[Show abstract][Hide abstract] ABSTRACT: Dasatinib is considered an effective treatment agent in imatinib-resistant and newly diagnosed chronic phase CML patients. Patients receiving dasatinib 100 mg once daily regime suffered significantly fewer thrombocytopenia and pleural effusion events than those receving 70 mg twice daily. Effective molecular monitoring and the proper management of pleural effusion during the first-line dasatinib administration in CML are essential. Pleural effusion may develop any time of the treatment and is easily managed by treatment interruption, dose reduction and supportive therapy. In this article, we intended to assess the rational of managing CML and pleural effusion that successfully managed with dose reduction and supportive care.
[Show abstract][Hide abstract] ABSTRACT: The current treatment of chronic phase chronic myeloid leukemia (CML) consists of oral tyrosine kinase inhibitors (TKIs). However, high-risk CML may present with an aggressive course which may result in blastic crisis or a "difficult-to-manage" state with available treatments. The aim of this paper is to report a patient with complicated CML resistant to treatment and progressed despite the administration of bosutinib, imatinib mesylate, nilotinib, dasatinib, interferon alpha 2a, cytotoxic chemotherapy, and allogeneic hematopoietic stem cell transplantation. The striking point of this case story is that no Abl kinase domain mutation against TKIs has been detected during this very complicated disease course of CML. Meanwhile, challenging cases will always be present despite the hope and progress in CML in the TKI era.
[Show abstract][Hide abstract] ABSTRACT: The renin-angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine-paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.
The Journal of international medical research 08/2009; 37(4):1018-28. · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of plasminogen activator inhibitor type 1 (PAI-1), the inhibitor of fibrinolysis; and thromboxane A2 and 6-keto-PGF1 alpha, the products of endoperoxides, in 16 patients affected with clonal thrombocytemia as compared with 16 patients with reactive thrombocytosis and 15 normal controls. In the clonal thrombocytemia group, plasma levels of PAI-1 antigen and activity were significantly higher than both reactive thrombocytosis and control group. Plasma levels of 6-keto-PGF1alpha were significantly higher in the clonal thrombocytemia group than the other two groups and also higher in the reactive thrombocytosis group than the control group, which was also significant. This study confirms that arachidonate metabolism is frequently deranged in patients with thrombocytosis and hypofibrinolysis due to increased PAI-1 plasma levels as shown in the clonal thrombocytosis group. This may explain the thrombotic tendency in myeloproliferative disorders.
Clinical and Applied Thrombosis/Hemostasis 05/2005; 11(2):197-201. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether a newly identified thrombophilia factor, activated factor VII (FVIIa), is associated with retinal vein occlusion (RVO).
54 consecutive cases with RVO seen between March and September 1999 were included in the study. 22 cases had central retinal vein occlusion (CRVO) and 32 had branch retinal vein occlusion (BRVO). Ophthalmoscopic examination with detailed medical history was followed by blood analyses for liver and renal functions, cholesterol, triglycerides, complete blood count, and coagulation factors including protein C activity, free protein S, antithrombin III, fibrinogen, and factor VIIa (FVIIa). Data were compared with those of the control group, composed of 19 cases under ophthalmological follow up for refractive errors, presbyopia, or senile cataract.
Hypertension was highly prevalent in cases with BRVO. Complete blood count, and liver and kidney function tests were within normal limits in the study group. Two cases had low protein C activity, and one had low free protein S. FVIIa levels were significantly higher in the RVO group than in the control group (p=0.0004). There was no significant difference in FVIIa levels between the CRVO and BRVO groups (p=0.51).
No haematological parameter except FVIIa differed significantly from that of the control group. Elevation of FVIIa level may play a part in the pathophysiology of both CRVO and BRVO.
British Journal of Ophthalmology 11/2001; 85(10):1174-8. · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Behçet's disease (BD) is a chronic relapsing systemic vasculitis of unknown etiology. BD is very rarely associated with neoplastic diseases. We report the case of a 39-year-old woman who had been treated for BD for 3 years. She presented with relapsing oral and genital lesions and persistent high-grade fever which had lasted for 1 month. The possible cause of the exacerbation of BD and fever in this patient was a mature ovarian teratoma. To our knowledge this is the first report of a patient with BD associated with a ovarian teratoma.
Modern Rheumatology 06/2001; 11(2):172-175. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Clinical and Applied Thrombosis/Hemostasis 05/2001; 7(2):126-30. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Internal Medicine 02/2001; 40(1):68-72. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of Behçet's disease (BD) is closely related to endothelial cells, leucocyte functions and autoimmunity. The aim of this study was to investigate circulating selectin adhesion molecules, which are known to play a significant part in the immune response especially by regulating interactions of the leucocytes with endothelium, in BD.
Plasma E-, L-, and P-selectin concentrations were evaluated in 11 patients with widespread BD (group I), 10 cases with merely mucocutaneous involvement (group II) and 15 age and sex matched healthy control subjects. The patients were newly or previously diagnosed cases not taking any drug for BD.
Plasma concentrations of all selectins were significantly higher in group I compared with group II. E-selectin and P-selectin were significantly increased in each subgroup of patients compared with the healthy controls. L-selectin concentrations were higher than the controls only in group I.
Increases in the selectins in BD may be a direct consequence of the leucocyte, endothelium and platelet activations observed during the disease process. However, abnormal/increased selectin expression to various triggers should also be considered. More prominent increases in patients with extensive disease suggest that circulating selectin concentrations are related to disease severity.
Annals of the Rheumatic Diseases 02/2000; 59(1):61-3. · 9.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: We report on two siblings with beta+-thalassemia intermedia. Molecular studies of the beta-globin gene indicated that the patients are homozygous for the -87 (C-->T) mutation. This genotype has not been previously described. Homozygosity for the -87 (C-->T) mutation produces a mild form of beta+-thalassemia associated with moderate Hb F elevation (26-38%) and highly elevated Hb A2 (10-8.6%) levels, respectively. Hematological parameters of homozygous -87 (C-->G) and -87 (C-->A) mutations, and compound heterozygous patients with either C-->T, C-->G, or C-->A at -87 and one of the severe beta+- or beta0-thalassemia mutations, are given for comparison.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the autonomic nervous system (ANS) function in patients with Behçet's disease by using power spectral analysis of heart rate variability (HRV). The study population consisted of 71 patients with Behçet's disease, and 26 normal volunteers. HRV was measured by power spectral analysis in supine and standing position. In supine position, Behçet's patients had increased low frequency component in absolute (LF) and normalized units (LF nU) but had lower values of high frequency component in absolute (HF) and normalized units (HF nU) than the controls (P < 0.05). In standing position, higher values were obtained in LF and LF nU but lower values of HF and HF nU in Behçet's patients than controls (P < 0.05). LF/HF was significantly higher in patients both in supine (2.5 +/- 1.0 vs. 1.2 +/- 0.8, P = 0.001) and standing (21.9 +/- 7 vs. 1.8 +/- 0.3, P < 0.001) positions. Our data suggest that patients with Behçet's disease may have asymptomatic ANS dysfunction, which is in the form of increased sympathetic and decreased parasympathetic modulation, and power spectral analysis of HRV is beneficial in assessing the ANS function.
Journal of the Autonomic Nervous System 09/1999; 77(2-3):190-4.
[Show abstract][Hide abstract] ABSTRACT: Nasopharyngeal angiofibroma is a highly vascular tumour which occurs almost exclusively in adolescent males. Although it is histologically benign, it may cause serious clinical problems because of its tendency to bleed profusely during surgery. This paper presents the first case of nasopharyngeal angiofibroma in a patient with haemophilia A, another well-known disease of bleeding tendency. In this case the tumoural mass was surgically removed with effective factor VIII replacement without any bleeding complication.
[Show abstract][Hide abstract] ABSTRACT: In this study, soluble thrombomodulin (TM) was measured as an indicator of endothelial injury in acute myelocytic leukemia (AML) together with fibronectin (FN) and thrombospondin (TS). The study group comprised of 17 (6 men, 11 women; aged 34 +/- 10 years; range 21-61 years) newly diagnosed AML patients. There was infection in 6 patients. Twelve (4 men, 8 women; aged 31 +/- 11 years; range 18-55 years) healthy subjects were studied as the control group. Plasma soluble TM levels were significantly higher in AML patients than in the healthy control group (116.6 +/- 13.7 vs 37.2 +/- 1.75 ng/ml, respectively (mean +/- SEM), p < 0.01). Plasma FN levels were found to be significantly higher in AML patients compared to the control group (15.9 +/- 2.69 vs 8.1 +/- 2.46 ng/ml, respectively (mean +/- SEM). p < 0.01 ). Plasma FN levels in infected patients were significantly lower than in non-infected patients (6.47 +/- 1.3 vs 21.0 +/- 3.1 ng/ml, respectively (mean +/- SD), p < 0.01). Plasma TS levels in the patient group were significantly lower than in the control group (20.6 +/- 1.45 vs 120.8 +/- 18.2 ng/ml, respectively (mean +/- SEM), p < 0.01). In one patient with M7 megakaryoblastic leukemia who also had a high platelet count, plasma TS levels were significantly higher than that in other patients.
[Show abstract][Hide abstract] ABSTRACT: 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.
Rheumatology International 02/1999; 19(1-2):11-4. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Circulating thrombopoietin and interleukin-6 concentrations were investigated in two different settings of thrombocytopenia. Twenty patients with autoimmune thrombocytopenic purpura (ATP), 12 patients with aplastic anemia (AA) and 15 healthy subjects were studied. Thrombopoietin was significantly increased in AA and deficient in ATP. Interleukin-6 was significantly increased in ATP, compared to both other groups.
[Show abstract][Hide abstract] ABSTRACT: In Behcet's disease, prominent clinical manifestations include involvement of mucocutaneous, ocular, gastrointestinal, respiratory, neurologic, urogenital, articular and cardiovascular systems. Patients with Behcet's disease have higher incidence of ventricular arrhythmia than healthy subjects. However there is a little information about the mechanism of ventricular arrhythmias in Behcet's disease. The aim of the study was to investigate whether dispersion of ventricular repolarisation was an arrhythmogenic mechanism. QT dispersion parameters were measured in 73 Behcet patients and QT dispersion was defined as the difference between the maximum and minimum QT interval in any of the 12 leads of surface electrocardiogram. Corrected QT dispersion for heart rate was calculated by Bazett's formula. The results were compared with the data from 51 matched controls without a history of cardiac disease. We found QT dispersion was greater in Behcet patients (58±12 vs. 37±8 ms, P=0.001) as was corrected QT dispersion (81±14 vs. 52±11 ms, P=0.001). There was no significant difference in minimum or maximum QT intervals between Behcet patients and controls (P>0.05). We found a correlation between QT dispersion and grade of premature ventricular complexes (r=0.7, P=0.002). Our findings suggest that increased dispersion of repolarisation may account for the development of ventricular arrhythmias in Behcet's disease.
International Journal of Cardiology 12/1998; · 6.18 Impact Factor