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H Yorgun,
U Canpolat,
K Aytemir,
A H Ateş,
E B Kaya,
A Akdoğan,
H Sunman,
A Gökçay Canpolat, M Çalgüneri,
G Kabakçi,
L Tokgözoğlu,
A Oto
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ABSTRACT: Cardiovascular involvement is one of the leading causes of death among patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate cardiac autonomic functions in SLE patients.
We enrolled 36 patients (25 female; mean age 34.2 ± 10.2 years) with SLE and 32 healthy subjects (23 female; mean age 35.0 ± 10.3 years). All participants underwent 24-h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting first, second, and third-minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV), heart rate turbulence (HRT) and QT dispersion analysis. The mean SLE duration was 8.4 ± 4.0 years.
According to the baseline demographic characteristics, both groups were similar with regard to age, gender, body mass index and left ventricular ejection fraction. Mean HRR1 (32.6 ± 10.9 vs. 42.5 ± 6.5, p = 0.038), HRR2 (51.0 ± 16.9 vs. 61.0 ± 10.8, p = 0.01) and HRR3 (52.8 ± 17.5 vs. 65.8 ± 9.8, p < 0.001) values were significantly higher in control group. When HRV was considered, SDNN, SDANN, RMSSD, PNN50 and high frequency (HF) component were significantly decreased in patients with SLE compared with healthy controls, but low frequency (LF) component and LF/HF were significantly higher in SLE patients. In addition, HRT onset and HRT slope values were significantly less negative in SLE patients. QT dispersion was significantly greater in SLE patients than healthy subjects (81.3 ± 15.8 vs. 53.2 ± 13.1, p < 0.001).
Our study results suggest that cardiac autonomic functions are impaired in SLE patients despite the absence of overt cardiac involvement and symptoms. Further studies are needed to elucidate the prognostic significance and clinical implications of impaired autonomic functions in patients with SLE.
Lupus 10/2011; 21(4):373-9. · 2.34 Impact Factor
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Annals of the Rheumatic Diseases 12/2004; 63(11):1527. · 8.73 Impact Factor
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Annals of the Rheumatic Diseases 06/2003; 62(5):492-3. · 8.73 Impact Factor
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ABSTRACT: Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO may also act as an acute-phase reactant, and it has been suggested as a component of inflammatory reactions. In this study our objective was to investigate serum TPO levels in patients with rheumatoid arthritis, a complex chronic inflammatory disorder not uncommonly associated with thrombocytosis. Bloodstream TPO concentrations were assessed in 13 RA patients with platelet counts between 450 and 650 x 10(9)/l, 10 RA patients with platelet counts >650 x 10(9)/l, 15 RA patients with normal platelet counts and 12 healthy controls. RA patients with normal platelet counts had TPO levels comparable with healthy controls. TPO concentrations in patients with mild thrombocytosis were significantly elevated, whereas patients with markedly increased thrombocyte counts had prominently decreased TPO levels. These results indicate that TPO seems to be associated with reactive thrombocytosis in RA patients with active disease. In patients with extremely increased thrombocytosis serum TPO levels might be regulated by increased platelet mass via receptor-mediated uptake and metabolism.
Clinical Rheumatology 12/2002; 21(6):453-6. · 2.00 Impact Factor
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ABSTRACT: Tissue factor pathway inhibitor (TFPI) is an anticoagulant which modulates the tissue factor (TF) dependent pathway, acting on the factor VIIa/TF complex, factor Xa, and thrombin. Although most TFPI is found in association with plasma lipoproteins and platelets, the functional pool is bound to vascular endothelium and is released into the circulation on stimulation with heparin or low molecular weight heparin (LMWH).
To assess the vascular endothelial TFPI pool in patients with Behçet's disease (BD) or systemic lupus erythematosus (SLE).
Plasma TFPI concentrations were determined before, and 20 and 60 minutes after subcutaneous LMWH injection in 15 newly diagnosed patients with BD and 12 with SLE, and in 12 healthy controls.
Baseline median TFPI was 149.5 ng/ml in healthy subjects, and the percentage change in TFPI at 20 minutes (((value at 20th min - baseline value)/baseline value) x 100) was 575.2. TFPI concentrations in patients with BD were initially normal at baseline (136.0 ng/ml), but the percentage change (44.7) was significantly lower than in the patients with SLE and the controls. Baseline TFPI concentrations in patients with SLE (83.0 ng/ml) were lower than in the control group, but the TFPI response to stimulation with LMWH reached a level (626.4%) comparable to that of the controls.
Depletion of the functional endothelial pool in BD and low circulating concentrations of TFPI despite an intact pool in SLE may be important in the pathogenesis of thrombosis in these vasculitic syndromes.
Annals of the Rheumatic Diseases 01/2002; 60(12):1149-51. · 8.73 Impact Factor
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Annals of the Rheumatic Diseases 09/2001; 60(8):814-5. · 8.73 Impact Factor
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ABSTRACT: We assessed plasma concentrations of fibronectin (FN) and thrombospondin (TSP) during acute attacks and attack-free periods of patients with familial Mediterranean fever (FMF). Seven female and three male FMF patients (mean age 34+/-7 years) were enrolled in the study. Plasma samples were obtained during acute FMF attacks and after 3 months of freedom from attacks. Erythrocyte sedimentation rate, C-reactive protein, and white blood cell count were evaluated concurrently. Plasma levels of FN and TSP were assayed by enzyme-linked immunosorbent assay (ELISA). Both FN and TSP concentrations were found to increase during acute attacks. Levels of adhesive molecules decreased during attack-free periods (P < 0.05). Significant correlations were found between FN and TSP levels and the concentrations of acute-phase response indicators (P< 0.05). This study disclosed for the first time significantly higher increments in the plasma levels of FN and TSP during acute FMF attacks than in attack-free periods. Therefore, the two matrix glycoproteins may play precipitating and/or regulatory roles in the inflammatory processes of these attacks.
Rheumatology International 08/2001; 20(6):217-20. · 1.88 Impact Factor
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ABSTRACT: Nitric oxide (NO) is produced in increased amounts in inflammatory conditions and may cause tissue injury by reacting with superoxide to yield peroxynitrite, a powerful toxin. Superoxide dismutase (SOD) scavenges superoxide and inhibits the formation of peroxynitrite, thereby suppressing the resulting injury and regulating the bioavailability of NO. We conducted a study to assess serum NO and SOD in patients with Behçet's disease (BD) and correlate their levels with disease activity.
Serum NO concentrations and SOD activities were determined in 25 BD patients (mean age: 36 years; male/female: 13/12) and in 15 healthy controls. BD patients were allocated into two groups according to disease activity (active/inactive: 11/14).
In patients with active disease, NO levels were found to be significantly elevated, while SOD activities were comparable to the control group. Conversely, patients with inactive disease exhibited markedly high SOD activities and normal NO levels. Moreover, there was a positive correlation between SOD activity and NO levels in patients with inactive BD (r = 0.562, p < 0.05).
We propose that NO-associated injury of tissues, particularly the endothelium, may be important in the etiopathogenesis of vasculitis in BD, and SOD may play a protective role against inflammation.
Clinical and experimental rheumatology 01/2001; 19(5 Suppl 24):S25-9. · 2.15 Impact Factor
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ABSTRACT: To investigate the synovial fluid levels of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-1 receptor antagonist (IL-1ra), soluble IL-2 receptor (sIL-2r) and IL-8 in patients with Behçet's disease (BD) and to compare them to levels in rheumatoid arthritis (RA), and osteoarthritis (OA).
The cytokine levels of BD (n = 14), RA (n = 15) and OA (n = 15) patients were assessed by enzyme-linked immunosorbent method.
Median synovial IL-1 beta and TNF-alpha levels were higher in RA compared to BD and OA patients. IL-1 beta levels were also higher in BD than OA whereas TNF levels were similar in these two groups. IL-1ra and TGF-beta activity in BD were higher than OA but lower than RA. sIL-2r and IL-8 levels were increased in BD and RA in comparison to OA patients.
The arthritis of BD is non-erosive and accordingly, its synovial fluid contains lower levels of cytokines primarily involved in cartilage destruction, namely IL-1 beta and TNF-alpha, than RA. IL-1ra and TGF might serve as protective factors against erosion in the inflamed joints. High synovial fluid levels of sIL-2r and IL-8 probably reflect a non-specific inflammatory process.
Clinical and experimental rheumatology 01/2001; 19(5 Suppl 24):S37-41. · 2.15 Impact Factor
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ABSTRACT: Cold intolerance, cold induced peripheral vasospasm, Raynaud's phenomenon, livedo reticularis and immunoglobulin deposition in the skin are often encountered clinical and laboratory findings in patients with primary fibromyalgia (FM). These findings are suggestive of vascular injury.
Eighty patients (4 male, 76 female) with fulfilling primary FM criteria (FM (+) patient group), 60 patients (3 male, 57 female) with chronic musculoskeletal complaints but without FM (FM (-) patient control group) and 40 healthy volunteers (1 male, 39 female) without musculoskeletal complaints (healthy control group) were enrolled in this cross-sectional study. The study was carried out in two steps. In the first step, the clinical findings, routine laboratory tests, autoantibodies and radiological findings were investigated. The second step were consisted of the laboratory investigations of thrombomodulin and fibronectin as the mediators indicating vascular injury and proinflammatory cytokines in FM patients with Raynaud's phenomenon and/or livedo reticularis and in control groups.
There were no differences between study and control groups with regard to laboratory, radiological and immunological (ANA, AntidsDNA, ENA, anticardiolipin IgG and IgM) results. No statistically significant differences were found in the levels of proinflammatory cytokines between FM (+) patient group and control groups (p > 0.05). Thrombomodulin was also shown statistically insignificant difference between FM (+) patient group and control groups (p > 0.05). However, fibronectin, another mediator of vascular injury, was higher in FM (+) patient group and the differences between FM (+) patients and each control groups were statistically significant (p < 0.0001).
Our results were suggestive of the presence of a non-immunological vascular injury in FM patients with Raynaud's phenomenon and/or livedo reticularis.
Nagoya journal of medical science 12/2000; 63(3-4):115-22.
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ABSTRACT: To investigate circulating thrombopoietin (TPO) concentrations in systemic sclerosis (SSc).
TPO concentrations were measured by ELISA in serum samples of 13 patients (11 female, 2 male) with diffuse SSc, 15 healthy controls (13 female, 2 male), and 15 patients (13 female, 2 male) with rheumatoid arthritis (RA). Thrombocyte counts of patients with SSc and RA and controls were recorded.
Median TPO concentrations were 115 (164) in SSc, 76 (32) in RA, and 62 (34) pg/ml in controls. Median serum TPO concentration in the SSc group was significantly higher than other groups; there was no difference between controls and patients with RA (p<0.001 for both comparisons). Median platelet counts of SSc, RA, and controls were 224+/-58x10(9)/l, 238+/-44x10(9)/l, and 272+/-35x10(9)/l, respectively. There was no correlation between thrombocyte counts and TPO levels in any group.
We show that patients with SSc have higher serum TPO concentrations compared to healthy controls and patients with RA. It can be hypothesized that TPO mediated release of particular growth factors may participate in the pathogenesis of the fibrotic process of SSc.
The Journal of Rheumatology 10/1999; 26(9):1939-41. · 3.69 Impact Factor
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ABSTRACT: To determine whether patients with idiopathic systemic lupus erythematosus (SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 genotypes and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clinical features of SLE.
Debrisoquine sulfate (10 mg p.o.) was given to 159 healthy volunteers and 39 idiopathic SLE patients. Genotypic assay was carried out in 80 healthy volunteers and 32 patients. A 10-ml blood sample was drawn for genotypic assay. Debrisoquine and 4-hydroxydebrisoquine were determined in 8-h urine samples. Blood samples were analysed for the presence of mutations in the CYP2D6 gene, by using polymerase chain reaction (PCR) specific for CYP2D6*3 and CYP2D6*4 alleles.
The metabolic ratio of debrisoquine to 4-hydroxydebrisoquine ranged from 0.01 to 86.98 in healthy subjects and from 0.02 to 96 in SLE patients. We observed the poor metabolizer(PM) debrisoquine phenotype in three of 39 patients with idiopathic SLE (7.6%) and five of 159 healthy subjects (3.1%). There was no significant difference in the frequency of PM phenotypes between idiopathic SLE and healthy subjects (Fisher's exact test, P = 0.19). No significant difference in the distribution of overall genotypes and allele frequencies were observed between the two groups. No significant relationships were found between specific clinical features and the overall genotype.
The results of this study confirm that CYP2D6 activity is not impaired in SLE and that there is no association between SLE and phenotypic CYP2D6 status. The results also showed that there was no difference in the frequency of CYP2D6A and CYP2D6B alleles between controls and patients with SLE.
European Journal of Clinical Pharmacology 04/1999; 55(1):21-5. · 2.85 Impact Factor
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ABSTRACT: The aetiology of systemic lupus erythematosus (SLE) is still unknown. In several cases, however, chemicals or drugs were identified as aetiological agents and associations with certain phenotypes of drug metabolising enzymes have been reported. The purpose of this study was to discover if there is an association between CYP2C19 polymorphism and susceptibility to SLE.
Racemic mephenytoin (100 mg orally) was given to healthy volunteers (n = 161) and SLE patients (n = 37) and then S-mephenytoin and R-mephenytoin were determined in eight hour urine samples. A 10 ml blood sample was obtained from healthy volunteers (n = 80) and SLE patients (n = 69) for genotypic assay. Each blood sample was tested for the detection of CYP2C19*1 and CYP2C19*2 (formerly wt and m1 respectively) by oligonucleotide ligation assay.
The ratio of S/R-mephenytoin ranged from < 0.1 to 1.293 in healthy subjects and from < 0.1 to 1.067 in SLE patients. PM phenotype was observed in 2 of 37 patients with idiopathic SLE (5.4%) and 6 of 161 healthy subjects (3.7%). There were no significant differences in the frequency of PM phenotypes between the groups (Fisher's exact test, p = 0.64) or in the frequency distribution profiles of ratios of S-mephenytoin to R-mephenytoin. No significant differences in distribution of overall genotypes and in allele frequencies were observed between the two groups. No significant relation was found between clinical features and the overall genotype.
The results of this study indicate that CYP2C19 genotype does not represent a genetic predisposition in idiopathic SLE patients.
Annals of the Rheumatic Diseases 03/1999; 58(3):182-5. · 8.73 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not fully understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragment1+2 (PF1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin (sTM) levels. SLE disease activity was determined using the SLE Disease Activity Index (SLEDAI). Concentrations of TAT, PAP, PF1+2 and sTM were significantly elevated (P<0.0001, P=0.0002, P<0.0001, and P<0.0001, respectively), while TFPI antigen levels were found to be reduced (P<0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-ds DNA levels were correlated positively with plasma TAT (P<0.05), PF1+2 (P<0.05), and sTM (P<0.01) concentrations and negatively with plasma TFPI levels (P<0.05). SLEDAI scores were correlated positively with plasma TAT (P<0.01), PF1+2 (<0.01), and sTM (P<0.01) levels. This study illustrates that both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.
Lupus 01/1999; 8(9):737-41. · 2.34 Impact Factor
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ABSTRACT: To compare plasma concentrations of soluble P-selectin (sP-selectin) in patients with rheumatoid arthritis (RA) and thrombocytosis with those with RA with normal platelet counts and healthy controls, and to explore the relationship between clinical and serological measures of disease activity.
Nineteen patients with RA with marked thrombocytosis, 20 with normal platelet counts, and 24 controls were enrolled. Ritchie articular index and morning stiffness were recorded as clinical markers of disease activity. Blood samples were collected for platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma sP-selectin determinations. Correlations between sP-selectin and clinical and serological markers of disease activity were noted.
Patients with RA and thrombocytosis compared to patients with normal platelet counts showed evidence of more active disease when ESR, CRP, morning stiffness, and Ritchie articular index were considered. The thrombocyte count in patients with RA with marked thrombocytosis revealed a positive correlation with CRP and Ritchie articular score. Plasma sP-selectin levels were found to be significantly higher in patients with RA compared to controls. sP-selectin levels were significantly higher in patients with RA with thrombocytosis compared to those with normal platelet counts, and positive correlations were observed between plasma sP-selectin levels and Ritchie index, morning stiffness, and thrombocyte counts in those patients.
Elevated plasma sP-selectin levels in RA could indicate the presence of a continuous underlying inflammatory stimulus. In addition, the augmented increase in patients with RA and thrombocytosis and its correlation with clinical activity may imply the cytokine-adhesion molecule interaction mediates the chronic inflammation of RA.
The Journal of Rheumatology 07/1998; 25(6):1054-8. · 3.69 Impact Factor
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The New Zealand medical journal 04/1997; 110(1039):80-1.
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ABSTRACT: Because exposure to streptococcal antigens might be a major disease activity-provoking factor in Behçet's disease, this study was undertaken to evaluate the effectiveness of benzathine penicillin in the prophylaxis of recurrent arthritis episodes during the course of this disease.
A prospective, randomized study design was used to allocate patients to receive colchicine alone or colchicine plus benzathine penicillin for 24 months.
The duration, severity, and pattern of arthritis episodes were found to be similar in the 2 treatment groups, but the number of arthritis episodes was significantly reduced, and the duration of episode-free time significantly prolonged, in the penicillin group compared with the colchicine-alone group.
Penicillin treatment was demonstrated to offer adjunctive benefits in the prevention of arthritis episodes which are not obtainable with colchicine monotherapy. This finding could provide additional evidence for antigen triggering in the pathogenesis of Behçet's disease.
Arthritis & Rheumatism 01/1997; 39(12):2062-5. · 7.87 Impact Factor
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ABSTRACT: 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.
Acta Haematologica 02/1996; 95(2):107-11. · 1.35 Impact Factor
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ABSTRACT: Particular interleukins, namely interleukin (IL)-6, IL-4 and IL-1, with pro-inflammatory mediator activities have also been shown to be involved in the regulation of megakaryocytopoiesis. As rheumatoid arthritis (RA) is not uncommonly associated with reactive thrombocytosis, we investigated serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations in RA patients with marked thrombocytosis, and compared them to the levels in RA patients with normal platelet counts and healthy volunteers. IL-1 beta. IL-4 and IL-6 concentrations were found to be correlated with the disease activity in both groups of RA patients, with higher serum levels of each cytokine in the thrombocythaemic group. Significant positive correlations of IL-1 beta and IL-4 with the platelet counts were documented only in patients with thrombocytosis. According to our results. IL-6 and IL-1 beta were found to be good indicators of disease activity in RA, while IL-1 beta and IL-4 seemed to be related more with the process of reactive thrombocytosis secondary to rheumatoid inflammation.
Rheumatology International 02/1996; 16(1):5-8. · 1.88 Impact Factor
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ABSTRACT: Recent studies point out a probable role of streptococcal antigens in the pathogenesis of Behçet's disease (BD). This has led to the proposal of benzathine penicillin as a therapeutic modality in BD.
A prospective study was conducted to compare the efficacy of colchicine and colchicine + benzathine penicillin treatments on mucocutaneous manifestations of BD.
60 patients (group I) were given colchicine alone and 94 (group II) were given colchicine + benzathine penicillin. Frequency, number, duration and severity of oral aphthous ulcers, genital ulcers and erythema nodosum were determined before and after treatment.
In group I, all parameters of oral ulcers and the frequency and healing time of genital ulcers and erythema nodosum decreased significantly. In group II, all parameters of oral aphthous ulcers, genital ulcers and erythema nodosum were significantly improved. When treatment results in the two groups were compared, the decrements in the frequency and duration of oral ulcers and erythema nodosum and the frequency of genital ulcers were significantly greater in group II than in group I (p < 0.05).
We conclude that prophylactic benzathine penicillin combined with colchicine is more effective in controlling mucocutaneous manifestations of BD than colchicine alone.
Dermatology 01/1996; 192(2):125-8. · 2.05 Impact Factor
