Semra Dündar

Impaired haemostatic kinetics and endothelial function in Behçet's disease

Objectives. This study was planned to explore the alterations of endothelial functions in the prethrombotic state of Behçets disease (BD) patients.

Risk Factor Assessment and Prognosis of Eye Involvement in Behçet's Disease in Turkey

BACKGROUND Behcets disease (BD) shows great regional differences in clinical manifestations and prognosis, including eye involvement. Thus, it is hard to predict in which patient the eyes will be involved and what the outcome will be. In this study we assessed various risk factors for eye involvement and attempted to predict the visual outcome in our patient population in Turkey. METHODS Data from a total of 224 patients with BD, diagnosed between 1982 and 1996, were analyzed retrospectively. A detailed physical examination and ophthalmologic work up were performed on each patient. Factors that might contribute to eye involvement were investigated, after which prognostic factors for vision were evaluated. RESULTS Eighty-eight patients had eye involvement during a median follow-up of 32 months. The risk of involvement was highest within the first year of diagnosis. Young age was the most significant factor for eye involvement (P < 0.0001), but vascular thrombosis, central nervous system (CNS) involvement, and male gender were other risk factors (P < 0.001; P < 0.01; and P < 0.05, respectively). The most important determinant for the prognosis of vision was CNS involvement (P < 0.0001). Vascular thrombosis and an age of < or = 32 were other risk factors for visual impairment (P < 0.001 and P < 0.05, respectively). The risk of eye involvement and prognosis for vision were similar with different treatment regimens (P > 0.05). CONCLUSION It is suggested that the first 2 years after diagnosis is the most critical period for eye involvement, and conventional forms of therapy generally are unsuccessful in preventing such involvement. It seems reasonable to treat patients who are at increased risk for eye involvement more aggressively, especially within the first 2 years of disease onset.

Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial

BACKGROUND Sight-threatening eye involvement is a serious complication of Behçets disease. Extraocular complications such as arthritis, vascular occlusive disorders, mucocutaneous lesions, and central-nervous-system disease may lead to morbidity and even death. We designed a prospective study in newly diagnosed patients without previous eye disease to assess whether prevention of eye involvement and extraocular manifestations, and preservation of visual acuity are possible with combination treatments with and without interferon alfa-2b. METHODS Patients were randomly assigned 3 million units interferon alfa-2b subcutaneously every other day for the first 6 months plus 1.5 mg colchicine orally daily and 1.2 million units benzathine penicillin intramuscularly every 3 weeks (n=67), or colchicine and benzathine penicillin alone (n=68). The primary endpoint was visual-acuity loss. Analysis was by intention to treat. FINDINGS Significantly fewer patients who were treated with interferon had eye involvement than did patients who did not receive interferon (eight vs 27, relative risk 0.21 [95% CI 0.09-0.50], p<0.001). Ocular attack rate was 0.2 (SD 0.62) per year with interferon therapy and 1.02 (1.13) without interferon therapy (p=0.0001). Visual-acuity loss was significantly lower among patients treated with interferon than in those without interferon (two vs 13, relative risk 0.13 [95% CI 0.03-0.60], p=0.003). Arthritis episodes, vascular events, and mucocutaneous lesions were also less frequent in patients treated with interferon than in those not receiving interferon. No serious side-effects were reported. INTERPRETATION Therapy with interferon alfa-2b, colchicine, and benzathine penicillin seems to be an effective regimen in Behçets disease for the prevention of recurrent eye attacks and extraocular complications, and for the protection of vision.

Selectin adhesion molecules in Behçet's disease

OBJECTIVES The pathogenesis of Behçets 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Effects of interferon-α2a treatment on serum levels of tumor necrosis factor-α, tumor necrosis factor-α2 receptor, interleukin-2, interleukin-2 receptor, and E-selectin in Behçet's disease

Abstract This study was performed to investigate serum levels of various cytokines and E-selectin in patients with Behçets disease (BD) before and after treatment with interferon-α2a (IFN-α). The study population consisted of 22 patients with active BD; 15 age- and sex-matched healthy adults served as the control group. IFN-α (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-α (TNF-α), TNF-α2-receptor (TNFα2R), interleukin-2 (IL-2), IL-2 receptor (IL-2R), and E-selectin were measured by sandwich-type enzyme immunoassay. Baseline E-selectin, TNF-α, and TNF-α2R 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-α in the treatment of BD. Serum levels of TNF-α, TNF-α2R, 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-α-induced disease remission.

Is elevated level of soluble endothelial protein C receptor a new risk factor for retinal vein occlusion

Background:  To evaluate the systemic and thrombophilic risk factors for retinal vein occlusion (RVO) and to determine whether the elevated level of soluble endothelial protein C receptor (sEPCR) is a risk factor for thrombosis.

Platelet Factor 4, β-Thromboglobulin and Thrombospondin Levels in Type I Diabetes Mellitus Patients

The proteins β-thromboglobulin, platelet factor 4 and thrombospondin are stored in platelet α-granules and released from the platelet by the release reaction. The assays of these proteins were studied in patients with type I diabetes mellitus (n = 30) and a healthy control group (n = 15). Platelet factor 4 and β-thromboglobulin levels were not significantly different in both groups but thrombospondin concentrations in diabetic patients were significantly higher than those of the control group (136.6 ± 14.2 ng/ml vs 91.2 ± 14.3 ng/ml, P < 0.05). When the diabetic patients were divided into those with or without complications, the diabetic patients with complications (n = 11) had significantly elevated plasma thrombospondin concentrations compared with the control group (150.4 ± 23.7 ng/ml vs 91.2 ± 14.3 ng/ml, P < 0.05), while thrombospondin concentrations in the control group were not statistically different from the diabetic patients without complications. Plasma β-thromboglobulin and platelet factor 4 levels were not significantly different between the diabetic and the control group. It is suggested that thrombospondin may be a convenient marker of in vivo platelet release reaction.

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.

Megakaryocyte-Related Interleukins in Reactive Thrombocytosis versus Autonomous Thrombocythemia

The primary thrombocytosis (thrombocythemia) associated with myeloproliferative disorders is believed to be due to autonomous platelet production. Secondary or reactive thrombocytosis can be observed in a number of clinical circumstances, and may be related to persistent overproduction of some thrombocytopoietic factors acting on megakaryocytes. Several cytokines, including IL-6, IL-1 and IL-4 have been shown to act alone or in concert, to affect various cellular stages of megakaryocytopoiesis in humans. The aim of this study is to assess the serum concentrations of these cytokines in myeloproliferative disorders (MPD) with thrombocythemia and in rheumatoid arthritis (RA) with marked reactive thrombocytosis. Twenty-two patients (14 men, 8 women) with MPD and thrombocythemia (platelet counts > 500 x 10(9)/1; range 507-996 x 10(9)/1), 33 RA patients (28 women, 5 men) with marked thrombocytosis (platelet counts > 500 x 10(9)/1; range 500-745 x 10(9)/ 1), 27 RA patients (24 women, 3 men) with normal platelet counts (range 168-399 x 10(9)/1) and 15 healthy volunteers (8 women, 7 men) with normal platelet counts (range 161-385 x 10(9)/1) enrolled in the study. Serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations were measured in these four groups. Of the 22 patients with MPD, 10 had chronic myelogenous leukemia, 5 had polycythemia vera, 6 had essential thrombocytosis and 1 had osteomyelofibrosis. Serum interleukin concentrations in patients with MPD and thrombocythemia were either suppressed or similar to those of normal subjects, whereas IL-6, IL-1 beta and IL-4 levels were increased in RA patients with reactive thrombocytosis. We conclude that thrombocythemia associated with MPD is an autonomous phenomenon, and is not regulated by cytokines which affect megakaryocytopoiesis.

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.