The effect of serum lipid levels on peripheral blood hematopoietic stem cell levels.

INTRODUCTION: There are limited numbers of available retrospective studies on various hematological diseases treated with stem cell mobilization therapy. In the present study, we aimed to demonstrate the effects of serum lipid levels on peripheral blood CD34+ (PBCD34+) cell counts as well as the changes in serum lipid levels during stem cell mobilization process. METHOD: PBCD34+ cell counts were compared between hypercholesterolemic patients and healthy individuals. Additionally, total cholesterol (TChol), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglyceride (TG) levels were measured from healthy donors who underwent stem cell mobilization, at different time points (prior to filgrastim [phase 1], prior to apheresis [phase II], and the first week following apheresis [phase III]. RESULTS: In the hypercholesterolemia group, the PBCD34+ cell count was found to be higher among patients with elevated LDL-C (2.6 ± 0.35/µL vs. 1.7 ± 0.17/µL, p = 0.003) and TChol (2.6 ± 0.34/µL vs. 1.7 ± 0.14/µL, p = 0.006) in comparison to the healthy controls. In the mobilization group, phase II HDL-C levels (35.3 ± 2.8 mg/dL) were found to be lower than both phase I (45.6 ± 2.1 mg/dL) and phase III (44.5 ± 2.6 mg/dL) (p = 0.007). Phase II TChol levels (183.5 ± 10.0 mg/dL) were lower than both phase I (216.8 ± 8.5 mg/dL) and phase III (212.2 ± 8.4 mg/dL) (p = 0.02). At phase II, there was an inverse correlation between PBCD34+ cell count and HDL-C (r = - 0.57, p = 0.003). DISCUSSION: Our results indicate that, while increased LDL-C level is the determinant of baseline PBCD34+ cell count, reduced HDL-C is the determinant of PBCD34+ cell count during mobilization process.

Single center experience of biotinidase deficiency: 259 patients and six novel mutations.

Background Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling. It is classified into two levels based on the biotinidase enzyme activity: partial deficiency (10%-30% enzyme activity) and profound deficiency (0%-10% enzyme activity). The aims of this study were to evaluate our patients with BD, identify the spectrum of biotinidase (BTD) gene mutations in Turkish patients and to determine the clinical and laboratory findings of our patients and their follow-up period. Methods A total of 259 patients who were diagnosed with BD were enrolled in the study. One hundred and forty-eight patients were male (57.1%), and 111 patients were female (42.9%). Results The number of patients detected by newborn screening was 221 (85.3%). By family screening, 31 (12%) patients were diagnosed with BD. Seven patients (2.7%) had different initial complaints and were diagnosed with BD. Partial BD was detected in 186 (71.8%) patients, and the profound deficiency was detected in 73 (28.2%) patients. Most of our patients were asymptomatic. The most commonly found variants were p.D444H, p.R157H, c.98_104delinsTCC. The novel mutations which were detected in this study are p.D401N(c.1201G>A), p.A82G (c.245C>G), p.F128S(c.383T>C), c617_619del/TTG (p.Val207del), p.A287T(c.859G>A), p.S491H(c.1471A>G). The most common mutation was p.R157H in profound BD and p.D444H in partial BD. All diagnosed patients were treated with biotin. Conclusions The diagnosis of BD should be based on plasma biotinidase activity and molecular analysis. We determined the clinical and genetic spectra of a large group of patients with BD from Western Turkey. The frequent mutations in our study were similar to the literature. In this study, six novel mutations were described.

The relationship between lipoprotein-associated phospholipase A2 with cardiovascular risk factors in testosterone deficiency.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) which is believed to play a role in atherosclerotic inflammatory process due to its function in hydrolysis of phospholipids and release of pro-inflammatory products, is considered as a novel biomarker for vascular risk. In this study we aimed to investigate the alterations in Lp-PLA2 and its relationship with other cardiovascular risk factors in patients with testosterone deficiency. MATERIAL AND METHODS: Forty hypogonadic male and 30 healthy male aged between 18-50 years were enrolled in this study. Height-weight, waist-to-hip circumference, body mass index (BMI) blood pressure, and body fat measurements were performed in all subjects. Blood glucose, albumin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, high sensitive C-reactive protein (hs-CRP), apo-A1, apo-B, fibrinogen, insulin, total testosterone, sex hormone binding globulin (SHBG), small dense low-density lipoprotein (sd-LDL), paraoxonase 1, oxidized low-density lipoprotein (ox-LDL) and Lp-PLA 2 values were measured. Free and bioavailable testosterone levels were calculated. Data management was carried out with the statistical program SAS Version 9.2. Statistical evaluations were performed using Analysis of Variance (ANOVA), Kruskal-Wallis test, Wilcoxon test, correlation analysis and chi-square analysis. P values <0.05 were considered statistically significant. RESULTS: In patients with hypogonadism, significant increase in Lp-PLA2 levels were accompanied with risk factors of atherosclerosis, such as increase in total cholesterol, apo-B, sd-LDL, weight, BMI, body fat percentage, and decrease in paraoxonase 1 levels. Although the differences were not significant, similarly ox-LDL, hs-CRP, triglyceride, LDL-cholesterol levels were found to be higher in patients with hypogonadism compared to the control group. The mean level of Lp-PLA2 was the highest when compared with the group of secondary hypogonadism with the lowest testosterone level. CONLUSION: Our study has demonstrated that the testosterone deficiency increases cardiovascular risk via its effects on lipid metabolism and Lp-PLA2 can be used to assess this risk.

Relationship between first trimester aneuploidy screening test serum analytes and placenta accreta.

OBJECTIVE: The aim of this study is to determine whether there is a relationship between first trimester serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fßhCG) MoM values and placenta accreta in women who had placenta previa. STUDY DESIGN: A total of 88 patients with placenta previa who had first trimester aneuploidy screening test results were enrolled in the study. Nineteen of these patients were also diagnosed with placenta accreta. As probable markers of excessive placental invasion, serum PAPP-A and fßhCG MoM values were compared in two groups with and without placenta accreta. RESULTS: Patients with placenta accreta had higher statistically significant serum PAPP-A (1.20 versus 0.865, respectively, p = 0.045) and fßhCG MoM (1.42 versus 0.93, respectively, p = 0.042) values than patients without accreta. CONCLUSIONS: Higher first trimester serum PAPP-A and fßhCG MoM values seem to be associated with placenta accreta in women with placenta previa. Further studies are needed to use these promising additional tools for early detection of placenta accreta.

Prognostic utility of serum neopterin in obstructive jaundice secondary to malignant lesions treated by percutaneous transhepatic biliary drainage.

PURPOSE: To perform biochemical profiles before and after percutaneous transhepatic biliary drainage (PTBD) and investigate the potential utility of measuring C-reactive protein (CRP), circulating cytokines, and neopterin, a marker of cell-mediated immunity, to predict outcomes of patients with obstructive jaundice. MATERIALS AND METHODS: In a prospective study, 47 patients with obstructive jaundice secondary to malignant lesions were evaluated before, at the fifth hour after, and on the fifth day after PTBD for neopterin, nitrate, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, CRP levels, and liver function. RESULTS: Neopterin levels on day 5 after PTBD were significantly higher than the levels before treatment and at the fifth hour. However, nitrate, cytokine, white blood cell, albumin, and creatinine levels were not significantly different. On the fifth day after PTBD, CRP levels were significantly higher and total bilirubin, direct bilirubin, alkaline phosphatase, aspartate transaminase, and alanine transaminase values were lower than the before-treatment values. Seven patients (15%) died within 30 days after drainage. On the fifth day after PTBD, neopterin, IL-6, IL-10, and creatinine levels were significantly higher and albumin levels were lower in the early mortality group. The performance characteristics of neopterin and creatinine were statistically significant in predicting mortality. CONCLUSIONS: Neopterin levels increased after PTBD, indicating cellular immune activation. The nonsignificant change in cytokine levels may be related to low enduring release in malignancy. The extremely elevated levels of neopterin and creatinine after PTBD might serve as harbingers of early death in patients with cholestasis secondary to malignant lesions.

Relation between NT-proBNP levels, iron overload, and early stage of myocardial dysfunction in ß-thalassemia major patients.

BACKGROUND: Heart failure (HF) secondary to myocardial iron loading remains the leading cause of death in ß-thalassemia major (ß-TM) patients. The early diagnosis and treatment of HF in these patients is related to survival. We aimed to evaluate myocardial performance using conventional and tissue Doppler echocardiography and its relation to plasma NT-proBNP levels and iron overload indices in ß-TM patients with preserved systolic function. METHODS: The study population included 49 ß-TM patients (24.0 ± 4.2 years) and 48 age-matched healthy controls. Doppler-echocardiographic study was performed and blood samples for NT-proBNP measurements were drawn on the third day following blood transfusion. Patients were divided as group-1, without diastolic dysfunction: E/E' ratio < 9 and group-2, with suspected diastolic dysfunction: E/E' ratio ≥ 9. RESULTS: NT-proBNP levels and E/E' ratio were increased in patients compared with controls (P < 0.001 and P < 0.001) but did not correlate with each other. A strong positive correlation was detected between NT-proBNP levels and mean ferritin levels in ß-TM patients (r(s) = 0.939; P < 0.001). Median NT-proBNP levels were significantly higher in group-1 in comparison to controls [51.2 (41.51-113.5) vs 30.1 (17.97-68.16) ng/mL, P < 0.01]. NT-proBNP levels were also increased in group-2 in comparison to group-1 but this increase was not statistically significant. CONCLUSION: NT-proBNP secretion begins in the early phase of the disease before the increase in diastolic pressure becomes overt. While there was a strong correlation between the plasma NT-proBNP levels and iron overload, there was no correlation between NT-proBNP levels and diastolic dysfunction parameters in patients in the third decade of life.

Fibroblast growth factor-19 levels in type 2 diabetic patients with metabolic syndrome.

This study aimed to examine fibroblast growth factor-19 (FGF-19) in type 2 diabetic (T2DM) patients with metabolic syndrome (MetS) and to evaluate the relationship between FGF-19 and other cardiovascular risk factors, such as atherogenic index of plasma (AIP) and hsCRP. 26 T2DM patients with MetS and 12 healthy controls were enrolled in the study. Serum FGF-19 levels were measured by sandwich ELISA, and compared with other cardiovascular risk factors; lipid profile, AIP, glucose, HbA1c, and hsCRP. AIP was calculated as log (TG/HDL-c). The median (1-3.quartile) FGF-19 levels in T2DM patients with MetS and healthy controls were 122.90 (108.63-237.60) pg/ml and 293.45 (153.64-370.31) pg/ml, respectively (P=0.003). Patients were also grouped by body mass index (BMI) <30 kg/m(2) (n=13) and ≥30 kg/m(2) (n=13) with median (1-3.quartile) FGF-19 values 168.70 (113.54-275.77) pg/mL and 115.89 (97.94-200.40) pg/mL, respectively (P=0.007). Significant negative correlations were found between FGF-19 and BMI, triglyceride, log (TG/HDL-c), hsCRP, and HbA1c (r=-0.526, P=0.001; r=-0.327, P=0.05; r=-0.312, P=0.05; r=-0.435, P=0.006; r=-0.357, P=0.028, respectively). We showed that FGF-19 levels are low in T2DM patients with MetS. The negative relationship between FGF-19 and several known cardiovascular risk factors such as TG, log (TG/HDL-c), hsCRP and HbA1c in diabetic patients with MetS suggests that FGF-19 can be used as a contributing marker.

Effects of percutaneous transhepatic biliary drainage on renal function in patients with obstructive jaundice.

PURPOSE: We assessed the effects of percutaneous transhepatic biliary drainage on renal function in patients with obstructive jaundice using the estimated glomerular filtration rate (eGFR) and evaluated the factors associated with renal dysfunction. MATERIALS AND METHODS: Between July 2007 and September 2009, 108 consecutive patients (69 men 39 women; median age, 59 years; range, 29-87 years) with obstructive jaundice (20 benign, 88 malignant) that were unsuitable for endoscopic retrograde cholangiopancreticography were evaluated at admission and at follow-up exams five and thirty days after percutaneous transhepatic biliary drainage. Two patients with suspected contrast-induced nephropathy were excluded. Renal function was assessed by measuring levels of urea, creatinine and electrolytes and evaluating the modification of diet in the renal disease formula for eGFR. RESULTS: eGFR was < 60 mL/min/1.73 m2 before percutaneous transhepatic biliary drainage in 27 patients (25%) and increased significantly 30 days after percutaneous transhepatic biliary drainage (P = 0.008). In the malignant external drainage subgroup, there was a significant increase in eGFR on the fifth day after percutaneous transhepatic biliary drainage (P = 0.038). The procedure-related mortality rate was zero. Nine malignant patients (8.49%) died within thirty days due to underlying diseases. On the fifth day, eGFR was significantly lower in these patients than in surviving patients (P = 0.049), and bilirubin levels were significantly higher before the intervention than in surviving patients (P = 0.04). Multiple logistic regression analysis showed that serum direct bilirubin is a significant predictor of renal function (P = 0.049). CONCLUSION: Obstructive jaundice is associated with renal dysfunction, and serum direct bilirubin is a significant predictor of renal function. Percutaneous transhepatic biliary drainage improves renal function and is crucial for prognosis of obstructive jaundice.

The detection of left ventricular diastolic dysfunction in hypertensive patients: Performance of N-terminal probrain natriuretic peptide.

AIM: Diastolic dysfunction (DD) results in increased cardiovascular risk in hypertensives. We studied the performance of N-terminal probrain natriuretic peptide (NT-proBNP) in detecting DD. MATERIALS AND METHODS: 241 hypertensive patients admitted to cardiology polyclinics were included in this study. They were grouped according to the presence of DD. Group 1: Essential hypertensive patients without DD (n= 119); group 2: essential hypertensive patients with DD (n= 122). All underwent trans-thoracic echocardiography for the evaluation of transvalvular flow, morphology, left ventricular wall motion abnormalities and ejection fraction. NT-proBNP levels were measured by an electrochemiluminescence immunoassay. RESULTS: The systolic blood pressure (BP) (mean+/-SD) was 140+/-12 mmHg in group 1 and 144+/-16 mmHg in group 2 (p=0.049), the diastolic BP (mean+/-SD) was 88+/-10 mmHg in group 1 and 90+/-14 mmHg in group 2 (p=0.043). The median (1st-3rd quartile) NT-proBNP level in group 2 was significantly higher than group 1 [121.05 (61.03-207.66) and 31.17 (17.07-54.09) pg/ml, respectively (p<0.001)]. In the receiver operating characteristics analysis, the area under the curve was 0.862 (95% CI 0.816-0.908). At the cut-off of 45 pg/ml, sensitivity was 86.9%, specificity was 62.4%, and at the cut-off 65 pg/ml, sensitivity was 74.6%, specificity was 83.8%. CONCLUSION: Plasma NT-proBNP levels may be useful for identifying patients with DD and it is conceivable to use a cut-off level 65 pg/ml as a "rule in" test.

Pleural fluid neopterin levels in tuberculous pleurisy.

OBJECTIVES: Neopterin is produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It is regarded as a biochemical marker of cell-mediated immune response. This study was designed to assess the diagnostic value of pleural fluid neopterin levels in tuberculous pleurisy in comparison with adenosine deaminase activity. DESIGN AND METHODS: Pleural fluid adenosine deaminase (ADA) activity and neopterin levels were measured in 16 patients with tuberculous pleurisy (TP) and 19 patients with malignant pleurisy (MP). ADA activity was determined by a colorimetric method, whereas neopterin levels were determined by a reversed-phase liquid chromatography technique. All values were given as median (min-max). RESULTS: The mean age was 45.43+/-20.39 years in the TP group and 60.42+/-11.02 years in the MP group (p=0.026). The median pleural fluid ADA activity was 51.75 U/L (3.50-62.40 U/L) in the TP group and was 2.30 U/L (1-8.20 U/L) in the MP group. The difference was statistically significant (p<0.001). The median pleural fluid neopterin levels were 13.15 nmol/L (1.86-59.50 nmol/L) and 2.44 nmol/L (0.92-27.60 nmol/L) in the TP group and the MP group, respectively (p=0.021). In order to evaluate the diagnostic value of pleural fluid neopterin concentrations, receiver-operating-characteristic curve analysis was performed. CONCLUSION: Pleural fluid neopterin concentration is significantly higher in TP when compared to MP, however when compared, its clinical use as a diagnostic marker is not valuable as ADA.