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    Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever
    (Springer, 2017) Kucuksahin, Orhan; Yildizgoren, Mustafa Turgut; Ilgen, Ufuk; Ates, Askin; Kinikli, Gulay; Turgay, Murat; Erten, Sukran
    Objective: To investigate the effect of anti-interleukin-1 (anti-IL-1) treatment on the frequency and severity of attacks and other disease-related clinical parameters and to evaluate the adverse effects associated with anti-IL-1 treatment in 26 patients with refractory familial mediterranean fever (FMF).Methods: The study included 26 FMF patients followed up in our centre using colchicine for 4 months to 30 years. The treatment was switched to anti-IL-1 treatment for various reasons; 20 cases were resistant to colchicine, 8 were intolerant to colchicine, and 3 had prolonged arthritis under colchicine. Clinical response was monitored through the number of attacks, and laboratory inflammation was monitored through erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A concentrations. Colchicine resistance was defined as at least two attacks/month together with C-reactive protein and serum amyloid A levels above the normal range between attacks. The colchicine dose was increased to 2mg/day before they were considered colchicine-resistant.Results: 24 patients used anakinra (100mg/day), and 2 used canakinumab (150mg/month), for -36 months. Sixteen patients with colchicine resistance had no attacks under anti-IL-1 treatment, and 4 had decreased frequency and duration of attacks. Seven of 8 patients intolerant to colchicine used anakinra, and 6 were attack-free under treatment, while 1 using canakinumab had attacks under treatment. One patient with prolonged arthritis used canakinumab but arthritis showed progression and the treatment was changed to IL-6 inhibitor. Three patients had injection site erythema and one had fatigue with anti-IL-1 treatment. Topical steroids with systemic antihistaminics were sufficient for symptom control in two cases, but canakinumab treatment was given due to severe injection site erythema in one case.Conclusion: Anti-IL-1 agents are rational treatment modalities in patients resistant or intolerant to colchicine. Anti-IL-1 agents can control FMF attacks quite effectively and they have a promising role in the treatment of FMF.
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    Bosentan For Digital Ulcers in Patients With Systemic Sclerosis: Single Center Experience
    (Turkish League Against Rheumatism, 2016) Kucuksahin, Orhan; Yildizgoren, Mustafa Turgut; Gerede, Demet Menekse; Maras, Yuksel; Erten, Sukran
    Objectives: This study aims to investigate the effects of bosentan on the prevention and treatment of digital ulcers in systemic sclerosis (SSc) patients. Patients and methods: The study included 30 patients (4 males, 26 females; mean age 49.6 +/- 15.4 years; range 23 to 71 years) diagnosed with SSc and treated with bosentan for digital ulcers. Bosentan was administered to all patients for a mean of 14 +/- 10.3 months. All SSc cases were refractory to calcium channel antagonists or angiotensin II inhibitors. The diagnosis of SSc was based on the American College of Rheumatology criteria and patients were classified as limited or diffuse cutaneous SSc according to the LeRoy classification. Results: Mean disease duration was 8.8 +/- 8.0 years and mean duration of digital ulcers was 29.4 +/- 6.6 months. Under the bosentan treatment, eight patients (26.7%) developed new digital ulcers; all of these patients had diffuse cutaneous SSc. Health Assessment Questionnaire scores improved after 12 months and 24 months of treatment (p<0.001). Three patients (10%) developed pulmonary arterial hypertension under bosentan treatment [ two patients (6.6%) had SSc-associated pulmonary arterial hypertension and one patient (3.3%) had interstitial fibrosis-associated pulmonary arterial hypertension]. The anti-centromere antibody positive patients were predominantly classified as limited cutaneous SSc. Of the patients positive for anti-topoisomerase-1 antibodies, a high proportion was classified as diffuse cutaneous SSc. Pulmonary fibrosis was most frequent in the anti-topoisomerase-1 antibody subset. New digital ulcers developed mainly in the anti-topoisomerase-1 antibody positive patients. Conclusion: Bosentan may be used either alone or in combination with other treatments when digital ulcers worsen and may be expected to suppress the development of new ulcers and severe pain. Further preclinical studies are required shedding light on the etiopathogenesis of SSc and larger clinical trials are needed for more definitive treatment strategies.