| 51. |
- Dahlberg, L., et al.
(författare)
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A longitudinal study of cartilage matrix metabolism in patients with cruciate ligament rupture-synovial fluid concentrations of aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinase-1
- 1994
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Ingår i: British Journal of Rheumatology. - : Oxford University Press (OUP). - 0263-7103. ; 33:12, s. 1107-1111
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Tidskriftsartikel (refereegranskat)abstract
- This is the first study which quantifies aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinases-1 (TIMP-1) in SF samples prospectively obtained from the same patient at different time intervals after a cruciate ligament injury of the knee. Aggrecan fragment concentrations were determined by dye precipitation with Alcian Blue. Stromelysin-1 and TIMP-1 were analysed by immunoassay. Ten healthy volunteers formed the reference group. Immediately after knee injury, all marker concentrations were higher as compared to the reference group. The high marker concentrations decreased gradually with time, and in samples obtained between 6 months and 6 years after the injury, median concentrations of some of the markers were not different compared to reference levels. This was in contrast to results from previous cross-sectional studies, where chronic phase median concentrations of all markers were consistently higher than reference levels. In previous cross-sectional studies, however, the samples were obtained at arthroscopy done because of knee complaints at different times after a knee injury. In the present study, the knee injured patients visited the orthopaedic outpatient ward only for SF sampling, and they had no or only minor knee symptoms. We conclude that the temporal changes of marker concentrations in joint fluid after knee injury, suggested from cross-sectional studies, have now been confirmed in a longitudinal, prospective cohort study. We further find that in patients with mild knee symptoms in the chronic phase after cruciate ligament injury, median SF levels of aggrecan fragments, stromelysin-1, and TIMP-1 are lower than in patients with significant knee complaints after the same type of injury. This suggests a possible relationship between joint fluid marker concentrations, joint pathology, and cartilage metabolism.
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| 52. |
- Dahlqvist, Johanna, 1979-, et al.
(författare)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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Ingår i: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Tidskriftsartikel (refereegranskat)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 53. |
- Dahlqvist, Solbritt Rantapää, et al.
(författare)
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Acetylator phenotypes in primary Sjögren's syndrome
- 1994
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Ingår i: British Journal of Rheumatology. - : Oxford University Press (OUP). - 0263-7103 .- 1460-2172. ; 33:4, s. 405-406
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Tidskriftsartikel (refereegranskat)
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| 54. |
- Dahlqvist, Solbritt Rantapää, et al.
(författare)
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Cell-cycle effects of the antirheumatic agent cph82
- 1994
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Ingår i: British Journal of Rheumatology. - : Oxford University Press (OUP). - 0263-7103 .- 1460-2172. ; 33:4, s. 327-331
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Tidskriftsartikel (refereegranskat)abstract
- The benzylidated podophyllotoxin glycoside CPH82, a potentially useful drug for treatment of RA, was tested in vitro on nine human haematopoietic cell lines for cell kinetic effects. Previous studies have shown CPH82 to behave like a colchinetype ‘metaphase’ blocker.The distribution of cells within different cell cycle compartments (G1, S, G2 and M) was analysed by a novel method using dual parameter flow cytometric analysis of stage specific antigens (proliferating cell nuclear antigen and Ki-67). With CPH82 concentrations chosen to mimic clinical conditions, eight out of nine lines showed an accumulation of cells in the G2 phase of the cell cycle. In many lines a delayed progress through S seemed to occur. Three lines were blocked in both G1 and G2, whereas the major effect on one line (HL-60) was an accumulation of cells in the G1 phase. Progression of M cells seemed only slightly delayed for some cell lines. In comparison with two related ‘metaphase’ blocking agents (podophyllotoxin and taxol), CPH82 had a different and dose-dependent pattern of cell cycle retardation. It is speculated that the cell kinetic action of CPH82 might give insight into the question why it, unlike other ‘metaphase’ blockers, has proved valuable in the treatment of RA.
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| 55. |
- Dahlqvist, Solbritt Rantapää, et al.
(författare)
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The effect of cph-82 on the growth of human-lymphocytes in vitro : definition of cytobiological action
- 1989
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Ingår i: British Journal of Rheumatology. - : Oxford University Press (OUP). - 0263-7103 .- 1460-2172. ; 28:5, s. 418-421
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Tidskriftsartikel (refereegranskat)abstract
- A drug composed of two semisynthetic podophyltine derivatives, CPH 82, has recently been launched for the treatment of severe rheumatoid arthritis. The present in vitro study of PHA-stimulated human T-lymphocytes showed that CPH 82 arrested cell division in a metaphase-like configuration. The cell cycle effects of CPH 82 were indistinguishable from the cell cycle effects of the classical microtubule depolymerizers, Colcemid (a colchicine derivative) and podophyllotoxin. A CPH 82 concentration of 1 (µg/ml, which is close to therapeutic serum concentrations, had an almost maximal effect on cell division. It is suggested that at least part of the anti-inflammatory effect of CPH 82 is due to a colchicine-like activity on, for example, proliferating lymphocytes.
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| 56. |
- de Rooy, Diederik P C, et al.
(författare)
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Loss of metacarpal bone density predicts RA development in recent-onset arthritis
- 2012
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Ingår i: Rheumatology. - : Oxford University Press (OUP): Policy B. - 1462-0324 .- 1462-0332. ; 51:6, s. 1037-1041
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Serum samples taken before the onset of RA suggest that one of the first features of RA is BMD loss. We determined the ability of radiographic BMD loss to predict RA development and arthritis persistency in patients with early undifferentiated arthritis (UA). less thanbrgreater than less thanbrgreater thanMethods. Five hundred and seventeen patients with early UA, included in the Leiden Early Arthritis Clinic, were assessed. Of these, 101 had hand radiographs made at first visit as well as after 6 months. BMD loss was measured using digital X-ray radiogrammetry (DXR) online. The outcome measures fulfilled the 1987 ACR criteria for RA after 1 year and arthritis persistency during a mean follow-up of 7 years. Additionally, it was assessed whether BMD measurements improved predictions compared with a validated prediction rule. less thanbrgreater than less thanbrgreater thanResults. A total of 53.8% of UA patients developed RA and 67.5% had persistent disease after 7 years follow-up. Highly elevated BMD loss (epsilon 2.5 mg/cm(2)/month) was present in 16.3% of patients and associated with RA development [odds ratio (OR) 6.1, 95% CI 1.2, 29.2, positive predictive value (PPV) 85%, negative predictive value (NPV) 52%, sensitivity 26%, specificity 95%]. BMD loss may have an independent effect of anti-CCP when tested in a logistic regression analysis (OR 4.1, 95% CI 0.8, 21.2), although the CI is large. All UA patients that were unclassified with the prediction rule and had highly elevated BMD loss progressed to RA. BMD loss was not significantly associated with arthritis persistency (HR = 0.56, 95% CI 0.14, 2.29). less thanbrgreater than less thanbrgreater thanConclusion. Present data suggest that BMD loss predicts RA development. These findings need to be verified in larger studies.
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| 57. |
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| 58. |
- Deminger, Anna, 1973, et al.
(författare)
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Elevated serum level of hepatocyte growth factor predicts development of new syndesmophytes in men with ankylosing spondylitis
- 2021
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 60:4, s. 1804-1813
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study baseline serum hepatocyte growth factor (s-HGF) as a predictor of spinal radiographic progression overall and by sex and to analyse factors correlated to changes in s-HGF in patients with AS. METHODS: At baseline and the 5-year follow-up, s-HGF was analysed with ELISA. Spinal radiographs were graded according to modified Stoke Ankylosing Spondylitis Spinal Score. Radiographic progression was defined as ≥2 modified Stoke Ankylosing Spondylitis Spinal Score units/5 years or development of ≥1 syndesmophyte. Logistic regression analyses were used. RESULTS: Of 204 baseline participants, 163 (80%) completed all examinations at the 5-year follow-up (54% men). Baseline s-HGF was significantly higher in men who developed ≥1 syndesmophyte compared with non-progressors, median (interquartile range) baseline s-HGF 1551 (1449-1898) vs 1436 (1200-1569) pg/ml, P = 0.003. The calculated optimal cut-off point for baseline s-HGF ≥1520 pg/ml showed a sensitivity of 70%, a specificity of 69% and univariate odds radio (95% CI) of 5.25 (1.69, 14.10) as predictor of development of ≥1 new syndesmophyte in men. Baseline s-HGF ≥1520 pg/ml remained significantly associated with development of ≥1 new syndesmophyte in men in an analysis adjusted for the baseline variables age, smoking, presence of syndesmophytes and CRP, odds radio 3.97 (1.36, 11.60). In women, no association with HGF and radiographic progression was found. Changes in s-HGF were positively correlated with changes in ESR and CRP. CONCLUSION: In this prospective cohort study elevated s-HGF was shown to be associated with development of new syndesmophytes in men with AS.
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| 59. |
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| 60. |
- Di Giuseppe, D., et al.
(författare)
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Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden
- 2021
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:9, s. 3596-3605
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch. Methods Patients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab or rituximab were identified in the national Swedish Rheumatology Quality Register. Moreover, patients switching from an originator to its biosimilar were identified and individually matched to patients continuing on the originator. One-year treatment retention was calculated and hazard ratios (HR) for discontinuation with 95% CIs were estimated, adjusting for comorbidities and socio-economic factors. Results In total, 21 443 first treatment courses were identified. The proportion of patients still on the drug at 1 year and the HR for discontinuation revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on the drug at 1 year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared with Enbrel was 0.91 (95% CI 0.83, 0.99). For infliximab, the proportion still on the drug at 1 year was 67% for Remicade and 66% for Remsima/Inflectra and the HR compared with Remicade was 1.16 (95% CI 1.02, 1.33). Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared with those who remained on originator therapy. Conclusion This large observational study supports the equivalence of biologic DMARD biosimilar products and originators when used in routine rheumatology care.
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