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    A novel indicator of widespread endothelial damage and ischemia in diabetic patients: ischemia-modified albumin
    (Springer, 2009) Ukinc, Kubilay; Eminagaoglu, Selcuk; Ersoz, Halil Onder; Erem, Cihangir; Karahan, Caner; Hacihasanoglu, Arif Bayram; Kocak, Mustafa
    Ischemia-modified albumin (IMA) is a novel marker of tissue ischemia. Nowadays, IMA is accepted as a marker of oxidative stress. In this study, we aimed at establishing an association between IMA and hyperglycemia, blood pressure, lipid parameters, microvascular complications, hsCRP, and microalbuminuria in type 2 diabetes patients without overt macrovascular disease and acute ischemia. Fifty type 2 diabetes mellitus patients without a history of macrovascular disease or end-stage renal disease were enrolled into the study. Age-matched 30 healthy individuals were also included in the study as a control group. Plasma IMA (0.329 +/- A 0.046 and 0.265 +/- A 0.045 AbsU; P < 0.0001) and hsCRP levels (0.51 +/- A 0.36 and 0.32 +/- A 0.17 mg/dl; P < 0.0001) were significantly higher in the diabetic group compared to healthy controls. IMA level was significantly correlated with hsCRP (r = 0.76; P < 0.0001), HbA1c (r = 0.72; P < 0.0001), microalbuminuria (r = 0.40; P = 0.004), systolic blood pressure (r = 0.28; P = 0.049), diastolic blood pressure (r = 0.44; P = 0.005), and HOMA-IR (r = 0.42; P = 0.005) levels in the entire diabetic subjects. In the diabetic patients group, presence of microalbuminuria was associated with a higher plasma IMA level (0.355 +/- A 0.035 and 0.265 +/- A 0.0045 AbsU; P < 0.0001, patients with microalbuminuria and control subjects, respectively). In the type 2 diabetes patients with nephropathy, IMA level (0.355 +/- A 0.035 and 0.311 +/- A 0.046 AbsU; P = 0.002) was determined higher compared to the diabetes patients without nephropathy. Diabetic patients without an overt cardiovascular disease still have a higher serum IMA level compared to healthy controls. The correlation of high plasma IMA levels with high hsCRP and microalbuminuria levels in diabetic subjects indicates the presence of a chronic ischemic process. Therefore, elevated IMA levels may indicate an underlying subclinical vascular disease in type 2 diabetes mellitus patients.
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    Diagnostic value of prostate-specific antigen (PSA) and free prostate specific antigen (fPSA) in women with ovulatory and anovulatory polycystic ovary syndrome
    (Springer, 2009) Ukinc, Kubilay; Ersoz, Halil Onder; Erem, Cihangir; Hacihasanoglu, Arif Bayram
    Diagnosis of polycystic ovary syndrome (PCOS) is very difficult in women with ovulatory cycles. We assessed the diagnostic value of prostate-specific antigen (PSA) and free prostate-specific antigen (fPSA) in women with ovulatory or anovulatory PCOS. Study group consisted of 62 women with PCOS and 35 healthy female controls. PCOS group was divided into two subgroups as anovulatory (n = 42; 68%, Group A) and ovulatory group (n = 20; 32%, Group B). A cut-off level of PSA and fPSA was established for the sensitivity, specificity, positive likelihood ratio, area under curve, diagnostic accuracy, and positive and negative predictive values of diagnosis of PCOS. In group A, a PSA level of greater than 10 pg/ml yielded a sensitivity of 73.2%, a specificity of 80%, and a diagnostic accuracy of 73%, with a positive predictive value of 88.2% and a negative predictive value of 59.3%. An fPSA level of greater than 2.1 pg/ml yielded a sensitivity of 71.2%, a specificity of 80.4%, and a diagnostic accuracy of 87%, with a positive predictive value of 87.2% and a negative predictive value of 58.4%. In group B, a PSA level of greater than 10 pg/ml yielded a sensitivity of 65%, a specificity of 80%, and a diagnostic accuracy of 73%, with a positive predictive value of 76.5% and a negative predictive value of 69.6%. An fPSA level of greater than 2.1 pg/ml yielded a sensitivity of 65.4%, a specificity of 80.4%, and a diagnostic accuracy of 87%, with a positive predictive value of 75.5% and a negative predictive value of 68.4%. Circulating androgens and hirsutism are independently associated with the degrees of PSA and fPSA in PCOS women. Increased plasma levels of PSA (> 10 pg/ml) and fPSA (> 2.1 pg/ml) could be helpful as a diagnostic tool for women with ovulatory or anovulatory PCOS.
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    Effects of one year simvastatin and atorvastatin treatments on acute phase reactants in uncontrolled type 2 diabetic patients
    (Humana Press Inc, 2009) Ukinc, Kubilay; Ersoz, Halil Onder; Erem, Cihangir; Hacihasanoglu, Arif Bayram; Karti, Suleyman Sami
    Type 2 diabetes mellitus is the leading cause of macrovascular diseases and related death. Additionally, diabetes mellitus is frequently complicated by other cardiovascular risk factors, such as hypercholesterolemia, hypertension, obesity, hypercoagulability, and inflammation. We wanted to evaluate and compare the effects of treating with a one-year course of atorvastatin or simvastatin on inflammatory markers such as high sensitive C-reactive protein (hsCRP), fibrinogen, and ferritin in uncontrolled type 2 diabetic patients. Also, we planned to investigate the correlation between inflammatory markers and metabolic parameters. Fifty type 2 diabetic patients (30 women, 20 men; mean age: 49.9 +/- A 8.5 years) were enrolled into the study. Twenty healthy subjects, matched on body mass index and age, were also included in the study as a control group. Diabetic patients were divided into two groups and received simvastatin or atorvastatin (Group S and A, respectively). After 1 year of statin treatment (Group A), there were significant decreases in total cholesterol (217.3 +/- A 46.5-173.8 +/- A 37.2 mg/dl; P < 0.0001), LDL-cholesterol (146.7 +/- A 50.3-102.3 +/- A 31.1 mg/dl, P < 0.0001), hsCRP (0.88 +/- A 0.62-0.35 +/- A 0.18 mg/dl, P < 0.0001), fibrinogen (258.2 +/- A 16.9-215.5 +/- A 10.6 mg/l; P < 0.0001), and ferritin (118.2 +/- A 73.9-81.2 +/- A 72.5 ng/ml, P < 0.0001) levels compared to basal values. In the S group, there were significant decreases in total cholesterol (224.4 +/- A 61.2-175.0 +/- A 47.8 mg/dl; P < 0.0001), LDL-cholesterol (140.9 +/- A 56.7-110.9 +/- A 42.2 mg/dl, P < 0.0001), hsCRP (0.98 +/- A 1.3-0.46 +/- A 0.25 mg/dl, P < 0.0001), fibrinogen (265.7 +/- A 26.8-222.1 +/- A 20.6 mg/l; P < 0.0001), and ferritin (136.7 +/- A 101.1-85.6 +/- A 32.1 ng/ml, P < 0.0001) levels compared to basal values. At the end of the study, a dagger hsCRP, a dagger fibrinogen, and a dagger ferritin levels were correlated with a dagger LDL (r = 0.42; P = 0.005, with a dagger hsCRP), (r = 0.40; P = 0.008, with a dagger fibrinogen), (r = 0.46; P = 0.002, with a dagger ferritin) and a dagger HDL (r = -0.50; P < 0.0001, with a dagger hsCRP), (r = -0.32; p = 0.042, with a dagger fibrinogen), (r = -0.48; P < 0.0001, with a dagger ferritin) cholesterol levels. Atorvastatin and simvastatin treatments were found to be effective for the control of hypercholesterolemia and resulted in a significant decrease in acute phase reactants in uncontrolled type 2 diabetic patients.
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    Methyltetrahydrofolate reductase C677T gene mutation and hyperhomocysteinemia as a novel risk factor for diabetic nephropathy
    (Springer, 2009) Ukinc, Kubilay; Ersoz, Halil Onder; Karahan, Caner; Erem, Cihangir; Eminagaoglu, Selcuk; Hacihasanoglu, Arif Bayram; Yilmaz, Mustafa
    Hyperhomocysteinemia is a well-defined risk factor for endothelial dysfunction and atherosclerosis. A point mutation (677 C-T) of MTHFR gene results in a significant increase at plasma homocysteine levels. In this study we aimed to evaluate the effects of MTHFR gene mutation and consequent hyperhomocysteinemia on the development of diabetic microvascular complications in comparison with the other defined risk factors. Diabetic patients without a history of macrovascular complication or overt nephropathy enrolled into the study. The presence of MTHFR 677 C-T point mutation was evaluated by Real-Time PCR technique by using a LightCycler. MTHFR heterozygous mutation was present in 24 patients over 52. Patients with diabetes were divided into two groups according to the presence of MTHFR gene mutation. Both groups were well matched regarding age and diabetes duration. Metabolic parameters, plasma homocysteine, microalbuminuria, folic acid, and vitamin B12 levels were also studied. Presence of neuropathy and retinopathy were evaluated by specific tests. Duration of diabetes, BMI, systolic and diastolic blood pressure, plasma CRP, HbA1c, and lipid levels were not different between the two groups. Plasma homocysteine (12.89 +/- A 1.74 and 8.98 +/- A 1.91 mu mol/l; P < 0.0001) and microalbuminuria levels (73.40 +/- A 98.15 and 29.53 +/- A 5.08 mg/day; P = 0.021) were significantly higher in the group with MTHFR gene mutation while creatinine clearance levels (101.1 +/- A 42.6 and 136.21 +/- A 51.50 ml/min; P = 0.008) were significantly lower. Sixteen over 22 (73%) of the patients with diabetic nephropathy had MTHFR gene mutation, while this was only 27% (8 over 30) in normoalbuminuric patients (P = 0.017). There was a significant correlation of plasma homocysteine level with microalbuminuria (r = 0.54; P = 0.031) in the patients with diabetic nephropathy who had C677T polymorphism. We did not find any specific association of MTHFR gene mutation and hyperhomocysteinemia with retinopathy or neuropathy.