Vahap Okan

Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the presence of autoantibodies developing against thrombocyte membrane glycoproteins (GPs), such as GPIIa/IIIa and GPIb/IX. Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were investigated in 71 patients with chronic ITP and 71 healthy controls, and they were compared with the clinical parameters. The polymorphisms in the SNPs were investigated with the polymerase chain reaction, polymerase chain reaction with sequence specific primer, and polymerase chain reaction-restriction fragment length polymorphism methods. It was found that the high expression of TNF-alpha (−308) AG phenotype significantly increased in cases with ITP (odds ratio, OR: 0.318, 95% confidence intervals, CI: 0.103–0.987, p < 0.05). TT genotype in TGF-beta 1 (codon 10) significantly decreased in ITP in comparison with the controls (OR: 0.342, 95% CI: 0.149–0.787, p = 0.016). IFN-gamma (+874) TT genotype was detected to be high in cases with ITP (OR: 3.301, 95% CI: 1.400–7.784, p < 0.05), whereas AA genotype was found to be significantly lower (OR: 4.993, 95% CI: 1.586–15.721, p < 0.05). MBL (codon 54) BB genotype (OR: 1.164, 95% CI: 1.059–1.279, p < 0.05) and IL1A A1/A2 genotype (OR: 0.249, 95% CI: 0.076–0.815, p < 0.05) were found to be significantly higher in cases with ITP than in healthy controls. TNF-alpha (−308) AG phenotype was detected to be significantly higher in steroid-refractory and splenectomized cases at the end of the first year than in the steroid–responsive (complete response (CR) and remission (R)) cases (OR: 4.137, 95% CI: 1.156–14.807, p < 0.05). When we compared the cases, from whom we obtained a CR at their first steroid response, with 12 cases, who entered R but from whom we could not obtain any CR, the frequencies of IFN-gamma (+874) AA genotype were found as 12 (20.3%) and 6 (50%) (OR: 0.082, 95% CI: 0.009–0.793, p < 0.05). MBL (codon 54) AB genotype was detected to be significantly higher in CR patients than in R cases (OR: 1.273, 95% CI: 1.110–1.459, p < 0.05). With these findings, it was found that TNF-alpha/AG, TGF-beta 1/TT, IFN-gamma/TT, MBL/BB, and IL-1RA A1/A2 genotypes were detected as the genes of susceptibility to ITP, while TNF-alpha/AG, IFN-gamma/AA, and MBL/AB genotypes might be important in response to steroid treatment.

Angiotensin-converting enzyme gene polymorphism and microvascular complications in Turkish type 2 diabetic patients

The aim of this study was to investigate whether an association exists between the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and microvascular complications of type 2 diabetes mellitus in Turkish patients. A total of 239 type 2 diabetic patients and 138 sex and age matched control subjects were included into the study. The I/D polymorphism was determined by polymerase chain reaction (PCR). Nephropathy status was determined according to urinary albumin/creatinine ratio (microg/mg) (<30 normoalbuminuria, 30-300 microalbuminuria, >300 macroalbuminuria) and retinopathy was evaluated by fundoscopic examination and by flourescein fundus angiography. The distribution of ACE I/D polymorphism and allele frequencies in diabetic patients were not significantly different from controls, DD genotype 32.2 versus 37.2%; ID genotype 50.6 versus 47.1%; and II 17.2 versus 15.2%; D allele 57.5 versus 61.2%; I allele 42.5 versus 38.8%. Genotype distribution between normo-, micro- and macroalbuminuric patients did not differ significantly (DD:ID:II (%), normoalbuminuria, 35:46:19; microalbuminuria, 28:55:17; macroalbuminuria, 31:55:14). There was also no difference in genotype distribution between patients with and without retinopathy (DD:ID:II (%), retinopathy positive, 32:51:17; retinopathy negative, 33:49:18). In conclusion, the ACE I/D polymorphism does not seem to be associated with diabetic nephropathy and retinopathy in Turkish type 2 diabetic patients.

Red Cell Indices and Functions Differentiating Patients with the β-Thalassaemia Trait from those with Iron Deficiency Anaemia

This study examined the diagnostic accuracy of nine indices to discriminate between patients with mild-to-moderate (haemoglobin 8.5 − 11 g/dl) or moderate-to-severe (haemoglobin < 8.5 g/dl) iron deficiency anaemia (IDA) from those with β-thalassaemia (β-TT) (n = 100 per group). Indices examined were red blood cell (RBC) count, RBC distribution width (RDW), Mentzer index (MI), Shine and Lal index (S&L), England and Fraser index (E&F), Srivastava index (S), Green and King index (G&K), RDW index (RDWI), and Ricerca index (R). Index sensitivity, specificity, and positive and negative prognostic values were examined. Youdens indices were calculated and showed: S&L > G&K > E&F > RBC = RDWI > MI > S > R > RDW to differentiate between β-TT and mild-to-moderate IDA; and S&L > G&K > E&F = RDWI > RBC > R > MI > S > RDW to differentiate between β-TT or moderate-to-severe IDA. For both groups, S&L and G&K offered the best discrimination and RDW the worst. S&L showed the highest Youden index for β-TT and IDA discrimination, but sensitivity and specificity were not 100%. In both mild and severe IDA, the S&L index may be used to differentiate cases of β-TT from IDA cases, but large clinical trials are needed to explore this further.

Frequency of silent myocardial ischemia in type 2 diabetic patients and the relation with poor glycemic control

Abstract.The aim of the study was to investigate the frequency of silent myocardial ischemia in type 2 diabetic patients without any clinical or laboratory findings of myocardial ischemia and to examine the related factors for silent myocardial ischemia. A total of 116 type 2 diabetic patients (82 women) with a disease duration of 5–20 years were included in the study. All patients underwent stress and resting myocardial perfusion single-photon emission computed tomographic (SPECT) study with 99mTc-MIBI. Coronary angiography was performed in patients with ischemia established at myocardial perfusion SPECT. Ischemia was determined in 18 (15.5%) patients by myocardial perfusion SPECT. Coronary angiography performed in 17 of these patients confirmed coronary stenosis >50% in 11 patients. Thus, the prevalence of silent myocardial ischemia was 9.6%. Significant relations were found between silent myocardial ischemia and male sex, high HbA1C level and retinopathy. Type 2 diabetic patients (especially men) with poorly controlled diabetes mellitus or retinopathy should be screened for silent myocardial ischemia.

Brucellosis‐induced immune thrombocytopenia mimicking ITP: a report of seven cases

Brucellosis continues to be an important cause of fever in underdeveloped countries and in rural areas of developed world. It is a multisystemic disease, associated with wide variety of symptoms. A wide variety of symptoms, including haematological abnormalities, such as anaemia, thrombocytopenia, pancytopenia, dissemine intravascular coagulation and leucopoenia could be seen, all of which are more common than usually thought. In this short study, we present a relatively uncommon haematological manifestation that of isolated thrombocytopenia mimicking idiopathic thrombocytopenic purpura, which we observed in seven of 114 patients who were diagnosed with brucellosis in our hospital over a 2‐year period. Having given brucellosis treatment with rifampicin and doxycycline, complete remission was achieved and thrombocyte count returned to normal in all cases.

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: A retrospective multicenter study

UNLABELLED Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. TTP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of TTP. Also, TTP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in TTP patients. AIM We aimed to present our experience in 163 patients with TTP treated with TPE during the past 5years from 10 centers of Turkey. PATIENTS AND METHODS One hundered and sixty-three patients with TTP treated with TPE during the past 5years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1-1.5times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150×10(9)/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. RESULTS Fifty-eight percent (95/163) of the patients were females. The median age of the patients was 42years (range; 16-82). The median age of male patients was significantly higher than female (53 vs. 34years; p<0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary TTP comprised of 85.9% (140/163) of the patients and secondary TTP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary TTP. The median number of TPE was 13 (range; 1-80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p<0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary TTP (85% vs. 87%, respectively; p=0.806). There was no advantage of TPE+prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p=0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TTP [15% (21/140) vs. 13% (3/23); p=0.806]. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE+prednisolone [14% (12/86) vs. 3% (2/67), p<0.001]. CONCLUSIONS TPE is an effective treatment for TTP and is associated with high CR rate in both primary and secondary TTP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP and if these two criteria met in a patient, TPE should be performed immediately.

DNA repair genes polymorphisms in multiple myeloma: no association with XRCC1 (Arg399Gln) polymorphism, but the XRCC4 (VNTR in intron 3 and G-1394T) and XPD (Lys751Gln) polymorphisms is associated with the disease in Turkish patients.

Abstract Objective: This study aims to investigate the association between the polymorphisms in DNA repair genes (XPD, XRCC1, and XRCC4) and clinical parameters in patients with multiple myeloma (MM), their effects on prognosis and their roles in susceptibility to MM. Patients and methods: Sixty patients, diagnosed with MM and 70 individuals as the healthy control group were included in the study. Gene polymorphisms were detected with the polymerase chain reaction and/or polymerase chain reaction–restriction fragment length polymorphism method. When the genotype frequencies of XPD (Llys751Gln) and XRCC1 (Arg399Gln) genes were examined in the patient and control groups, no significant difference was detected, while a significant association was found in XRCC4 (VNTR in intron 3 and G-1394T) polymorphisms. A significant association was found in the MM patients group for AA genotype and event-free survival (EFS) in terms of XPD (751) gene polymorphism (P = 0·047). When VNTR intron 3 polymorphism was compared for genotype frequency, DD genotype was found to be significantly low (P = 0·012) in the patient group, whereas GG and TT genotypes were found to be significantly lower in the patient group for the genotype frequency XRCC4 (G-1394T) polymorphism when compared to the control group (P = 0·015, P = 0·010, respectively). Results: These data provide support for the hypothesis that a common variation in the genes encoding XRCC4 DNA repair proteins may contribute to susceptibility to myeloma. These findings require further validation in independent populations.

Pregnancy in patients with chronic myeloid leukemia treated with imatinib.

Pregnancy in patients with chronic myeloid leukemia treated with imatinib Mehmet Yilmaz a; Osman Demirhan b; Ercan Kucukosmanoglu c; Mustafa Pehlivan a; Vahap Okan a; Ozcan Balat d; Sacide Pehlivan e a Department of Hematology, School of Medicine, Gaziantep University, Gaziantep, Turkey b Department of Medical Biology and Genetics, Faculty of Medicine, Cukurova University, Adana, Turkey c Departments of Pediatrics, d Obstetrics and Gynecology, e Medical Biology and Genetics, School of Medicine, Gaziantep University, Gaziantep, Turkey

Modified IDARAM chemotherapy regimen for primary central nervous system lymphoma: experience of three cases

Abstract The use of radiotherapy (RT) with chemotherapy has improved disease free survival and control in primary central nervous system lymphoma (PCNSL). We have encountered three patients with histologically documented central nervous system lymphoma. In all patients pathological diagnosis was B-cell lymphoma. We modified IDARAM regimen to R-IDARAM to enhance and optimize chemotherapeutic components for the treatment of PCNSL. We made three changes: (i) we added rituximab 375 mg/m2 day 1; (ii) increased dose of MTX from 2 to 3 g/m2; and (iii) administered two additional courses of R-IDARAM after cranial RT. Following complete staging after course 2, radiotherapy was applied at a dosage of 3600–4140 cGy in conventional schedule (180 or 200 cGy per day) to whole brain (with 3600 cGy to eyes in one case because of eye involvement) and then 2 additional courses of R-IDARAM (totally four courses) chemotherapy regimen were applied. Complete remission (CR) was achieved after first two cycles of R-IDARAM in patient 1 and 3 and after four cycles in patient 2. Currently, three patients have been alive for 29, 10, 15 months respectively. Currently there is no standard treatment modality for PCNSL. Increased dosage of MTX, adding rituximab and consolidation of the IDARAM to R-IDARAM regimen may improve disease control and outcome in PCNSL patients.

Angiotensin-converting enzyme gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients.

OBJECTIVE It has been suggested that the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) may be associated with atherosclerosis. The aim of the study was to examine the association between ACE gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients. METHODS AND RESULTS A total of 152 (97 female, 55 male) type 2 diabetic patients were included into the study. All patients underwent myocardial perfusion scintigraphic examination and forty-five of them with a perfusion defect underwent coronary angiography.Thirty-eight patients with a coronary stenosis of more than 50% on coronary angiography were considered as having coronary heart disease. The I/D polymorphism was determined by polymerase chain reaction. There was no statistically significant difference in genotypic and allelic frequencies of the ACE I/D polymorphism among patients with and without coronary heart disease (DD:ID:II (%), 32:58:11 and 39:44:17, respectively). CONCLUSIONS ACE gene polymorphism is not a significant parameter to determine coronary heart disease in Turkish type 2 diabetic patients.Objective — It has been suggested that the insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) may be associated with atherosclerosis.The aim of the study was to examine the association between ACE gene polymorphism and coronary heart disease in Turkish type 2 diabetic patients. Methods and results — A total of 152 (97 female, 55 male) type 2 diabetic patients were included into the study. All patients underwent myocardial perfusion scintigraphic examination and forty-five of them with a perfusion defect underwent coronary angiography.Thirty-eight patients with a coronary stenosis of more than 50% on coronary angiography were considered as having coronary heart disease.The I/D polymorphism was determined by polymerase chain reaction.There was no statistically significant difference in genotypic and allelic frequencies of the ACE I/D polymorphism among patients with and without coronary heart disease (DD:ID:II (%), 32:58:11 and 39:44:17, respectively). Conclusions — ACE gene polymorphism is not a significant parameter to determine coronary heart disease in Turkish type 2 diabetic patients.