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Öğe Acute myocardial infarction in a patient with essential thrombocythemia treated with glycoprotein IIb/IIIa inhibitor(Sage Publications Inc, 2004) Gül, Ç; Kürüm, T; Demir, M; Özbay, G; Vural, Ö; Iqbal, O; Fareed, JEssential thrombocythemia (ET) rarely causes obstruction of coronary arteries or acute myocardial infarction. Treatment of acute myocardial infarction in patients with ET may be a problem due to the important role of platelets in the pathogenesis of infarction. There is no reported case of acute myocardial infarction with essential thrombocythemia treated with a glycoprotein IIb/IIIa inhibitor. In this report, a 49-year-old woman with essential thrombocythemia, admitted with a diagnosis of acute inferolateral myocardial infarction, was treated with tirofiban, a glycoprotein IIb/IIIa receptor blocker.Öğe Anticoagulant and antiprotease effects of a novel heparinlike compound from shrimp (Penaeus brasiliensis) and its neutralization by heparinase I(Sage Publications Inc, 2001) Demir, M; Iqbal, O; Dietrich, CP; Hoppensteadt, DA; Ahmad, S; Daud, AN; Fareed, JHeparin is usually obtained from mammalian organs, such as beef lung, beef mucosa, porcine mucosa, and sheep intestinal mucosa. Because of the increased use of heparin in the production of low-molecular-weight heparin (LMWH), there is a growing shortage of the raw material needed to produce LMWHs. A previous report described the structural features of a novel LMWH from the shrimp (Penaeus brasiliensis). In order to compare anticoagulant and antiprotease effects of this heparin, global anticoagulant tests, such as the prothrombin time, activated partial thromboplastin time, thrombin time, and Heptest(R), were used. Amidolytic anti-Xa and anti-IIa activities were also measured. The relative susceptibility of this heparin to flavobacterial heparinase was also evaluated. The United States Pharmacopeia (USP) potency of shrimp heparin (SH) was found to be 28 U/mg. SH produced a concentration-dependent prolongation of all of the clotting tests and exhibited marked inhibition of FXa and FIIa. Heparinase treatment resulted in a marked decrease of the anticoagulant effects and neutralized the in vitro anti-IIa actions. However, the anti-Xa activities were only partially neutralized. Protamine sulfate was only partially effective in neutralizing the anticoagulant and antithrombin effects of SH. SH also produced marked prolongation of activated clotting time, which was neutralized by heparinase but not by protamine sulfate. These results suggest that SH is a strong anticoagulant with comparable properties to mammalian heparins and can be used in the development of clinically useful antithrombotic-anticoagulant drugs.Öğe Anticoagulant and antiprotease profiles of a novel natural heparinomimetic mannopentaose phosphate sulfate (PI-88)(Lippincott Williams & Wilkins, 2001) Demir, M; Iqbal, O; Hoppensteadt, DA; Piccolo, P; Ahmad, S; Schultz, CL; Linhardt, RJHeparinomimetic mannopentaose phosphate sulfate (PI-88) (Progen Industries Ltd. Brisbane, Australia), currently developed as an anticoagulant and antiproliferative agent, mainly is composed of a pentomannan. However, tetrasaccharide and disaccharide components are also present. The molecular profile and the anticoagulant potency of PI-88 are investigated in this study. Gel permeation chromatography and polyacrylamide gel electrophoresis analyses were carried out to determine the molecular profile and separation of components of PI-88, respectively. Potentiation of antithrombin III (ATIII) and heparin cofactor-II (HC-LI) activity were measured using chromogenic substrate assay. In order to determine anticoagulant and antiprotease effects of PI-88, various global anticoagulant tests, such as the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Heptest(R) (Haemachem Inc., St. Louis), ecarin clotting time (ECT), activated clotting time (ACT), and thromboelastography (TEG) were used. Anti-Xa and anti-IIa activities also were measured. The effect of PI-88 on the release of tissue factor pathway inhibitor (TFPI) was performed in nonhuman primates who received PI-88 and in endothelial cell culture systems. The relative susceptibility of PI-88 to heparinase I, protamine sulfate (PS), and platelet factor 4 (PF4) also was evaluated. The high-performance liquid chromatography profiles of PI-88 showed that its average molecular weight is approximately 2300 Da. Separation and gradient electrophoretic patterns of PI-88 showed that it is composed of five different fractions. This agent activates HC-II through inhibiting the thrombin generation but not inhibiting ATIII. Although PI-88 produced a concentration-dependent prolongation of all of the clotting tests, ECT gave the best correlation in the dose-response curve (ECT, r(2) = 0.94; TT, r(2) = 0.84; APTT, r(2) = 0.69). Heparinomimetic mannopentaose phosphate sulfate (PI-88) exhibited marked inhibition of FIIa, but not of FXa. Heparinase I failed to produce significant neutralization of PI-88 in all the assays used, whereas PS and PF4 partially neutralized the effects of this compound. Heparinomimetic mannopentaose phosphate sulfate (PI-88) produced fivefold increase in the TFPI levels at 15 minutes after intravenous (IV) injection to primates. The incubation of PI-88 in endothelial cell culture system also showed a strong effect on TFPI release. These results suggest that PI-88 exhibited strong antithrombotic and anticoagulant activity in addition to its known antiproliferative properties. Because of the molecular characteristics and the dual nature of the pharmacologic action of PI-88, this agent represents an attractive pharmacologic agent for the control of thrombotic and proliferative disorders.Öğe Bone metastasis from primary splenic angiosarcoma to the sacrum demonstrated by Tc-99m-labeled red blood cell and Tc-99m MDP bone scintigraphy(Lippincott Williams & Wilkins, 2001) Çermik, TF; Yüksel, M; Demir, M; Özyilmaz, F; Kaya, M; Vural, Ö; Berkarda, S[Abstract Not Available]Öğe Candida arthritis in a patient with chronic myelogenous leukemia (CML) in blastic transformation, unresponsive to fluconazole, but treated effectively with liposomal amphotericin B(Springer-Verlag, 2002) Turgut, B; Vural, Ö; Demir, M; Kaldir, MCandida arthritis is quite rare and might be caused either by direct intra-articular inoculation of Candida or secondary to hematogeneous seeding of Candida in immunocompromised hosts. Until now less than 50 cases of Candida arthritis have been reported in the literature. We report a case of Candida arthritis, which occurred in a patient with chronic myelogenous leukemia (CML) in blastic transformation. Aggressive chemotherapy and broad-spectrum antibiotics for a prolonged period for febrile neutropenia had been given to the patient. Arthritis of the left knee appeared during the recovery phase of leukopenia. Despite treatment with fluconazole, no clinical or microbiological improvement was obtained. Thus, administration of liposomal amphotericin B was started and after 3 days there was improvement. We can conclude that fluconazole might not be sufficient in some Candida arthritis cases and liposomal amphotericin B might be a good alternative in these resistant cases.Öğe Clinical and laboratory validation of the 2nd International Standard of low molecular weight heparin (IS 2003-01/608) in the anti-Xa. Anti-LIA heptest and prothrombinase induced clotting (PiCT) tests(Amer Soc Hematology, 2005) Hoppensteadt, D; Jeske, W; Fareed, D; Baltasar, F; Walenga, JM; Tobu, M; Demir, M[Abstract Not Available]Öğe Comparative study on the anticoagulant effects of low molecular weight heparins as measured by whole blood ACT, anti-Xa and a newly developed prothrombinase induced clotting time (PiCT) assay(Amer Soc Hematology, 2005) Hoppensteadt, D; Tobu, M; Wahi, R; Iqbal, O; Walenga, JM; Demir, M; Baltasar, F[Abstract Not Available]Öğe Ecarin clotting time is sensitive to heparinoids: Comparison of two different techniques(Lippincott Williams & Wilkins, 2001) Demir, M; Iqbal, O; Untch, B; Hoppensteadt, DA; Gaikwad, BS; Fareed, JEcarin clotting time (ECT) is currently developed for the specific monitoring of antithrombin drugs, such as hirudin, argatroban, and hirulog. Aqueous reagent and dry chemistry technology have become available for ECT monitoring of antithrombin agents. Currently, many heparinoids and heparinomimetic drugs are being developed. These agents activate heparin cofactor II (HCII) and primarily mediate their effects by inhibiting thrombin. Although the test is specific for antithrombin agents, heparin cofactor II-mediated thrombin inhibitors are capable of prolonging the ECT. In order to study the relative effects of some of these agents, ECT was measured in human plasma supplemented with PI-88 (a sulfated pentomanose; Progen Industries Limited, Sydney, Australia), aprosulate, pentosan polysulfate, dermatan sulfate, unfractionated heparin (UFH), and recombinant hirudin (r-hirudin). All agents were supplemented to the citrated-pooled plasma prepared from 10 healthy volunteers at a graded dosage of 0 to 100 mug/ml. These techniques gave comparable results for all of the agents used (PI-88, r(2) = 0.99; r-hirudin, r(2) = 0.98; UFH, r(2) = 0.98; dermatan sulfate, r(2) = 0.95; aprosulate, r(2) = 0.95; pentosan polysulfate, r(2) = 0.94). The relative anticoagulant effects of various agents used on ECT varied widely, exhibiting their potency in the following order: r-hirudin = pentosan polysulfate > dermatan sulfate > PI-88 > aprosulate > UFH. The sensitivity of ECT was adjusted by varying the concentration of the ecarin reagent. The results suggest that HCII-mediated inhibition of thrombin can be detected by using ECT reagents.Öğe The effects of rosiglitazone treatment on the fibrinolytic system in patients with type 2 diabetes mellitus(Sage Publications Inc, 2006) Guldiken, S; Turgut, B; Demir, M; Arikan, E; Kara, M; Vural, O; Tugrul, APatients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFQ t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.Öğe Factor V Leiden mutation and other thrombophilia markers in childhood ischemic stroke(Sage Publications Inc, 2005) Duran, R; Biner, B; Demir, M; Çeltik, C; Karasalihoglu, SThe aim of this study was to evaluate the association between ischemic childhood stroke and thrombophilia. The prevalence of thrombophilia risk factors in 30 unrelated children with ischemic stroke were compared with 33 age-matched control subjects. Patients and control group were tested for the presence of activated protein C (APC) resistance, antiphospholipid antibodies (APLA), increased factor VIII levels, and for the deficiency of protein C (PC), protein S (PS), and antithrombin. When APCR was detected in patients or in controls, factor V Leiden (FVL) mutation was also tested. Seventeen of 30 patients (56.6%) had at least one thrombophilia marker compared with only 5 of 33 control subjects (15.1%). Three children with ischemic stroke (10%) were affected with a combination of two or more thrombophilia markers whereas none of the children in the control group had a combination of risk factors. Seven of 30 children with ischemic stroke (23.3%) and one of 33 control subjects (3.03%) had APC resistance and in all of them FVL mutation were found. The prevalence of FVL mutation was higher among pediatric stroke patients than among control subjects (p < 0.05). None of the patients but one child from the control group (3.03%) had PS deficiency. Antithrombin and PC deficiencies and the presence of APLA and increased factor VIII levels were more frequent in the pediatric stroke patients than in controls but the difference was not statistically significant (p > 0.05). These data confirm that stroke in children is commonly associated with a combination of multiple risk factors and especially the prevalence of FVL mutation is increased in children with ischemic stroke compared with control subjects.Öğe Global anticoagulant effects of a novel sulfated pentomanan oligosaccharide mixture(Lippincott Williams & Wilkins, 2001) Piccolo, P; Iqbal, O; Demir, M; Ma, Q; Gerbutavicius, R; Fareed, JPI-88 is a potent antiproliferative agent, which is developed for various indications in cancer. This agent is obtained from yeast fermentation and is primarily composed of pentamannose and tetramannose oligosaccharide units. PI-88 is capable of producing anticoagulant effects, which are mediated by heparin cofactor II. The purpose of this study was to determine the anticoagulant properties of PI-88 in native whole blood, freshly drawn from human volunteers, supplemented with PI-88 at various concentrations (0-100 mug/mL). Whole blood activated clotting time (ACT) was measured using Hemochron instruments. PI-88 produced a strong anticoagulant effect at 100 mug/mL (479.0 +/- 59.5 sec). This anticoagulant effect was comparable to that observed in interventional cardiology and open-heart surgery. At the lower level, PI-88 produced concentration-dependent effects on ACT. Using thromboelastographic techniques (TEG), the effect of PI-88 was measured in terms of various parameters. PI-88 produced potent anticoagulant effects in the TEG studies. At the concentration of 25 mug/mL, it produced a complete anticoagulant effect in whole blood. Whole blood samples supplemented with PI-88 showed a concentration-dependent decrease in the generation of various markers of clotting activation. These results clearly suggest that PI-88 exerts an anticoagulant effect in whole blood. Because of the low-molecular-weight nature and a novel mechanism of action, this new drug may be considered for further development, particularly in cancer patients.Öğe Global fibrinolytic capacity in patients with subclinical hypothyroidism(Japan Endocrine Society, 2005) Guldiken, S; Demir, M; Turgut, B; Altun, BU; Arikan, E; Kara, MSubclinical hypothyroidism (SH) represents the earliest stages of hypothyroidism but the benefits of detecting and treating SH are not well known. The aim of this Study was to evaluate the alterations in global fibrinolytic capacity (GFC), which indicates the overall fibrinolytic activity, in patients with SH. The study group comprised of 15 patients with SH and 15 healthy controls. The GFC was significantly lower in patients with SH than in control group (p < 0.002). This result suggests a relative hypercoagulable state in SH.Öğe Hypercoagulopathy in stroke patients with nonvalvular atrial fibrillation(Westminster Publ Inc, 2006) Turgut, N; Akdemir, O; Turgut, B; Demir, M; Ekuklu, G; Vural, Ö; Özbay, GThe coagulation system is activated and coagulation activation markers are elevated in acute ischemic stroke with nonvalvular atrial fibrillation (NVAF). The etiology, severity, and prognosis of the ischemic stroke might be estimated with the level of the activation of the coagulation system. In this study, prothrombin F1+2 (F1+2), D-dimer, and fibrinogen levels were measured in patients with acute ischemic stroke with and without NVAF, and stroke severity was compared with these hemostatic parameters. Of 55 patients, 29 had sinus rhythm (group I), 26 had NVAF (group II); 20 healthy subjects (group III) were included in the study. Subtypes of cerebral infarction were classified. The patients underwent stroke severity, electrocardiography, echocardiography, cranial computed tomography, cervical duplex ultrasonography, and hemostatic parameter studies. In group II, F1+2 level (2.83 +/- 0.89) was significantly higher than in group I (2.33 +/- 0.80) and III (1.94 +/- 0.64) (p values: group I-II, 0.036; groups II-III, 0.001; groups I-III, 0.104). In group III, fibrinogen level (251.64 +/- 60.96) was significantly lower than that in groups I (347.97 +/- 111.49) and II (364.04 +/- 86.20) (p = 0.001). D-dimer was not significantly different between groups. In group I, lacunar syndrome (LACS), and in group II, partial and total anterior circulation syndrome (PACS + TAGS) were more common (p = 0.013, p = 0.001, respectively). In group II, Scandinavian Stroke Scale scores were lower than those in group I (group I = 45.2 +/- 14, group II = 35.4 +/- 18.9, p = 0.02). In conclusion, activation of coagulation, demonstrated by increment F1+2, is more abundant in the stroke patients with NVAF than in the stroke patients with sinus rhythm. Our results also showed that activation of the hemostatic system might be related to stroke subtype and stroke severity. It is suggested that the oral anticoagulation treatment as prophylaxis is important in the prevention of stroke in patients with NVAFÖğe Hyperhomocysteinemia in cancer patients with thrombosis is independent of methylene tetrahydrofolate reductase gene mutation.(Amer Soc Hematology, 2004) Fareed, J; Tobu, M; Hoppensteadt, DA; Cunanan, J; Iqbal, O; Demir, M; Deitcher, S[Abstract Not Available]Öğe Immunoglobulin concentration in human intervertebral disc herniations(Springer Wien, 1999) Görgülü, A; Yalniz, E; Demir, M; Çobanoglu, SThe pathogenesis of low back pain and sciatica is poorly understood. In this prospective study, we determined local production of IgM and IgG in nucleus pulposus, serum and cerebrospinal fluid by rate nephelometry in patients with herniated lumbar disc (n = 20). Patients operated for anterior stabilizations because of fresh fracture in the lumbar or thoracolumbar spine and scoliosis constituted the control group (n = 10). In the patients with lumbar disc herniation, the ratio IgM(NP)/IgM(S) x 10(3), IgG(CSF)/IgG(S) x 10(3), and IgM(CSF)/IgM, x 103 was significantly increased when compared with control group values (p < 0.001). We found a close relationship of the ratio IgM(NP)/IgM(S) x 10(3) between low SLR (<40 degrees) (p = 0.02) and the duration of sciatric pain less than 2 months (p = 0.002). The results indicate a connection between the clinical findings and IgM production in nucleus pulposus. This fact may contribute in some way to the inflammatory origin of sciatica.Öğe Inflammatory pseudotumor of the spleen with EBV positivity: report of a case(Wiley-Blackwell, 2004) Puyan, FO; Bilgi, S; Unlu, E; Yalcin, O; Altaner, S; Demir, M; Cakir, BInflammatory pseudotumor (IPT) of the spleen is a rare benign tumor with unknown etiology. It causes problems in the diagnosis because of mimicking some hematopoetic malignancies. Here we report the case of a 36-yr-old woman complaining of nausea and insomnia. Laboratory investigations were limited to increase of leukocyte and thrombocyte count. Ultrasonography and magnetic resonance (MR) imaging showed circumscribed solid lobulated mass, measuring about 6.5 cm in diameter, located in the dorsal region of the spleen. Splenectomy was performed with the differential diagnosis including hamartoma and lymphoma of the spleen. Histological examination of the sharply demarcated splenic mass consisted of myofibroblasts and admixture of inflammatory cells. Immunohistochemistry and in situ hybridization were performed. IPT of the spleen was diagnosed. Epstein-Barr virus (EBV) was detected in the tumor by in situ hybridization. This rare entity is presented because of its clinical, radiological and pathological difficulties in the differential diagnosis.Öğe An interesting presentation of intrathoracic extramedullary hematopoiesis in a patient with thalassemia intermedia(Blackwell Publishing Ltd, 2003) Turgut, B; Pamuk, GE; Vural, Ö; Demir, M; Ünlü, E; Çelik, H; Çakir, BExtramedullary hematopoiesis (EMH) occurs as a compensatory mechanism for bone marrow dysfunction in severe thalassemia. In addition to the more common locations, such as liver, spleen and lymph nodes, a mass of EMH may occasionally occur in the thorax. Intrathoracic EMH is usually asymptomatic. A 69-year-old woman who initially presented with hematuria, dysuria, and left inguinal pain was found to have paravertebral masses in the thorax. Histopathologic examination of a CT-guided needle aspiration biopsy of the masses showed the presence of trilineage hematopoiesis. We present this unusual case, in which EMH was diagnosed by chance in an elderly patient with no symptoms related to thalassemia.Öğe Is plasma level of von Willebrand factor the predictor of endothelial dysfunction in women with polycystic ovary syndrome?(Pergamon-Elsevier Science Ltd, 2005) Guldiken, S; Kilic-Okman, T; Demir, M; Arikan, E; Kucuk, M[Abstract Not Available]Öğe Metastatic squamous cell carcinoma of the skin in chronic myeloid leukaemia(Blackwell Publishing Ltd, 2003) Pamuk, GE; Turgut, B; Vurul, Ö; Demir, M; Tek, M; Altaner, SHydroxyurea is a ribonucleotide diphosphate reductase inhibitor used in the treatment of patients with myeloproliferative disorders. Hydroxyurea has some dermatological side-effects. It has recently been recognized that hydroxyurea can induce squamous cell and basal cell carcinomas of skin. We present the case of an elderly man with chronic myeloid leukaemia who was treated with hydroxyurea for 4 years, with good control of his disease. However, in addition to the appearance of various skin lesions and cutaneous squamous cell carcinoma after 3 years of therapy, he was found to have a metastatic squamous cell carcinoma after 4 years. Hydroxyurea was discontinued, and he underwent surgery and radiotherapy. The patient subsequently died of ventricular fibrillation. We present this case to draw attention to the association between hydroxyurea and secondary skin cancers and to emphasize the need for dermatological examination before and during the course of hydroxyurea therapy.Öğe Molecular and pharmacologic profile of tinzaparin and a comparable low-molecular-weight bacterial sulfaminoheparosan(Sage Publications Inc, 2004) Maddineni, J; Ma, Q; Hoppensteadt, DA; Demir, M; Manoni, M; Cornelli, U; Fareed, JLow-molecular-weight heparins (LMWH) represent depolymerized porcine mucosal heparin derivatives, which are commonly used for the management of thrombotic disorders. Because of their widespread usage, the supplies of the raw material namely unfractionated heparin are nearly exhausted. Porcine mucosal tissue is almost exclusively used for the preparation of these agents. Thus, there is a timely need for the production of heparin like drugs from other sources. Fermentation techniques have been used to produce carbohydrates such as dextran and innulin for therapeutic purposes. Bacterial cell wall polysaccharide mimics the linear hexose units, which constitute heparin. Utilizing Escherichia coli cell membranes produced by fermentation technology, chemical sulfation and enzymatic epimerization, sulfamincheparosan type of polymer mimicking the structure of heparin has been produced. These semi-synthetic sulfaminoheparosans exhibit biologic actions comparable to that observed with heparin. The sulfaminoheparosan core can also be degraded to obtain low-molecular-weight (LMW) derivatives mimicking LMWHs. Using this technique, a novel LMW sulfaminoheparosan derivative (Q93C/239) was produced by Inalco, Milan, Italy. To compare this heparin analogue, a LMWH, namely tinzaparin, was used to determine the relative anticoagulant, antiprotease, and molecular profile. Additional studies were carried out to determine the susceptibility of this agent to heparinase-I. These comparative studies exhibited both antiprotease and anticoagulant properties similar to those of tinzaparin. However LMW sulfaminoheparosan resisted heparinase-I digestion at low heparinase-I concentrations. These studies demonstrate that the sulfaminoheparosan derived LMW components exhibit similar molecular and anticoagulant profile as tinzaparin and warrant additional preclinical and clinical development to determine their potential usefulness as antithrombotic agents.
