mg/dl, P<0.01), low-density lipoprotein (LDL)-cholesterol (Q1: 146.9±37.2 vs Q4: 171.8±35.3 mg/dl, P<0.001), atherogenic index of plasma (AIP) (Q1: -0.224±0.238 vs Q4:-0.087±0.254, P<0.01), apolipoprotein B (ApoB) (Q1: 100.7±23.1 vs Q4: 113.9±23.8 mg/dl, P<0.001) and higher high-density lipoprotein (HDL)-cholesterol (QI: 60.7±14.5 vs Q4: 52.9±13.0 mg/dl, P<0.01). Accordingly, women in the highest free androgen index (FAI) quartile had higher AIP (Q1: -0.232±0.254 vs Q4: -0.078±0.243, P<0.001) and ApoB (Q1: 102.4±25.5 vs Q4: 114.2±25.8mg /dl, P<0.01) and lower HDL-cholesterol (Q1: 62.0±15.7 vs Q4: 51.9±11.6mg/dl, P<0.001) and apolipoprotein A (Q1: 159.6±25.6 vs Q4: 147.9±24.1 mg/dl, P<0.01) compared with women in the lowest FAI quartile. These differences remained significant after adjustment for age, body mass index (BMI), insulin resistance and social habits. The free estrogen index (FEI) exhibited similar associations to the FAL HOMA-IR showed an independent positive association with total testosterone (Q1: 2.00±1.36 vs Q4: 2.66±1.60, P<0.01), FAI (Q1: 1.70±1.12 vs Q4: 3.04±1.66, P<0.001) and FEI (Q1: 1.70±0.91 vs Q4: 3.08±1.77, P<0.001). Conclusions: Increased androgenicity in healthy postmenopausal women is associated with an unfavorable cardiovascular risk profile. High endogenous estradiol is related to a pro-atherogenic lipid profile, an association which may, in part, be mediated by insulin resistance. © 2006 Society of the European Journal of Endocrinology.

Background: Intrauterine fetal development is characterized by increased rates of proliferation and apoptosis, while both these processes may be attenuated post-natally. Aim: Tissue polypeptide specific antigen and sFas serum concentrations were determined during pregnancy and post-natally, in order to evaluate their alterations during these crucial periods. Materials and Methods: Forty-seven healthy pregnant women, their full-term newborns and 35 healthy adults (controls) were included in the study. Markers were measured: a) in maternal serum (MS), during the 1st, 2nd, 3rd trimester and at the 1st stage of labor; b) in the umbilical cord (UC), during the 2nd stage of labor; c) in neonatal serum in the 1st (1N) and 5th (5N) day after birth; and d) in controls. Results: The serum TPS concentrations in MS increased significantly with gestational age, being higher in the 3rd trimester and labor, than those in controls (p<0.001). TPS values were significantly lower in the UC, compared to those in MS (p<0.001), while they were markedly elevated in 1N, compared to MS and UC (p<0.001), and subsequently decreased in 5N (p<0.001), remaining higher, than those in the controls (p<0.001). Serum sFas concentrations in the MS depended significantly on gestational age (p<0.001), being significantly lower in the first trimester, than those in the second (p<0.003), the third (p<0.03), in labor and controls (p<0.005). sFas concentrations in the UC were significantly lower than in MS and controls (p<0.001), while they increased significantly in 5 N samples (p<0.01). Conclusion: Our results demonstrate: a) a higher apoptosis rate in the first trimester of pregnancy, possibly affecting maternal immuno-tolerance, followed by a down-regulation during the post-natal period; b) a progressively increased proliferation from the first trimester to parturition, reflecting the fetal and placental growth and development, that seems to be thereafter moderated.

The objective of the study was to evaluate the efficacy and safety of 800 microg of misoprostol every 12 h, for a period of 36 h for pharmacological abortion. A group of 162 volunteer women with gestations between 50 and 63 days received misoprostol every 12 h up to a maximum of three doses for abortion. Outcome measures assessed included: successful abortion (complete abortion without requiring surgery), side effects, and a decrease in hemoglobin, mean time of vaginal bleeding, mean expulsion time and mean time of returning of menses. Complete abortion occurred in 148 of 162 (91%, 95% confidence interval 87.95) patients. The mean decrease in hemoglobin was statistically significant (p = 0.001). Vaginal bleeding lasted 8.0 +/- 3.2 days, spotting 8.0 +/- 3.5 days, and total bleeding 16 +/- 4.0 days. The mean expulsion time was 8.5 +/- 4.0 h. According to the observed outcomes, 800 microg of misoprostol vaginally could be a valid method to terminate pregnancies up to 9 weeks of gestation.

Objective: To assess endogenous androgen and insulin resistance status in postmenopausal women receiving continuous combined hormone therapy (HT), tibolone, raloxifene or no therapy. Methods: A total of 427 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Among them 84 were taking HT (46 women conjugated equine estrogens 0.625 mg; medroxyprogesterone acetate, 5 mg, CEE/MPA; and 38 women 17β-estradiol 2 mg; norethisterone acetate 1 mg, E2/NETA); 83 were taking tibolone 2.5 mg; 50 were taking raloxifene HCl 60 mg; and 210 women were not receiving any therapy. Main outcome measures were FSH, LH, estradiol, total testosterone, SHBG, free androgen index (FAI), Δ4-Androstendione (Δ4-A), Dehydroepiandrosterone sulphate (DHEAS) and HOMA insulin resistance index (HOMA-IR). Results: In women not on hormone therapy smoking and older age was associated with lower DHEAS levels. FAI values increased linearly with increasing BMI. Age and BMI were positive determinants of HOMA-IR, while no association was identified between endogenous sex steroids and insulin resistance. CEE/MPA therapy was associated with higher SHBG, lower FAI and lower HOMA-IR values compared to women not on therapy (age and BMI-adjusted SHBG: CEE/MPA 148.8 nmol/l, controls 58.7 nmol/l, p < 0.01; age-adjusted FAI: CEE/MPA 0.8, controls 3.2, p < 0.05; age-adjusted HOMA-IR: CEE/MPA 1.3, controls 2.6, p < 0.05). On the contrary, E2/NETA treatment had no effect on these parameters. Women on tibolone had lower SHBG, higher FAI and similar HOMA-IR values compared to controls (age and BMI-adjusted SHBG: 24.1 nmol/l, p < 0.01; FAI: 6.0, p < 0.05; HOMA-IR: 2.3, p = NS). Raloxifene users did not exhibit any difference with respect to sex steroids and HOMA-IR levels. Conclusions: CEE/MPA users had lower free testosterone and improved insulin sensitivity. Tibolone on the other hand associated with higher free testosterone, while raloxifene did not relate to any of these parameters. © 2004 Elsevier Ireland Ltd. All rights reserved.

Objective. We investigated the dose-related effect of dopexamine and dopamine on free radical production and lipid peroxidation estimated by MDA measurements in an ischaemia-reperfusion model of supraceliac aortic repair. Design. Prospective, randomized, blinded experimental study. Materials. Twenty-five healthy pigs. Methods. All experiments were performed under general endotracheal anaesthesia. Supraceliac aortic cross clamping was performed in all pigs. The pigs were randomly assigned into five groups (n = 5 in each group) and received a continuous intravenous infusion of normal saline (CTL), dopamine 2 μg kg-1 min-1 (dopa 2), dopamine 8 μg kg-1 min-1 (dopa 8), dopexamine 2 μg kg-1 min-1 (dopex 2), dopexamine 8 μg kg-1 min-1 (dopex 8). Cardiac output, mean arterial pressure, arterial blood gas analysis and blood sampling for plasma MDA measurements (to reveal lipid peroxidation) were recorded after induction of anaesthesia (baseline), 60 and 120 min after cross-clamping of aorta (ischaemia phase), and 60 and 120 min after restoration of flow (reperfusion phase). Results. Dopexamine and dopamine at 8 μg kg-1 min-1 reduced MDA at 60 and 120 min after reperfusion. Conclusion. Dopexamine seems superior to dopamine in reducing oxygen free radicals and subsequent lipid peroxidation during reperfusion after supraceliac aortic cross clamping in pigs. © 2005 Elsevier Ltd. All rights reserved.

Objective. We investigated the dose-related effect of dopexamine and dopamine on free radical production and lipid peroxidation estimated by MDA measurements in an ischaemia-reperfusion model of supraceliac aortic repair. Design. Prospective, randomized, blinded experimental study. Materials. Twenty-five healthy pigs. Methods. All experiments were performed under general endotracheal anaesthesia. Supraceliac aortic cross clamping was performed in all pigs. The pigs were randomly assigned into five groups (n = 5 in each group) and received a continuous intravenous infusion of normal saline (CTL), dopamine 2 μg kg-1 min-1 (dopa 2), dopamine 8 μg kg-1 min-1 (dopa 8), dopexamine 2 μg kg-1 min-1 (dopex 2), dopexamine 8 μg kg-1 min-1 (dopex 8). Cardiac output, mean arterial pressure, arterial blood gas analysis and blood sampling for plasma MDA measurements (to reveal lipid peroxidation) were recorded after induction of anaesthesia (baseline), 60 and 120 min after cross-clamping of aorta (ischaemia phase), and 60 and 120 min after restoration of flow (reperfusion phase). Results. Dopexamine and dopamine at 8 μg kg-1 min-1 reduced MDA at 60 and 120 min after reperfusion. Conclusion. Dopexamine seems superior to dopamine in reducing oxygen free radicals and subsequent lipid peroxidation during reperfusion after supraceliac aortic cross clamping in pigs. © 2005 Elsevier Ltd. All rights reserved.

Objective: To evaluate the effect of estrogen replacement therapy (ERT), continuous combined hormone replacement therapy (HRT) and tibolone on serum leptin levels in healthy postmenopausal women. Methods: Eighty-four healthy postmenopausal women aged 43-63 years were studied prospectively. Hysterectomized women (n=16) received conjugated equine estrogens (CEE) 0.625 mg. Women with an intact uterus were randomly allocated either to CEE+medroxyprogesterone acetate (CEE/MPA) 5 mg or tibolone 2.5 mg. Serum leptin levels were assessed at baseline and after 6 months of treatment. Results: The three groups did not differ with respect to age, body mass index (BMI) or baseline serum leptin levels. Overweight women (BMI>25 kg/m2) had higher baseline leptin levels (27.0±11.4 ng/ml) compared to their lean counterparts (BMI≤25 kg/m2; leptin: 16.5±8.1 ng/ml, P=0.0001). Neither CEE nor CEE/MPA had any effect on serum leptin levels at the end of 6 months either in overweight or in lean women (overweight: CEE baseline 34.4±13.3 ng/ml, 6 months 36.9±15.8, P=0.89, CEE/MPA baseline 22.4±9.8 ng/ml, 6 months 26.8±8.7 ng/ml, P=0.1; lean: CEE baseline 12.6±4.4 ng/ml, 6 months 13.2±5.8 ng/ml, P=0.36, CEE/MPA baseline 17.2±10.6 ng/ml, 6 months 18.8±8.8 ng/ml, P=0.31). Similarly serum leptin remained unchanged at the end of the study in both lean and overweight women on tibolone (overweight: baseline 22.9±8.1 ng/ml, 6 months 18.5±12 ng/ml, P=0.37; lean: baseline 13.2±5.6 ng/ml, 6 months 17.3±8.4 ng/ml). Conclusion: BMI is a strong determinant of serum leptin levels in healthy postmenopausal women. Neither ERT/HRT nor tibolone exert any effect on serum leptin after 6 months in lean or overweight postmenopausal women. Further studies are required to verify the exact role of estrogen and tibolone on leptin production and function in postmenopausal women. © 2003 Elsevier Ireland Ltd. All rights reserved.

The European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) opened a Register for European Specialists in Clinical Chemistry and Laboratory Medicine in 1997. The operation of the Register is undertaken by a Register Committee (EC4RC). During the last 6 years more than 1500 specialists in clinical chemistry and laboratory medicine have joined the Register. In this article a Code of Conduct for Registrants which was approved at the EC4 Register Committee meeting in Amsterdam, 8 November 2003 is presented. © 2004 by Walter de Gruyter.

Objective: To assess the effect of continuous combined hormone replacement therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in postmenopausal women. Study design: Ninety-five postmenopausal women aged 41-68 years were included in the study. Seventy-three women with climacteric complaints, osteopenia or osteoporosis received either conjugated equine estrogens 0.625mg combined with medroxyprogesterone acetate 5mg (CEE/MPA, n=31) or tibolone 2.5mg (n=42). Twenty-two healthy women, matched for chronological and menopausal age, served as controls. Serum tHcy levels were assessed at baseline, 6, 12 and 18 months. Results: No difference was recorded between groups regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy levels decreased significantly in the CEE/MPA compared to baseline (change at 18 months: -3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup of women with baseline tHcy levels above the median (change at 18 months: -15.0%, P<0.01). No change in tHcy levels was detected in the tibolone group throughout the study period, either in the whole group (change at 18 months: 1.9%, NS) or in the subgroup with baseline tHcy levels above the median (change at 18 months: -3.23%, NS). Conclusion: Continuous CEE/MPA reduces tHcy especially in women with high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at least during the first 18 months of therapy. Larger studies with longer follow-up are required to confirm these results. © 2003 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE: To evaluate age-related differentiation of immune response in newborns by measuring serum concentrations of interleukin-2 (IL-2), interleukin-4 (IL-4) and interferon-γ (IFN-γ) during the perinatal period. Subjects and methods: Fifty-seven healthy term neonates, their mothers and 25 healthy adults (controls) age-matched to the mothers were included in the study. Cytokine concentrations were measured in the umbilical cord (UC), and in first-day (1N) and fifth-day (5N) neonatal samples, compared with those in maternal serum (MS) and control serum samples. Results: Serum IL-2 concentrations in the UC were markedly elevated compared with those in MS and controls (p < 0.0001), decreasing significantly thereafter up to 5N (p < 0,001). IL-4 serum concentrations did not differ significantly between the UC, 1N and 5N samples; they were, however, markedly elevated compared with those in MS (p < 0.001, p < 0.0007 and p < 0.0001, respectively) and controls (p < 0.05, p < 0.01 and p < 0.006, respectively). IFN-γ serum concentrations were significantly lower in the UC compared with those in controls (p < 0.04), increasing significantly up to 5N (p < 0.03). Both IFN-γ/IL-2 and IFN-γ/IL-4 ratios increased significantly in 5N, compared with those in the UC (p < 0.001 and p < 0.03). Conclusion: Our findings indicate a differential cytokine balance at birth with enhanced expression of IL-2 and IL-4 against IFN-γ. However, a regularization of immune response seems to proceed quickly during the early neonatal life.

Objective: Atrial natriuretic peptide (ANP) plasma levels are increased in patients with valvular heart disease. The present study investigates possible changes after mitral or aortic valve replacement (MVR, AVR). Methods: In this prospective study, ANP plasma levels were measured in 11 patients undergoing MVR for mitral stenosis, in 11 patients undergoing AVR for aortic valve stenosis, and in 6 patients without heart disease undergoing thoracotomy for lung resection (control group). Blood samples were collected preoperatively (1 day before), during, and 8 days after the operation by serial blood sampling and were determined by radioimmunoassay method. ANP values were correlated with the duration of cardiopulmonary bypass (CPB), the aortic cross-clamping time, and the left atrial filling pressures. Results: ANP plasma levels were increased in all patients with valvular heart disease preoperatively and did not change during anesthesia or CPB; nor were they correlated with CPB duration or atrial filling pressures. The left atriotomy did not alter ANP plasma levels. The intracardiac surgical manipulations as well as CPB did not influence the ANP secretion intraoperatively and during the first postoperative week. Patients who underwent lung resection showed no change of ANP plasma levels perioperatively. Conclusion: ANP levels are not altered during and 1 week after valve replacement and, therefore, do not reflect hemodynamic changes perioperatively. © 2004 Elsevier Inc. All rights reserved.

The aim of this study was to evaluate factors that influence leptin levels in postmenopausal women. One hundred and forty-four postmenopausal women were evaluated cross-sectionally. In every woman a complete medical history was obtained, body mass index (BMI) was recorded and morning fasting blood was obtained for the determination of serum leptin, follicle stimulating hormone (FSH), estradiol, testosterone, Δ4androstendione, clehydroepiandrosterone sulphate (DHEAS) and insulin. In univariate analysis, age, BMI and insulin were positively correlated with serum leptin, while DHEAS showed a negative association with leptin concentrations (age r=0.21, p=0.005, BMI r=0.41, p=0.0001, insulin r=0.20, p=0.008, DHEAS r=-0.28, p=0.0001). In stepwise multivariate regression analysis serum leptin could be best predicted from BMI, serum insulin and serum DHEAS [leptin= (1.41 * BMI) - (0.01 * DHEAS) + (3.26 * insulin) -26.3; model r2=0.24, p=0.001]. In conclusion, BMI and serum insulin have a positive while serum DHEAS has a negative impact on serum leptin. Neither endogenous estradiol, nor endogenous testosterone are associated with leptin levels. Further studies are needed to elucidate the role of leptin in determining body weight and composition in postmenopausal women. © 2003, Editrice Kurtis.

The European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) opened a Register for European Chemists in 1997. The operation of the Register is undertaken by a Register Committee (EC4RC). During the last 5 years more than 1400 clinical chemists entered the register. In this article an update of the first Guide to the Register is given, based on the experience of 5 years of operation and the development of the discipline. The registration is valid for 5 year. In a second part the procedure and the conditions for re-registration are presented.

Background: After birth, apoptosis rates might slow down, compared to those in utero. Thus, factors, attenuating the apoptotic process, like the soluble forms of Fas/FasL system, may increase. Aim - study design: Soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations were measured in maternal serum (MS), umbilical cord (UC) and neonatal serum in the first (1N) and fifth (5N) days after birth in order to evaluate the alterations of these molecules during the early neonatal period. Subjects and methods: Soluble molecules were estimated in 35 healthy, appropriate for gestational age, full-term neonates, their mothers and in 25 healthy, nonpregnant women, age-matched to the mothers (controls), using enzyme immunoassays. Results: sFas concentrations in MS (p<0.01), UC (p<0.0001), 1N (p<0.0003) and 5N (p<0.02) were lower than those in controls. Neonatal sFas concentrations showed a significant increase from UC to 5N (p<0.001). In contrast, sFasL concentrations were significantly elevated in all neonatal samples (UC, 1N and 5N) compared to those in MS and controls (p<0.0001), showing also a significant elevation from UC to 5N (p<0.0001). Conclusion: Our results demonstrate increasing serum concentrations of the soluble molecules sFas and sFasL during the first days after birth, indicating possibly a gradual decrease of apoptosis in early neonatal life. © 2003 Elsevier Ireland Ltd. All rights reserved.

Objective: To determine postnatal changes in neonatal serum concentrations of interferon-γ (IFN-γ), interleukin-4 (IL-4) and its soluble receptor (sIL-4R). Methods: Forty-five healthy term neonates, 25 of the neonates' mothers and 27 healthy adults (controls) participated in the study. Cytokine concentrations were measured in blood samples from the umbilical cord, from the neonates on the 1st and 5th day after birth, from mothers and from controls. Results: IFN-γ concentrations were significantly lower in the umbilical cord, compared to concentrations in the controls (p < 0.04), and increased significantly from the umbilical cord to levels in neonates on day 5 (p < 0.03). In mothers and the umbilical cord, IFN-γ concentrations were dependent on the mode of delivery, being higher after vaginal delivery than after elective Cesarean section (p < 0.005; p < 0.006, respectively). IL-4 concentrations in the umbilical cord for 1-day and 5-day neonates were significantly elevated compared to those in mothers (p < 0.001; p < 0.0007; p < 0.0001, respectively) and controls (p < 0.05; p < 0.01; p < 0.006, respectively). sIL-4R concentrations in all neonatal samples were significantly elevated compared to those in controls (p < 0.0001), the highest being found in 1-day-old neonates. A strong negative correlation was found between IL-4 and sIL-4R concentrations in 1- and 5-day-old neonates (r = -0.48, p < 0.002; r = -0.45, p < 0.0065, respectively). Moreover, IFN-γ/IL-4 ratio increased significantly from the umbilical cord to 5 days of life (p < 0.03). Conclusions: Our findings indicate an earlier development of IL-4 than IFN-γ, which could be viewed as a developmental characteristic in the ontogeny of the immune system.

BACKGROUND: In contrast to cellular receptors, soluble receptors do not enhance the cellular activation because they do not have transmembranic and cytoplasmic parts, acting thereby as endogenous regulatory mechanisms against systemic functions of cytokines. Aim: To measure serum concentrations of the soluble interleukin-2 receptor (sIL2R), soluble interleukin-4 receptor (sIL4R), soluble interleukin-6 receptor (sIL6R), and soluble tumor necrosis factor-α receptor I and soluble tumor necrosis factor-α receptor II, during the perinatal and early neonatal period, in order to evaluate their role in activation of immune response in labor and the first days postpartum. Methods: Soluble receptor serum concentrations were determined by enzyme-linked immunosorbent assay, in 45 healthy, full-termed neonates during the first and fifth days after birth, in 25 of their mothers (MS), in 25 samples of umbilical cords (UC) and in 25 healthy adult donors age-matched with the mothers (controls). Results: Soluble receptor serum concentrations showed considerable changes during labor and early neonatal life, being significantly higher both in MS (except sIL6R) and in neonatal sample UC, first and fifth days after birth, compared with controls (p < 0.0001). Neonatal serum sIL2R and sIL6R increased significantly from birth to the fifth day, while the remaining receptors showed a rapid increase in the first day (p < 0.0001), declining significantly thereafter (p < 0.0001). Conclusion: Our Findings suggest that the elevated concentrations of all studied soluble cytokine receptors reflect the activation of immune response, and represent also regulatory protective mechanisms for mother and fetus-neonate against the systemic function of cytokines during labor and early neonatal life.

Recent studies suggest that leptin, the product of the obese gene, is produced by the placenta during pregnancy. The present study addressed the question whether second trimester maternal serum leptin could be altered by fetal Down syndrome or Edwards syndrome. Maternal serum leptin concentrations were measured in 18 pregnancies complicated with Down syndrome, six pregnancies complicated with Edwards syndrome and 183 uncomplicated pregnancies during the second trimester of pregnancy. The present results demonstrate that leptin concentrations in uncomplicated pregnancies slightly decrease from the 16th week of pregnancy, reaching a minimum of 18.8 ng/ml around the 20th week, and then rapidly increase to 28.2 ng/ml by the 24th week. Leptin correlation with maternal body weight decreases from r=0.695 at 16-17 week of gestation to r=0.544 at < 22 weeks of gestation. There was no significant difference between the mean MoMs of Down syndrome- (0.926) or Edwards syndrome- (0.960) affected pregnancies and normal pregnancies (1.002). A weak correlation (r=0.18, p<0.02) was observed between corrected leptin MoMs and human chorionic gonadotrophin (hCG) MoMs in normal pregnancies. It is assumed that around the 20th week of pregnancy placental leptin production is activated or at least is accelerated and it is added to the amount of leptin produced by maternal adipose tissue. Fetal Down syndrome or Edwards syndrome does not seem to alter maternal leptin concentration and therefore leptin cannot be used as a marker for these chromosomal abnormalities in the early second trimester of pregnancy. Copyright © 2002 John Wiley & Sons, Ltd.

Objective: To study the effect of 17β-estradiol+norethisterone acetate and raloxifene on the endometrium and uterine volume in postmenopausal women. Methods: Patients were randomly assigned to 17β-estradiol 2 mg+norethisterone acetate 1mg (E2+NETA) daily (n=90) or raloxifene HCl 60 mg (Evista) daily (n=43). Transvaginal sonography was done at baseline and at 6, 12 and 18 months, and at 6 and 12 months in-patients treated with E2+NETA and EVISTA respectively. Patients were asked to record bleeding-spotting episodes. Whenever required patients were referred for hysteroscopy±biopsy of the endometrium. Results: Patients under E2+NETA had a higher bleeding-spotting incidence (48.6%) compared with EVISTA (7.7%). Endometrial thickness increased significantly under E2+NETA as compared with baseline; however, at end point thickness reverted to baseline values. Evista had a non-stimulatory effect on the endometrium. Changes in uterine volume were not statistically significant. Conclusions: Both treatment regimens provided comparable uterine safety. However, raloxifene exhibited a more favorable safety profile on the uterus as expressed in the bleeding-spotting incidence and the effect on endometrial thickness and uterine volume. Transvaginal sonography appears to be a dependable method for monitoring the effect of treatment on the uterus. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Objective: To evaluate postpartum MCH changes in the early postpartum period, and to examine whether neonatal MCA is related to that in maternal serum (MS) or milk. Study design: MCA was measured by EIA on the second and fifth postpartum day in serum and BM from 30 lactating women and their single term neonates. Sera from 20 healthy women (controls), were also analyzed. Results: All neonatal antigen concentrations were below the cut-off level for MCA (11ng/ml). MS MCA was significantly increased compared with that in controls (P<0.00001), while antigen values in BM were highly elevated (P<0.00001), with a significant increase (P<0.0003) from the second to the fifth postpartum day. A strong correlation was found between the second and fifth day postpartum samples in MS, neonatal serum and BM MCA concentrations (rs=0.94, P<0.00001; rs=0.75, P<0.00001 and rs=0.69, P<0.0001, respectively). A significant correlation was also found in MCA values on the fifth postpartum day between neonatal serum and BM (rs=0.54, P<0.02). Conclusions: From these findings one may speculate on some ripening process in milk production and a possible transition of MCA from the neonatal gastro-intestinal tract into circulation. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Immunomediators seem to have a central role in the immune system of both human milk and newborn infants. CD31/PECAM-1 is an adhesion molecule, member of Ig gene superfamily, mediating cell-cell adhesion in both homophilic and heterophilic ways. Levels of the soluble form of PECAM-1 (sPECAM-1) were evaluated on the 2nd and 5th day postpartum in breast milk and serum paired samples from 20 lactating women as well as in time-matched serum from their single, term, healthy neonates. Concentrations of sPECAM-1 in breast milk (median, range) on both the 2nd (2.05 ng/ml, 0.0-7.2) and 5th day postpartum (0.89 ng/ml, 0.0-3.6) were about 10 and 20 times lower than those (mean ± SD) in controls (healthy adults) (19.83 ± 5.17, p < 7 × 10-8), showing a significant fall from the 2nd to the 5th day postpartum (p < 0.0005). Maternal serum sPECAM-1 values (mean ± SD) were significantly lower on the 2nd day postpartum (14.21 ± 5.15 ng/ml) than those in controls (p < 0.002), but reached control values on the 5th day postpartum after a significant rise (p < 0.0075). Neonatal serum sPECAM-1 values with no significant difference between the 2nd (14.4 ± 4.11 ng/ml) and 5th day of life (14.54 ± 4.99 ng/ml) were significantly lower than those in controls (p < 0.002). Values of sPECAM-1 in milk and sera of lactating mothers and their neonates on the 2nd day postpartum depended on the mode of delivery, being significantly lower after caesarean section (p < 0.034, p < 0.0075 and p < 0.035, respectively). In conclusion, our findings in the early postpartum period demonstrate that: (a) sPECAM-1 is present in human milk in low and decreasing concentrations; (b) the shedding of sPECAM-1 is an established component of the neonatal immune system from birth, though in lower concentrations than in adults, possibly reflecting its immaturity; and (c) the mode of delivery has a significant effect on sPECAM-1 values in milk and sera of lactating mothers and their neonates; the lower values after caesarean section may reveal a deranged endothelial homeostasis. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

An association between symptomatic carotid stenosis and recent infection with Chlamydia pneumoniae is reported. Thirty-five patients (20 symptomatic and 15 asymptomatic) with carotid stenosis of 70% to 90% underwent carotid endarterectomy. Endarterectomy was performed without patch and shunt; the average occlusion time of the internal carotid artery was 14 ±3 min. The atheromatic plaque and a portion of the thyroid artery were examined with polymerase chain reaction and peripheral vein blood was obtained for serologic detection of systematic infection, and lgG and lgM antibodies to C. pneumoniae by enzyme-linked immunosorbent assay. Twenty of 35 patients (57.1%) had increased titers of IgG antibodies to C. pneumoniae. Eight patients revealed IgG plus lgM antibodies; two of the eight had IgG, IgM, and positive findings on polymerase chain reaction. No C. pneumoniae was detected on the thyroid arteries. Sixty-five percent (13/20) of the patients with increased IgG antibodies to C. pneumoniae, 87.5% (7/8) with lgG + lgM, and 100% with lgG + lgM + positive polymerase chain reaction were symptomatic. Plaque morphology in association with symptoms did not reveal a significant correlation between soft plaques and symptoms, whereas the majority of the symptomatic patients had plaques of type III-V. Patients having recent contamination and positive polymerase chain reaction had a significant relationship between C. pneumoniae infection and symptomatic carotid disease. This supports the hypothesis that C. pneumoniae infection can produce a kind of instability of the carotid plaque. The results of this study demonstrate that patients with advanced atherosclerotic carotid disease have an increased incidence of C. pneumoniae infection. Recent infection could be responsible for instability of the carotid plaque, causing cerebral ischemic episodes.

Objective: To determine the concentration of angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and angiogenin) in the follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte. Design: Prospective study. Setting: Academic tertiary-care institution. Patient(s): IVF patients with unexplained or tubal factor infertility.Intervention(s): Analysis of VEGF, bFGF, and angiogenin FF and CM concentrations. Main Outcome Measure(s): Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations.Result(s): VEGF, bFGF, and angiogenin were determined in FF and CM. FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature. CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized. Positive correlations were observed between angiogenic factors in CM. Conclusion(s): VEGF, bFGF, and angiogenin (determined for the first time) are secreted in the FF and CM. Elevated CM VEGF concentrations, probably implying oocyte-cumulus complex hypoxia, are negatively associated with oocyte fertilization. Elevated FF angiogenin concentrations are positively associated with oocyte maturity, possibly indicating angiogenin's biological role beyond neovascularization. Copyright © 2001 American Society for Reproductive Medicine.

Objectives: To assess total homocysteine (tHcy) and folate levels in postmenopausal women and investigate whether age, menopause duration, kind of menopause and tobacco use had an effect on these levels. Methods: Total homocysteine and folate levels were measured in fasting blood samples of 200 postmenopausal women with normal thyroid and renal function tests. Patients were not receiving vitamins or hormone replacement therapy. Results: Total homocysteine levels increased significantly after 60 years while folate levels showed a decrease trend after 65 years. Menopause duration had no effect on folate levels and increased significantly tHcy levels after > 180 months duration. The kind of menopause did not influence tHcy and folate levels. Tobacco use reduced significantly folate levels. Conclusions: Age seems to be the principal factor influencing tHcy levels. We believe that decreased folate levels also reflect an age-associated inadequate dietary intake. Tobacco use did not alter tHcy levels; however, we found smoking to lower folate levels. © 2001 Elsevier Science Ireland Ltd. All rights reserved.

Objective - The purpose of this study was to evaluate thyroid function and TSH and cortisol (F) secretion in hyperandrogenemic women with nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (Group A) when compared with women with hyperandrogenemic symptoms (menstrual irregularities, hirsutism, acne, seborrhea and sterility) of other etiologies (Group B). Methods - Seventy-two women were subjected to stimulation of the adrenal cortex with i.v. ACTH administration in the early proliferative phase of the menstrual cycle. Basal plasma TSH, T3, T4, and FTI as well as basal and ACTH-stimulated plasma F and 17-hydroxyprogesterone levels were determined. Results - According to internationally accepted criteria and HLA haplotyping, we diagnosed 28 NC-CAH patients as well as affected heterozygotes of the disease. No significant difference was found in the plasma T3, T4, or FTI or F concentrations between the women of the two groups. On the contrary, plasma TSH levels were significantly lower in patients with 21-hydroxylase deficiency when compared to the women with hyperandrogenemic symptoms of other etiologies. Conclusion - The results of this study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to altered ACTH secretion patterns.

Objective: To assess the usefulness of Mucin-like carcinoma-associated antigen (MCA) in monitoring pregnant patients with breast cancer. Study design: Maternal serum (MS) and amniotic fluid (AF) antigen values were measured by an enzyme immunoassay in 30 pregnant women during the second trimester, in 28 during the third and in 26 at parturition. Sera only from 26 women in the first trimester and from 26 healthy, non-pregnant women (controls) were also analyzed. Results: Maternal serum MCA concentrations increased significantly with gestational age (p<0.0001). The frequency of elevated serum values was 5% in the first, 35% in the second and 100% in the third trimester and at parturition. Antigen values in AF were markedly higher than those in MS (p<0.0001) and increased also significantly with advancing gestation (p<0.0001). A strong correlation was observed between MS and AF antigen values (r=0.77, p<0.0001). Maternal serum values at parturition were dependent on the mode of delivery, being higher in the cases who delivered vaginally, compared to those delivered by elective caesarean section (p<0.006). Conclusion: Our data suggest that pregnancy affects significantly maternal serum MCA. Consequently, MCA seems to be a non-reliable marker in monitoring pregnant patients. Copyright ?? 2001 Elsevier Science Ireland Ltd.

OBJECTIVES: Maternal serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in preeclampsia to investigate whether these molecules could be helpful with regard to this pregnancy complication. STUDY DESIGN: The study population was composed of 30 preeclamptic patients with a mean gestational age of 35.5 ± 4.6 weeks and 20 age-matched and gestational age-matched normotensive uncomplicated pregnancies (controls). Blood samples from 7 of the 30 preeclamptic patients and 15 of the 20 controls in the second trimester were also analyzed. Data were analyzed by parametric methods. RESULTS: Significantly higher maternal serum sVCAM-1 levels were found in both groups of preeclamptic patients with and without fetal growth restriction (981 ± 145 ng/ml; n = 13;p < 0.0005 and 846 ± 84 ng/ml;p < 0.02, respectively) compared with controls (668 ± 186 ng/ml). In contrast, no significant difference was found in maternal serum sICAM-1 levels between preeclamptic and nonnotensive pregnancies, or in both adhesion molecules (1) in the controls between second and third trimester samples and (2) in the second trimester between pregnant women who developed preeclampsia later and gestational age-matched controls. CONCLUSION: These findings show a selective significant elevation of maternal serum sVCAM-1 in preeclampsia, with the highest values in cases complicated with fetal growth restriction, perhaps reflecting its angiogenic function. Hence, sVCAM-1 could be helpful in the diagnosis of this fetal complication in preeclampsia.

Aim: TPS concentrations were measured throughout normal pregnancy in maternal serum (MS) and amniotic fluid (AF) in order to evaluate the usefulness of TPS in the follow-up of pregnancy breast cancer patients. Patients and Methods: Following informed consent, 30 pregnant women during the 2nd trimester, 28 during the 3rd and 26 at parturition were included in the study. For comparison, 28 women in the 1st trimester and 28 healthy, non pregnant women (controls) were also studied. Both MS and AF antigen values were measured by an enzyme immunoassay (BEKI Diagnostics). Results: Maternal serum TPS concentrations increased significantly with gestational age (p < 0.0001), being significantly higher in the 3rd trimester and during labor than those in the controls (p < 0.0001). Amniotic fluid TPS values were markedly elevated, compared with those in MS (p < 0.0001, paired-t-test), declining significantly from the 2nd to the 3rd trimester (p < 0.0015) and labor. Both MS and AF TPS values during labor depended on the mode of delivery, being higher in the cases terminated by vaginal delivery, compared to those by elective cesarean section. Conclusion: Maternal serum TPS values are influenced significantly by pregnancy, and thus, this antigen, as tumor marker seems to be reliable only during early pregnancy.

Both E- and L-selectin are cell adhesion molecules. E-selectin is expressed by activated endothelial cells, whereas L-selectin by quiescent leukocytes and is rapidly cleaved off after activation. Both selectins take part in the first step of the 'adhesion cascade', the 'rolling of leukocytes', leading to the extravasation of the white cells to the sites of inflammation, infection or damage. For this reason their soluble forms (sE- and sL-selectin, respectively), are considered early and reliable markers of the immune activation and response. Moreover, sE-selectin has been reported to be a potent angiogenic factor and a reliable marker of infection and sepsis in neonates, as well as endothelial activation, while sL-selectin of the leukocyte function and maturity. Following informed maternal consent, we evaluated prospectively by ELISA, sE- and sL-selectin in the serum of 40 (19 females, 21 males), healthy, term, infection-free neonates, on the second and fifth day of life, and compared them with the respective values in 20 healthy adults (10 females, 10 males), with the purpose of examining the pattern of their values in the early postpartum days, and to establish reference values for both selectins. Values (mean±S.D.) of sE-selectin both on the second (139±48 ng/ml) and fifth day of life (111±35 ng/ml) were found to be highly increased, as compared with those in controls (48±13 ng/ml; P<4x10-11 and P<4x10-10, respectively), while sL-selectin values on both the second (674±223 ng/ml) and the fifth day of life (684±221 ng/ml), were significantly lower than those in controls (938±181 ng/ml); P<0.0001 and P<0.0003, respectively). A significant decrease was noted in sE-selectin values, from the second to the fifth day of life (P<10-7), while sL-selectin values showed no significant change in the same time interval. A strong correlation was found between values on the second and the fifth day of life of both sE- and sL-selectin (r(P)=0.885 and r(P)=0.813, respectively; P<0.00001). Neonatal values of both sE- and sL-selectin on the second or on the fifth day of life, did not depend on the perinatal factors, neonatal sex, or birth weight, mode of delivery, and maternal age or parity. In conclusion, in the very early neonatal period, our findings of highly increased sE-selectin, while low sL-selectin, suggest an immune and more specifically endothelial activation and an immature and decreased leukocyte function. Copyright (C) 2000 Elsevier Science Ireland Ltd.

In breast milk and paired serum from 70 lactating women and 40 of their term, infection-free neonates, on the 2nd and 5th day postpartum slCAM-1, sVCAM-1, sE- and sL-selectin were measured by ELISA and compared with those in 26 healthy adults (controls). Seven infant formulas and fresh milk from five cows were also analyzed. Human colostrum values of slCAM-1, sVCAM-1 (similar to those in maternal and control serum), sE-selectin and sL-selectin (~10 and ~100 times lower than in maternal and control serum) were significantly higher than those in milk, while they varied widely. None of the adhesion molecules was detected in fresh cow's milk or infant formulas. Exclusively breast-fed infants showed significantly higher values of slCAM-1 and sL-selectin on the 2nd day of life than those supplemented also with formula. Only slCAM-1 values correlated positively between colostrum and time-matched maternal serum. These findings show in human milk important amounts of slCAM-1 and sVCAM-1 but minimal amounts of sE- and sL-selectin, which could affect the immune system of the neonate.

We aimed to study maternal and infant serum leptin concentrations during the perinatal period and their relationship to the body weight of mothers and newborns. Serum leptin values were measured by enzyme-linked immunoadsorbent assay (ELISA) (R&D systems) in 26 healthy, term neonates during the first (N1) and fifth (N5) day after birth and were compared with serum leptin values in maternal blood (MS), amniotic fluid (AF), and umbilical cord (UC) at delivery. Twenty-five healthy, nonpregnant women, age and body weight-matched to the mothers, were used as controls (C). Infant serum leptin concentrations declined significantly after birth from UC to the N5 samples (p < 0.003). MS leptin values were significantly higher than UC, N1, N5, and C values (p < 0.001), while AF values were significantly lower than in controls (p < 0.001). UC, but not MS leptin values correlated significantly with the birth weight of infants (r = 0.6; p < 0.03). The elevated values of leptin in maternal serum and the regressing pattern of infant leptin values after birth suggest an additional, probably placental source of this protein during pregnancy, possibly contributing to the regulation of fetal body weight.

Aim: To measure MCA and CA153 concentrations in maternal serum (MS) and amniotic fluid (AF) paired samples during normal pregnancy, in order to evaluate the usefulness of these markers in monitoring pregnant patients with a history of breast cancer. Patients and Methods: Serum and AF MCA and CA153 values were measured in 20 pregnant women during the 1st trimester, 29 cases in the 2nd, 26 in the 3rd and 20 at parturition and compared with those of 20 healthy, age-matched, non pregnant women (controls). Results: MS values of MCA increased significantly with gestation age (p < 0.0001), being higher in the 3rd trimester and in labor than in control values (p < 0.0001). MCA values in AF were remarkably higher than those in MS and increased significantly with advancing gestation (p < 0.0001). In contrast, CA153 values in AF, which were marginally higher than in MS, did not differ significantly with the progression of pregnancy. Conclusions: Maternal serum MCA values are significantly influenced during pregnancy. Thus, this marker seems to be reliable only during early pregnancy. In contrast, CA153 remains a useful marker in monitoring pregnant breast cancer patients.

Objectives: The non-penetrating Vascular Clip System (VCS) was tested experimentally and compared with the conventional suture method on the venous system. Materials and Nethods: In five pigs, 30 transverse venotomies were carried out in the jugular and renal veins, and vena cava. Fifteen venotomies were reconstructed using autosuture clips and 15 using the standard needle and suture method. Eight weeks later, following phlebography, the specimens were examined macro- and microscopically. Results: For both methods, the veins remained patent; however, significant stenosis of 8.9% (95% CI: 0.6-17.1) for the renal vein and 8.5% (95% CI: 1.2-15.7) for the vena cava occurred when the suture technique was used. The intima to media height ratio remained the same. The anastomosis time with the clips was significantly shorter (p < 0.05), while the endothelium remained intact without any hyperplasia or inflammatory changes, which are usual findings of the suture technique. Conclusion: Early and mid-term results show that the VCS clipped anastomotic technique seems to be effective and acceptable for venous reconstructions.

Background. Comparison of carotid endarterectomy in patients with and without occluded contralateral carotid artery. Methods. Design: evaluation of results without using shunt or patch. Setting: Aretaeion Hospital, Medical School, University of Athens. Subjects: 235 patients, divided into group I of 40 patients with and group II of 195 patients without occluded contralateral carotid artery. Intervention: carotid endarterectomy under general anesthesia. Main outcome measures: heparin administration, stable hemodynamic status during clamping, short duration monitoring postoperatively. Results. Postoperative morbidity of both groups was 2.5 (6/235) and mortality 1.7 (4/235). Group I: mortality rate was 2.5 (1/40) major and minor stroke each 2.5 (1/40) and group II: 1.5 (3/195) and 1 (2/195) respectively (NS). Four to 108 months later, 30 (12/40) of group I and 21 (41/195) of group II died. Conclusions. Endarterectomy of the carotid artery under general anesthesia without use of shunt and patch in patients with or without occlusion of the contralateral carotid artery presented the same comparative results. Candidates for carotid endarterectomy should be screened systematically for coronary disease preoperatively and annual stress testing postoperatively, tactics which may improve early and late mortality rate after carotid surgery.

Inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured in the serum of healthy, term neonates on the first (N1), fifth (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and in adult controls. All three cytokines were significantly elevated in N1 and N5, compared with those in UC and adults (P<0.0001). IL-1β and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-α increased significantly from N1 to N5 and declined thereafter. TNF-α values in UC were significantly higher than in adults, but lower than in N40 (P<0.0001), while IL-1β and IL-6 values in UC did not differ from those in N40 and in adults. IL-1β and IL-6, but not TNF-α values in MS were significantly higher than those in controls (P<0.0001). IL-1β values in MS were significantly higher than those in N1 (P<0.0001), while those of IL-6 and TNF-α were significantly lower (P<0.0001). Moreover, IL-1β values were dependent on the mode of delivery in N1 (P<0.001), in MS (P<0.02) and in UC (0.03), while IL-1β and TNF-α values in N1 were strongly interrelated (r=0.7; P<0.01). In conclusion, the increased values of IL-1β, IL-6 and TNF-α during the perinatal period might reflect a newborn immune response to the stress of delivery and to environmental changes after birth. Copyright (C) 1999 Elsevier Science Ireland Ltd.

The aim of this study was to evaluate the effect of increasing postnatal age on soluble intercellular adhesion molecule-1 (sICAM-1), a very early and sensitive marker of immune activation and response in the serum of newborn infants. Serum sICAM-1 was measured by EIA (T Cell Diagnostics) in 20 healthy adults (controls) and in 43 (24 females/19 males) healthy neonates, of whom 28 were full term, and 15 were born at a gestational age between 35 and 38 weeks of pregnancy, on the 1st, 5th and 30th day of life. Neonatal serum sICAM-1 values showed a very significant increase (P < 0.01) from the 1st day (137.3 ± 62.0 ng/ml) to the 5th day (259.3 ± 124.0 ng/ml) and then to the 30th day of life (415.0 ± 114.0 ng/ml), being significantly lower on the 1st day (P < 0.01), whereas significantly higher on the 30th day of life (P < 0.05), than those in healthy adults (305 ± 195 ng/ml). Serum sICAM-1 values on the 1st day of life depended on both the mode of delivery (significantly higher in neonates born vaginally) and the gestational age at birth (significantly lower in those born at a gestational age over 38 weeks). A significant strong correlation was found in sICAM-1 values between the 1st and the 5th day following delivery (r(p) = 0.77, P < 0.009). Conclusion: The results of this study demonstrate a significant rise of serum sICAM-1 during the 1st month of life in healthy neonates suggesting a progressively increased activation of the neonatal immune system.

The purpose of this prospective study was to determine the incidence of any form of 21α-hydroxylase deficiency among Greek women with hyperandrogenic symptoms, and to test the predictive value of basal serum 17-hydroxyprogesterone (17-OHP) in the early follicular phase as a screening index for patient preselection to adrenocorticotropic hormone (ACTH) testing. Eighty-eight unselected women with hyperandrogenic symptoms were examined in the Gynecological Endocrinology Unit of the Second Department of Obstetrics and Gynecology of Athens University. Using the ACTH-stimulated 17-OHP values at 60 minutes (17-OHP60) the study population was divided into four groups (A, B, C and D). Clinical and basal hormonal parameters as well as serum 17-OHP60 values and human leukocyte antigens were studied. Both clinical and basal hormonal parameters could be used to distinguish only patients with severe 21α-hydroxylase deficiency (group A). In contrast, patients with moderate non-classical congenital adrenal hyperplasia (NC-CAH; group B), heterozygotes for NC-CAH (group C), and unaffected females (group D) can be diagnosed and classified only by serum 17-OHP60 values. In conclusion, the incidence of NC-CAH in Greek females with hyperandrogenic symptoms is 3.4%. The positive predictive value of basal 17-OHP is only 13% for this disease. Only 17-OHP60 helps to diagnose and classify moderate and mild forms of NC-CAH. Thus, it seems that ACTH testing is imperative in every subject suspected of this enzymatic disorder.

Objective - To determine the degree of hypophyseal deficiency in Kallmann's syndrome, and the effects of Gn-RH priming and HRT. Patients and Methods - Seven female patients with complete Kallmann's syndrome were subjected to dynamic tests (chlorpromazine, TRH and double Gn-RH provocation test) immediately after their first admission to the hospital. In five patients the diagnosis was established for the first time (unprimed patients), while in the other two cases the diagnosis has been established earlier and the patients were already receiving hormonal replacement therapy (HRT-primed patients). In the 5 unprimed patients, 100 μg Gn-RH s.c. were administered daily for 28-32 days and the double Gn-RH test was repeated immediately after. Results - The gonadotropic response of the unprimed patients in the administration of Gn-RH was insufficient, mainly in the second stimulation, with secretory dominance of FSH (ratio LH/FSH <1), while after the monthly Gn-RH priming, the gonadotropic response to Gn-RH had improved, with a considerable increase in the peak values of plasma FSH and LH after both stimulations, and the LH/FSH ratio was reversed to >1. In the two primed patients, the gonadotropic response to Gn-RH administration was better in both stimulations than that of the unprimed patients. Conclusions - Both the short-term Gn-RH and the long-term HRT priming improve the secretory promptitude of the hypophyseal cells for both gonadotropins, while after long-term Gn-RH priming the LH-secreting cells are capable of both release and synthesis of the hormone, as can be seen by the results of the second stimulation in the Gn-RH primed patients. Consequently, for women with Kallmann's syndrome who wish to become pregnant, ovulation induction and conception can be achieved sooner and with less cost if they are previously primed.

Pretreatment values of CEA, CA125, SCC and TPS were measured in 130 women with 1) ovarian carcinoma (n = 25), 2) breast cancer (n = 20), 3) endometrial cancer (n = 14), 4) cervical squamous cell carcinoma (n = 20), 5) cervical adenocarcinoma (n = 9) and 6) benign gynaecological diseases (n = 42) in order to evaluate the usefulness of multiple markers in diagnosing and monitoring patients with gynaecological cancer. Antigen values were significantly higher in the cancer groups than those in the benign one (p < 0.0001). CEA values were significantly elevated in the 2nd and 5th groups, CA125 in the 1st and 5th, SCC in the 4th and 5th, and TPS in the 1st, 2nd and 5th compared to the remaining groups (p < 0.04-p < 0.0001). In advanced stage diseases, significantly higher antigen values, except for SCC, than those in limited rumours were measured (p < 0.05-p < 0.0001). In conclusion, our results suggest that, multiple markers may be more efficienti than the use of single markers in accurately identifying malignant from benign gynaecological diseases and in monitoring cancer patients.

SERUM levels of IL-1β, IL-6 and TNF-α were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine Values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1β and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-α increased significantly from N1 to N5 and declined thereafter. MS∞IL-1β and IL-6, but not MS∞TNF- α, were significantly higher than those of controls (P<0.0001). IL-1β values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1β, IL-6 and TNF-α during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.

Maternal serum (MS) and amniotic fluid (AF) antigen concentrations were measured, by a microparticle EIA, in 28 pregnant women during the 2nd trimester, in 27 during the 3rd and in 34 during labor. Extremely elevated and scattered over a broad range antigen values were observed in AF, compared to those in MS samples (p < 0.0001). CEA values in both MS (100% < 5 ng/mL) and in AF did not differ significantly with advancing gestation, while CA125 in MS (6.5% > 32.5 U/mL) and in AF declined significantly with gestational age (p < 0.0001). In contrast SCC values in both MS (42.5% > 1.5 ng/mL) and in AF increased significantly with the progression of pregnancy (p < 0.0001). Amniotic fluid CA125 and less prominent SCC values were significantly higher in the 2nd trimester pregnancies, complicated by fetal anomalies, compared to those in normal pregnancies (p < 0.02 and p < 0.05 respectively). Serum CA125 was lower in the prolonged pregnancies (p < 0.05), while CEA and SCC in AF were significantly elevated (p < 0.003 and p < 0.01, respectively). A good correlation was found in CA125 and SCC values between MS and AF (r = 0.43, p < 0.0001; r = 0.32, p < 0.004 respectively), while no correlation was observed between MS and AF CEA values. In conclusion, the presence of considerable CEA, CA125 and SCC levels in amniotic fluid during pregnancy suggests their involvement in biological functions, associated with fetal development and maturation. Maternal serum CEA, in contrast to CA125 and SCC, is not influenced by pregnancy, remaining a reliable tumor marker in monitoring also pregnant cancer patients.

Carcinoembryonic antigen (CEA), CA125, and squamous cell carcinoma antigen (SCC) were evaluated in paired vaginal fluid and serum samples from 69 women, mean age 40.6 (20-78) years. Fifteen of the subjects were normal females (controls), 12 were pregnant, 20 had benign gynecological diseases, 5 presented severe cervical dysplasias and 17 suffered from cancer of the genital tract. Highly elevated CEA, CA125 and SCC concentrations (median, range) were found in vaginal fluid: 186 ng/ml (12-5 420); 890 U/ml (54-65 000); 1 600 ng/ml (27-13 000) respectively, compared with those in the paired serum samples: 1 ng/ml (0.5-8.6); 12 U/ml (3.0-1 590); 1 ng/ml (0.3-19). Vaginal fluid CEA, CA125 and SCC values were significantly different among the five studied groups (p < 0.0002; p < 0.02; p < 0.002 respectively), being significantly higher in the patients with benign gynecological diseases, compared with those in the patients with malignancies of the genital tract (p < 0.0001; p < 0.02; p < 0.005), and those in controls (p < 0.02; p < 0.007; p < 0.02 respectively). The results of this study suggest that: 1) CEA, CA125 and SCC seem to be normal constituents of vaginal fluid. 2) The distribution of CEA, CA125 and SCC between vaginal fluid and the circulation is affected by pregnancy, inflammation and cancer of the genital tract.

Background: Cytokines are considered as part of host defence to infection or injury. Material and Methods: Pretreatment values of TNF and sIL-2R were measured in 132 women with a) ovarian carcinoma (n = 25), b) breast cancer (n = 20), c) endometrial cancer (n = 15), d) cervical squamous cell carcinoma (n = 19), e) cervical adenocarcinoma (n = 11) and f) benign gynecological diseases (n = 42) in order to evaluate whether these cytokines could be useful in the discrimination of malignant from benign gynecological diseases. Results: Both TNF and sIL-2R were significantly higher in all cancer groups together (mean ± SD:30 ± 11 pg/mL and 1293 ± 465 U/mL respectively), than those in the benign group (16.0 ± 6 pg/mL and 626 ± 233 U/mL, respectively; p < 0.001), while no significant differences were found for TNF and sIL-2R values in the five cancer groups. Significantly higher cytokine values were measured in the advanced stage diseases (33 ± 11 pg/mL and 1705 ± 192 U/mL), than those in the limited cancer (26 ± 12 pg/mL, p < 0.05 and 916 (521 U/mL, p < 0.001). Conclusions: Our results suggest that, cytokines may be useful in the discrimination of malignant from benign gynecological diseases and in monitoring tumor activity in patients early in the malignancy process.

The authors investigated 125 patients suffering from primary Raynaud's phenomenon by the following laboratory hematologic parameters: (1) cryofibrinogen and cryoglobulins; (2) serum albumins and immunoglobulins IgG, IgA, and IgM, as well as complement factors C3 and C4; (3) clotting inhibitors, antithrombin III, protein C and protein S, as well as α1 antitrypsin. Results were as follows: 77 (62%) patients had cryofibrinogen in their blood plasma, 50 (40%) patients had precipitation of cryoglobulins, and 65 (52%) patients had an increase of α2 globulin in the serum electrophoresis. Of the immunoglobulins, IgM was found increased in 42 patients (34%). Of the clotting time inhibitors, antithrombin III (AT III) had a lower activity in 50 (40%) patients as compared with that of normal subjects. Protein C, protein S, and α1 antitrypsin levels were lower in 21 (16.8%), 13 (10.4%), and 10 (8%) of patients, respectively. Statistical analysis of the results showed that all the protein fractions except for γ- globulin presented a statistically significant difference as compared with those of the controls (P <0.0001). Immunoglobulins IgG and IgA of the patients were significantly lower than those of the normal controls (P <0.001). The C3 and C4 factors of the complement presented statistically significant lower values (P < 0.001 and P < 0.0001 respectively). Finally, AT III appeared in lower values than those of the normal controls, being statistically significant (P < 0.0001). These results suggest that patients with primary Raynaud's phenomenon present changes in the levels of certain hematologic parameters, a fact that is probably connected with etiology. Thus further study and assessment might contribute to the diagnosis, discovery of the subjective systemic etiology, and better therapeutic management of Raynaud's phenomenon.

Twenty-one women presenting with different diseases, with absolute or relative contraindications to hormonal contraception or the use of intrauterine devices, received 300-600 μg/day buserelin intranasally from the 1st to the 21st day, and 5 mg/day norethisterone acetate orally from the 16th to the 23rd day of the cycle for a total of 245 cycles. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and testosterone were determined on days 3-5 and 13-15 of the cycle, while progesterone determinations and ovarian sonography were performed during the second half of the cycle. According to progesterone values, 92.7% of the treatment cycles were anovulatory, while in one cycle pregnancy was detected (0.4%). Values of serum LH, FSH and estradiol were low, and in most of the cycles ovarian follicular development was limited to follicles ≤ 11 mm. In 21 treatment cycles (9%), statistically significant increases in FSH (p < 0.0001) and LH (p < 0.02), as well as ovarian proliferation to preovulatory follicles or luteinized follicles, were found. It appears that in spite of the high cost of medication and monitoring of patients, this regimen could be useful as an alternative in cases where other forms of contraception are contraindicated or have failed.

The polypeptide angiogenin, a normal constituent of human plasma, might be involved in endothelium homeostasis, angiogenesis, and neovascularization accompanying various diseases. This study aimed at determining angiogenin serum concentrations in the perinatal period of healthy newborns and at forming a baseline for this protein, which in the future may serve as a diagnostic index in developmental errors of the placenta and/or newborn. One milliliter of blood was drawn on d 1 and 4 of life from 30 healthy full-term neonates, and angiogenin serum concentrations were measured by an enzyme immunoassay using a commercially available kit. In 10 cases angiogenin serum concentrations were also measured in the maternal serum before delivery and in the umbilical vein serum. Angiogenin serum concentrations (μg/L) were significantly higher in maternal serum (225.7 ± 49.6) compared with umbilical vein serum (119.0 ± 34.2) (p < 0.0002), as well as that compared with day 1 (166.4 ± 44.9) (p < 0.01) but not to d 4 neonatal serum (240.8 ± 52.6). Angiogenin serum concentrations showed a statistically significant increase from d 1 to 4 (p < 10-7), as well as from umbilical cord serum to d I neonatal serum (p < 0.0002). A statistically significant correlation existed between values in umbilical cord serum and d I neonatal serum (r = 0.84, n = 10, p < 0.002) and between those in d I and 4 neonatal serum (r = 0.37, n = 30, p < 0.04). Sex, birth weight, or mode of delivery did not influence angiogenin serum concentrations. We conclude that a rapid increase of angiogenin serum concentrations to maternal levels takes place during the first four postnatal days in healthy full-term neonates.

Methods. Twenty-four healthy subjects and 16 patients with lymphedema and lipedema were studied with MRI and ultratomography. Results. In chronic lymphedema, ultrasonography revealed a statistically significant increase of the subcutaneous fat without difference in skin thickness as compared to the healthy subjects. MRI revealed in lymphedema a statistically significant increase of skin thickness + subcutaneous tissue + muscular mass (p = 0.048); in lipedema, a statistically significant increase of skin thickness and subcutaneous tissue (p < 0.0001) as compared to the healthy controls. Conclusions. MRI offers strong qualitative and quantitative parameters in the diagnosis of lymphedema and lipolymphedema, while ultrasonography is expected to improve its diagnostic efficiency with the aid of high frequency echo with more sophisticated resolution apparatus. Age, weight and height of the patient as well as duration of the disease do not seem to affect the above-mentioned parameters.

Objective: To determine whether failure to achieve pregnancy after repeated ET after ovum donation was due to an endometrial defect or to the embryo quality. Design: Retrospective data analysis. Setting: A private infertility center. Patient(s): Four hundred sixty-seven donors (513 cycles) undergoing IVF donating oocytes to 266 recipients (423 cycles). Intervention(s): Hormonal endometrial preparation with increasing dosages of valerate E2 (2, 4, and 6 mg) and 100 mg of P. Main Outcome Measure(s): Pregnancy rates (PRs) and abortion rates in patients undergoing one to seven ETs after ovum donation. Result(s): Pregnancy rates in recipients that had one or two ETs were significantly higher (34.8%) compared with those of recipients having three or more ETs (15.1%). Abortion rates were significantly higher (54.5%) in recipients repeating more than three ETs than in the recipients having one or two ETs (29.1%). Conclusion(s): Recipients that had failed to establish a pregnancy after two ETs had a lower PR in successive attempts, possibly because of a defect of their endometrial lining.

a-i.r Inhibin, has been recently proposed as a useful tumor marker for mucinous ovarian carcinomas (Ca), as the widely used tumor marker for ovarian malignancies, CA125 is efficient only in nonmucinous ovarian Ca, and, together with CEA, fails to detect minimal disease and show long half-life in serum after successful surgery. Moreover, conflicting evidence has been reported as to whether inhibin in ovarian malignancies is the biologically active dimer α-βA inhibin or the inactive free α-subunits and inhibin precursors. Serum α-βA i.r inhibin, CA125 and CEA were measured preoperatively and 8 days postoperatively in 39 postmenopausal patients with ovarian cancer (13 mucinous, 15 serous and 11 difference other ovarian Ca) in comparison with 20 age-matched healthy women (Controls), 18 patients with benign ovarian tumors and 10 patients with nonovarian gynecological malignancies. Serum α-βA i.r inhibin values were very low in controls (0.121 U/ml; 0.060-0.250) while they were greatly elevated in both benign (67% sensitivity) and malignant ovarian tumors (100% sensitivity in mucinous Ca, 80% in serous and 90.9% in other ovarian, 0.250 U/ml). In contrast, in non-ovarian malignancies no increased values of α-βA inhibin were found (0% sensitivity). Our results on the sensitivity of CA125 and CEA are in agreement with previous studies. After successful surgery the very high concentrations of α-βA i.r inhibin were reduced very rapidly (8 days) to normal postmenopausal values in contrast to those of CA125 and CEA, that remained elevated. Serum α-βA i.r inhibin seems to be very useful in monitoring after treatment the patients with any type of ovarian malignancy and specifically those with mucinous ovarian cancer.

Objective: To compare the pregnancy rates achieved by intrauterine insemination or timed intercourse in gonadotrophin stimulated cycles in couples whose only detectable abnormality was poor sperm quality. Design: Sixty-two couples with primary or secondary infertility due to male factor entered the study. The 62 couples were randomly equally divided into two groups. Each group began one of the two treatment modalities (controlled ovarian hyperstimulation in conjunction with timed intercourse or intrauterine insemination) for three consecutive cycles and then switched to the alternative treatment after one rest cycle, if pregnancy was not achieved. Results: Five pregnancies (3.9%) were achieved after 128 cycles with timed intercourse and 15 pregnancies (11.5%) after 130 cycles with intrauterine insemination. The difference was found to be statistically significant (P < 0.05). Conclusion: We suggest that intrauterine insemination during hMG stimulated cycles improves the pregnancy rates of couples whose only detectable abnormality is poor sperm quality.

Late onset congenital adrenal hyperplasia due to 21α-hydroxylase deficiency (LO21OH def), as many other diseases, is the cause of hirsutism, menstrual disorders, infertility (PCO-like symptoms). We evaluated the reliability of a new biochemical marker for screening LO-21OH def in 47 women with PCO-like symptoms and 11 men, members of their families, comparing the results of separation using this new marker with those of HLA-haplotyping in 21 members of the patient population. All subjects were stimulated with 0.25 mg synthetic ACTH iv. Serum progesterone (P), 17-hy-droxyprogesterone (17-OHP) and cortisol (F) at 0, 15, 30, 45 and 60 min following ACTH administration were determined and the new marker, namely the difference between 60min and 0min of the ratio F/17-OHP [Δ F/17-OHP (60 min–0 min)] was calculated. According to the established biochemical criteria for the detection of LO-21OH def cases, (Gutai 30 min ≥12 ng/dl/min and 17-OHP 60 min ≥12 ng/ml for severe 21-OH def and Gutai 30 min<6.5 ng/dl/min and 17-OHP 60 min<5 ng/ml for “healthy” individuals regarding 21-OH def) two groups, A and B respectively, were separated from the patient population. In group A (n=8), with LO-21 OH def, the new marker showed negative values in all cases, while in group B (n=9), without LO-21 OH def, this marker was positive. The remaining subjects, depending on the results of the new marker were separated in 2 subgroups, Cneg (n=28), with negative values, composed, consequently, of members with 21-OH def and Cpos (n=13), with positive values, composed, consequently, of subjects with absence of LO-21OH def. HLA-typing was in agreement with the results of screening by the new marker, in 20 out of 21 cases, while there was only one false negative result. In conclusion, the proposed biochemical marker ΔF/17-OHP (60 min–0 min) seems to be a reliable parameter for the LO-21OH def detection among young women with PCO-like symptoms as well as males suspected for congenital adrenal hyperplasia. © 1995, Italian Society of Endocrinology (SIE). All rights reserved.

Objective: To study the effect of pentoxifylline on sperm motility, oocyte fertilization, embryo cleavage, and quality as well as pregnancy outcome on asthenospermic patients participating in an IVF program. Design: Prospective randomized study. Setting: Private IVF unit. Patients: Ninety seven couples, 24 of whom were repeating IVF. Two semen specimens were obtained from each patient and each specimen was divided equally into two parts, nontreated (control semen) and pentoxifylline-treated (treated semen). Main Outcome Measure: Sperm progressive motility, oocyte fertilization. Results: Overall and progressive motility did not differ significantly between the two semen specimens. There was a significant increase in the progressive motility of the pentoxifylline-treated semen compared with control semen. No significant difference was noticed between control and treated semen in fertilization rate, cleavage rate, embryo quality, and pregnancy rate. The percentage of patients who fertilized only with control semen (9.3%) was not significantly different from that of patients who fertilized only with treated semen (10.3%). Couples who were repeating IVF did not show significant difference in fertilization between the present study and previous attempts. Conclusion: Our results showed that although the sperm progressive motility is improved after pentoxifylline treatment, it is doubtful whether this effect is of any clinical significance.

Serum α-immunoreactive inhibin was evaluated in 16 male renal transplant recipients with stabilized renal function of mean age 38.5 ± 10.7 years and was compared to that in sex- and age-matched 17 haemodialyzed patients; 10 patients with chronic renal failure and 26 healthy normal men (controls). Serum LH, FSH, prolactin and testosterone were also measured simultaneously, in the same samples. In renal transplant recipients, inhibin was found significantly higher than that in controls (P<0.001), 25% however of the values were in the normal range. In contrast, all haemodialyzed patients showed highly elevated inhibin values (P<0.0001). In patients with chronic renal failure values of inhibin were also highly elevated compared to those in normals. A negative correlation was noticed between inhibin and FSH only in controls (r(s) = -0.610, P<0.005). In renal transplant recipients, inhibin showed a strong correlation with serum creatinine (sCr) (r(s) = 0.710, P<0.008), while in the case of graft rejection the rise of sCr was immediately followed by a parallel increase of inhibin. In conclusion, the highly elevated inhibin in uraemic men not improved by haemodialysis and persistent after successful renal transplantation, might be implicated in the pronounced hypergonadotropic hypogonadism of haemodialyzed patients and the remaining dysfunction of hypothalamic-pituitary-testicular axis in renal transplant recipients.

The aim of this study was to classify the degree of 21αhydroxylase deficiency in patients suspected for non-classic 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). In 66 selected subjects (45 young women with polycystic ovary (PCO)-like symptoms and members of their families, of whom 12 were men), progesterone, 17-hydroxyprogesterone (17-OHP) and cortisol were measured at 0, 15, 30, 45 and 60 min after adrenocorticotropic hormone (ACTH) stimulation. The markers [(17-OHP at 30 min - 17-OHP at 0 min) + (progesterone at 30 min - progesterone at 0 min)]/30 proposed by Gutai and the ratio of cortisol to 17-OHP at 30 min (cortisol30/17-OHP30) were calculated and cluster analysis was performed using the above two markers and 17-OHP at 60 min (17-OHP60). Our patients were grouped by cluster analysis into four Groups: I, II, III and IV (n = 3, 11, 35 and 16, respectively) with (1) Gutai (x±SE) 107.0±21.7, 29.9±4.4, 10.5±0.54 and 4.0±0.37 ng/dl per min, respectively, (2) 17-OHP60 169.7±28.3, 10.8±1.3, 4.6±0.2 and 3.7±0.4 ng/ml, respectively, and (3) cortisol/17-OHP30 0.97±0.28, 38.5±6.9, 82.3±5.5 and 112.0±8.9, respectively. All three markers showed highly significant differences between the four groups (p < 0.0001). The patterns of 17-OHP, cortisol and cortisol/17-OHP ratio following ACTH testing revealed the degree of 21-hydroxylase deficiency in every group. HLA typing effected in 20 studied individuals confirmed the classification derived from cluster analysis. Thus, it seems that Groups I, II and III include, respectively, patients with severe, mild and minimal forms of non-classic 21-hydroxylase-deficient CAH, while in patients of Group IV the hyperandrogenemic symptoms are of different etiology. In conclusion, the concurrent evaluation of the three markers together with the variations of 17-OHP, cortisol and the cortisol/17-OHP ratio after ACTH testing enhance the accurate identification of a patient suspected for non-classic 21-hydroxylase-deficient CAH in relation to the severity of the enzymatic defect. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Serum and follicular fluid levels of CEA, CA 125 and SCC of women participating in an IVF program, in 42 cycles stimulated with GnRH-a and gonadotropins and in 26 unstimulated cycles triggered with HCG, were evaluated and compared with (a) steroid and gonadotropin levels, (b) the results of IVF, and (c) serum values in a control group of women with spontaneous normal ovulatory cycles. In the control group, serum antigens did not vary significantly during the 3 phases of the cycle. In stimulated cycles the median values in serum were 0.7 ng/ml (range, 0.0-2.1) for CEA, 14.0 U/ml (3.3-32.4) for CA 125 and 2.05 ng/ml (1.1-17.8) for SCC, whereas the median values in follicular fluid were 0.6 (0.0-27.9), 21.5 (0-670) and 21.4 (1-360), respectively. In unstimulated cycles the median values and ranges in serum were 0.9 (0.4-3.9), 12.1 (4.8-63.4) and 1.85 (0.7-4.4), respectively, whereas in follicular fluid they were 2.9 (0.4-180.7), 32 (1.7-600) and 231 (10.8-904). Different follicles of the same patients in stimulated cycles showed a wide divergence for all three antigens. In unstimulated cycles all three antigens in follicular fluid were strongly correlated and a significant inverse correlation was observed between LH and both CA 125 and SCC in serum. In either group of cycles, no significant relationship was found between any serum or follicular fluid antigen and estradiol or testosterone, pregnancy rate, or oocyte quality and fertilization. Thus, in both stimulated and unstimulated cycles follicular fluid contains CEA, CA 125 and SCC in considerable amounts while in serum only SCC was found elevated. It seems that no correlation exists between any of the three antigens and steroidogenesis or the results of the IVF-ET. © 1994.

sIL-2R and NSE were measured in 24 patients with small cell carcinoma (SCC) of the lung, in 25 patients with non small cell carcinoma (NSCC) and in 20 controls matched for age, sex and smoking habits. Significantly elevated values of sIL-2R and NSE were found in the SCC group (mean ± SEM: 2103 ± 314.4 U/ml and 44.5 ± 7.3 ng/ml repsectively), compared to those in the NSCC group (1079 ± 104.5 U/ml and 3.64 ± 0.8 ng/ml, p < 10-7 respectively) and to controls (561 ± 44.6 U/ml and 1.7 ± 0.3 ng/ml p < 10-5). In the SCC group, 83.3% of sIL-2R and 87.5% of NSE values were above cut-off (900 U/ml and 10 ng/ml respectively), while in the NSCC group, 48% of sIL-2R and only 8% of NSE values were above cut-off. In the controls, all values of both parameters were below cut-off. The results suggest that sIL-2R and NSE in concurrent measurements may help in decision making as regards treatment and prognosis.

The authors conclude that serum levels of sIL-2R and β2M may play a role in the early diagnosis and identification of patients with chronic rejection.

In several studies in humans and animals it has been suggested that high osmolality and ionicity of contrast media are responsible for higher nephrotoxicity. To examine this suggestion, we evaluated the renal effects of three different contrast media-an ionic high osmolar, an ionic low osmolar, and a nonionic-following intravenous and renal arterial administration, in a population of 84 unselected, nondiabetic patients with adequate renal function. The results showed that the nephrotoxicity is minimal and equal for all three contrast media and for both routes of their administration, and it is concluded that in this category of patients the far higher cost of the newer low osmolar ionics and nonionics should be considered seriously in regard to nephrotoxicity. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

The cycles of 11 renal transplant recipients (RTR), at least 24 months after stabilization of graft function and four hemodialyzed (HD) patients, menstruating regularly, were evaluated by concurrent and systematic determinations throughout the cycle of LH, FSH, estradiol, progesterone, testosterone, prolactin and SHBG and in the case of RTR also by ultrasound follow-up. Biphasic estradiol secretion, midcycle LH and FSH surge, duration of luteal phase, midluteal progesterone values and in the case of RTR, ultrasonic parameters were consistent with: (1) normal ovulatory cycles in five RTR; (2) ovulatory cycles with luteal phase deficiency in five RTR and two HD patients; (3) anovulatory cycles in one RTR and two HD patients. Thus, in HD patients only abnormal cycles of central etiology were found, while in RTR, luteal phase deficiency was a very common syndrome, in equal percentage with normal ovulatory cycles. © 1992.

Carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125) and squamous cell carcinoma (SCC) antigen were measured in 56 full-termed pregnancies by enzyme-immunoassays (EIA-MEIA). The measurements were done in maternal serum (MS), umbilical cord blood (UCB) and amniotic fluid (AF) samples, during delivery. Very high antigen levels were found in AF samples (median: CEA = 124 ng/ml; CA-125 = 710 U/ml; SCC = 710 ng/ml) compared to UCB and MS. CEA and SCC showed significantly lower value's in MS (0.6 and 1.7 ng/ml, respectively) than in UCB (1.6 ng/ml, P = 7.7 × 10-9; 3.55 ng/ml, P = 6.5 × 10-6, respectively), while CA-125 had significantly higher values in MS (6 U/ml) than in UCB (0.0 U/ml, P = 17 × 10-6; Wilcoxon paired test). All CEA values in MS were below cut-off (≤ 5 ng/ml), while 10% of CA-125 and 30% of SCC values were above cut-off (≤ 35 U /ml and ≤ 2.5 ng/ml, respectively). Amniotic fluid CEA with meconium had higher values (P = 0.0002), while the highest CA-125 values in AF samples were found in primiparae (P = 0.02). Moreover SCC in AF samples from vaginal delivered pregnancies showed significantly higher values, compared to those from cesarean section (P = 4.2 × 10-7; Mann-Whitney U-test). Thus, our findings suggest that pregnancy has an influence on maternal serum SCC and CA-125 values, while CEA is independent of gestation and seems to conserve its diagnostic value during pregnancy as well. © 1992.

α-Immunoreactive inhibin was measured using an enzyme immunoassay kit in the culture medium (Ham's F-10 medium supplemented with 14% heat-inactivated human serum) from day 3 or 4 to day 14 post-fertilization of 31 surplus pre-embryos from eight women participating in an in-vitro fertilization programme. Inhibin secretion was demonstrated in all of them from the fourth day after fertilization (mean ± SEM: 3.0 ± 0.7U) and was independent of the morphological development of pre-embryos (2-4 cells, n = 4; 6-8 cells, n = 4; 8-10 cells, n = 9; 10-12 cells, n = 4; morulae, n = 5 and blastocysts, n = 4). On days 7,10,13 and 14 post-fertilization, mean inhibin values ± SEM for non-disintegrated pre-embryos were respectively: 6.5 ± 0.9U, 12.3 ± 2.0U, 16.8 ± 3.2U and 20.2 ± 3.7U; however, when disintegration was noted on days 10 and 13 after fertilization, inhibin mean values were 9.0 ± 1.4U and 8.4 ± 1.7U respectively. Inhibin levels were significantly correlated with human chorionic gonadotrophin levels in the same culture media only on day 13, while correlation with pregnancy specific β1-glycoprotein occurred on day 7 post-fertilization. In conclusion, early human pre-embryos secrete α-immunoreactive inhibin before the cytotrophoblast is formed. This secretion increases significantly with time when development is continued, while disintegration is followed by a net decline in the rate of inhibin release.

Objective: To study and compare the secretion of pregnancy specific β1- glycoprotein (SP1) and human chorionic gonadotropin (hCG) by human pre- embryos, cultured in vitro, with their respective morphological development. Design: Spare human pre-embryos from randomly selected women participating in a program of in vitro fertilization (IVF) were studied prospectively. Setting: Pre-embryos were cultured, and hormone release was determined in academic research laboratories. Patients, Participants: Pre-embryos (n = 108) cultured for 14 days after fertilization in Ham's F-10 medium (GIBCO Ltd., Paisley, Scotland) were observed, and hCG and SP1 were measured in the culture media at regular intervals. Main Outcome Measures: Discordant secretion of SP1 and hCG. Results: Of the 98 bipronucleate pre-embryos, 53.6% formed blastocysts, 17.3% of which hatched. Human chorionic gonadotropin was detected from day 7 after fertilization concomitantly with blastocyst formation, thereafter showing a logarithmic increase (maximum 10,650 mIU) until the first signs of embryonic disintegration. Pregnancy- specific β1-glycoprotein release started 3 to 4 days after fertilization independently of the morphological development and the future production of hCG, thereafter displaying a nonlogarithmic increase (maximum 41 ng). Conclusions: Hormone secretion and morphological development are unique for each pre-embryo. Human chorionic gonadotropin and SP1 seem to have different biochemical and physiological regulation.

Are follicles where no oocytes are retrieved "empty follicles"? © 1992 Plenum Publishing Corporation.

Pleural fluid and serum soluble Interleukin-2 receptors (sIL-2R) were measured by an enzyme-immunoassay in 13 patients with tuberculous pleurisy, in 28 patients with carcinomatous pleurisy and in 17 transudates from patients with congestive heart failure. Significantly higher values of sIL-2R were observed in exudative than in transudative (x̄ ± SLM = 713 ± 111 U/ml) pleural fluid samples, the highest being found in tuberculous (3777 ± 501 U/ml) and the intermediate in carcinomatous exudates (1981 ± 160 U/ml) (p < 0.0001, one way ANOVA). Serum sIL-2R were significantly higher in cacrinomatous and transudative groups than in age- and sex-matched controls (p < 0.002; one way ANOVA), while there was no significant difference between the tuberculous group and controls. The pleura/serum sIL-2R ratio was significantly higher in tuberculous (5.32 ± 0.60), than in carcinomatous pleurisy (2.67 ± 6.20) and higher still than in transudates (0.76 ± 0.10) (p < 0.001; one way ANOVA). In conclusion, the pleura/serum sIL-2R ratio may be a helpful parameter in differentiating tuberculous from carcinomatous pleurisy and an additional confirmatory one for distinguishing transudates from exudates.

A successful pregnancy of a young woman with late-onset congenital adrenal hyperplasia (LOCAH) is reported. Exogenous glucocorticoids are the most commonly used regimen in such cases both for suppression of adrenal overstimulation and avoiding masculinization of a female fetus. In our LOCAH patient methylprednisolone has been used for treatment. We present the management and the outcome of this pregnancy, as well as the hormonal follow-up. © 1991.

Serum levels of soluble interleukin-2 receptors (sIL-2R), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), β-chorionic gonadotropin (β-HCG), pregnancy-specific glycoprotein (SP1), and β2-microglobulin (β2M) were taken in 92 patients with primary lung cancer and 43 controls. The mean value of sIL-2R in the cancer group was twice as high as that of the controls (P less than 0.001) and the highest values were observed in those with small cell carcinoma (SCC) (P less than 0.0001). Of the cancer patients, 51.1% had CEA values higher than the cutoff level of 5 ng/ml. Extended-disease patients had a higher percentage of increased CEA values than those with limited disease. Adenocarcinoma (ADCC) and SCC groups had the highest percentages of increased CEA levels. There was no significant difference between the groups for β-HCG, AFP, SP1, and β2M, and intermarker correlation was not seen. The results suggest that sIL-2R and CEA may be useful in monitoring the extent of disease and possibly indicate the histologic subtype, thus having a bearing on treatment and prognosis.

The effect of pregnancy on maternal serum total cortisol (MSFT) was studied systematically in the course of 90 normal pregnancies (n = 204). Moreover, the evaluation of MSFT determinations in abnormal pregnancies, intrauterine growth retardation (IUGR) and obstetrical complications, premature rupture of the membranes (PROM), premature delivery (PD), and full term pregnancies with post maturity syndrome (PMS) were also investigated. MSFT was measured by an enzyme immunoassay. Gradual increase in MSFT was found from the 6th week of pregnancy to the 40th week of pregnancy and a sharp rise was noted during the last 2 weeks before the onset of labor (P < 0.002). In IUGR, MSFT was significantly lower (P < 0.001). In the cases of PROM and PD, MSFT was highly elevated (P < 0.0001), independently of the gestational age. In pregnancies with well documented PMS, MSFT was much lower than in normal full term pregnancies with even a downward trend in serial determinations (P < 0.0001). © 1990.

Maternal serum total estrogens (O(T)) human placental lactogen (HPL), pregnancy specific β1-glycoprotein (SP1) and progesterone (P) were measured by enzymeimmunoassays (EIA) in pregnancies with placental insufficiency and low birthweight infants (LBWI). It was demonstrated that these cases could be classified into three groups: Group I: The low levels of placental hormones and O(T) were significantly correlated with each other (p < 0.05 - p < 0.001), as well as with the low birthweight (p < 0.001) in pregnancies with placental insufficiency and LBWI, in which a high percentage (50%) were small for gestational age (SGA). Group II: In cases of simple placental insufficiency, the low levels of placental hormones showed a significant correlation with each other (p < 0.05) whereas only the rather normal O(T) values were correlated with the birthweight of the infant (p < 0.02). Group III: IN pregnancies with SGA, but without apparent placental insufficiency the normal concentration of placental hormones showed a high correlation with each other (p < 0.001) while only the subnormal O(T) levels were correlated significantly with the low infant birthweight (p < 0.05). SP1 values showed abnormally steep increase in cases with perinatal asphyxia.