Hüseyin Tutkak

Plasma von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and antithrombin III levels in Behçet's disease.

Sixty-three patients with Behçets disease (BD), 30 patients with recurrent oral ulcer and 30 healthy individuals as control group were included in the study. ISG criteria was used for the diagnosis of BD and patients were classified as active and inactive and evaluated accordingly. In the patient and control groups, von Willebrand factor (vWF), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) levels were determined using ELISA method and antithrombin III (AT-III) by nephelometric methods. High levels of endothelial product, vWF in the active Behçet patient group (p < 0.005) supports endothelial destruction due to vasculitis related with BD. In the active patient group tPA levels were significantly lower (p < 0.05) than the inactive and control groups with higher levels of PAI (p < 0.05 and p < 0.01) respectively. In Behçet disease, besides the decrease in tPA synthesis, high PAI levels also can affect tPA decrease and lead to inhibition of fibrinolytic activity. In active Behçet group, levels of AT-III were low and no significant difference was observed in recurrent oral ulcer and control groups. This situation may arise from the excessive use of AT-III in active disease. In conclusion, high levels of vWF in Behçet patients is thought to arise from vasculitis and high levels of PAI from the accumulation of thrombocytes on the damaged surface of endothelium leading to a decrease in tPA levels and inhibition of fibrinolytic activity.

Cytokine inhibitors: soluble tumor necrosis factor receptor 1 and interleukin-1 receptor antagonist in Behçet’s disease

Serum levels of proinflammatory cytokines, interleukin-1 beta (IL-1β), tumor necrosis factor alpha, (TNF-α), and their inhibitors, IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor 1 (sTNFR1), were determined by enzyme-linked immunosorbent assay in 104 patients with Behçet’s disease (65 active, 39 inactive) and 40 healthy controls. The levels of IL-1β and IL-1ra were significantly higher in both active and inactive patients than in control subjects (P<0.01 and P< 0.01, respectively). The concentrations of TNF-α and sTNFR1 were found to be higher in active patients than in controls (P< 0.01 and P< 0.001, respectively). There were no significant differences in the serum levels of these cytokines and their inhibitors between active and inactive patients. Significant increases in mean C-reactive protein level and erythrocyte sedimentation rate were found in patients with active vs inactive disease (P< 0.001 and P< 0.05, respectively). C-reactive protein values correlated with erythrocyte sedimentation rate but not with cytokines or their inhibitors. Our conclusion is that elevated serum TNF-α and sTNFR1 seem to be important inflammatory mediators in Behçet’s disease. The statistically significant increase in these levels may arise from the severity of inflammation in the tissue or organ involved.

Impact of TNF-alpha and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients.

Objectives:We investigated the role of cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in cachexia development in newly diagnosed nonsmall cell lung cancer (NSCLC) patients. Methods:We evaluated 44 (M/F:41/3) NSCLC patients and 12 (M/F:10/2) age matched healthy smokers. NSCLC cases with a weight loss of ≥10% consisted the cachectic group (n:23, M/F:21/2) and the ones with <10% weight loss consisted the noncachectic group (n:21, M/F:19/2). Results:Body mass index (BMI) of cachectics was significantly lower than that of noncachectics (21.0 ± 2.9 versus 24.5 ± 3.6, P = 0.02) and controls (21.0 ± 2.9 versus 25.5 ± 2.6, P = 0.01). Serum TNF-α level did not differ between cachectic and noncachectics (37.3 ± 39.1 and 51.6 ± 84.2 pg/mL, respectively). However, it was significantly higher in NSCLC patients compared with controls (44.1 ± 64.3 and 15.1 ± 14.3 pg/mL, P = 0.03). Serum IL-6 level was not different between 3 groups (6.4 ± 4.1, 8.9 ± 16.3, and 4.1 ± 3.5 pg/mL, respectively) but it correlated significantly with TNF-α (r = 0.4, P = 0.006) and BMI (r = −0.3, P = 0.03). Erythrocyte sedimentation rate (ESR) correlated significantly with TNF-α (r = 0.4, P = 0.003) and BMI (r = −0.3, P = 0.03). Among 44 cases, survival of 12 and 17 patients was recorded in cachectics and noncachectics, with no statistical difference (12.2 ± 3.7 and 11.2 ± 1.0 months, respectively). Conclusions:TNF-α and IL-6 levels did not differ significantly between cachectics and noncachectics. However, significant correlations between IL-6, BMI, and TNF-α suggested that these cytokines acted as cofactors in weight loss. Survival was neither influenced by BMI, nor the cytokine levels in the present study. The significant correlation of ESR with TNF-α suggested that ESR could provide valuable clue for considerable weight loss in the follow-up of NSCLC patients.

Diagnostic and prognostic role of serum glypican 3 in patients with hepatocellular carcinoma

α‐Feto protein (AFP) is the widely used tumor marker in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to assess the diagnostic and prognostic validity of a novel marker, serum Glypican‐3 (GPC3) and to compare AFP in patients with HCC. One hundred and twenty‐eight patients (75 patients with HCC, 55 patients with cirrhosis, and 28 healthy controls) were included in this study. Cut‐off value of GPC3 was 3.9 pg/ml. AFP was divided into four subgroups, according to cut‐off values with 13, 20, 100, and 200 ng/ml. Sensitivity, specificity, and positive and negative predictive values of GPC3 and AFP13, AFP20, AFP100, AFP200 subgroups and also GPC3+AFP13, GPC3+AFP20, GPC3+AFP100, GPC3+AFP200 combinations were compared. Serum GPC3 levels were significantly higher in patients with HCC and cirrhosis compared with control subjects (P<0.05). The median serum GPC3 levels were 3.9 pg/ml in controls, 5.51 pg/ml in patients with cirrhosis, and 5.13 pg/ml in those with HCC. The median serum AFP levels were 1.37 ng/ml in controls, 2.32 ng/ml in cirrhotics, and 50.65 ng/ml in HCC patients. The sensitivity, specificity, and positive and negative predictive values of GPC3 was 61.33, 41.82, 58.97, and 44.43%, respectively. The values for AFP were 68.57, 94.55, 94.12, and 70.27%, respectively. There was no correlation between GPC3 levels and prognostic parameters. GPC3 is not a useful diagnostic and prognostic marker for HCC. J. Clin. Lab. Anal. 25:350–353, 2011.

Diagnostic and Prognostic Validity of Golgi Protein 73 in Hepatocellular Carcinoma

We regret to inform you that the criticism raised by the Editorial Board is correct concerning the similarity between some parts of the texts present in our article published in Digestion [2011;83:83–88], and the papers in the Journal of Hepatology [2005;43:1007–1012] and in Hepatology [2009;49:1421–1423], although the research data are completely independent. We apologize for this unfortunate error, which was established during the writing process of the manuscript by the author Harun Erdal. Although the final version of the submitted paper had been examined by all authors, they failed to recognize the ‘transferred parts’ of the papers in the Journal of Hepatology [2005;43:1007–1012] and in Hepatology [2009;49:1421–1423]. Thus, for the sake of scientific clarity and based on the above-mentioned facts, we prefer to retract our paper Diagnostic and Prognostic Validity of Golgi Protein 73 in Hepatocellular Carcinoma. Digestion 2011;83:83–88 (DOI:10.1159/000320379). Authors, Hasan Özkan Harun Erdal Hüseyin Tutkak Zihni Karaeren Mustafa Yakut Osman Yüksel Seyfettin Köklü

Association of HLA Class I and Class II Antigens with Rheumatic Fever in a Turkish Population

The distribution of class I and class II HLA antigens of 100 Turkish patients with rheumatic fever, 77 of whom had cardiac involvement, was examined. We compared the results with a control group of identical origin. The frequency of HLA A10 and HLA B35 antigens were found significantly higher in patients with rheumatic fever (p < 0.05, p < 0.01, respectively). The frequency of HLA A10 and HLA DRw11 in patients with cardiac involvement were significantly higher than in those without cardiac involvement (p < 0.05, p < 0.01, respectively). On the other hand, HLA Cw2 antigen frequency was found significantly higher in patients without cardiac involvement than in those with rheumatic heart disease (p < 0.05). We support the concept that rheumatic fever is an immunological reaction to group A, beta hemolytic streptococci in individuals who have genetic predisposition.

Effect of losartan on circulating Tnfα levels and left ventricular systolic performance in patients with heart failure

Background Tumor necrosis factor alpha (TNFα) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFα levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFα levels and ejection fraction (EF) in patients with congestive heart failure. Methods Forty patients with heart failure and EF ≤ 40% were enrolled into the study. All of the patients have been given diuretic and digitalis therapy. Twenty patients were given losartan (50 mg/d) (Group I, 10 women, 10 men, 12 dilated cardiomyopathy, 8 ischemic heart disease, mean age 64.9 ± 8.9), and another 20 patients were not given losartan because of hypotension or renal dysfunction (Group II, 13 men, 7 women, 10 dilated cardiomyopathy, 10 ischemic heart disease, mean age 61.2 ±10.5). EF was measured at the initial evaluation and on the fifteenth day of the therapy by echocardiographic examination using an acoustic quantification method. Circulating TNFα levels were also measured at the initial evaluation and on the fifteenth day of therapy by the ELISA method. Results Losartan significantly increased EF and decreased TNFα (EF increased from 29.4 ± 7.3% to 36.0 ± 8.5%, P < 0.001, and TNFα decreased from 39.2 ± 37.4 pg/ml to 27.0 ± 30.0 pg/ml, P < 0.05). Changes in TNFα levels and EF were not found to be correlated (r=−0.28, P=0.24). However, in the control group, EF and TNFα levels were similar at baseline and at the fifteenth day (EF 31.4 ± 8.1% vs 31.7 ± 7.8%, P=0.1, and TNFα 91.5 ± 86.0 pg/ml vs 110.0 ± 80.7 pg/ml, P=0.1, respectively). Conclusions Losartan improves left ventricular systolic function and decreases TNFα level. The decreased TNFα level seems to be independent of EF.

Elevated levels of soluble intercellular adhesion molecule-1 correlate with disease activity in Behçet's disease

The objective of this study was to measure soluble intercellular adhesion molecule-1 (sICAM-1) in patients with Behçets disease (BD) and to analyse the relationship of sICAM-1 levels with clinical and some laboratory measures of disease activity. Forty patients with BD fulfilling the International Study Group Criteria for the diagnosis of BD and 20 healthy controls were studied. Twenty patients had active, and 20 patients had inactive disease. Serum sICAM-1 was determined by a sandwich ELISA. The mean (±SD) sICAM-1 level was significantly higher in the whole BD group (297.3±86.6 ng/ml) than in the healthy controls (213±83.5 ng/ml; P< 0.05). The mean sICAM-1 levels in active and inactive BD patients were 315.7±76.3 ng/ml and 258.3±73.3 ng/ml, respectively. The mean sICAM-1 level in active patients was significantly higher than in inactive patients and healthy controls (P< 0.02 and P< 0.001, respectively). No statistically significant difference in mean sICAM-1 levels was found between inactive BD patients and healthy controls (P>0.05). There was no statistically significant difference between the mean sICAM-1 levels of active patients with (351.3±77.2 ng/ml) or without vascular lesions (292±68.8; P>0.05). In spite of a positive correlation between disease activity and both erythrocyte sedimentation rate and C-reactive protein (CRP; P< 0.01), we found no correlation between sICAM-1 and either of them (P>0.05). The elevated levels of sICAM-1 may be due to endothelial cell activation and/or damage or may be the result of inflammation. In either case it did not seem to be superior to more conventional measures of disease activity.

Serum levels of IL-1beta, TNF-alpha, IL-8, and acute phase proteins in seronegative spondyloarthropathies

OBJECTIVES Some immunological abnormalities have been described in seronegative spondyloarthropathies (SpA). The aim of this study is to determine the serum levels of IL-1beta, TNF-alpha and IL-8, which are proinflammatory cytokines in active and inactive patients with SpA, to compare the results with those of controls and to investigate a relationship with clinical activity and acute phase proteins. METHODS Forty-two patients (34 males and eight females) and 22 healthy controls (17 M and 5 F) were included in the study. All patients fulfilled Amor criteria for the classification of SpA. Among patients 23 had active and 19 had inactive disease. IL-1beta, TNF-alpha and IL-8 were determined by enzyme-linked immunosorbent assay ( ELISA), acute phase proteins were measured by nephelometric assay. RESULTS There was no statistically significant difference between mean IL-1beta levels of patient groups and controls. Serum mean TNF-a levels in active and inactive patients were significantly increased as compared to that in the controls (P < 0.05, P < 0.05, respectively). Serum mean IL-8 levels in active patients was significantly increased as compared to that in the controls and in inactive patients (P < 0.01, P < 0.01, respectively). High serum IL-8 levels correlated well with C-reactive protein and haptoglobulin, but there was no correlation between IL-1beta or TNF-alpha levels and acute phase proteins such as C-reactive protein, alpha-1 acid glycoprotein, alpha-1 antitrypsin and haptoglobulin. CONCLUSIONS These results suggest that serum IL-8 may reflect clinical activity of the disease and may be helpful for monitoring patients with SpA.

Antinucleosome Antibodies and Systemic Lupus Erythematosus

Abstract:  The aim of this study is to investigate the prevalence of antinucleosome antibody in systemic lupus erythematosus (SLE) and their association with disease activity and renal involvement. The study included 131 patients with SLE, 74 rheumatoid arthritis, 26 systemic sclerosis, and 50 healthy individuals. Antinucleosome antibody and anti‐dsDNA antibody were measured by an enzyme‐linked immunosorbent assay (ELISA). Antinuclear antibody was tested by immunofluorescence using HEp‐2 cells. Out of 131 SLE patients, 72 (54.9%) were seropositive for antinucleosome antibody, which was significantly higher than only 3 of 74 (4%) patients with rheumatoid arthritis (χ2= 52.82, P < 0.001); none of the patients with systemic sclerosis and 50 healthy individuals were seropositive. The sensitivity and specificity of antinucleosome antibodies in SLE were 83.6% and 70%, respectively. Fifty‐one (38.9%) of SLE patients had renal involvement. Among these patients, the rate of antinucleosome positivity and anti‐dsDNA were 74.5% and 78.4%, respectively. Antinucleosome antibodies were found to be 31.4% positive in SLE patients lacking anti‐dsDNA antibody. Antinucleosome antibodies significantly correlated with disease activity (r= 0.428, P < 0.001) and anti‐dsDNA (r= 0518, P < 0.001). The positivity of antinucleosome antibodies was significantly higher in patients with renal disease than the subjects without renal disease (χ2= 12.89, P < 0.001). The results of our study have revealed that in SLE patients, antinucleosome antibody could be a useful parameter for the assessment of disease activity or renal involvement.