An investigation of the relation between catalase C262T gene polymorphism and catalase enzyme activity in leukemia patients.

INTRODUCTION: Catalase (CAT), an antioxidant enzyme, catalyzes conversion of hydrogen peroxide to water and molecular oxygen, protecting cells against oxidative stress. The aim of this study was to investigate the possible association between CAT C262T polymorphism in the promoter region of the CAT gene and leukemia risk and to determine the relationship between CAT genotypes and CAT enzyme activities. MATERIAL AND METHODS: Genotypes of 102 cases and 112 healthy controls' genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism methods. Catalase activity was measured with the method of Aebi. RESULTS: The frequencies of the T allele among the cases and controls were 28.4% and 25.9%, respectively (p = 0.75). The frequencies of CC, CT, and TT among cases were 57.8%, 27.4%, and 14.7%, respectively, while in controls, the frequencies of CC, CT, and TT were 54.4%, 39.3%, and 6.3%, respectively, which were not significantly different. Although CAT enzyme activity was lower in leukemia patients with TT genotypes than in controls, this did not reach statistical significance (p = 0.37). CONCLUSIONS: This is the first report showing that CAT C262T polymorphism is not a genetic predisposing factor for the risk of leukemia in the Turkish population. However, additional research is needed to confirm these findings.

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention.

OBJECTIVE: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. MATERIALS AND METHODS: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with ß-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). RESULTS: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all ß-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. CONCLUSION: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.

Cholesterol Levels in Patients with Chronic Lymphocytic Leukemia.

Low cholesterol levels may be accompanied by solid tumors or hematological malignancies such as multiple myeloma. Decreased cholesterol levels have been reported in some experimental studies about chronic lymphocytic leukemia (CLL). It may be associated with tumoral cell metabolism. Herein, we examine blood lipid profiles of patients with newly diagnosed CLL (284 male, 276 female, mean age 64 ± 11 years) as defined by National Cancer Institute criteria. The control group consisted of 71 healthy subjects with mean age 55 ± 9 years (28 male, 43 females). 60% of patients with Binet A, while 25% were Binet C. Decreased levels of total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) were observed in patients with CLL than control group (p < 0,001). There was no statistical significance between CLL and control group for triglycerides (TG) and very low density lipoprotein (VLDL), also between HDL-C, VLDL, TG and grades. Cholesterol may metabolized by abnormal lymphocytes in CLL patients.

Change in plasma a disintegrin and metalloprotease with thrombospondin type-1 repeats-13 and von Willebrand factor levels in venous thromboembolic patients.

OBJECTIVES: Venous thromboembolism (VTE) is an important cause of morbidity and mortality. A disintegrin and metalloprotease with thrombospondin type-1 repeats-13 (ADAMTS-13) is a metalloprotease that cleaves plasma von Willebrand factor (VWF) multimers. The presence of large VWF multimers in the plasma due to ADAMTS-13 deficiency is the main factor in the pathogenesis of thrombotic thrombocytopenic purpura. The present study aimed to investigate the relation of plasma levels of ADAMTS-13 and VWF antigen with VTE. METHODS: The present study included 30 patients with VTE and age- and gender-matched 30 healthy subjects. Patients with any condition (diabetes, icterus, hyperlipidemia, physical, or surgical trauma, acute coronary syndrome, pregnancy, renal insufficiency, liver disease, malignancy, collagen tissue disease, chronic or acute inflammation, drug use affecting thrombocyte function) that could affect plasma VWF antigen or ADAMTS-13 levels were excluded. Plasma ADAMTS-13 and VWF antigen levels in the VTE and control groups were quantitatively determined by enzyme-linked immunosorbent assay method. RESULTS: The median ADAMTS-13 level was 280 ng/ml (minimum-maximum, 70-1120 ng/ml) in the VTE group and 665 ng/ml (minimum-maximum, 350-2500 ng/ml) in the control group; the difference between the groups was significant (P < 0.0001). The mean VWF antigen level was 1750 ± 616 mU/ml in the patient group, which was significantly higher than that of the control group (950 ± 496 mU/ml) (P < 0.0001). CONCLUSION: Significantly lower ADAMTS-13 levels and significantly higher VWF antigen levels were concluded to be the result of a pathological process rather than an etiological factor for VTE.

Seasonal Association of Immune Thrombocytopenia in Adults.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disorder. It is characterized by thrombocytopenia due to thrombocyte destruction mediated by autoantibodies; however, cytotoxic and defective regulatory T-lymphocytes play an important role in its pathogenesis. While childhood ITP is usually acute, self-limiting and generally seasonal in nature, ITP in adults is usually chronic; its relation with seasons has not been studied. AIMS: We investigated whether months and/or seasons have triggering roles in adults with ITP. STUDY DESIGN: Descriptive study. METHODS: A retrospective case review of adult patients with primary ITP diagnosed at various University Hospitals in cities where Mediterranean climate is seen was performed. Demographic data, date of referral and treatments were recorded. Corticosteroid-resistant, chronic and refractory cases were determined. Relation between sex, corticosteroid-resistant, chronic and refractory ITP with the seasons was also investigated. RESULTS: The study included 165 patients (124 female, mean age=42.8±16.6). Most cases of primary ITP were diagnosed in the spring (p=0.015). Rates of patients diagnosed according to the seasons were as follows: 35.8% in spring, 23% in summer, 20.6% in fall, and 20.6% in winter. With respect to months, the majority of cases occurred in May (18.2%). Time of diagnosis according to the seasons did not differ between genders (p=0.699). First-line treatment was corticosteroids in 97.3%, but 35% of the cases were corticosteroid-resistant. Steroid-resistant patients were mostly diagnosed in the spring (52.1%) (p=0.001). ITP was chronic in 52.7% of the patients and they were also diagnosed mostly in the spring (62.7%) (p=0.149). CONCLUSION: This is the first study showing seasonal association of ITP in adults and we have observed that ITP in adults is mostly diagnosed in the spring. The reason why more patients are diagnosed in the spring may be due to the existence of atmospheric pollens reaching maximum levels in the spring in places where a Mediterranean climate is seen.

[Flavivirus seroepidemiology in blood donors in Mersin province, Turkey]. / Mersin ili kan donörlerinde flavivirus seroepidemiyolojisi.

Among the vector-borne flaviviruses, West Nile virus (WNV), tick-borne encephalitis virus (TBEV) and Dengue virus (DENV) constitute the most frequently-observed pathogens with significant public health impact in endemic regions throughout the globe. This seroepidemiological study was undertaken to investigate human exposure to DENV, WNV and TBEV, as well as other flaviviruses via various serological assays in the Mediterranean province of Mersin, Turkey, where scarce data is currently present for the circulation of these agent. A total of 920 sera were collected after informed consent from asymptomatic blood donors (all were male; age range: 18-63 yrs, mean age: 35.17 ± 9.56 yrs) were taken between August 2010 and April 2011. All samples were initially screened via a commercial ELISA kit for DENV IgM and IgG. Reactive samples were further evaluated via commercial indirect immunofluorescence tests (IIFTs) for yellow fever virus (YFV) IgG, TBEV IgG and via ELISA for WNV IgG. Moreover, presence of neutralizing antibodies were investigated in all reactive samples via plaque reduction neutralization (PRNT) assay for WNV, whose activity has been detected previously in the region. Samples interpreted as positive for TBEV IgG were further evaluated for specificity by TBEV PRNT assay. DENV IgM reactive samples were also assessed for NS1 antigens and IgM/IgG antibodies via a commercial immunochromatographic assay (ICA). DENV IgM and IgG antibodies were detected in 0.9% (8/920) and 16.6% (153/920) of the samples, respectively. One sample was simultaneously positive for IgM and IgG. WNV PRNT revealed positive results in 85.6% (137/160) of the reactive samples, which indicated frequent WNV exposure and frequent development of cross-reactions in the screening assay. Positive or borderline DENV IgM reactivity was identified in 0.43% (4/920) of the samples, which remained negative for NS1 antigen and antibodies in the ICA. Antibody specificity in two samples, positive for DENV and TBEV IgG in IIFT could not be confirmed by TBEV PRNT. A total of 19 reactive samples (19/920, 2.1%), that comprise seven borderline and six positive DENV IgG positivities as well as six samples with IgG positivity for different virus combinations remained negative after DENV confirmatory and WNV/TBEV PRNT assays. When the samples with borderline results were omitted from the evaluation, 12 samples (12/920, 1.3%) were considered to represent exposure to DENV or an antigenically-similar flavivirus. These findings indicated the activity of and frequent exposure (137/920, 14.9%) to WNV, as previously suggested in the study region. In 1.3% of the samples, probable exposure to DENV or other flaviviruses was revealed and this requires further serosurveillance efforts. WNV must be considered in the etiology of febrile diseases or viral neuroinvasive infections of unexplained etiology in the study area.

Mean platelet volume and related factors in patients at different stages of diabetic nephropathy: a preliminary study.

INTRODUCTION: Mean platelet volume (MPV) is an independent cardiovascular disease predictor, and characteristics of MPV in patients with diabetic nephropathy (DN) are not well known. AIM: To determine the MPV levels in patients at different stages of DN. PATIENTS AND METHODS: The MPV levels were investigated in healthy participants (group 1, n = 157), patients with type 2 diabetes mellitus without complication (group 2, n = 160), diabetic patients with clinical proteinuria (group 3, n = 144), and in patients with chronic kidney disease due to DN (group 4, n = 160). FINDINGS: The MPV level was higher in all diabetic patients than that in normal participants (P < .05). The MPV values had a positive correlation with the serum creatinine and proteinuria, and a negative correlation with the glomerular filtration rate ([GFR] P < .001 for all, r values; .72, and .82, and -.92, respectively). CONCLUSION: The MPV values were higher in diabetic groups than that in normal participants. Both GFR and proteinuria were the most powerful determinants of MPV.

Bloodstream infections and mortality-related factors in febrile neutropenic cancer patients.

BACKGROUND: We performed a prospective observational cohort study to evaluate the causative bacteria and to identify risk factors for mortality in febrile neutropenic (FN) patients with blood stream infection (BSI). MATERIAL/METHODS: We conducted a prospective data collection on all patients with bacteremia or fungemia. The patients were assigned into low-risk and high-risk groups in accordance with the Multinational Association for Supportive Care in Cancer (MASCC) Risk Index. RESULTS: Throughout the study period, the patients developed 420 FN episodes. Out of 420 episodes, only 90 (21.4%) were found to have bloodstream infection. The mean age of the patients was 45.6±18.4 years and 55.6% of the patients were male. A total of 98 isolates were recovered from the cases of BSI. Coagulase-negative Staphylococcus spp (CoNS) were the most common isolates overall (33.7%). There was a significant increase in the rate of gram-negative bacteria throughout the study period (p=0.028). Overall mortality was 33%. Multivariate analyses showed that MASCC risk scores (p=0.0001, OR=15.1, CI%95 4.5-50.7), ICU wards (p=0.0002, OR= 8.6, Cl%95 1.101-68,157) and CoNS (p=0.004, OR=12.12, CI%95 2.3-64.7) were independent risk factors associated with mortality. BSI due to CoNS was associated with lower mortality; however, MASCC high risk score and ICU stay were associated with higher mortality. CONCLUSIONS: The MASCC risk-index score and emergence of CoNS in positive blood cultures are valuable tools in the management of FN.

Serum stem cell factor level in renal transplant recipients with posttransplant erythrocytosis.

The etiology of posttransplant erythrocytosis (PTE) remains unclear, and the most frequently suggested causative factors are still a matter of controversy. We aimed to investigate serum-soluble stem cell factor (sSCF) along with serum erythropoietin (EPO) levels in renal transplant recipients (RTRs) with PTE. Thirteen RTRs with PTE, 42 RTRs without PTE, and 42 healthy controls were included. Serum sSCF and EPO levels were determined using an enzyme-linked immunosorbent assay kit. Expected and observed/expected EPO levels were calculated. Serum sSCF levels and observed/expected EPO were significantly higher in RTRs with PTE than both RTRs without PTE and controls. In RTRs with PTE, sSCF level was significantly correlated with hematocrit and observed/expected EPO, respectively. Significant correlation was also observed between hematocrit level and observed/expected EPO in RTRs with PTE. Increased sSCF level and inadequate suppression of EPO production seem to have a role in the pathogenesis of PTE.

[Investigation of SEN virus genotypes D and H among blood donors in Mersin University Medical School Hospital]. / Mersin Universitesi Tip Fakültesi Hastanesi kan donörlerinde SEN virusu genotip D ve H varliginin arastirilmasi.

SEN virus is a recently discovered DNA virus, and eight genotypes (A to H) were detected by phylogenetic analysis. Genotype D (SENV-D) and H (SENV-H) are thought to be associated in the etiology of post-transfusion hepatitis. Although no strong association was revealed between liver pathology and SEN virus, the viral replication in hepatocytes and transmission by blood transfusions were well characterized. The aim of this study was to investigate the prevalence of SENV-D and SENV-H in blood donors. One hundred serum samples were included in the study which were obtained from blood donors comprised of 98 male and 2 female with a mean age 36.4 years who were enrolled at Mersin University Faculty of Medicine blood center. The DNAs of SENV-D and SENV-H were detected with polymerase chain reaction (PCR), by using D10S/L2AS and C5S/L2AS primers, respectively. SEN virus DNA positivity was detected in 25 of 100 (25%) sera, of which 10 (10%) were positive for SENV-D and 15 (15%) were positive for SENV-H DNA. Although, the number of samples were not sufficient to reflect the general prevalence, our study relatively reveals that asymptomatic carriage rate of these viruses were 25% in our province.

Factor V Leiden mutation in venous thrombosis in southeast Turkey.

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1,000. Factor V Leiden mutation (G1691A) (FVL) is the most common risk factor in venous thrombosis. The prevalence of FVL for thrombosis varies greatly in different regions of the world. FVL mutation has been identified both by conventional method and fluorescence resonance energy transfer (FRET) with the LightCycler. Sixty-one patients with VT, different in age and sex, were consecutively entered into this study to assess the prevalence of FVL in VT in southeast Turkey. FVL mutation was found in 24.6% (15/61). Fourteen individuals were heterozygous and 1 homozygous, a rate of 22.9% and 1.6%, respectively. In conclusion, the authors suggest that FVL mutation is common in patients with venous thrombosis in southeast Turkey.

Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey.

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1000. The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world. Prothrombin G20210A (PT G20210A) gene mutation has been recently identified as a common risk factor in venous thrombosis. Sixty-one patients with VT, differing in age and sex, and 340 healthy subjects were consecutively enrolled into our study to determine the prevalence of PT G20210A in VT and in the healthy population of the southeast of Turkey. The mutation was identified with fluorescence resonance energy transfer (FRET) with the LightCycler polymerase chain reaction. The PT G20210A mutation was found to be 6.5% (4/61) in the VT group and 1.2% (4/340) in the healthy group ( P = 0.021). Three patients with VT had a heterozygous PT G20210A mutation, and the other patient with VT had both Factor V Leiden and PT G20210A mutations. We showed that this method may be used safely for detection of the PT G20210A gene mutation, and the prevalence of PT G20210A mutation is significantly higher in patients with VT than in the healthy population in the southeast of Turkey.

Non-Hodgkin's lymphoma in southeast Turkey: clinicopathologic features of 490 cases.

We have carried out a retrospective analysis of 490 non-Hodgkin's lymphomas (NHLs), followed at our clinic, with the purpose of evaluating the clinicopathologic features of these patients. The patients were assessed with regard to their characteristics including age, gender, histologic distribution, stage, extranodal involvement, presenting symptoms, and biopsied site. Of the patients 314 (64%) were male and 176 (36%) were female. The overall median age was 43 years (range: 14-90). The patients were classified according to the Working Formulation (WF) system: 71 (14.4%) were low grade, 342 (69.8%) were intermediate grade, 43 (8.7%) were high grade, and 34 (6.7%) had other lymphomas. Intermediate-grade non-Hodgkin's lymphomas formed the largest group, of whom 320 patients' paraffin blocks were available for Revised European and American lymphoma (REAL) classification: 78% were B-cell lymphomas, whereas 16% were T/NK lymphomas. Six percent of cases were unclassified lymphomas. Diffuse large B-cell lymphoma (DLBCL) was the most commonly observed histopathologic type in 132 (41%) patients. Extranodal involvement was found in 218 (44.5%) patients. The most commonly affected extranodal sites were small bowel, stomach, and tonsil in 72 (33%), 63 (29%), and 19 (8.7%) patients, respectively. According to the Ann Arbor staging system, the vast majority of patients (89.4%) were advanced stage. In conclusion,The characteristics of NHLs in our region show some differences from the other sites of Turkey and the world.

Hepatitis C virus in patients with non-Hodgkin's lymphoma in southeastern Anatolia region of Turkey: a prospective case-control study of 119 patients.

Hepatitis C virus (HCV) has been associated with several extrahepatic disorders including mixed cryoglobulinemia (MC), autoimmune thyroiditis, Sjogren's syndrome. Such associations have led to the suggestion that HCV may participate in the development of various immunmediated disorders. Recently, it has been hypothesised that HCV might act as a trigger for the development of monoclonal B-cell disorders such as non-Hodgkin's lymphoma (NHL). Discordant data have been reported in different geographic regions of the world. The aim of this prospective case-control study was to detect the prevalence of HCV in patients with NHL in southeastern Anatolia region of Turkey. In this study, HCV antibody prevalence and cryoglobulinemia were investigated in 119 patients with histologically diagnosed NHL. The control group consisted of 117 patients who visited the outpatient clinic of internal medicine. None of the patients had HCV antibody positive (0%) with the enzyme immunoassay and reverse transcriptase polymerase chain reaction (RT-PCR). One of the control patients had positive HCV antibody (0.9%). Our data does not support the association between HCV infection and NHL in southeastern Anatolia region of Turkey.

Serum levels of intercellular adhesion molecule-1 and nitric oxide in patients with chronic hepatitis related to hepatitis C virus: connection fibrosis.

BACKGROUND/AIMS: Chronicity of inflammation or fibrosis of liver parenchyma in patients with hepatitis C virus infection can be related to features of immunological responses in the liver. Adhesive interactions and free radicals are two important aspects of this inflammatory response. The aim of this study was to investigate serum sICAM-1 and nitric oxide levels in the sera of patients with post-hepatitis C chronic hepatitis. METHODOLOGY: Twenty chronic hepatitis patients diagnosed histopathologically and positive for antihepatitis C virus antibody and 20 healthy carriers of hepatitis C virus were included as study and control groups, respectively. Serum hepatitis C virus-RNA, sICAM-I, nitric oxide, blb, albumin and ALT determinations were made in the specimens of each subject in the study and control group. RESULTS: The mean serum sICAM-I levels of study and control subjects were 463.85 +/- 20.42 ng/mL and 241.85 +/- 13.71 ng/mL, respectively (p < 0.01). The same values for nitric oxide levels were 53.57 +/- 3.63 mumol/L and 32.17 +/- 2.19 mumol/L in the same order and also significantly different from each other (p < 0.01). There was a close correlation between fibrosis scores and serum sICAM-I levels (r = 0.77, p < 0.001), serum albumin (r = -0.54, p = 0.014) and ALT (r = 0.49, p = 0.02). Nitric oxide levels, on the other hand, negatively correlated with fibrosis scores (r = -0.59, p = 0.006), sICAM-1 (r = -0.57, p = 0.009) and ALT (r = -0.54, p = 0.013). CONCLUSIONS: Increased serum levels of sICAM are associated with increased fibrotic changes of patients with hepatitis C virus infection, whereas, nitric oxide which may be a suppressor molecule for fibrosing levels are inversely related to fibrotic process.