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Öğe Acquired activated protein C resistance in sarcoma patients(2012) Soyer N.; Kececi B.; Eroglu Z.; Kamer S.; Ozcelik C.; Cagirgan S.; Tombuloglu M.; Sabah D.; Donmez A.Acquired activated protein C resistance (aAPCR) is seen more frequently in solid and hematological cancer patients. We aimed to investigate the presence of aAPCR and the frequency of clinically detectable thrombosis in sarcoma patients. Normalized activated protein C sensitivity ratio (nAPCSR), factor V Leiden (FVL) mutation, factor V (FV) levels and factor VIII (FVIII) levels were prospectively measured in 52 patients and in 52 healthy controls. Clinically detectable thrombosis was present in one patient (1.92%). Compared with healthy controls (106%), the sarcoma patients had significantly lower values of the nAPCSR at pre (87.25%) and post (94.35%) treatment period (P < 0.0001). aAPCR was found as 4.2, 13 and 0%, respectively. The post-treatment FV levels (178.1 U/dl) were significantly (P < 0.001) higher than the pretreatment levels (147.5 U/dl). Inverse correlation was found between post-treatment FV levels and nAPCSR values (r = -0.38, P < 0.02). We found out a slightly increased frequency of venous thromboembolism in sarcoma patients. As an original finding which has not been reported previously in the literature, we also found out a decrease in the nAPCSR, persisting even after treatment. Thirdly, we found out that the significantly higher rate of aAPCR at the time of diagnosis totally disappeared after treatment. Copyright © 2012 Lippincott Williams & Wilkins.Öğe Activated protein C resistance in Behcet's disease(2000) Zarrinanbour H.; Keser G.; Donmez A.; Cagirgan S.; Oksel F.; Aksu K.; Tombuloglu M.We investigated activated protein C resistance (aPCR) using modified activated partial thromboplastin time (aPTT) in 32 patients with Behcet's disease (BD) and 9 healthy controls. None of the healthy controls were found to have aPCR. However, 11 out of 32 Behcet's patients (34.3%) were found to have aPCR. The frequency of aPCR was increased to 44.4% among 18 Behcet's patients having a history of venous thrombosis. In the subgroup of 14 patients without venous thrombosis, aPCR frequency was %22.2. Our findings show that, besides other factors, aPCR may also predispose patients to venous thrombosis in BD. The detection of aPCR, using modified aPTT may serve as a routine screening test to determine the necessity of prophylactic anticoagulation treatment in patients with BD.Öğe Activated protein C resistance in preeclampsia(2004) Cagirgan S.; Donmez A.; Ispahi C.Objectives: Recently, hereditary and acquired diseases that lead to thromboembolic events by changing the hemostatic balance have attracted interest as a cause of preeclampsia. In this study the incidence of activated protein C resistance (APCR) in preeclamptic women was evaluated. Methods: Activated protein C sensitivity ratio (APC-SR) was measured by the modified activated partial thromboplastin time (APTT) method in 19 preeclamptic and 12 healthy pregnant women and 26 normal women as the controls. Results below the levels of 2 were accepted as the presence of APCR. Results: Median APC-SR values of 2.12 and 2.01 in preeclamptic and healthy pregnant women, respectively, were found significantly lower than the normal control values of 2.31 (p = 0.0005, p = 0.001). APCR was detected in 31% of preeclamptic patients, 16.6% of healthy pregnant women and 7.6% of normal controls. Conclusion: APCR was found significantly higher in preeclamptic women and it may play an important role in the pathogenesis of preeclampsia.Öğe Asecretory POEMS syndrome with widespread osteosclerotic lesions(2000) Tombuloglu M.; Saydam, G..; Donmez A.; Cagirgan S.; Hekimgil M.; Soydan S.; Sencan M.; Buyukkececi F.POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) is a rare disease and constitutes 1-2% of plasma cell dyscrasia. Most of the patients have few sclerotic bone lesions and more than 90% of patients have serum and/or urinary M-protein. In this report, we present a patient with POEMS syndrome who had severe polyneuropathy and unusual widespread osteosclerotic lesions without M-protein in serum and urine. According to our knowledge, this is the first case of asecretory POEMS syndrome with multiple sclerotic lesions and polyneuropathy. Our patient is still well and able to work actively 4 years after diagnosis with the treatment of 12 courses of VAD by reducing the vincristine dosage.Öğe The effect of cholesterol levels on hematopoietic stem cell mobilization(2012) Donmez A.; Kabaroglu C.; Arik B.; Tombuloglu M.Data regarding effects of cholesterol levels on hematopoietic stem cell mobilization are limited. We retrospectively reviewed the relationship between serum total cholesterol levels and peripheral blood CD34 (PBCD34) cell counts in 52 granulocyte colony stimulating factor (G-CSF) induced mobilization cycles with or without chemotherapy. The cholesterol levels between the poor and good mobilization groups (median 172. mg/dl vs. 183.5. mg/dl, respectively, p=0.18) were not different. No significant correlation was obtained between the cholesterol levels and PBCD34 counts (r=0.02, p=0.85). No significant correlation was obtained between cholesterol levels and PBCD34 counts in patients neither mobilized with G-CSF alone (r=-0.02, p=0.9) nor G-CSF plus chemotherapy (r=0.04, p=0.8). The results of the study indicate that there was no effect of cholesterol on hematopoietic stem cell mobilization. Prospective cohort studies are needed to demonstrate the effect of cholesterol on mobilization and its extent in humans. © 2012 Elsevier Ltd.Öğe The effect of serum lipid levels on peripheral blood hematopoietic stem cell levels(Elsevier Ltd, 2021) Yildirim Simsir I.; Donmez A.; Kabaroglu C.; Yavasoglu I.; Basol G.; Gungor A.; Tombuloglu M.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/?L vs. 1.7 ± 0.17/?L, p = 0.003) and TChol (2.6 ± 0.34/?L vs. 1.7 ± 0.14/?L, 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. © 2021 Elsevier LtdÖğe Inflammation-induced thrombosis: Mechanisms, disease associations and management(2012) Aksu K.; Donmez A.; Keser G.Although inflammation-induced thrombosis is a well-known entity, its pathogenesis remains complicated. There are complex interactions between inflammation and hemostasis, involving proinflammatory cytokines, chemokines, adhesion molecules, tissue factor expression, platelet and endothelial activation, and microparticles. Inflammation increases procoagulant factors, and also inhibits natural anticoagulant pathways and fibrinolytic activity, causing a thrombotic tendency. Besides, chronic inflammation may cause endothelial damage, resulting in the loss of physiologic anticoagulant, antiaggregant and vasodilatory properties of endothelium. However, inflammation-induced venous thrombosis may develop even in the absence of vessel wall damage. On the other hand, coagulation also augments inflammation, causing a vicious cycle. This is mainly achieved by means of thrombin-induced secretion of proinflammatory cytokines and growth factors. Platelets may also trigger inflammation by activating the dendritic cells. There are many systemic inflammatory diseases characterized by thrombotic tendency, including Behçet disease (BD), antineutrophilic cytoplasmic antibody-associated vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus erythematosus, antiphosholipid syndrome, familial Mediterranean fever, thromboangiitis obliterans (TAO) and inflammatory bowel diseases. Inflammation-induced thrombosis may respond to immunosuppressive (IS) treatment, as in the case of BD. However effectiveness of this treatment can not be generalized to all other inflammatory diseases. For instance, IS agents do not have any beneficial role in the management of TAO. Heparin, antiplatelet agents such as aspirin and clopidogrel, colchicine and statins also have some antiinflammatory activity. However, decreased responsiveness to aspirin and clopidogrel treatments may be observed in inflammatory diseases, due to antiplatelet resistance caused by systemic inflammation. In the present review, we aimed to discuss the details of the complex crosstalk between inflammation and hemostasis in the context of available data. We also intended to overview the major inflammatory diseases with thrombotic tendency, as well as to discuss the general principles of the management of inflammation-induced thrombosis. © 2012 Bentham Science Publishers.Öğe The loss of CD34+ cells in peripheral hematopoietic stem cell products cryopreserved by non-controlled rate freezing and stored at -80 °C after overnight storage(Elsevier Ltd, 2014) Donmez A.; Yilmaz F.; Soyer N.; Cagirgan S.; Arik B.; Tombuloglu M.Although peripheral blood stem cell (PBSC) products cryopreserved by non-controlled rate freezing and stored at -80 °C after overnight storage are used frequently, data regarding the rate of loss of CD34+ cells in these products are limited. In this prospective study, CD34+ cells were counted at three (fresh, post-overnight and post-thaw) points in 83 PBSC products from 41 patients by flow cytometry. Compared to fresh products, the mean losses of post-overnight and post-thaw total CD34+ cells are 16.3% and 38.4% (p = 0.02), and the mean losses of post-overnight and post-thaw viable CD34+ cells are 16.5% and 48.5%, respectively (p < 0.001). The numbers of fresh viable, post-thaw total and post-thaw viable CD34+ cells were inversely correlated with the durations of neutrophil and platelet engraftment. Our results indicate that the mean loss of post-thaw total and viable CD34+ cells is approximately 20% higher than that observed in standard cryopreservation methods. In addition, fresh viable, post-thaw total and especially post-thaw viable CD34+ cell levels are valuable predictors of both neutrophil and platelet engraftments. © 2014 Elsevier Ltd.Öğe The management of upper gastrointestinal bleeding in hemophilia patients by sclerotherapy [Hemofili hastalarinda ust gastrointestinal sistem kanamasinin endoskopik skleroterapi ile tedavisi](1998) Yonetci N.; Yilmaz M.; Ozutemiz O.; Gunsar F.; Donmez A.; Tekesin O.; Batur Y.; Cavusoglu H.Upper gastrointestinal bleeding is a common finding in hemophilia patient's and has an incidence of 20%. Endoscopic sclerotherapy is a widely and successfully used treatment for upper gastrointestinal bleeding in Turkey as in other countries. Studies regarding the effectiveness of sclerotherapy in patients who have bleeding diathesis and upper gastrointestinal bleeding, such as in hemophilia, are limited in number. In our study, seven hemophilia patients with an age rance of 32 to 55 were studied. All patients had upper gastrointestinal bleeding and the effectiveness of sclerotherapy was retrospectively analyzed from 1991 to 1995. All patients were endoscopically examined with in the first 24 hours of admission was duodenal ulcer was diagnosed in four cases, hemorrhagic gastritis in two, and gastric ulcer in one. In four of the patients, active bleeding was observed and injection sclerotherapy (adrenalin 1/10.000 and polydocanol % 1) was performed successfully, with hemostasis occuring during endoscopy. These patients had a history of former gastrointestinal bleeding. In addition to sclerotherapy, factor VIII and fresh blood were administered. In two patients there was a recurrence of bleeding after 6 mounts but endoscopicaly active bleeding could not be seen. Conclusion: Endoscopic injection sclerotherapy is a safe and effective method in the treatment of upper gastrointestinal bleeding in hemophilia.Öğe The plasma levels of activated thrombin activatable fibrinolysis inhibitor and thrombomodulin in Behçet Disease and their association with thrombosis(2010) Donmez A.; Aksu K.; Aydin H.; Keser G.; Cagirgan S.; Doganavsargil E.; Tombuloglu M.Objective: To investigate the plasma levels of activated thrombin activatable fibrinolysis inhibitor (aTAFI) and thrombomodulin (TM) in Behçet disease (BD) and their relationship with thrombosis. Methods: Plasma aTAFI and TM levels were measured by ELISA in 89 patients with BD (18 having venous thrombosis) and in 86 healthy controls. Results: Compared with healthy controls, the BD group had significantly lower levels of aTAFI (13.49 ± 8.88 µg/ml vs. 26.76 ± 11.57 µg/ml, p < 0.0001) and significantly higher levels of TM (3.26 ± 1.85 ng/ml vs. 2.6 ± 0.69 ng/ml, p = 0.0003). Neither aTAFI, nor TM levels differed significantly between BD patients with and without thrombosis (p > 0.05). Despite a tendency to positive correlation (r = 0.37, p = 0.0004) between plasma levels of aTAFI and TM in healthy controls, there was a tendency for negative correlation (r = -0.51, p < 0.0001) between these two parameters in BD patients. Conclusion: The plasma aTAFI and TM levels do not seem to be related with the presence of thrombosis observed in BD. Increased plasma TM levels in BD may simply reflect endothelial cell activation and dysfunction. © 2010 Elsevier Ltd All rights reserved.Öğe Retrospective evaluation of patients with hairy cell leukemia: Single center experience(2007) Saydam, G..; Vural F.; Soyer N.A.; Ocakci S.; Donmez A.; Cagirgan S.; Tombuloglu M.Objective: Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disease which is characterized by circulating B lymphocytes with prominent cytoplasmic projections. Treatment of patients with HCL has changed rapidly during the last 40 years by the introduction of the purine analogs into clinical setting. Splenectomy was the first effective treatment modality increasing the survival. Recently, given the effectiveness of the purine analogs, as well as the ease of administration, other therapies have been abandoned. The aim of this study is to retrospectively evaluate the patients with HCL treated and followed-up in our Center. Method: We retrospectively evaluated 15 patients (14 male, 1 female)who were diagnosed, treated and followed-up in our centerbetween 1992 and 2004. Median age was 50 (28-79) years and median symptom duration was 11.5 months (2-48). Median follow up duration was 48 months (9-148). The most prominent symptoms were as follows; weakness (60%), fever (20%), night sweatening (20%), fatigue (20%). Splenomegaly was found in 14 (93%) of the patients while hepatomegaly was seen only in 3 patients. Pancytopenia was determined in all patients. Peripheral blood smear, bone marrow aspiration and biopsy were applied to all patients. TRAP test was evaluated in 10 patients and was positive in 9 of them. Results: Four patients were treated with interferon alpha only, 1 patient was treated with splenectomy, 3 patients were treated with interferon alpha+cladribine and 6 patients were treated with only cladribine. Splenic radiotherapy was given to only 1 patient. Pancytopenia disappeared after treatment in 13 patients. Relapse was detected in 3 patients after interferon use and all these patients were treated with cladribine. Spleen size reduced to normal size in 13 patients after therapy. All patients are still alive under regular follow up. Conclusion: Cladribine was found to be effective treatment modality in HCL patients either in first line setting or in relapsed patients. It also provides long term survival for our patients. © Hellenic Society of Haematology.Öğe Risk factors for microbial contamination of peripheral blood stem cell products(2012) Donmez A.; Aydemir S.; Arik B.; Tunger A.; Cilli F.; Orman M.; Tombuloglu M.Background: Despite the well-known contamination rates and presence of microbial agents in stem cell products, the risk factors affecting microbial contamination have not been well described. Study design and methods: In a 12-year period, we retrospectively reviewed culture results of peripheral blood stem cell products with the intent of identifying risk factors for microbial contamination. Results: Microbial contamination was detected in 28 (5.7%) products of the postprocessing period and in 18 (3.66%) products of the postthawing period. Large-volume leukapheresis (LVL; odds ratio [OR], 5.85; 95% confidence interval [CI], 1.52-22.49; p = 0.01) and high numbers of stem cell culture sampling (OR, 1.4; 95% CI, 1.03-1.91; p = 0.03) were found to be risk factors for postprocessing bacterial contamination. The presence of postprocessing bacterial contamination was a risk factor for postthawing (OR, 28.89; 95% CI, 6.67-125.15; p < 0.001) and posttransplant (OR, 3.25; 95% CI, 1.24-8.50; p = 0.01) microbial growth. In transplants that were performed using contaminated products, the same pathogen was detected in 20% of patients and different pathogens were found in 35% of patients. Conclusion: Cultures should be carefully monitored in LVL products and in samples with high numbers of cultures performed. Growth of different bacterial pathogens must be considered in transplants that are performed with contaminated products. © 2011 American Association of Blood Banks.Öğe Severe intestinal graft versus host disease after donor lymphocyte infusion; response to extracorporeal photochemotherapy(2005) Vural F.; Donmez A.; Doganavşargil B.; Çagyrgan S.; Alper H.; Tombuloglu M.We present a patient with acute myelogenous leukemia who developed severe acute intestinal graft versus host disease (GVHD) after donor lymphocyte infusion (DLI) following non-myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBCT). One month after DLI, patient developed severe abdominal cramps, watery diarrhea without any signs or symptoms of the skin and liver GVHD. Treatment with steroid, cyclosporine A, tacrolimus and mycophenolat mofetil were not effective in controlling intestinal symptoms. Extracorporeal photochemotherapy (ECP), a recently used procedure in the treatment of GVHD was employed periodically and the symptoms subsided gradually. Acute GVHD after DLI may occur severely and atypically, but being limited to the intestine has rarely been reported. © 2005 Elsevier Ltd. All rights reserved.Öğe Thrombin activatable fibrinolysis inhibitor in Behçet's disease(2005) Donmez A.; Aksu K.; Celik H.A.; Keser G.; Cagirgan S.; Omay S.B.; Inal V.; Aydin H.H.; Tombuloglu M.; Doganavsargil E.Thrombin activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase downregulating plasmin formation, thereby causing a tendency for thrombosis development. Since, Behçet's disease (BD) is a systemic vasculitis, which is commonly complicated by arterial and venous thrombosis, we aimed to find out plasma TAFI levels in BD, compared with healthy controls. We also searched whether plasma TAFI levels were significantly different between Behçet's subgroups with and without thrombosis. In this study, 105 BD patients (M/F: 64/41; mean age 36±1 years), followed up by Ege University Rheumatology Department were enrolled. The exclusion criteria were hemophilia, hyperlipidemia, diabetes mellitus, hepatic diseases renal failure, antiphospholipid positivity, oral contraceptive use and pregnancy. Age-and sex-matched healthy controls (n=53) were also included. Plasma TAFI levels were measured by ELISA. Since TAFI is also an acute-phase reactant, we also measured other inflammatory markers such as C-reactive protein (CRP). Plasma TAFI levels were significantly higher in Behçet's patients (91.1±7.4 ng/ml) compared with healthy controls (14.3±4.5 ng/ml) (P<0.001), but there were no significant difference between the subgroups with and without thrombosis. In BD, there was no correlation between plasma TAFI levels and CRP. Regardless of manifest thrombosis, plasma TAFI levels in BD were significantly higher than in healthy controls. High TAFI levels might possibly contribute to the thrombotic tendency in BD. Future studies investigating TAFI gene polymorphism and functional activity are clearly needed, to clarify the exact role of TAFI in Behçet's thrombosis. © 2004 Elsevier Ltd. All rights reserved.Öğe Use of proton pump inhibitors in hematopoietic stem cell transplantation does not increase the frequency of febrile neutropenia(Verduci Editore, 2015) Ozkan M.C.; Donmez A.; Arslan A.; Aydemir S.; Tombuloglu M.OBJECTIVE: Despite the fact that proton pump inhibitor (PPI) use is a risk factor for infections in heterogeneous groups of patients, there are only a limited data related to PPI use and febrile neutropenic episodes (FNEs) in hematopoietic stem cell transplantation (HSCT) patients. PATIENTS AND METHODS: In a 7-year period, we retrospectively reviewed 145 HSCT data to identify a risk factor for PPI use for febrile neutropenia. The follow-up process of 125 (86.2%) of the HSCTs was complicated with FNEs. RESULTS: A multivariate analysis indicated that PPI use was not significantly associated with FNEs (Odds ratio [OR]: 0.46; 95% Confidence Interval [CI] 0.12-2.16; p = 0.24) or bacterial culture positivity (OR: 1.37; 95% CI 0.45-4.18; p = 0.58). CONCLUSIONS: Our study revealed that PPI use does not appear to be a risk factor for FNE or bacterial culture positivity for HSCT patients but further studies are needed.
