Background:Inflammatory lesions of hand are frquent clinical feature in rheumatoid artritis (RA),... more Background:Inflammatory lesions of hand are frquent clinical feature in rheumatoid artritis (RA), with lower frequency in pts with systemic sclerosis (SSc), also. MR is useful method for detecting and quantification of inflammatory lesion of the hand (bone oedema, erosions, synovitis) in RA and SSc.Objectives:The aim of the study was to compare MR hand feature in SSc (experimental) and RA (control group) and to detect the localisation of the highest OMERACT RAMRISinflammatory score on the hand in pts with SSc and RAMethods:110 pts with SSc and 60 with RA were investigated (mean age 53y). All the pts underwenr clinical examination, X ray and MR on the dominant hand and wrist. Contrast enhanced low field MRI of the wrist and MCP2-5 joints was performend to all the pts. MRI inflammatory changes (bone oedema,erosions, synovitis)were assessed and scored by OMERACT RAMRIS scoring system.Results:Clinical examination confirmed synovitis in 17.1%, and 78% of patients with SSc using MR I (p &...
Background: Matrics metalloproteinases (MMPs) are the key enzymes responsible for the joint destr... more Background: Matrics metalloproteinases (MMPs) are the key enzymes responsible for the joint destruction in rheumatoid arthritis (RA). Objectives: The aim of this study was to examine the association of baseline levels of metalloproteinases-9 (MMP-9) in serum and synovial fluid (SF) with structural damage of hand and feet joints in patients with early RA and also with imunoserological markers of the disease. Methods: The study enrolled 134 subjects with knee synovitis: 72 patients with early DMARD-naive RA (symptom duration ≤12 months) and 62 patients with osteoarthritis (OA), as control group. Synovial fluid was obtained by an arthrocentesis of the knee joint. Joint damage was estimated by hands, knee and feet radiography. With regard to the presence of destructive joint changes on initial x-ray, RA patients were classified as erosive and nonerosive form of disease. ELISA assay was used for the detection of MMP–9 activity in serum and SF as well for the imunoserology tests: rheumato...
Background Circulating immune complex (CIC) are forming in a normal immune response, as a consequ... more Background Circulating immune complex (CIC) are forming in a normal immune response, as a consequence of attachment of specifically reactive antibodies to antigens. As a result, most antigens are neutralised and/or eliminated. However, in some circumstances, CIC deposits in tissues with subsequent phlogogenic responces. Systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) are organ nonspecific autoimmune diseases with a high prevalence of positive test for CIC. It seems that systemic character of these diseases is due to vascular entrapment of CIC in various tissues. Application of various methods on the same serum sample regularly gives a different level of CIC. Objectives Our objective was to correlate the levels of CIC measured with two different assays in sera of patients with SLE, SSc, and RA. Methods We used precipitation test with polyethylene glycol (PEG), molecular weight 6000 and C1q binding assay (C1q) with laser nephelometer in sera ...
Background Objectives The aim was to evaluate the efficacy and tolerability of low dose of longte... more Background Objectives The aim was to evaluate the efficacy and tolerability of low dose of longterm Methotrexate (MTX) treatment of rheumatoid arthritis (RA). Methods This study examines prospectively the response to oral MTX (5 ? 12,5 mg) over a 5 year period of 70 patients (pts) with active RA. 54 pts were female, mean age 53,61 ± 12,8 years range (27 ? 76) and mean diseases duration 9,76 ± 7,58 years (range 0,6 ? 35). Patients who were receiving Prednizone at entry to the trial, were maintained by the same dose, not exceeding 10 mg/day. Clinical evaluation were performed by the same physician ? investigator every 3 months for the first year of the study and every 6 months thereafter. Every 4 weeks complete blood cound and every 12 weeks thereafter complete erytrocyte sedimentation (ERS), blood count, serum creatinine and liver blood tests were obtained. Patients were assessed at 0 stage (beginning) with 70 pts, after 3 months (mts) (with 62), 6 mts (with 52), 12 mts (with 49), 24...
Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymo... more Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with erosive arthritis and rapid radiological progression of the disease. The examined group included 131 patients with early RA. Using the PCR-RFLP method, the TNF-Alpha-308 G/A gene polymorphism was determined for all patients. In relation to the presence of the A allele of the examined polymorphism, the patients were divided into two subgroups: subgroup A (G/A and A/A genotypes) and subgroup G (G/G genotype). Based on the presence of the destructive changes in joints found in the initial radiographs, the findings were classified as erosive and non-erosive RA. Radiological progression was assessed on the basis of the annual change in the Larsen score – LS (0-200). Group A comprised 62 (47.33%) patients, while group G comprised 69 (52.67%) patients. The presence of cysts and erosions in subgroups A and G was compared before the start of the methotrexate therapy. It ...
Background In recent years, potential biological markers of systemic lupus erythematosus (SLE) an... more Background In recent years, potential biological markers of systemic lupus erythematosus (SLE) and LN activity have been intensely sought for. Among them, it seems that monocyte chemoattractant protein-1 (MCP-1) has a prominent place as a marker of LN activity. Objectives Our aim in this paper was to investigate the level of MCP-1 in the serum and urine of SLE patients and to establish its correlation with SLE and LN activity. Methods The study involved 72 patients with SLE, hospitalized in the Rheumatology Clinic, Institute “Niška Banja”, during 2011, in whom the diagnose was made using the criteria of the ARA revised in 1997, 27 with LN and 45 without signs of LN, as well as 30 healthy individuals. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used to assess the disease activity. In addition to other standard laboratory and immunological analyses, the level of MCP-1 was determined in SLE patients and controls in their serum and urine samples using the sandwich enzyme immunosorbent assay method, in accordance with the manufacturer's directions (R&D Systems, Inc. Minneapolis, USA). Results The examinees in the investigated group were aged 46.4±9.3 years on the average. Average age of control subjects was 44.7±9.5 years. In SLE group there were 66 (91.7%) women and 6 (8.3%) men, and in control group 27 (90%) women and 3 (10%) men. Average disease duration in the studied group was 11.2±8.1 years. Average SLEDAI value was 10.9±6.9, with a median of 8. Our investigation showed that mean MCP-1 values in the sera of SLE patients were significantly higher compared to average values in controls (728.7±879.7 pg/ml vs. 225.9±42.0 pg/ml; p<0.001). Mean values of MCP-1 in the urine of SLE patients were also significantly higher, regardless of disease activity, renal involvement, and treatment used, compared to healthy controls (179.2±181.5 pg/ml vs. 94.7±31.6 pg/ml; p<0.01). For the cut-off of >266.7 pg/ml the specificity and sensitivity of serum MCP-1 for SLE diagnosis was 90% and 77.8% respectively (95% CI 0.817-0.946; AUC 0.894), and for the cut-off of >166.0 pg/ml the specificity and sensitivity of urine MCP-1 was 100% and 44.4% respectively (95% CI 0.588-0.776; AUC 0.688). Our results demonstrated that the urinary and not serum MCP-1 was in a positive correlation with proteinuria (r=0.839; p<0.001) and in negative correlation with glomerular filtration assessed using the Modification of Diet in Renal Disease (MDRD) formula (r=-0.293; p<0.05). Both serum and urinary MCP-1 demonstrated a positive correlation with SLEDAI (r=0.318; p<0.01 and r=0.431; p<0.001). Conclusions Serum and urine MCP-1 can be an indicant of global SLE activity. Urine MCP-1 can be a marker of LN activity, since it is in correlation with renal damage and function parameters – in a positive correlation with proteinuria, and in negative one with glomerular filtration. Future longitudinal studies of this cytokine in a larger number of SLE patients could perhaps provide us with some conclusive answers about the significance of MCP-1 determination in early detection of subclinical forms of LN, predictions of disease relapses, and timely treatment of SLE patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3854
To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arth... more To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweigh...
Background Methotexate (MTX) has one of the best efficacy/toxicity ratios. Toxic effects, rather ... more Background Methotexate (MTX) has one of the best efficacy/toxicity ratios. Toxic effects, rather than lack of response, were the major reason for discontinuing MTX. Objectives Our aim was to determine the frequency and spectrum of side effects in patients with rheumatoid arthritis (RA) receiving low doses of MTX and eventually to determine existence of risk factors for appearance of side effects. Methods During five years period, 70 patients with active RA were enrolled in a prospective study. They all fulfilled ARA criteria. There were 54 women and 16 man, between 27 and 76 years. The mean duration of disease was 9,76 ± 7,58 years. They were treated with low doses of MTX (5 ? 12,5 mg once a week; mean dose 7,5 mg once a week). The mean duration of MTX treatment was 2,82 ± 2,27 years. MTX was given to 27 (38,57%) patients without prior treatment with disease modifying antirheumatic drugs. Most of the patients were treated with NSAID and low doses of prednison, according to indicatio...
Background Treatment of osteoporosis may be expected to affect the remodelling phase of bone repa... more Background Treatment of osteoporosis may be expected to affect the remodelling phase of bone repair and therefore promote fracture healing. Ibandronat significantly increase bone mineral density (BMD) and reduce the risk of vertebral, hip and non vertebral fractures in women with postmenopausal osteoporosis Objectives To confirm the efficacy and safety of 1 year ibandronate in OP pts: 150mg oral monthly or quarterly intravenously; to analyze the impact of risk factors and fractures on the efficacy of ibandronate treatment Methods 190 pts with primary OP,average 62.1y, average menopause 16.8y, treated 1 year with oral monthly or quarterly iv injection of ibandronate were included. BMD was measured by DXA Hologic at lumbar spine and proximal femur; OP is defined as the mean BMD expressed as a T-score <-2.5 and> = -5.0. The profil RTG of TH-LS spine was done before and after the therapy. Substitution of the optimal dose of vitamin D and calcium was applied. Results Previous fracture (37.6%)and smoking (33.5%) were the most common risk factors;75.1% pts had OP and more than one risk factor. Total number of vertebral and nonvertebral fractures at baseline was 71; 25 vertebral, 46 nonvertebral.After therapy, the number of new fractures was 18; 8 vertebral, 10 nonvertebral. After 1 year of oral monthly ibandronate BMD was increased at the spine for 3.0%,hip 3.5%,after ibandronate injection spine BMD was increased for 4.6%, hip 3.6%. Spine and hip BMD increase was higher in pts with OP and multiple risk factors (spine, p=0.000, hip, p=0.01)than those with one risk factor (spine, p=0.04; hip, p=0.02). Pts with multiple fractures and OP had a greater increase in spine and hipBMD(spine, p=0.000; hip, p=0.001) compared to those with 1 or without fracture (spine, p=0.04; hip, p=0.05). Pts with OP and previous BF treatment had no sign. BMD increase at the spine (p=0.334), nor on the hip (p=0.2)opposed to those not previously treated, with statistically sign. BMD increasing(spine, p=0.000, hip, p=0.006). Adverse events were rare,did not lead to stopped the treatment:7.8%pts had a flu like sy,1.1% LS pain,1.1% SVPT, stopped after medical therapy Conclusions Ibandronate is effective,safe drug, orally applied monthly or quarterly iv. in OP pts, especially those with multiple risk factors and multiple fractures Disclosure of Interest None Declared
Background:Inflammatory lesions of hand are frquent clinical feature in rheumatoid artritis (RA),... more Background:Inflammatory lesions of hand are frquent clinical feature in rheumatoid artritis (RA), with lower frequency in pts with systemic sclerosis (SSc), also. MR is useful method for detecting and quantification of inflammatory lesion of the hand (bone oedema, erosions, synovitis) in RA and SSc.Objectives:The aim of the study was to compare MR hand feature in SSc (experimental) and RA (control group) and to detect the localisation of the highest OMERACT RAMRISinflammatory score on the hand in pts with SSc and RAMethods:110 pts with SSc and 60 with RA were investigated (mean age 53y). All the pts underwenr clinical examination, X ray and MR on the dominant hand and wrist. Contrast enhanced low field MRI of the wrist and MCP2-5 joints was performend to all the pts. MRI inflammatory changes (bone oedema,erosions, synovitis)were assessed and scored by OMERACT RAMRIS scoring system.Results:Clinical examination confirmed synovitis in 17.1%, and 78% of patients with SSc using MR I (p &...
Background: Matrics metalloproteinases (MMPs) are the key enzymes responsible for the joint destr... more Background: Matrics metalloproteinases (MMPs) are the key enzymes responsible for the joint destruction in rheumatoid arthritis (RA). Objectives: The aim of this study was to examine the association of baseline levels of metalloproteinases-9 (MMP-9) in serum and synovial fluid (SF) with structural damage of hand and feet joints in patients with early RA and also with imunoserological markers of the disease. Methods: The study enrolled 134 subjects with knee synovitis: 72 patients with early DMARD-naive RA (symptom duration ≤12 months) and 62 patients with osteoarthritis (OA), as control group. Synovial fluid was obtained by an arthrocentesis of the knee joint. Joint damage was estimated by hands, knee and feet radiography. With regard to the presence of destructive joint changes on initial x-ray, RA patients were classified as erosive and nonerosive form of disease. ELISA assay was used for the detection of MMP–9 activity in serum and SF as well for the imunoserology tests: rheumato...
Background Circulating immune complex (CIC) are forming in a normal immune response, as a consequ... more Background Circulating immune complex (CIC) are forming in a normal immune response, as a consequence of attachment of specifically reactive antibodies to antigens. As a result, most antigens are neutralised and/or eliminated. However, in some circumstances, CIC deposits in tissues with subsequent phlogogenic responces. Systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA) are organ nonspecific autoimmune diseases with a high prevalence of positive test for CIC. It seems that systemic character of these diseases is due to vascular entrapment of CIC in various tissues. Application of various methods on the same serum sample regularly gives a different level of CIC. Objectives Our objective was to correlate the levels of CIC measured with two different assays in sera of patients with SLE, SSc, and RA. Methods We used precipitation test with polyethylene glycol (PEG), molecular weight 6000 and C1q binding assay (C1q) with laser nephelometer in sera ...
Background Objectives The aim was to evaluate the efficacy and tolerability of low dose of longte... more Background Objectives The aim was to evaluate the efficacy and tolerability of low dose of longterm Methotrexate (MTX) treatment of rheumatoid arthritis (RA). Methods This study examines prospectively the response to oral MTX (5 ? 12,5 mg) over a 5 year period of 70 patients (pts) with active RA. 54 pts were female, mean age 53,61 ± 12,8 years range (27 ? 76) and mean diseases duration 9,76 ± 7,58 years (range 0,6 ? 35). Patients who were receiving Prednizone at entry to the trial, were maintained by the same dose, not exceeding 10 mg/day. Clinical evaluation were performed by the same physician ? investigator every 3 months for the first year of the study and every 6 months thereafter. Every 4 weeks complete blood cound and every 12 weeks thereafter complete erytrocyte sedimentation (ERS), blood count, serum creatinine and liver blood tests were obtained. Patients were assessed at 0 stage (beginning) with 70 pts, after 3 months (mts) (with 62), 6 mts (with 52), 12 mts (with 49), 24...
Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymo... more Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with erosive arthritis and rapid radiological progression of the disease. The examined group included 131 patients with early RA. Using the PCR-RFLP method, the TNF-Alpha-308 G/A gene polymorphism was determined for all patients. In relation to the presence of the A allele of the examined polymorphism, the patients were divided into two subgroups: subgroup A (G/A and A/A genotypes) and subgroup G (G/G genotype). Based on the presence of the destructive changes in joints found in the initial radiographs, the findings were classified as erosive and non-erosive RA. Radiological progression was assessed on the basis of the annual change in the Larsen score – LS (0-200). Group A comprised 62 (47.33%) patients, while group G comprised 69 (52.67%) patients. The presence of cysts and erosions in subgroups A and G was compared before the start of the methotrexate therapy. It ...
Background In recent years, potential biological markers of systemic lupus erythematosus (SLE) an... more Background In recent years, potential biological markers of systemic lupus erythematosus (SLE) and LN activity have been intensely sought for. Among them, it seems that monocyte chemoattractant protein-1 (MCP-1) has a prominent place as a marker of LN activity. Objectives Our aim in this paper was to investigate the level of MCP-1 in the serum and urine of SLE patients and to establish its correlation with SLE and LN activity. Methods The study involved 72 patients with SLE, hospitalized in the Rheumatology Clinic, Institute “Niška Banja”, during 2011, in whom the diagnose was made using the criteria of the ARA revised in 1997, 27 with LN and 45 without signs of LN, as well as 30 healthy individuals. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used to assess the disease activity. In addition to other standard laboratory and immunological analyses, the level of MCP-1 was determined in SLE patients and controls in their serum and urine samples using the sandwich enzyme immunosorbent assay method, in accordance with the manufacturer's directions (R&D Systems, Inc. Minneapolis, USA). Results The examinees in the investigated group were aged 46.4±9.3 years on the average. Average age of control subjects was 44.7±9.5 years. In SLE group there were 66 (91.7%) women and 6 (8.3%) men, and in control group 27 (90%) women and 3 (10%) men. Average disease duration in the studied group was 11.2±8.1 years. Average SLEDAI value was 10.9±6.9, with a median of 8. Our investigation showed that mean MCP-1 values in the sera of SLE patients were significantly higher compared to average values in controls (728.7±879.7 pg/ml vs. 225.9±42.0 pg/ml; p<0.001). Mean values of MCP-1 in the urine of SLE patients were also significantly higher, regardless of disease activity, renal involvement, and treatment used, compared to healthy controls (179.2±181.5 pg/ml vs. 94.7±31.6 pg/ml; p<0.01). For the cut-off of >266.7 pg/ml the specificity and sensitivity of serum MCP-1 for SLE diagnosis was 90% and 77.8% respectively (95% CI 0.817-0.946; AUC 0.894), and for the cut-off of >166.0 pg/ml the specificity and sensitivity of urine MCP-1 was 100% and 44.4% respectively (95% CI 0.588-0.776; AUC 0.688). Our results demonstrated that the urinary and not serum MCP-1 was in a positive correlation with proteinuria (r=0.839; p<0.001) and in negative correlation with glomerular filtration assessed using the Modification of Diet in Renal Disease (MDRD) formula (r=-0.293; p<0.05). Both serum and urinary MCP-1 demonstrated a positive correlation with SLEDAI (r=0.318; p<0.01 and r=0.431; p<0.001). Conclusions Serum and urine MCP-1 can be an indicant of global SLE activity. Urine MCP-1 can be a marker of LN activity, since it is in correlation with renal damage and function parameters – in a positive correlation with proteinuria, and in negative one with glomerular filtration. Future longitudinal studies of this cytokine in a larger number of SLE patients could perhaps provide us with some conclusive answers about the significance of MCP-1 determination in early detection of subclinical forms of LN, predictions of disease relapses, and timely treatment of SLE patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3854
To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arth... more To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweigh...
Background Methotexate (MTX) has one of the best efficacy/toxicity ratios. Toxic effects, rather ... more Background Methotexate (MTX) has one of the best efficacy/toxicity ratios. Toxic effects, rather than lack of response, were the major reason for discontinuing MTX. Objectives Our aim was to determine the frequency and spectrum of side effects in patients with rheumatoid arthritis (RA) receiving low doses of MTX and eventually to determine existence of risk factors for appearance of side effects. Methods During five years period, 70 patients with active RA were enrolled in a prospective study. They all fulfilled ARA criteria. There were 54 women and 16 man, between 27 and 76 years. The mean duration of disease was 9,76 ± 7,58 years. They were treated with low doses of MTX (5 ? 12,5 mg once a week; mean dose 7,5 mg once a week). The mean duration of MTX treatment was 2,82 ± 2,27 years. MTX was given to 27 (38,57%) patients without prior treatment with disease modifying antirheumatic drugs. Most of the patients were treated with NSAID and low doses of prednison, according to indicatio...
Background Treatment of osteoporosis may be expected to affect the remodelling phase of bone repa... more Background Treatment of osteoporosis may be expected to affect the remodelling phase of bone repair and therefore promote fracture healing. Ibandronat significantly increase bone mineral density (BMD) and reduce the risk of vertebral, hip and non vertebral fractures in women with postmenopausal osteoporosis Objectives To confirm the efficacy and safety of 1 year ibandronate in OP pts: 150mg oral monthly or quarterly intravenously; to analyze the impact of risk factors and fractures on the efficacy of ibandronate treatment Methods 190 pts with primary OP,average 62.1y, average menopause 16.8y, treated 1 year with oral monthly or quarterly iv injection of ibandronate were included. BMD was measured by DXA Hologic at lumbar spine and proximal femur; OP is defined as the mean BMD expressed as a T-score <-2.5 and> = -5.0. The profil RTG of TH-LS spine was done before and after the therapy. Substitution of the optimal dose of vitamin D and calcium was applied. Results Previous fracture (37.6%)and smoking (33.5%) were the most common risk factors;75.1% pts had OP and more than one risk factor. Total number of vertebral and nonvertebral fractures at baseline was 71; 25 vertebral, 46 nonvertebral.After therapy, the number of new fractures was 18; 8 vertebral, 10 nonvertebral. After 1 year of oral monthly ibandronate BMD was increased at the spine for 3.0%,hip 3.5%,after ibandronate injection spine BMD was increased for 4.6%, hip 3.6%. Spine and hip BMD increase was higher in pts with OP and multiple risk factors (spine, p=0.000, hip, p=0.01)than those with one risk factor (spine, p=0.04; hip, p=0.02). Pts with multiple fractures and OP had a greater increase in spine and hipBMD(spine, p=0.000; hip, p=0.001) compared to those with 1 or without fracture (spine, p=0.04; hip, p=0.05). Pts with OP and previous BF treatment had no sign. BMD increase at the spine (p=0.334), nor on the hip (p=0.2)opposed to those not previously treated, with statistically sign. BMD increasing(spine, p=0.000, hip, p=0.006). Adverse events were rare,did not lead to stopped the treatment:7.8%pts had a flu like sy,1.1% LS pain,1.1% SVPT, stopped after medical therapy Conclusions Ibandronate is effective,safe drug, orally applied monthly or quarterly iv. in OP pts, especially those with multiple risk factors and multiple fractures Disclosure of Interest None Declared
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