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Biomedical subjects

I C Haznedaroglu

Publications and source records attributed to I C Haznedaroglu.

At least 19 recordsLinked to original sources
PubMed2002

Rational use of the PFA-100 device for screening of platelet function disorders and von Willebrand disease.

Two hundred and five patients referred for evaluation of platelet functions and 126 healthy controls were tested with the PFA-100 instrument. A cut-off value of 150 s for collagen/epinephrine (CEPI) closure time (CT) produced most acceptable sensitivity (90%), specificity (85.2%), and positive (82.6%) and negative (91.6%) predictivity values for screening of platelet function disorders and von Willebrand disease (vWD). All patients with vWD and Glanzmann thrombasthenia could be detected by PFA-100. Both CEPI and collagen/adenosine diphosphate (CADP) CTs were elevated in all of these cases. Sensitivity of the device was 81.6% for patients with platelet secretion defects. CADP CT was normal in 63.9% of the patients in this subgroup. Specificity (47%) and positive predictivity (57%) of the instrument were diminished in patients with low hemoglobin concentrations. Depending on the results, an algorithm was developed for screening of platelet function disorders and vWD with PFA-100.

Algorithms↗
PubMed2001

Two common genetic thrombotic risk factors: factor V Leiden and prothrombin G20210A in adult Turkish patients with thrombosis.

The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world, both in patients with thrombosis and in the general population. Factor V Leiden (FVL) and prothrombin G20210A (PT G20210A) mutations are the most common genetic defects leading to thrombosis. We have previously reported that those two thrombotic risk alleles are frequently found in Turkish children with thrombosis. The aim of the present study was to investigate the frequency of FVL and PT G20210A and their clinical manifestations in adult Turkish patients with thrombosis. Between January 1997 and February 2000, 146 patients with documented thrombosis were investigated in our center for the presence of the FVL and PT G20210A mutations. Forty-five of 146 patients with thrombosis (30.8%) were detected to have FVL mutation. Among those cases with the FVL mutation, seven (4.8%) had homozygote and 38 (26%) had heterozygote mutation. The PT G20210A mutation was detected in 10 of the 146 patients with thrombosis (6.8%). Another six cases (4.1%) had both FVL and PT G20210A mutations. The overall frequency of these two common risk alleles in our adult population with thrombosis was 41.6%. Our findings reveal that FVL and PT G20210A mutations are significant genetic risk factors contributing to the pathophysiology of thrombosis in the Turkish population.

Adolescent↗
PubMed2001

Plasma fibronectin- and thrombospondin-adhesive molecules during acute attacks and attack-free periods of familial Mediterranean fever.

We assessed plasma concentrations of fibronectin (FN) and thrombospondin (TSP) during acute attacks and attack-free periods of patients with familial Mediterranean fever (FMF). Seven female and three male FMF patients (mean age 34+/-7 years) were enrolled in the study. Plasma samples were obtained during acute FMF attacks and after 3 months of freedom from attacks. Erythrocyte sedimentation rate, C-reactive protein, and white blood cell count were evaluated concurrently. Plasma levels of FN and TSP were assayed by enzyme-linked immunosorbent assay (ELISA). Both FN and TSP concentrations were found to increase during acute attacks. Levels of adhesive molecules decreased during attack-free periods (P < 0.05). Significant correlations were found between FN and TSP levels and the concentrations of acute-phase response indicators (P< 0.05). This study disclosed for the first time significantly higher increments in the plasma levels of FN and TSP during acute FMF attacks than in attack-free periods. Therefore, the two matrix glycoproteins may play precipitating and/or regulatory roles in the inflammatory processes of these attacks.

Adult↗
PubMed2001

Acute graft-vs-host disease: pathobiology and management.

Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and mortality. GVHD occurs when transplanted donor T lymphocytes react to foreign host cells. It causes a wide variety of host tissue injuries. This review focuses on the pathobiological basis, clinical aspects, and current management strategies of acute GVHD. Afferent phase of acute GVHD starts with myeloablative conditioning, i.e., before the infusion of the graft. Total-body irradiation (TBI) or high-dose chemotherapy regimens cause extensive damage and activation in host tissues, which release inflammatory cytokines and enhance recipient major histocompatibility complex (MHC) antigens. Recognition of the foreign host antigens by donor T cells and activation, stimulation, and proliferation of T cells is crucial in the afferent phase. Effector phase of acute GVHD results in direct and indirect damage to host cells. The skin, gastrointestinal tract, and liver are major target organs of acute GVHD. Combination drug prophylaxis in GVHD is essential in all patients undergoing allogeneic HSCT. Steroids have remained the standard for the treatment of acute GVHD. Several clinical trials have evaluated monoclonal antibodies or receptor antagonist therapy for steroid-resistant acute GVHD, with different successes in a variety of settings. There are some newer promising agents like mycophenolate mofetil, glutamic acid-lysine-alanine-tyrosine (GLAT), rapamycin, and trimetrexate currently entering in the clinical studies, and other agents are in development. Future experimental and clinical studies on GVHD will shed further light on the better understanding of the disease pathobiology and generate the tools to treat malignant disorders with allogeneic HSCT with specific graft-vs-tumor effects devoid of GVHD.

Acute Disease↗
PubMed2001

Cytokines, endothelium, and adhesive molecules in pathologic thrombopoiesis.

Clonal thrombocytosis (CT) associated with myeloproliferative disorders (MPD) is believed to be secondary to autonomous unregulated platelet production. Secondary or reactive thrombocytosis (RT) can be observed in a number of clinical circumstances and may be related to persistent production of some thrombopoietic factors acting on megakaryocytes (MK). The goal of this study is to assess the serum concentrations of these cytokines in control subjects and patients with MPD associated with thrombocythemia, RT, and autoimmune thrombocytopenic purpura (ATP). Eleven patients with MPD, five with chronic myeloid leukemia (CML), three with polycythemia vera (PCV), two with essential thrombocythemia (ET), one with myelofibrosis, 15 with RT, eight with ATP, and 12 healthy volunteers were enrolled in the study. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF), fibronectin, intracellular adhesion molecule-1 (ICAM-1), and thrombomodulin (TM) were measured in these groups. Interleukin- 1beta, IL-6, and TNF levels were high in patients with RT and ATP, suggesting that these cytokines act on early uncommitted progenitors, promoting commitment along the MK lineage and leading to thrombocytosis or compensation for thrombocytopenia. TM was significantly increased in patients with MPD compared to all other groups, probably indicating the presence of subclinical endothelial damage. Fibronectin levels were high in MPD and RT patients. This finding can be secondary to high platelet turnover in these patients. We found that ICAM-1 levels were high in patients with clonal thrombocytosis. ICAM-1 can be one of the factors initiating the events ultimately leading to clonal thrombocytosis. Thrombocythemia associated with MPD is an autonomous phenomenon not regulated by cytokines.

Case-Control Studies↗
PubMed2001

Cardiac and great vessel thrombosis in Behçet's disease.

Behçet's disease (BD) is a chronic relapsing systemic vasculitis in which orogenital ulceration is a prominent feature. The disease affects many systems and causes hypercoagulability. We present a 27-year-old male patient who exhibited widespread great vessel thrombosis including right atrial and ventricular thrombi in the setting of right-sided infectious endocarditis and orogenital aphthous ulcerations and erythema nodosum due to BD. We reviewed the enigmatic prothrombotic state of BD, and discuss our prior experiences in this field.

Adult↗
PubMed2000

Behçet's disease.

Explore the source record for details and available documents.

Behcet Syndrome↗
PubMed2000

Serum L-selectin and P-selectin levels in lymphomas.

The migration of normal and malignant lymphoid cells is governed by specific adhesion molecules. Selectins comprise a family of adhesion receptors expressed by leukocytes, platelets and endothelial cells. In this study, the serum levels of soluble L-selectin and P-selectin were measured in patients with non-Hodgkin's lymphoma and Hodgkin's disease and found to be significantly elevated in both patient groups compared to healthy controls. This result provides evidence that alterations in the expression and function of adhesion molecules may play an important role in the progression of lymphomas. Further studies are awaited to establish the exact roles of these adhesion molecules in distinct patterns of growth and spread of lymphomas.

Adult↗
PubMed1999

Effects of interferon-alpha2a treatment on serum levels of tumor necrosis factor-alpha, tumor necrosis factor-alpha2 receptor, interleukin-2, interleukin-2 receptor, and E-selectin in Behçet's disease.

This study was performed to investigate serum levels of various cytokines and E-selectin in patients with Behçet's disease (BD) before and after treatment with interferon-alpha2a (IFN-alpha). The study population consisted of 22 patients with active BD; 15 age- and sex-matched healthy adults served as the control group. IFN-alpha (3 million units subcutaneously) was given to all patients twice a week for 3 months. Twenty of twenty-two patients experienced clinical improvement with this therapy. Pre- and post-treatment serum levels of tumor necrosis factor-alpha (TNF-alpha), TNF-alpha2-receptor (TNFalpha2R), interleukin-2 (IL-2), IL-2 receptor (IL-2R), and E-selectin were measured by sandwich-type enzyme immunoassay. Baseline E-selectin, TNF-alpha, and TNF-alpha2R levels of the patients were increased in comparison with the control group and post-treatment values. However, IL-2 and IL-2R levels did not change either with treatment or compared with the control group levels. In conclusion, these results confirm the previously described efficacy of IFN-alpha in the treatment of BD. Serum levels of TNF-alpha, TNF-alpha2R, and E-selectin are prominently increased during active stage of the disease, indicating presence of immune system activation and endothelial injury/activation. Improvement of the pathological cytokinemia and endothelial disturbance accompany interferon-alpha-induced disease remission.

Adult↗
PubMed1999

Increased systemic coagulation activity in patients with rheumatic mitral stenosis: assessment of the clinical and echocardiographic determinants.

In this study, we aimed to determine systemic coagulation activity in patients with rheumatic mitral stenosis and to define determinants of a possible prethrombotic state. Peripheral venous plasma level of thrombin-antithrombin III complex was measured in 84 consecutive patients with rheumatic mitral stenosis who had no left atrial thrombus by transesophageal echocardiography. The patients had significantly higher thrombin-antithrombin III complex values (mean +/- SD = 9.6+/-15.9 ng/ ml) compared with the healthy subjects (2.1+/-1.8 ng/ml) (P<0.001). Among many clinical and echocardiographic variables, severe mitral regurgitation (odds ratio = 6.7, P<0.001) and left atrial spontaneous echo contrast (odds ratio = 22.8, P<0.001) appeared as significant predictors of the increased systemic coagulation activity in multivariate logistic regression analysis. In conclusion, systemic coagulation activity is increased in the patients with rheumatic mitral stenosis, and coexistence of severe mitral regurgitation and presence of left atrial spontaneous echo contrast are determinants of this increment.

Adult↗
PubMed1999

Selectins and IL-6 during the clinical course of idiopathic thrombocytopenic purpura.

'Stress thrombocytes', i.e. large and presumably hyperfunctioning platelets, is a well-known characteristic of patients with idiopathic thrombocytopenic purpura (ITP). Therefore, despite what may be severe thrombocytopenia these patients generally do not suffer from severe life-threatening hemorrhage. The plasma level of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet activation. Available data suggest that interleukin-6 (IL-6) may contribute to the regulation of megakaryocytopoiesis and platelet activity. The purpose of this study is to investigate the status and kinetics of IL-6 and selectins, which are involved in the platelet function, production, and immunologic functions, during the clinical course of ITP, that may be helpful for understanding the biology of the disease. Twenty-two ITP patients were studied prospectively in the course of their disease. Sixteen, 8 and 6 patients were available after platelet recovery, relapse and splenectomy, respectively. Fifteen healthy persons served as a control group. Higher levels of both sP-selectin and IL-6 were observed in all clinical stages of disease compared to the control group. However, more prominent elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001 vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001 vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin and soluble E-selectin levels were not different from the controls. Both sP-selectin (r = -0.32, p = 0.019) and IL-6 (r = -0. 41, p = 0.002) levels inversely correlated with platelet count during disease course. There was a positive correlation between the sL-selectin level and leukocyte count (r = 0.60, p < 0.001). These results suggest that residual platelets are activated in ITP, which offers a relatively benign clinical course compared to other thrombocytopenias. High IL-6 concentration during thrombocytopenia may be involved in compensatory megakaryocytopoiesis and augmented 'residual platelet' functions in ITP.

Adult↗
PubMed1999

Thrombopoietin and thrombospondin in renal allograft recipients.

Recipients of renal transplants appear to be at increased risk of thromboembolic events. Despite accumulating evidence for the hyperreactivity of platelets, the primary regulator of thrombopoiesis, thrombopoietin (TPO), has not yet been studied in renal transplant recipients. Thus, the aim of the present study was to quantify the levels of TPO and to assess its contribution to increased platelet reactivity in recipients of renal allografts. Serum concentrations of thrombospondin (TSP) were also determined in patients undergoing renal transplants in order to evaluate the role of this multifunctional protein in platelet hyperaggregability. Serum levels of TPO were significantly lower in renal transplant recipients (n = 27) than in healthy controls (30.8+/-20.6 pg/ml versus 129.9+/-113.6 pg/ml, P = 0.001). Serum concentrations of TPO were correlated neither with serum levels of creatinine nor duration of transplantation. However, levels of TPO were negatively correlated with platelet counts (r = -0.50, P = 0.007) in recipients of renal transplants. Plasma levels of TSP were higher in renal transplant patients than in the control group (104.5+/-54.7 ng/ml versus 63.4+/-41.5 ng/ml, P = 0.003). No significant correlation was found between levels of TPO and TSP. We conclude that, rather than the allograft function, the platelet mass determines the levels of TPO in recipients of renal transplants. Despite the low serum levels of TPO, and increased concentrations of TSP, TPO might still play a role in the hyperaggregability of platelets in patients undergoing renal transplants.

Adult↗
PubMed1999

Circulating thrombopoietin in systemic sclerosis.

OBJECTIVE: To investigate circulating thrombopoietin (TPO) concentrations in systemic sclerosis (SSc). METHODS: TPO concentrations were measured by ELISA in serum samples of 13 patients (11 female, 2 male) with diffuse SSc, 15 healthy controls (13 female, 2 male), and 15 patients (13 female, 2 male) with rheumatoid arthritis (RA). Thrombocyte counts of patients with SSc and RA and controls were recorded. RESULTS: Median TPO concentrations were 115 (164) in SSc, 76 (32) in RA, and 62 (34) pg/ml in controls. Median serum TPO concentration in the SSc group was significantly higher than other groups; there was no difference between controls and patients with RA (p<0.001 for both comparisons). Median platelet counts of SSc, RA, and controls were 224+/-58x10(9)/l, 238+/-44x10(9)/l, and 272+/-35x10(9)/l, respectively. There was no correlation between thrombocyte counts and TPO levels in any group. CONCLUSION: We show that patients with SSc have higher serum TPO concentrations compared to healthy controls and patients with RA. It can be hypothesized that TPO mediated release of particular growth factors may participate in the pathogenesis of the fibrotic process of SSc.

Adult↗
PubMed1999

Determinants of soluble CD23 antigen levels in hemodialysis patients: effect of 1.25 dihydroxyvitamin D3 and recombinant human erythropoietin treatment.

BACKGROUND: The immunodeficiency of end-stage renal disease (ESRD) paradoxically coexists with T cell and monocyte activation. In spite of well known defective antibody responses in ESRD, the functional status of B cells in the immune system dysregulation of uremia is still controversial. Soluble CD23 (sCD23) antigen is a recently identified B cell activation marker and is also involved in T cell activation process. Effects of parathyroid hormone (PTH), red blood cells and ferritin on T and B cell functions have been shown both in vivo and in vitro. PATIENTS AND METHODS: In this study, serum levels of sCD23 in hemodialysis patients were determined to evaluate the functional status of B cells and possible linkages between this cytokine and PTH levels, ferritin levels, red blood cell counts were investigated. RESULTS: Serum sCD23 levels were significantly elevated in hemodialysis patients relative to healthy controls (12.5+/-8.4 micro/l vs. 2.4+/-1.1 micro/l, p<0.001). Serum sCD23 levels were negatively correlated with red blood cell count (r = -0.61, p = 0.009) and serum PTH levels (r = -0.62, p = 0.008), while positively correlated with serum ferritin levels (r = 0.63, p = 0.007) in hemodialysis patients. We also investigated the immunumodulator effects of 1.25 dihydroxyvitamin D3 (1.25OHD3) and recombinant human erythropoietin (rHu-Epo) treatment in hemodialysis patients. 1.25OHD3 treatment for eight weeks did not change serum sCD23 levels in hemodialysis patients (n = 8). On the other side, rHu-Epo administration for 16 weeks led to a decrease in serum sCD23 levels (17.7+/-8.6 microg/l vs. 9.8+/-3.5 microg/l, p = 0.007) in these patients (n = 9). CONCLUSION: These results suggests that similar to T cells, B cells are activated in uremia and the degree of this activation is correlated with red blood cell count, serum parathyroid hormone levels and iron status of the hemodialysis patients. Moreover, B cell activation could be altered by recombinant human erythropoietin therapy in hemodialysis patients.

Adult↗
PubMed1998

Activation of blood coagulation in patients with mitral stenosis and sinus rhythm.

The aim of this study was to assess whether there is blood coagulation activation in patients with mitral stenosis (MS) and sinus rhythm (SR) and to investigate the value of left atrial spontaneous echo contrast (LASEC) as a predictive sign of increased coagulation activity. Using thrombin-antithrombin III complexes and prothrombin fragment 1+2 as in vivo hemostatic markers, we concluded that there is a hypercoagulable state in patients with MS and SR when LASEC is present.

Adult↗
PubMed1998

Thrombopoietin, interleukin-6, and P-selectin at diagnosis and during post-steroid recovery period of patients with autoimmune thrombocytopenic purpura.

Plasma concentrations of the most potent megakaryocytopoietic cytokines, thrombopoietin (TPO) and interleukin-6 (IL-6), and the platelet activation marker P-selectin were evaluated in 24 patients with autoimmune thrombocytopenic purpura (ATP) who responded to conventional steroid treatment, at diagnosis and after steroid-induced recovery. Baseline TPO concentration (median [interquartile range]=0 [17.52] pg/ml) was significantly decreased and IL-6 (38 [19.75] pg/ml) and P-selectin (485 [393.75] ng/ml) were significantly elevated compared with healthy subjects (100 [68] pg/ml, 8 [7] pg/ml and 166 [69] ng/ml, respectively). Following steroid treatment, all values approached normal, i.e., TPO (20 [18.75] pg/ml) was increased and IL-6 (19.5 [13] pg/ml) and P-selectin (248 [172.5] ng/ml) were decreased, significantly. The decrease of TPO in ATP is suggested to occur due to increased megakaryocyte mass and, consequently, TPO clearance. The non-lineage-specific cytokine IL-6 may be elevated to compensate for megakaryocytopoiesis/thrombopoiesis. The elevation of P-selectin may reflect compensatory platelet hyperactivation; however, this molecule also might be a marker of platelet destruction.

Adult↗