A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers.

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

The prevalence of hypertension, valve calcification and left ventricular hypertrophy and geometry in peritoneal dialysis patients.

BACKGROUND/AIMS: Cardiac valve calcification (CVC) and left ventricular (LV) abnormalities are common indicators of a poor prognosis in dialysis patients. We determined the prevalence of hypertension, CVC, LV hypertrophy (LVH) and LV geometry in peritoneal dialysis (PD) patients. METHODS: Eighty-seven patients (50 female; mean age 42 ± 13 years; mean dialysis duration 46 ± 24 months) on strict salt and volume restriction, none of whom were receiving antihypertensives, were included in the study. Blood pressure (BP), biochemical parameters, CVC, LVH and LV geometry were determined. RESULTS: Most patients were normotensive. CVC of the mitral and aortic valves and of both valves were noted in 22, 23 and 15% of patients, respectively. Patients with CVC had significantly higher diastolic BP (p = 0.023), cardiothoracic index (CTI; p = 0.037) and LV mass index (LVMI; p = 0.002). LVH, noted overall in 44% of cases, was present in 62 and 36% of the patients with and without CVC, respectively (p = 0.028). Of the whole group, only 50.6% had normal LV geometry. LVH was associated with lower serum albumin (p = 0.002), higher CTI (p = 0.027) and more frequent CVC (p = 0.028). LVMI was greater in patients with CVC (p = 0.002). CONCLUSION: Strict salt restriction and the achievement of ideal dry weight result in normotension in PD patients. CVC is associated with LVH, both of which are lower in normotensive patients.

Serum apelin-13 levels and total oxidant/antioxidant status of patients with Alzheimer's disease.

OBJECTIVE: We aimed to evaluate apelin-13 levels, total oxidant/antioxidant status in Alzheimer's disease (AD) and to investigate the relationship between these parameters. METHODS: Patients newly diagnosed with AD were enrolled in the study. The control group consisted of age- and gender-matched healthy individuals. Serum levels of apelin-13, total antioxidant status (TAS), and total oxidant status (TOS) were measured. Oxidative stress index was calculated (TOS/TAS) for each participant. RESULTS: We reported that serum apelin-13 and TAS values were significantly lower in the AD group compared with controls, and they found a fair but insignificant relationship between Apelin-13 and TAS values. CONCLUSION: According to our results, we suggested that insufficient apelin-13 and TAS levels may contribute to the pathogenesis of AD.

Evaluation of the Design and Methodology of Applications to the Local Ethics Committee.

Objectives: Proposals for scientific studies must have an original hypothesis and the appropriate design and methodology to test the premise. Methods: This study is an evaluation of the suitability of applications submitted to a local ethics committee (EC) and the rate of publication of that research. Results: A total of 899 files submitted for EC approval were retrospectively assessed. The EC found that the description of the methods in 44% of the applications was inaccurate, and that this type of error was most often seen in submissions from the surgical branch. In all, 52% of the applications for which we were informed about their final status were not published. Conclusion: The results suggest that improved training in epidemiology is required to reduce the number of application errors and that new regulations could help to motivate healthcare personnel to conduct scientific research and publish their findings.

Evaluation of Paraoxonase, Arylesterase, and Homocysteine Thiolactonase Activities in Patients with Diabetes and Incipient Diabetes Nephropathy.

BACKGROUND: The aim of this study is to examine the relationship among the changes in activities of paraoxonase (PON), arylesterase (ARE) and homocysteine thiolactonase (HTLase) enzyme having antioxidant properties and the development of diabetic nephropathy (DN), one of the most common complications of diabetes. METHODS: Normoalbuminuric type-2 diabetic patients (Group II, n=100), microalbuminuric type 2 diabetic patients (Group III, n=100) and the control group (Group I, n=100) were included in the study. The age and gender of the patient groups matched with the age and gender of the control group. HTLase, PON and ARE enzyme activities were measured by the spectrophotometric method using a g-thiobutyrinolactone, paraoxon, and phenylacetate substrates respectively. In this study, an autoanalyzer application was developed in order to measure HTLase enzyme activity for the first time. RESULTS: Serum HTLase, ARE and PON activities of Group III and Group II were significantly low compared to HTLase, ARE and PON results of Group I (p<0.05). CONCLUSIONS: Based on our results, PON, ARE and HTLase enzyme activities were found to be decreased due to the increase in the degree of DN.

Effects of nebulized corticosteroids therapy on hypothalamic-pituitary-adrenal axis in young children with recurrent or persistent wheeze.

Inhaled corticosteroids (ICS) are preferred drugs for the long-term treatment of all severities of asthma in children. However, data about the safety of ICS in infants is lacking. So, it is essential to do further clinical studies to examine the safety and efficacy of ICS in this population. In this study, the effects of nebulized budesonide and nebulized fluticasone propionate suspensions on hypothalamic-pituitary-adrenal axis is examined in infants with recurrent or persistent wheeze. Thirty-one children aged 6-24 months admitted to our hospital between January and December 2005 with symptoms of recurrent or persistent wheeze were included in the study. The patients were randomly allocated to receive 0.25 mg BUD or 0.25 mg fluticasone propionate twice daily for 6 wk and half dose for another 6 wk with a jet nebulizer at home. Blood samples for basal cortisol concentration, adrenocarticotropic hormone, glucose, HbA1c and electrolytes were obtained at the beginning and at the end of the study. Adrenal function assessment was based on changes in cosyntropin-stimulated plasma cortisol levels. The study was completed with 31 patients, 16 of whom received BUD and 15 FP. All patients except one had plasma cortisol concentrations above 500 nmol/l (18 microg/dl) or had an incremental rise in cortisol of >200 nmol/l after stimulation. Although nebulized steroids seem to be safe in infancy, we recommend that adrenal functions should be tested periodically during long-term treatment with nebulized steroids.

Plasma cortisol levels in migraineurs between attacks.

We have studied the plasma cortisol levels between attacks in order to investigate the role of hypothalamic-pituitary-adrenal axis in migraine patients. We have not found any statistically significance between plasma cortisol levels of patients and control group, after taking the blood of 25 patients and 24 healthy controls between 8.30-9.30 am.

Prognostic significance of NGAL in early stage chronic kidney disease.

BACKGROUND: Neutrophilgelatinase-associated lipocalin (NGAL) has been proven to be a useful biomarker for early detection of acute kidney injury, but it is not known whether adding NGAL measurements to conventional risk factors will improve the risk assessment in the setting of chronic kidney disease (CKD). The aim of the present study was to examine the correlation of NGAL with early stage renal impairment in CKD and to evaluate its prognostic value in these subjects. METHODS: This is a prospective observational cohort study of 54 patients with early stage (stage 1-2) CKD. Patients aged between 18 and 65 years with stable disease were enrolled in this study. Patients with a history of primary glomerulonephritis, diabetes mellitus, acute kidney injury, systemic diseases and stage 3-4-5 CKD were excluded from the study group. Estimated glomerular filtration (eGFR) rate was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The patients were followed for two years to determine the ability of baseline NGAL for prediction of renal outcome. In our study disease progression was defined as changes in eGFR (ΔeGFR) and proteinuria (Δproteinuria). Patients divided into two groups according to NGAL cut-off value as group 1 (N.=23, NGAL ≤98.71 ng/mL) and group 2 (N.=31, NGAL >98.71 ng/mL). RESULTS: Out of 54 patients (mean age: 45.6±7.6 years, 64.8% female, baseline eGFR: 84.6±16.8 mL/min/1.73 m2, baseline NGAL level: 157.47±121.52 ng/mL); 18 patients were stage 1 and 36 patients were stage 2 CKD. In the ROC analysis, we found that the optimal cut-off value of NGAL for predicting stage 2 CKD was 98.71ng/mL (P=0.005) with the 72.2% sensitivity and 72.2% specificity. In correlation analysis, we evaluated significantly positive correlations between NGAL and CKD stage (r=0.389, P=0.004), baseline/last serum creatinine level (r=0.530, P<0.001 and r=0.439, P=0.003; respectively), last proteinuria level (r=0.359, P=0.043). There were significantly negative correlation between NGAL and baseline/last eGFR (r=-0.498, P<0.001 and r=-0.462, P=0.002; respectively). Compared to the group 1, we determined that group 2 patients had further deterioration in renal functions regarding ΔeGFR (-1.12±12.6 mL/min vs. -1.46±12.4 mL/min: respectively, P=0.930) and Δproteinuria (98.1±569.3 mg/day vs. 339±701.6 mg/day; respectively, P=0.305); however these differences were not statistically significant at the end of the two years follow-up period. CONCLUSIONS: Altough NGAL has a positive correlation with disease severity, it does not seem to be a marker of disease progression in patients with early stage CKD. But further studies stated in different patient groups may also explain the usability of NGAL in clinical practice.

Effects of human Umbilical Cord Stem Cells and Granulocyte Colony- Stimulating Factor (G-CSF) on Carbon Tetrachloride-Induced Nephrotoxicity.

BACKGROUND: Recently, stem cells have been used to facilitate healing in animal models of renal failure induced by acute ischemic and nephrotoxic damage. Granulocyte colony-stimulating factor (G-CSF) has been reported to stimulate stem cell mobilization from bone marrow and these cells may contribute to renal repair. OBJECTIVES: In the present study, the effects of G-CSF and stem cell administration as monotherapy or in combination, and the relation of these effects with the duration of therapy, have been investigated in an experimental rat model of carbon tetrachloride (CCl4)-induced nephrotoxicity. MATERIALS AND METHODS: The fifty rats included in the study were distributed into 4 main groups, Group 1, 2, 3, and 4, and two subgroups for each group, except for Group 1. All rats received an intraperitoneal injection of CCl4. Then at 6 h, Groups 1, 2a, 3a, and 4a were administered saline, stem cells, G-CSF, and stem cell plus G-CSF, respectively. At 24 h, Groups 2b, 3b, and 4b were administered stem cells, G-CSF, and stem cell plus G-CSF, respectively. All animals were sacrificed 48 h after the CCl4 injections. Serum urea, creatinine, sodium, and potassium levels were measured from blood samples. Tissue α-glutathione S-transferase (GST) levels were also measured from renal tissues. RESULTS: Serum urea was reduced in all groups when compared to Group 1, but the decrease was statistically significant only in Group 3b (P = 0.04). Serum creatinine and sodium levels were similar in all groups (P > 0.05). Tissue GST levels were lower in all groups, but the reduction was significant only in Group 4a, which was administered stem cells + G-CSF at 6 h (P = 0.01). Tubular degeneration and/or tubular dilatation were the most common pathologic changes, and their incidence was similar in all groups (P > 0.05). CONCLUSIONS: Although both stem cell and G-CSF monotherapy led to damage reduction, the effect was not significant. However, the reduced damage by the combined use of stem cells and G-CSF, particularly during the early period, was statistically significant.

Late pregnancy associated plasma protein A levels decrease in preterm labor.

OBJECTIVE: The purpose of the present study is to evaluate late, 'at admission', Pregnancy-associated plasma protein-A (PAPP-A) levels as a predictor of preterm birth in women with complaints of preterm labor or preterm painful contractions. METHODS: Prospective cohort study of singleton gestations, 23-37 weeks, and symptoms of preterm labor. Primary end point was delivery < 37 weeks. Predictive PAPP-A values were calculated both for preterm delivery and threatened preterm delivery on receiver operator curve. RESULTS: In all, 41 women (38.3%) delivered before 37 weeks (Group 1); 32 women (30.7%) had symptoms of preterm labor but did not deliver preterm (Group 2); 31 women (29.7%) delivered term (Group 3, control). Mean PAPP-A levels in preterm-labor and its matched control were 33.4 ± 19.9 and 52.5 ± 25.4 mIU/ml, respectively, and difference was statistically significant (p = 0.003). Mean PAPP-A level in threatened preterm labor group was 47.6 ± 25.3 mIU/ml and difference was significant compared to preterm-labor, but not significant compared to control group (p = 0.028 and p = 0.74, respectively). CONCLUSION: Late PAPP-A levels decreased in preterm labor, levels < 29.8 mIU/ml was associated with increased risk for preterm birth, supporting active management whereas cutoff value of 33.6 mIU/ml is useful for discrimination of preterm birth from threatened preterm birth reaching to term.