High estradiol levels during a long agonist IVF protocol are associated with decreased food intake, higher leptin concentrations, and lower levels of high-sensitivity C-reactive protein.

PURPOSE: To study whether different hormonal phases affect appetite regulation, food intake, and concentrations of leptin, glucagon-like peptide-1 (GLP-1), and high-sensitivity C-reactive protein (hs-CRP) during a long agonist in vitro fertilization (IVF) protocol. METHODS: Fifty-four infertile women were encountered thrice, the first of which was at the beginning of their period (low estradiol). The other two visits were during a gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of a follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was the reference; the women served as their controls. The concentrations of leptin, GLP-1, and hs-CRP were assessed from plasma. Dietary intake was assessed using food records (FRs). In addition, weight, height, body mass index (BMI), and plasma levels of estradiol, glucose, HbA1c, insulin, and lipids were monitored. Twenty-six of the subjects also had a postprandial test. RESULTS: During the stimulation protocol, leptin concentrations elevated (P < 0.001), and energy intake decreased (P = 0.03), while estradiol levels increased (P < 0.001). GLP-1 levels unchanged (P = 0.75) and hs-CRP (P = 0.03) concentrations diminished, while estradiol levels increased. CONCLUSION: No increased food intake or weight gain occurred during the stimulation protocol; thus, leptin may protect from overeating during high estradiol levels, and leptin resistance may not occur during a short follow-up. Also, a favorable anti-inflammatory effect was detected. During this study, we observed no harmful metabolic effects, which might affect negatively maternal health.

Endothelial function and concentrations of high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha during a long agonist IVF protocol.

We examined possible changes in endothelial function during a long agonist in vitro fertilization (IVF) protocol. We measured flow-mediated dilatation (FMD) and FMD percent (FMD%) from the brachial artery and plasma levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-〈). We studied longitudinally three time points in 27 women undergoing a long agonist IVF treatment at Kuopio University Hospital. The first visit was at the beginning of their period (low estradiol). The other two visits were during gonadotrophin-releasing hormone (GnRH) analog downregulation (low estradiol) and at the end of follicle-stimulating hormone (FSH) stimulation (high estradiol). The first visit was used as the reference, and the women served as their own controls. During the stimulation protocol, FMD and FMD% remained. Toward the end of stimulation, hsCRP (P = 0.003), IL-6 (P = 0.04), and TNF-〈 (P = 0.008) concentrations all decreased, while estradiol levels increased (P < 0.001). Correlations between estradiol and proinflammatory factors or FMD were, however, non-significant. The only significant correlation appeared between FMD% and hsCRP at Visit 2 (r = 0.485, P = 0.01). In conclusion, IVF stimulation promoted no change in endothelial function, whereas hsCRP, IL-6, and TNF-〈 decreased. These findings indicate that estrogen may improve the cytokine profile among healthy women undergoing IVF, but this is not reflected in endothelial function.

The effect of maternal alcohol and drug abuse on first trimester screening analytes: a retrospective cohort study.

BACKGROUND: The purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use. METHODS: A routine combined FTS including measurements of maternal serum levels of free ß-human chorionic gonadotropin subunit (free ß-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9-11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11-13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed. RESULTS: Free ß-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free ß-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups. CONCLUSIONS: The present study shows increased free ß-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free ß-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.

Impact of obesity on angiogenic and inflammatory markers in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort.

BACKGROUND: While several studies have demonstrated that obesity increases the risk of pre-eclampsia (PE), the mechanisms have yet to be elucidated. We assessed the association between maternal/paternal obesity and PE and hypothesized that maternal body mass index (BMI) would be associated with an adverse inflammatory and angiogenic profile. High-sensitivity C-reactive protein (hs-CRP) and following serum angiogenic markers were determined: soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). METHODS: Data on BMI were available from 1450 pregnant women with PE and 1065 without PE. Serum concentrations of hs-CRP and angiogenic markers were available from a subset at first and third trimesters. RESULTS: Prepregnancy BMI was higher in the PE group than in controls (mean ± SD) 25.3 ± 5.2 vs. 24.1 ± 4,4, p < 0.001, adjusted for parity, mother's age, and smoking status before pregnancy. Increased hs-CRP concentrations were observed in both PE and non-PE women similarly according to BMI category. In women with PE, a higher BMI was associated with lower sFlt-1 and sEng concentrations throughout the pregnancy (p = 0.004, p = 0.008, respectively). There were no differences in PlGF in PE women according to BMI. CONCLUSIONS: We confirmed increased pre-pregnancy BMI in women with PE. Enhanced inflammatory state was confirmed in all women with overweight/obesity. Partly paradoxically we observed that PE women with obesity had less disturbed levels of angiogenic markers than normal weight women with PE. This should be taken into account when angiogenic markers are used in PE prediction.

Angiogenic profile in the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort.

OBJECTIVES: To study first and second/third trimester levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) in FINNPEC case-control cohort. The participants were further divided into subgroups based on parity and onset of the disease. Recommended cut-off values in aid of pre-eclampsia (PE) prediction and diagnosis were also tested. METHODS: First trimester serum samples were available from 221 women who later developed PE and 239 women who did not develop PE. Second/third trimester serum samples were available from 175 PE and 55 non-PE women. sFlt-1 and PlGF were measured electro-chemiluminescence immunoassays and sEng by ELISA. RESULTS: In all timepoints PlGF, endoglin and the sFlt-1/PlGF ratio were increased in the PE group compared to the non-PE group. The serum concentrations of sFlt-1 were increased only at second/third trimester in PE women. Higher concentrations of s-Flt1, endoglin and higher sFlt/PlGF ratio were found at the third trimester in primiparous women compared to multiparous women. Primiparous PE women also had lower concentrations of PlGF at the third trimester. The proportion of women exceeding all cut-offs of the sFlt-1/PlGF ratio (≥33, ≥38, ≥85 and ≥110) was greater in the PE group, but there were also pre-eclamptic women who met rule-out cut-off or did not meet rule-in cut-off. CONCLUSIONS: Primiparous pregnancies have more anti-angiogenic profile during second/third trimester compared with multiparous pregnancies. Our findings also suggest that certain maternal characteristics, e.g. BMI, smoking and pre-existing diseases, should be taken into account when different sFlt-1/PlGF ratio cut-offs are utilized.

Angiogenic profile and smoking in the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort.

OBJECTIVES: The biological mechanism by which smoking reduces the risk of pre-eclampsia (PE) is unresolved. We studied serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio, in addition to soluble endoglin (sEng) in early and late pregnancy to ascertain whether these factors are altered in women who smoke. SUBJECTS AND METHODS: First trimester serum samples were available from 217 women who later developed PE and 238 women who did not develop PE. Second/third trimester serum samples were available from 174 PE and 54 non-PE women. RESULTS: PE women who smoked during pregnancy had elevated first trimester concentrations of serum PlGF [geometric mean (95% CI): 39.8 (32.6-48.5) pg/ml, p = .001] and reduced sEng concentration [5.0 (4.6-5.6) ng/ml, p = .047] compared to PE non-smokers [30.0 (28.1-32.1) pg/ml and 6.1 (5.9-6.4) ng/ml, respectively]. Non-smoking women in the PE group had the highest sFlt-1/PlGF ratio in early and late pregnancy. CONCLUSIONS: The protective effect of smoking in reducing the risk of PE may be due to the early pregnancy change towards pro-angiogenic marker profile. Also, in late pregnancy, smoking exerted effect in sFlt-1/PlGF ratio in PE pregnancies, and may complicate its use as a prognostic and diagnostic marker. Key messages Smoking appears to have angiogenic effects in early pregnancy with reduced sEng concentrations and elevated PlGF concentrations in both normal and PE pregnancies. Throughout pregnancy, smoking exerted effect in PlGF concentration and sFlt-1/PlGF ratio in PE pregnancies, and thus may complicate its use as a prognostic and diagnostic marker.

Plasma amino-terminal pro B-type natriuretic peptide as a predictor of late cardiovascular mortality in patients with acute lung disorders: a prospective, observational cohort study.

AIMS: Pneumonia and acute exacerbations of obstructive lung diseases (AEOLD) are associated with a significant long-term mortality. Elevated level of amino-terminal pro B-type natriuretic peptide (NT-proBNP) is a predictor of late all-cause mortality in these disorders but the pathophysiological basis for this is unknown. The present study was conducted to define the predictive role of NT-proBNP on late cardiovascular mortality among patients with acute lung disorders. METHODS AND RESULTS: This prospective, observational cohort study included 269 hospitalized patients with pneumonia or AEOLD. Plasma level of NT-proBNP, age, sex, body mass index, arterial blood oxygen saturation, C-reactive protein, and urea were recorded. The survival and causes of death were recorded after a median of six years. NT-proBNP > 666 ng/mL was related to cardiovascular mortality with an adjusted hazard ratio of 2.93 (1.19-7.18). This risk was of similar magnitude to that associated with diabetes and greater than that associated with arterial hypertension, hypercholesterolemia, and smoking. NT-proBNP was also related to all-cause mortality with adjusted hazard ratio of 2.39 (1.49-3.85) per 10 times increase in NT-proBNP concentration. However, the association between NT-proBNP and non-cardiovascular mortality did not reach statistical significance [adjusted hazard ratio 1.89 (0.93-3.85)]. CONCLUSION: NT-proBNP concentration during pneumonia or AEOLD was strongly associated with late cardiovascular mortality but not with non-cardiovascular mortality. The results suggest that the increase in NT-proBNP during acute lung disorders may reveal occult cardiac diseases arousing a question whether patients with acute pulmonary disorders with elevated NT-proBNP levels should be subjected to further diagnostic or therapeutic cardiovascular interventions.

False-negative results in routine combined first-trimester screening for down syndrome in Finland.

We analyzed the frequency and possible causes of false-negative (Fn) screening results in first-trimester combined Down syndrome screening in Finland. During the study period (May 1, 2002, to December 31, 2008), 76,949 voluntary women with singleton pregnancies participated in screening. Maternal age at screening, week of gestation, levels of pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotropin (fß-hCG), and nuchal translucency (NT) measurement were compared and statistically analyzed between true-positive (Tp) and Fn cases. There were a total of 188 Down syndrome cases (1:409) in the screened population; 154 confirmed Tp and 34 Fn cases. Most Fn cases (n = 25) occurred at 12 + 0 to 13 + 6 weeks' gestation and only nine Fn cases presented between 10 and 11 weeks' gestation. According to the logistic regression analysis, the NT measurement was the most powerful discriminating factor in Fn screening results and accounted for 37.2% of Fn results. The second most important factor was fß-hCG, adding 14.0% to R(2), followed by PAPP-A, which contributed a further 14.3%. The chosen parameters explain 83.9% of Fn results, but 16.1% remain due to unknown factor(s). All investigated parameters contributed to Fn screening results, but fetal NT was the most discriminating factor leading to an Fn screening result.

First trimester biochemistry at different maternal ages.

BACKGROUND: The performance of first trimester biochemical screening was compared at different pregnancy weeks and maternal ages during 2002-2008 in a screened population of 76,949 women. METHODS: The detection rates, as well as the median multiples of a median (MOMs) of free ß-human chorionic gonadotropin (free ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A), were compared between completed gestational weeks 8-13 and between different maternal ages separated into 5-year groupings. RESULTS: The number of singleton Down syndrome pregnancies was 221. The median age of the screened women was 30 years and the proportion of women aged ≥ 35 years 16.9%. The median age of the women with a Down syndrome pregnancy was 37 years. In women aged <35 years, the biochemical markers provided a detection rate of only 38.6%, whereas in women aged ≥ 35 years, the biochemical markers detected 82.7% of cases (p<0.01). CONCLUSIONS: Biochemical screening works best amongst women aged ≥ 35 years. For younger mothers aged <35 years, combined screening should be the method of choice.

Decreased PAPP-A is associated with preeclampsia, premature delivery and small for gestational age infants but not with placental abruption.

OBJECTIVE: To investigate links between first trimester Down's syndrome screening markers and adverse pregnancy outcomes; preeclampsia (PE), small for gestational age (SGA), preterm delivery (PD) and placental abruption (PA) in spontaneous, chromosomally normal pregnancies. STUDY DESIGN: Cohort study in a university hospital. Data during pregnancy were routinely collected from a total study population of 2844 pregnant women between 2005 and 2007. Four study groups were pregnancies with PE (N=175), PA (N=17), PD (N=213) and SGA (N=275) plus a reference group with normal outcome (N=2164). The median MOMs of maternal serum concentrations of pregnancy associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were compared using two-tailed pooled t-tests, continuous variables were compared using Student's two-way t-tests, and Chi-square tests were used to analyse dichotomous variables. Fisher's exact test was used when there were fewer than five units in any of the classes. RESULTS: The median MOM of maternal serum PAPP-A was significantly lower in women with PE, PD and SGA (0.79, 0.80 and 0.79 MOM, respectively) than in the reference group (0.99 MOM) (p<0.01). The median MOM of maternal serum fß-hCG was also significantly lower in the SGA group (0.90 MOM) and in the PE and PD groups (0.86 and 0.92 MOM) than in the reference group (0.99 MOM, p=0.02). There was no detectable difference between the biochemical markers in the PA group and the reference group. No statistical difference was found between NT MOMs in the reference and study groups. CONCLUSION: The concentrations of first trimester screening (FTS) serum markers were lower in pregnancies where PE, PD and SGA occurred. In the latter two cases, there was an inverse association between incidence and PAPP-A and fß-hCG values. However, the development of PA during pregnancy could not be predicted from biochemical marker concentrations. The mechanism behind PA is probably less dependent on the placenta than on the decidua.

More invasive procedures are done to detect each case of Down's syndrome in younger women.

OBJECTIVE: To evaluate the performance of first-trimester combined screening in 5-year periods according to maternal age in a low-risk population. DESIGN: A prospective study. SETTING: Multicenter study in Finland. POPULATION: A total of 76949 voluntary women with singleton pregnancies participated in first-trimester combined screening in public healthcare between 1 May 2002 and 31 December 2008. METHODS: The serum samples were analyzed using the PerkinElmer AutoDELFIA® time-resolved fluoroimmunoassay kit for the measurement of pregnancy-associated plasma protein-A and free beta-human chorionic gonadotropin. Nuchal translucency was measured by trained personnel (midwives or physicians) in a university or central hospital. MAIN OUTCOME MEASURES: Performance, detection rate, false positive rate and the number of invasive procedures needed to detect a single case of Down's syndrome were analyzed. RESULTS: There was a direct connection between maternal age and the prevalence of Down's syndrome with a low prevalence in young women being 1:1 193 in the 25-29 age group and 1:150 in the 35-39 age group. Consequently, for a fixed false positive rate of 5%, the number of invasive procedures needed to detect one case of Down's syndrome is higher in younger women to achieve the same detection rate. CONCLUSIONS: In combined first trimester screening the risk for Down's syndrome is individual, varying with maternal age. This should be taken into consideration when counseling women.

Tracking serum lipid levels and the association of cholesterol concentrations, blood pressure and cigarette smoking with carotid artery intima-media thickness in young adults born small for gestational age.

BACKGROUND: Small birth size is associated with increased cardiovascular disease risk, but the mediating factors are poorly understood. METHODS AND RESULTS: Serum lipids, blood pressure (BP), carotid artery intima-media thickness (CA-IMT), and brachial artery flow-mediated dilatation (BA-FMD) were studied in 70 20-year-old subjects [35 sex- and age-matched pairs born small (SGA) and appropriate for gestational age (AGA)]. The SGA subjects had higher serum levels of low-density lipoprotein (LDL) cholesterol, total/high-density lipoprotein (HDL) and LDL/HDL cholesterol ratios, and lower HDL cholesterol levels than the AGA subjects (2.71 vs 2.37 mmol/L, P<0.05; 3.12 vs 2.80, P<0.01; 1.98 vs 1.61, P=0.002; 1.43 vs 1.56 mmol/L, P<0.05, respectively). In the SGA group, total and LDL cholesterol levels correlated inversely with adult height SD score (r=0.463, P=0.006 and r=0.413, P=0.015, respectively). CA-IMT or BA-FMD did not differ between the groups, but cigarette smoking, higher diastolic BP, and shorter birth length associated with higher CA-IMT in the whole study population. A clear tracking of cholesterol levels was found from 12 to 20 years. CONCLUSIONS: SGA subjects had more unfavorable lipid profiles than the controls, the shortest having the highest LDL cholesterol. Cigarette smoking, higher diastolic BP, and shorter birth length associated with higher CA-IMT in the whole study population. A clear tracking of cholesterol levels through adolescence enables early targeting of lifestyle counseling for reducing cardiovascular disease risk.

Insulin like growth factor-I in acute subarachnoid hemorrhage: a prospective cohort study.

INTRODUCTION: Neuroendocrine deficiencies may affect recovery after aneurysmal subarachnoid hemorrhage (aSAH). Insulin like growth factor-I (IGF-I) regulates neuronal growth and apoptosis in ischemic stroke. Our study was designed to a) characterize the behavior of serum IGF-I and growth hormone (GH) in the acute and late phases after aSAH reflecting possible pituitary gland function and b) evaluate the association between IGF-I and morbidity assessed by Glasgow outcome scale (GOS) and health related quality of life (HRQoL) in patients with aSAH. METHODS: In this prospective cohort study, patients with aSAH (n = 30) were compared to patients who underwent elective aneurysm surgery (n = 16). Serum GH and IGF-I concentrations were measured daily for five (controls) or seven (aSAH) days and at three months. GOS and 15d HRQoL was measured at three months. A mixed models method was used for testing between the groups. For factors possibly affecting HRQoL in aSAH patients, we constructed a Bayesian predicting model using a P-course Bayesian classifier. RESULTS: The mean IGF-I concentrations for days one to five were 8.1 +/- 3.5 nmol/l in patients with aSAH and 11.2 +/- 3.1 in the control group (P = 0.01). No corresponding difference was found at three months. Serum GH concentrations were similar in both patient groups. Severity of the aSAH did not affect serum IGF-I concentrations. Patients with GOS

Increased time-to-pregnancy and first trimester Down's syndrome screening.

BACKGROUND: Time-to-pregnancy (TTP) is a clinical tool used to measure uterine receptivity and a couples' fertility in spontaneously conceived pregnancies. The objective of this study was to examine the effects of TTP on first trimester Down's syndrome (DS) markers in spontaneous, chromosomally normal pregnancies and to compare the results to those in IVF pregnancies. METHODS: A case-control study was conducted amongst patients attending a university hospital in Finland. During 2005-2007 data on pregnant women in Kuopio, with singleton pregnancies, routinely collected by the Department of Obstetrics and Gynaecology of Kuopio University Hospital and Eastern Finland Laboratory Centre were compiled. The data comprised information gathered in first trimester DS screening [age of the mother, serum hCG free beta subunit (fbeta-hCG) and pregnancy-associated plasma protein A (S-PAPP-A) levels and the nuchal translucency (NT) of the fetus], body mass index, method of conception [spontaneous or in vitro fertilization (IVF)], TTP (in spontaneous pregnancies), maternal chronic diseases, smoking habits of the mother, outcome of the pregnancy and prior pregnancy complications. Spontaneous pregnancies were classified into three groups by TTP: 0-12 months (the reference group, N = 1164), 13-24 months (N = 112) and > or = 25 months (N = 70). Screening data from IVF pregnancies (N = 39) were collected for comparison. The size of the total study population was 1385. RESULTS: The median/geometric mean multiple of median (MOM) of S-PAPP-A was significantly lower (P < 0.01) in women with a TTP over 25 months (0.89/0.83 MOM) and in the IVF group (0.95/0.84 MOM) compared with the reference group (1.01/1.03 MOM). However, first trimester S-fbeta-hCG and NT MOMs were not statistically different between the study groups. Consequently, the proportion of DS screening positives was significantly higher in women with TTP > or = 25 months (12.9 versus 2.1%), but not in the IVF group (2.6%). CONCLUSIONS: A TTP of over 2 years altered the levels of DS screening serum markers to levels similar to those observed in IVF pregnancies, with a decrease in PAPP-A levels compared with the reference group. These results raise the possibility that such changes could be related to subfertility rather than to the use of assisted reproductive technology.

Pituitary-adrenal function in patients with acute subarachnoid haemorrhage: a prospective cohort study.

INTRODUCTION: Subarachnoid haemorrhage (SAH) may damage the hypothalamo-pituitary-adrenal gland (HPA) axis and disturb cortisol metabolism. There are no available data that relates to the response of the HPA axis in the acute phase of SAH. We aimed to characterise the behavior of serum adrenocorticotropic hormone (ACTH), total cortisol, stimulated total cortisol and free cortisol concentrations in acute aneurysmal SAH. METHODS: A prospective cohort study was conducted of patients with acute aneurysmal SAH (n = 30) admitted to a tertiary university hospital. Patients admitted for elective aneurysmal surgery (n = 16) served as the control group. An ACTH stimulation test was performed twice during the first week and at three months. The main outcome measure was description of the ACTH-cortisol response by calculating serum free cortisol and measuring total cortisol and ACTH concentrations. A mixed models method was used for testing between the groups, allowing heterogeneity between the groups. RESULTS: Patients with SAH had higher initial serum total cortisol (mean +/- SD; 793 +/- 312 nmol/L) and free cortisol concentrations (83 +/- 55 nmol/L) than control patients (535 +/- 193 nmol/L, p = 0.001 and 33 +/- 18 nmol/L, p < 0.001, respectively). Thereafter, there were no differences in this respect. Serum free and total cortisol concentrations correlated but were unaffected by the severity of SAH. ACTH concentrations were comparable between SAH and control groups. Patients with Hunt-Hess grades IV to V had higher ACTH concentrations at day one (10.7 +/- 7.1 pmol/l/L) and day five (8.2 +/- 7.7 pmol/L) than patients with grade I-III (day one: 3.8 +/- 2.0 pmol/L, p = 0.002; day five: 4.7 +/- 1.8 pmol/L, p = 0.04). CONCLUSIONS: Calculation of serum free cortisol concentration was not helpful in identifying patients with potential hypocortisolism. SAH severity did not affect cortisol concentrations, possibly indicating relative pituitary-adrenal insufficiency in patients with more severe bleeding. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00614887.

The Advia 120 red blood cells and reticulocyte indices are useful in diagnosis of iron-deficiency anemia.

We have investigated the red blood cell (RBC) and reticulocyte indices of the Advia 120 hematology system in assessment of body iron stores as well as in diagnostics of iron-deficiency anemia in two separate study populations. The first study population consisted of a total of 34 apparently healthy females who were found to be anemic (Hb<125gL1) in a screening test. The anemic subjects were classified on the basis of plasma transferrin receptor (TfR) concentration into an iron-deficiency anemia group (TfR concentration 2.4mgL1, n=14) and an adequate iron stores group (TfR concentration <2.4mgL1, n=20). Another study population consisted of 95 hospital patients of whom 31 had depleted iron stores according to TfR concentration. The same population was classified further on the basis of hemoglobin value (Hb<125gL1 for females, Hb<135gL1 for males) into patients with iron-deficiency anemia (n=21) and those with anemia together with adequate iron stores (n=44). In the population of young anemic female students the percentage of hypochromic RBC (%HYPOm) had a remarkably high ROC AUC of 0.98 when evaluating the diagnostic accuracy for the distinction between the patients with iron-deficiency anemia and those with anemia and adequate iron stores. Also, among the hospitalized patients %HYPOm had the highest ROC AUC of 0.77. The diagnostic efficiency provided by the red blood cell and reticulocyte indices was considerably lower in the heterogeneous group of hospitalized patients than in the group of female students. Nevertheless, the advanced RBC and reticulocyte indices may prove to be useful tools in the evaluation of iron status and diagnosis of iron-deficiency anemia.

Serum sialic acid and prostate-specific antigen in differential diagnosis of benign prostate hyperplasia and prostate cancer.

In order to improve the diagnostic accuracy of the serum total and free prostate-specific antigen (PSA) in differential diagnosis between benign prostate hyperplasia (BPH) and prostate cancer, the serum total sialic acid (TSA) was measured and logistic regression (LR) models were built. Significantly higher serum PSA (p<0.001) concentrations were observed in patients with prostate cancer compared to control subjects, but no statistically significant differences were found in serum TSA concentrations between these groups. Serum PSA reliably discriminated patients with prostate cancer from control subjects, the area under the ROC curve (AUC) being 0.991 (0.010). When serum PSA was in the gray zone, from 4 to 10 microg/l, the diagnostic accuracy of PSA in discriminating patients with prostate cancer from BPH patients was very poor, AUC being 0.563 (0.132). However, using the same set of patients the LR model combining serum PSA, free to total PSA ratio and TSA values, as well as digital rectal examination results, had good diagnostic accuracy in discriminating the prostate cancer patients from patients with BPH, the area under the ROC curve being 0.895 (0.054). The present data suggest that the logistic regression model combining laboratory measurements and results of the clinical examination may be a useful adjunct in the differential diagnosis of benign and malignant prostate disease.