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OBJECTIVE: To determine the levels of vascular endothelial growth factor (VEGF) in patients with active psoriatic arthritis, patients with inactive psoriatic arthritis, and healthy controls. Serum VEGF levels were correlated with clinical and laboratory features in patients with active psoriasis arthritis. METHODS: Serum samples from 14 patients with active psoriatic arthritis, 14 patients with inactive psoriatic arthritis, and 9 healthy controls were investigated. VEGF levels in the serum were measured using a sensitive sandwich ELISA. RESULTS: The mean serum VEGF concentration in patients with active PA was 394.4 pg/ml (394 +/- 171.8), in patients with inactive PA 200.4 pg/ml (200.4 +/- 115.7), and in healthy subjects 214.3 pg/ml (214.3 +/- 162.1). Patients with active psoriasis arthritis had significantly higher levels of VEGF compared to patients with inactive psoriasis arthritis and healthy individuals (p > 0.001). In contrast, VEGF levels were comparable in patients with inactive psoriatic arthritis and controls (p =0.659). Furthermore, in patients with psoriatic arthritis, VEGF levels were positively correlated with ESR, HAQ, PASI and VAS. CONCLUSION: VEGF levels may be regarded as a good indicator of active psoriasis arthritis.

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OBJECTIVE: The aim of the current study was to evaluate the short-term effects of anti-tumour necrosis factor alpha (infliximab) therapy on serum cartilage oligomeric matrix protein (COMP) levels, a possible biomarker of cartilage destruction. METHODS: Nine consecutive patients with active psoriatic arthritis (PsA) were treated with infliximab for 6 weeks. Serum COMP levels were measured and correlated to pre-established disease activity outcome variables: pain as assessed by the patient, using the 100 mm visual analogue scale (VAS), duration of morning stiffness (MGST), swollen joint count (SJC), tender joint count (TJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: Significant improvements in MGST, VAS, SJC and TJC values were observed after 6 weeks of therapy. Similar significant improvements were demonstrated in the ACR response rate and in eight (89%) patients the ACR20 was achieved. ESR and CRP decreased significantly over 6 weeks. Serum COMP levels also decreased significantly after 6 weeks of treatment (12.99 +/- 1.71 baseline, 10.22 +/- 1.1 after 6 weeks, P < 0.008). CONCLUSION: The results of our study suggest that short-term therapy with infliximab leads to decreased COMP levels in patients with PsA. COMP seems to be a good candidate for a biomarker reflecting cartilage response to this treatment in PsA patients.

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To examine the influence of intravenous steroid-treatment (IST) on serum levels of Cartilage oligomeric matrix protein (COMP) in patients with active rheumatoid arthritis (RA). Serum levels of COMP and C-reactive protein (CRP) were measured in 12 patients with highly active RA (Steinbrocker stages II-IV) and in 5 patients with highly active reactive arthritis (ReA) (positive testing for HLA-B27) before starting daily IST. Patients received a total steroid dosage between 100 and 500 mg of prednisolone. COMP was measured by a commercially available sandwich-type ELISA-kit developed by AnaMar Medical AB, Sweden. Statistical evaluation was calculated by paired t test. In the RA group, COMP levels ranged from 6.3 to 19.4 U/l (mean 12.9 U/l), CRP from 5 to 195 mg/l (mean 77.8 mg/l), the COMP levels of the ReA group ranged from 5.1 to 7.4 U/l (mean 7.9 U/l), the CRP levels from 13 to 126 mg/l (mean 49 mg/l). We found a significant difference between the initial COMP levels in RA+ and ReA patients (P<0.005). In contrast to the ReA group, serum-COMP levels of RA+ patients (P<0.004) and the VAS (P<0.0001) decreased significantly within 2-10 days after the first treatment with steroids. The CRP levels remained unchanged in both groups. Our results indicate that the intravenous treatment with steroids in patients with highly active RA leads to a significant decrease of cartilage degradation. COMP seems to be a valuable parameter not even as a prognostic factor, but as a marker for monitoring the therapy response in patients with RA.

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BACKGROUND: Although both strength training (ST) and endurance training (ET) seem to be beneficial in type 2 diabetes mellitus (T2D), little is known about post-exercise glucose profiles. The objective of the study was to report changes in blood glucose (BG) values after a 4-month ET and ST programme now that a device for continuous glucose monitoring has become available. MATERIALS AND METHODS: Fifteen participants, comprising four men age 56.5 +/- 0.9 years and 11 women age 57.4 +/- 0.9 years with T2D, were monitored with the MiniMed (Northridge, CA, USA) continuous glucose monitoring system (CGMS) for 48 h before and after 4 months of ET or ST. The ST consisted of three sets at the beginning, increasing to six sets per week at the end of the training period, including all major muscle groups and ET performed with an intensity of maximal oxygen uptake of 60% and a volume beginning at 15 min and advancing to a maximum of 30 min three times a week. RESULTS: A total of 17,549 single BG measurements pretraining (619.7 +/- 39.8) and post-training (550.3 +/- 30.1) were recorded, correlating to an average of 585 +/- 25.3 potential measurements per participant at the beginning and at the end of the study. The change in BG-value between the beginning (132 mg dL(-1)) and the end (118 mg dL(-1)) for all participants was significant (P = 0.028). The improvement in BG-value for the ST programme was significant (P = 0.02) but for the ET no significant change was measured (P = 0.48). Glycaemic control improved in the ST group and the mean BG was reduced by 15.6% (Cl 3-25%). CONCLUSION: In conclusion, the CGMS may be a useful tool in monitoring improvements in glycaemic control after different exercise programmes. Additionally, the CGMS may help to identify asymptomatic hypoglycaemia or hyperglycaemia after training programmes.

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Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the "Fernwärme run" (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwärme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo- and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

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OBJECTIVE: Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Among Northern Europeans the carrier frequency is estimated to be 1 in 10, while up to 1 in 200 is affected by the disease. Arthropathy is one early clinical manifestation of this disease, but the articular features are often misdiagnosed. In this study the two frequent mutations of the HLA-linked hemochromatosis gene (HFE) were investigated in a rheumatology clinic population. METHODS: Two hundred and six consecutive patients (mean age 57.7 years; 38 male/168 female) attending a rheumatology clinic over a period of 14 months were screened for HFE mutations (C282Y and H63D). All standard diagnostic procedures were used to identify the aetiology of the arthropathy. Mutations were evaluated by separation on PAGE of digested PCR amplificates of DNA (by SnapI and Bcl-I, for C282Y and H63D, respectively) obtained from PBMCs. RESULTS: The C282Y and H63D allele frequencies were 4.5 and 12.8 in patients with rheumatic diseases. Five patients were homozygote for H63D (2.4%), and one for C282Y (0.5%). Five patients were compound heterozygous (2.4%). The observed C282Y allele frequency in rheumatic patients with undifferentiated arthritis was 12.9 and exceeded that of healthy subjects (p = 0.01). CONCLUSIONS: Determination of the HFE genotype is clinically useful in patients with arthritis of unknown origin, to allow early diagnosis of hemochromatosis.

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INTRODUCTION: We aimed to determine the efficacy and safety of a cyclic intravenous therapy with pamidronate in patients with postmenopausal or glucocorticoid-induced osteoporosis. METHODS: We enrolled 86 Austrian female patients with postmenopausal (n = 69, mean age 68.13 +/- 1.14) or glucocorticoid-induced (n = 17, mean age 66.89 +/- 2.03) osteoporosis defined as a T-score of < -2.5 for bone mineral density (BMD) of the lumbar spine L1-L4. Patients received a single intravenous dose of 30 mg pamidronate at 3 months intervals. The per cent change in BMD was primary, whereas the safety and the biological response were secondary endpoints. RESULTS: Seventy-six female patients (88%) completed study. Sixty patients received pamidronate therapy for the treatment of late postmenopausal osteoporosis and 16 patients received the same treatment for glucocorticoid-induced osteoporosis. At the end of the trial, lumbar spine (L1-L4) BMD increased significantly in patients with postmenopausal osteoporosis (P = 0.000067), whereas in patients with glucocorticoid-induced osteoporosis no significant change was observed (P = 0.724). The increase in the Ward's triangle BMD did not reach significance level in postmenopausal women receiving pamidronate (P = 0.0740). However, pamidronate treatment for glucocorticoid-induced osteoporosis resulted in a significant increase in Ward's triangle BMD (P = 0.0029). The efficacy of pamidronate treatment for postmenopausal osteoporosis was also reflected in a decrease in circulating biochemical markers for bone formation, including alkaline phosphatase and osteocalcin. In addition, pamidronate was well tolerated with no incidence of severe gastrointestinal events. CONCLUSION: Cyclic intravenous administration of pamidronate is well-tolerated therapy in postmenopausal osteoporosis, and increases spinal BMD. Randomized controlled studies with adequate number of patients are needed to test the efficacy of the compound in the treatment of glucocorticoid-induced osteoporosis.

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OBJECTIVE: We measured markers of acute-phase response and immunological markers in morbid obese patients and in formerly morbid obese patients after a massive weight loss following adjustable gastric banding (GB). SUBJECTS: A total of 49 morbid obese female patients with a body mass index (BMI) above 40 kg/m(2) were investigated during a study period of 6 months. Of these, 24 patients received a gastric banding (GB) and lost a minimum of 20 kg in 1 y (GB group) and 25 patients maintained their weight (obese group). In sum, 13 normal weight subjects (BMI<24 kg/m(2)) were taken for controls. METHOD: Plasma concentration of the acute-phase proteins, C-reactive protein (CRP), orosomucoid, complement factors C3 and C4 and white blood cell count, lymphocyte subsets and serum immunoglobulins were analyzed. RESULTS: Acute-phase proteins were significantly lower in GB compared to morbid obese patients and remained significantly elevated in GB compared to controls. In addition, leukocytes, polymorphonuclear leukocytes and lymphocytes were significantly lower after GB and reached levels comparable to controls (except PMN). No difference in CD3 counts was observed in the three groups. CD4 increased and CD8 decreased in obese and GB patients when compared to controls whereas no statistical difference was found between obese and GB patients. CONCLUSION: Our results confirm the positive effect of GB followed by a massive weight loss without apparent malnutrition. Subclinical chronical inflammation in morbid obese patients leads to irregularities in leukocyte and lymphocyte subsets. These alterations can be positively influenced by GB.

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The aim of this study was to investigate the interaction of monocytes of the peripheral blood of patients with psoriatic arthritis with cultured human dermal microvascular endothelial cells (HDMEC) compared to monocytes from control persons. The surface expression of adhesion molecules (ADM) and other cell surface molecules in psoriatic arthritis and control monocytes was investigated by quantitative flow cytometry. The receptor densities of these molecules were determined in terms of monoclonal antibody (mAb) binding sites. Cocultivation experiments including peripheral blood mononuclear cells and HDMEC were performed to determine the adhesion to and transmigration through activated or resting endothelial cell monolayers. In order to achieve optimal responses of cellular functions, activation for adhesion experiments was induced by lipopolysaccharide (LPS), while in transmigration experiments the endothelial cells were activated by TNF-alpha. For transendothelial migration studies HDMEC cultivated on collagen gels were used. In the supernatants of cocultivated cells the cytokines IL-6 and IL-8 were determined by ELISA. A significantly reduced expression of CD11b in nonactivated psoriatic arthritis peripheral blood monocytes compared to control monocytes was verified (mean number of adhesion molecules/cell: 33,756 +/- 10,138 vs 61,023 +/- 6925). In agreement with these findings, adhesion to, as well as transendothelial migration through, activated HDMEC was found to be significantly reduced in psoriatic arthritis monocytes. Transendothelial migration engendered an enrichment of monocytes in the migrated cell fraction for both control and psoriatic arthritis peripheral blood mononuclear cells. The activation of HDMEC by LPS induced a highly significantly enhanced cytokine release for IL-6 and IL-8, irrespective of the origin of monocytes (psoriatic arthritis vs. controls). However, IL-8 production in the supernatants of nonactivated monocytes/HDMEC cocultures was significantly reduced in the case of monocytes from psoriatic arthritis patients (6650 +/- 2489.32 pg/ml) vs 9280.00 +/- 3209.51 pg/ml in control patients. Impaired adhesion as well as transendothelial migration of monocytes derived from peripheral blood of psoriatic arthritis patients can be explained by the reduced expression of adhesion molecules MAC-1 (CD11b/CD18) at the surface of monocytes. The reduced IL-8 production also corresponds to a diminished cellular interaction under nonflow conditions. These results support the view that there are systemic immunological alterations in psoriatic arthritis patients.

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CD44 is a widely expressed cell surface glycoprotein which is involved in many cell-cell and cell-matrix interactions. Expression of soluble CD44 splice variants is strictly regulated and is linked to a high rate of cell division. Serum levels of soluble CD44 variant 5 (sCD44v5) were determined in 14 patients with erosive RA. Patients were divided into two groups. In group 1 cyclosporin A treatment (CYA) was initiated after the first visit. In group 2 preliminary CYA was continued. Controls were performed after 6 months. We found a significant decrease of swollen joint count (SJC) and sCD44v5 in group 1. No effect of CYA was found on c-reactive protein, erythrocyte sedimentation rate and IgM-rheumatoid factor (IgM-RF). In group 2 a significant decrease of CRP was found. Therefore we conclude that measurement of sCD44v5 might be useful in monitoring RA+ patients with CYA.

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We determined the prognostic value of IgA rheumatoid factor in patients with rheumatoid arthritis. The results show clearly that only patients with high titers of IgARF during their course had an unfavorable prognosis determined by functional status and mortality.

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Inflammatory joint disease is mainly diagnosed on grounds of clinical investigation, laboratory testing (acute phase reactants), and radiography. Radionuclide imaging has recently been added to the armamentarium of clinician. This case report points out the role of three-phase bone scan and HIG (human immunoglobulin) scan in the discovery of the inflammatory nature of polyarthralgia in a young woman with equivocal clinical and laboratory results. In the aim of diagnosing arthritis early in its course scintigraphy proved to be superior to conventional radiography. It also allows more discriminating selection of subsequent X-ray examination to limit radiation exposure.

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It was the aim of this study to evaluate different markers of inflammation such as 99mTc-labelled human immunoglobulin G and 99mTc-nanocolloid with respect to their ability to detect inflammatory or degenerative affections of small joints of hand and fingers. While conventional bone scanning reveals good agreement with clinical findings it is not well suited for screening of inflammatory processes due to its poor specificity. In small joints conventional three-phase bone scan with information of perfusion, bloodpool and accumulation is not suitable due to the small ROI, low count rate with high statistics. Therefore we used inflammatory markers to overcome this problem. Immunoglobulin G was true positive in case of inflammatory lesions in 69%, and false positive in case of degenerative lesions in 24%, while nanocolloid was true positive in 72% and false positive in 14%, respectively. Significant differences were found between markers of inflammation and the bone scanning agent while both inflammatory markers, immunoglobulin G and nanocolloid demonstrated significant correlation. While bone scanning tracers detect all kinds of joint affections, immunoglobulin G and nanocolloid accumulate preferentially in inflammatory joints and therefore might be useful to differentiate between inflammatory and degenerative lesions.

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OBJECTIVE: To assess differences in soluble tumor necrosis factor receptor 55 (sTNF-R55), sTNF-R75, and soluble interleukin 2 receptor (sIL-2R) in synovial fluid (SF) of patients with psoriatic arthritis (PsA), a seronegative inflammatory joint disease, in comparison with those of patients with rheumatoid arthiritis (RA) and osteoarthritis (OA). METHODS: sIL-R were measured in SF with commercial sandwich ELISA and the results correlated with serological and clinical disease activity variables. RESULTS: In PsA SF the level of sTNF-R55 was 11.8 +/- 0.8 ng/ml and that of sTNF-R75 13.0 +/- 1.3 ng/ml. sIL-2R concentration in PsA SF was 800 +/- 84 U/ml. Compared to PsA SF, cytokine receptor levels in OA SF were significantly lower: 8.7 +/- 0.8 ng/ml for sTNF-R55 (p < 0.02); 7.1 +/- 0.9 ng/ml for sTNF-R75 (p < 0.0003); and 505 +/- 53 U/ml for sIL-2R (p < 0.009). In contrast RA SF cytokine receptor levels were even higher than those of PsA SF (sTNF-R55: 18.1 +/- 2.0 ng/ml, p < 0.04; sTNF-R75: 29.5 +/- 2.9 ng/ml, p < 0.0002; and for sIL-2R: 1957 +/- 290 U/ml, p < 0.03). CONCLUSION: In PsA SF sTNF-R55, sTNF-R75, and sIL-2R are upregulated compared to OA SF but are lower than in RA SF. Our results for TNF-R agree with recent findings in PsA, since TNF-alpha, an important stimulator for TNF-R, is also significantly lower in PsA than in RA. The upregulation of the cytokine receptors in PsA reconfirms its inflammatory nature, but indicates the more benign course of disease compared with RA.

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OBJECTIVE: The aim of this study was to investigate the concentrations of T cell derived cytokines in the synovial fluids (SFs) of patients with psoriatic arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Th1 type cytokines (interleukin 2 (IL2), tumour necrosis factor beta (TNF beta), and interferon gamma (INF gamma) and Th2 type cytokines (IL4, IL10) were measured by means of enzyme linked immunosorbent assays. RESULTS: IL2 was usually not detectable in any of the disease groups. TNF beta was found in 3 of 31 PsA SFs (mean (SEM) 11.1 (2.3) pg/ml) and in a significantly lower concentration than in 20 of the 40 RA SFs (42.2 (15.6) pg/ml; p < 0.002). INF gamma was measurable in 2 of 10 PsA and 6 of 16 RA SFs (p > 0.05). IL4 was present at low concentrations in 4 of 22 PsA SFs (0.41 (0.8) pg/ml), and in 15 of 20 RA SFs (0.63 (0.09) pg/ml; p < 0.01). IL10 was found in 4 of 27 PsA SFs (12.3 (0.9) pg/ml) and in 27 of 32 RA SFs (37.3 (4.9) pg/ml; p < 0.0001). In all OA SFs cytokine concentrations were below the limit of detection. CONCLUSION: The pattern of T cell derived cytokines in PsA SFs was similar to that of RA SFs. However, both the frequency and the concentrations of cytokines were lower in PsA SFs than in RA SFs, while OA SFs generally lacked any detectable T cell cytokines altogether. The presence of Th1 and Th2 cell derived cytokines in PsA SFs suggests the presence of activated T cells in the inflamed joint tissues and their participation in the immunoinflammatory events.

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Psoriatic arthritis (PA) is an inflammatory rheumatic disease that can concomitantly occur in patients with psoriasis vulgaris. Psoriatic synovitis shows alterations of the synovial microvasculature. Inflammatory cells adhere to endothelial cells (EC) and migrate through the vascular wall of postcapillary venules located in the subintimal layer of the synovial membrane. The aim of our study was to investigate, first, the phenotype of lymphocytes (LC) of PA patients using flow cytometry (FC) with regard to activation antigens and adhesion molecules; second, the adhesion of LC of PA patients on cultivated resting or activated (with thrombin, LPS, IFN-gamma, or TNF-alpha) human umbilical vein endothelial cells (HUVEC) by counting the Feulgen-stained nuclei of both adherent LC and HUVEC using image analysis; and third, the synthesis of IL-6 and IL-8 in both LC and HUVEC 24 hr after cell contact. These cytokines were determined qualitatively by immunofluorescence and quantitatively at the single-cell level by FC as well as in the supernatants of the cultures using commercial cytokine ELISAs. Fourth, we investigated whether or not the LC adhesion on HUVEC as well as the cytokine production could be inhibited by monoclonal antibodies against LC- or EC-specific adhesion molecules. In contrast to controls PA patients showed an increased surface expression of CD11a, b, and c as well as of CD44 but a reduced surface expression of CD49d/CD29, and CD49e/CD29, and cell-bound fibronectin on CD3+ LC. The activation markers CD25 and HLA-DR were found to be slightly enhanced in PA. The cell adhesion was generally enhanced in PA patients vs controls. It could be reduced with monoclonal antibodies (MoAbs) against CD11a and CD18 on IFN-gamma- or TNF-alpha-activated HUVEC but was generally enhanced after treatment of HUVEC with MoAbs against CD54, CD62E, or CD106. Due to LC adhesion on HUVEC IL-6 and IL-8 were produced in significantly higher amounts in PA patients compared to controls. This effect occurred already in resting but was enhanced in activated HUVEC. While IL-6 is mainly produced by HUVEC but also in smaller quantities by LC, IL-8 is synthesized only by HUVEC and could be modified by preincubation with MoAbs against LC- or EC-specific adhesion molecules in parallel to the cell adhesion. The experiments show that the main adhesion pathway in LC homing of PA patients is the interaction of the LC adhesion molecule CD11a/CD18 with CD54 on EC followed by an enhanced synthesis of proinflammatory and chemotactic cytokines. These results favor the hypothesis that the pathological alterations of the microvasculature in PA patients are generated by altered homing processes.

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