Dilek Solmaz

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

Objective: Obesity has been suggested as an independent risk factor for cardiovascular disease. Increasing evidence shows that engagement of soluble CD40 ligand (sCD40L) with its receptor plays a crucial role in the pathogenesis of atherosclerosis. The aim of the present study was to test whether obesity is associated with low-grade systemic inflammation as measured by serum high-sensitive C-reactive protein (hsCRP) and sCD40L concentration. Methods: Serum hsCRP and sCD40L concentrations were measured in 148 nondiabetic people. The participants were divided into three groups depending upon their body mass index (BMI) levels: Group 1 (normal weight), BMI<25 kg/m2; Group 2 (overweight), BMI 25 kg/m2 to 29.9 kg/m2; and Group 3 (obese), BMI≥30 kg/m2. Results: Obese people had more elevated hsCRP levels than both their normal weight and overweight counterparts (P=0.000 and P=0.000, respectively). Similarly, serum concentrations of sCD40L were significantly higher, statistically, in obese subjects compared with normal weight subjects (P=0.003). In addition, obese subjects had higher values of sCD40L than overweight subjects, but the difference did not reach statistical significance (P=0.063). The levels of high-density lipoprotein cholesterol were significantly lower in obese subjects compared to normal weight subjects (P=0.048). The analysis of platelet count disclosed a statistically significant difference between obese subjects and normal weight subjects (P=0.028). The levels of BMI were positively correlated with the serum levels of hsCRP and sCD40L in all subjects (r=0.514, P=0.000 and r=0.283, P=0.000, respectively). Levels of hsCRP were positively correlated with waist circumference, fasting glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, leukocytes, platelets, systolic and diastolic blood pressure. Similarly, soluble CD40L levels were positively correlated with waist circumference, fasting glucose and leukocytes. Conclusion: Obese patients showed a significant increase of hsCRP and sCD40L levels compared with normal weight subjects, which might contribute to the known proinflammatory milieu found in these patients.

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study

OBJECTIVE The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabetic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets.

Quality of life in patients with Takayasu's arteritis is impaired and comparable with rheumatoid arthritis and ankylosing spondylitis patients

The aims of the study were to assess the health-related quality of life (QOL) in patients with Takayasus arteritis (TA) by two different generic QOL instruments and to compare the results with those patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and healthy controls (HC). A cross-sectional study was performed in 51 patients with TA (41 women; mean age 38.4 ± 13.5), 43 RA (36 women; 55.2 ± 9.6), 31 AS (12 women; 41.2 ± 13.1), and 75 HC (53 women; 38.8 ± 10.9). Quality of life was assessed by using Short-Form 36 (SF-36) and Nottingham Health Profile (NHP). Separate dimensions of SF-36 and NHP and physical and mental summary scores of SF-36 as well were compared between patients and control groups. Physical and mental health summary scores and all SF-36 subscales, except for social functioning, were significantly lower in patients with TA than healthy controls. No significant differences between TA, RA, and AS patients were found in all SF-36 subscales and summary scores. NHP scores for energy level, pain, emotional reactions, and physical mobility were significantly higher in TA patients than controls. All NHP subscales, except for pain, were comparable in patients with TA, RA, and AS. Pain score was worse in RA patients. The NHP scores for sleep and social isolation were not different between patients and controls. Many aspects of QOL in patients with TA are significantly impaired in comparison with local healthy controls and similar to those in patients with RA and AS.

High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first- degree relatives: further evidence for the connection

IntroductionFamilial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Limited data suggest that the prevalence of sacroiliitis is increased in patients with FMF. In our present study, we assessed the prevalence of spondyloarthritis (SpA), including ankylosing spondylitis (AS), among a cohort of FMF patients and their unaffected first-degree relatives (FDRs).MethodsThe current study cohort comprised a consecutive group of 201 unrelated patients with FMF and 319 FDRs (≥ 16 years old). These subjects were examined according to a standard protocol.ResultsA total of 157 FMF patients (78.1%) and 233 (73%) unaffected FDRs reported back pain. Fifteen FMF patients (7.5%) and nine unaffected FDRs fulfilled the modified New York (mNY) criteria for AS. One additional FDR with AS was identified after review of the medical records. None of the FMF patients with AS was HLA-B27 positive. The allele frequency of M694V among the FMF patients with radiographic sacroiliitis was significantly higher in comparison with those without sacroiliitis (OR 4.3). When compared with the general population, the risk ratios for SpA and AS among the FDRs of our FMF patients were 3.3 (95% CI; 2.0 to 5.5) and for AS 2.9 (95% CI; 1.3 to 6.4), respectively.ConclusionsOur study suggests that a) factors other than HLA-B27 play a role in the association of FMF and SpA/AS; b) MEFV gene variations may be one of the geographic/region-specific potential pathogenetic links between these two disorders in the Turkish population.

Initial diagnosis of lumbar disc herniation is associated with a delay in diagnosis of ankylosing spondylitis.

Objective. There is often a considerable delay in diagnosis of ankylosing spondylitis (AS). In this multicenter study, we analyzed the delay and possible associated factors, including an initial diagnosis of lumbar disc herniation (LDH), which we frequently encounter in daily clinical practice. Methods. The study included 393 consecutive patients [258 men (65.6%), mean age 39.3 ± 10.8 yrs] with AS according to the modified New York criteria. Face-to-face interviews were done using a structured questionnaire, addressing all the potentially relevant factors. Results. The mean diagnostic delay was 8.1 ± 8.6 years in the whole study population. The shortest delay was observed when rheumatologists were the first physicians consulted (2.9 ± 5.3 yrs). An initial diagnosis of LDH was reported by 33% of the patients. The diagnostic delays in patients with an initial diagnosis of LDH and those without were 9.1 ± 8.5 years and 6.2 ± 7.4 years, respectively (p = 0.002). In a regression model, predictive factors for delay in diagnosis were age at onset of spondyloarthritic symptoms, back pain, education level, prior diagnosis of LDH, and surgical history for LDH. Conclusion. These results indicate the need to increase awareness of the concept of axial spondyloarthritis among specialists who might be the first physicians consulted by patients with AS for their back pain. There is also a need to develop strategies for early referral of such patients to rheumatologists.

Familial Mediterranean fever: risk factors, causes of death, and prognosis in the colchicine era.

We assessed the risk factors and causes of death in patients with familial Mediterranean fever (FMF) in an era when colchicine is the standard therapy for all patients. This study included all FMF patients who had presented to any of the internal medicine, rheumatology, or nephrology clinics at Dokuz Eylul University Hospital between 1992 and 2009. Of the 650 patients with FMF identified, 587 (90.3%) had either a face-to-face (n = 380) or telephone (n = 193) interview, or were confirmed as deceased. A structured questionnaire was used to obtain socioeconomic and demographic data, presenting and cumulative clinical features, and disease severity scores. During the follow-up period mortality was analyzed by calculating age- and sex-standardized mortality ratio (SMR) according to the mortality statistics of the Turkish population. Factors predictive of mortality were evaluated using Kaplan-Meier and Cox proportional hazard models. Sixty-three (9.7%) patients whose initial demographic and major clinical characteristics were similar to the rest of the group could not be contacted during the study period. Most (94.2%) patients were on colchicine at the time of the study. Thirty-seven (6.3%) patients had biopsy-verified amyloidosis, and 44 (7.5%) had renal disease. During a median follow-up of 6 years, 14 patients (9 women) died, and amyloidosis and its related complications were the leading causes of death in 7 patients. Univariate analysis revealed that increasing age, coronary heart disease, hypertension, renal disease, and amyloidosis were associated with mortality. However, Cox regression analysis showed amyloidosis as the only significant predictor of mortality (p < 0.001). The overall patient survival rate was not significantly different from the age- and sex-matched Turkish general population (SMR, 1.48; 95% confidence interval, 0.817–2.49). Our findings suggest that although the survival of FMF patients in the colchicine era is comparable to that of the general population, renal involvement still predicts mortality. AbbreviationsAA = amyloid A, CI = confidence interval, CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, FMF = familial Mediterranean fever, MEFV = MEditerranean FeVer gene, SAA = serum amyloid A, SMR = standardized mortality ratio.

Assessment of sex in a modern Turkish population using cranial anthropometric parameters

The utilization of radiological imaging methods in anthropometric studies is being expanded by the application of modern imaging methods, leading to a decrease in costs, a decrease in the time required for analysis and the ability to create three-dimensional images. This retrospective study investigated 400 patients within the 18-45-years age group (mean age: 30.7±11.2years) using cranial computed tomography images. We measured 14 anthropometric parameters (basion-bregma height, basion-prosthion length, maximum cranial length and cranial base lengths, maximum cranial breadth, bizygomatic diameter, upper facial breadth, bimastoid diameter, orbital breadth, orbital length, biorbital breadth, interorbital breadth, foramen magnum breadth and foramen magnum length) of cranial measurements. The intra- and inter-observer repeatability and consistency were good. From the results of logistic regression analysis using morphometric measurements, the most conspicuous measurements in terms of dimorphism were maximum cranial length, bizygomatic diameter, basion-bregma height, and cranial base length. The most dimorphic structure was the bizygomatic diameter with an accuracy rate of 83% in females and 77% in males. In this study, 87.5% of females and 87.0% of males were classified accurately by this model including four parameters with a sensitivity of 91.5% and specificity of 85.0%. In conclusion, CT cranial morphometric analysis may be reliable for the assessment of sex in the Turkish population and is recommended for comparison of data of modern populations with those of former populations. Additionally, cranial morphometric data that we obtained from modern Turkish population may reveal population specific data, which may help current criminal investigations and identification of disaster victims.

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

IntroductionThe current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA.MethodsThis study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerrs criteria, disease extent index-Takayasu, physicians global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay.ResultsUnacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity.ConclusionsThis study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity.

Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still's disease: Data from a large multicenter cohort.

BACKGROUND Adult-onset Stills disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. METHODS A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. RESULTS The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. CONCLUSION Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD.