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Biomedical subjects

T Saxne

Publications and source records attributed to T Saxne.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lower disease activity and disability in Swedish patients with rheumatoid arthritis in 1995 compared with 1978.

The aim of this study was to evaluate differences in disease activity, disability, and medical treatment in consecutive patients with rheumatoid arthritis seen at the outpatient clinics in Malmö, in 1978 (n = 148) and 1995 (n = 164). The groups were similar with regard to age, gender, disease duration, and the proportion having had hip or knee replacement surgery. The patients in 1995 had lower values for CRP (p<0.001), Ritchie Articular Index (mean values: 5.5 vs. 9.9, p<0.001), and Steinbrocker functional class index (mean values: 1.96 vs. 2.16, p<0.001) than the 1978 group. The 1995 patient group was also more extensively treated with DMARD:s (68 vs. 51%, p<0.01) and glucocorticosteroids (23 vs. 12%, p<0.02) and had historically been treated with almost twice as many DMARD:s (2.7 vs. 1.5, p<0.001). Similar findings regarding disease activity and disability were made when restricting the analysis to subgroups of patients that were seropositive or had a shorter disease duration (< 5 yrs). The lower disease severity in the 1995 group may be secondary to a more active medical treatment, although other possibilities such as differences in selection and secular changes in disease severity unrelated to medication cannot be excluded.

Adult↗
PubMed1998

Increased serum levels of cartilage oligomeric matrix protein in chronic erosive arthritis in rats.

OBJECTIVE: To investigate the utility of serum cartilage oligomeric matrix protein (COMP) for disease monitoring in rats with chronic pristane-induced arthritis, and to examine the influence of age, sex, and genes on COMP concentrations in rat serum. METHODS: Serum COMP levels were quantified by immunoassay. Sera were obtained from DA, E3, and (E3 x DA)F1 rats each week between the ages of 4 and 30 weeks. The (E3 x DA)F2 (second generation after intercrossing) rats were injected intradermally with the synthetic oil pristane. Arthritis was monitored by a macroscopic scoring system, and serum levels of COMP were measured on days 6, 35, and 49 after immunization. RESULTS: Serum levels of COMP decreased during growth, and reached a plateau after the age of 12 weeks. The DA rats had higher COMP levels than the E3 rats, and the (E3 x DA)F1 rats had intermediate levels. No differences were observed in these levels when the rats were grouped by sex. Arthritic (E3 x DA)F2 rats had increased serum concentrations of COMP on days 35 and 49 after pristane injection (P < 0.0001 versus the nonarthritic animals). COMP levels correlated with the severity of macroscopically detectable arthritis at both time points (r > 0.9). Rats with a chronic disease course were distinguished by higher serum concentrations of COMP during the acute stage than animals with similar clinical scores but with resolving arthritis (P < 0.01). CONCLUSION: Serum analyses of COMP offer promise for monitoring tissue involvement in experimental arthritis. Such analyses should be useful for monitoring therapeutic interventions aimed at retarding tissue destruction as well as for studies of the genetically determined regulation of COMP turnover and susceptibility to arthritis. The application of molecular marker measurements to experimental arthritis offers a new possibility for verifying the utility of such measurements in human arthritis.

Animals↗
PubMed1998

Genetic control of arthritis onset, severity and chronicity in a model for rheumatoid arthritis in rats.

Rheumatoid arthritis (RA) is a chronic and genetically complex inflammatory disorder that leads to erosive destruction of peripheral joints. The use of animal models mimicking RA, such as pristane-induced arthritis (PIA) in rats, should facilitate its genetic analysis. Pristane is a non-immunogenic synthetic oil that, after a single subcutaneous injection into DA rats, induces arthritis restricted to peripheral joints with a chronic relapsing disease course. To identify genes involved in the control of chronic arthritis, we made crosses between susceptible DA rats and resistant E3 rats and analysed the progeny with microsatellite markers covering the entire rat genome. Our results show that different arthritis phenotypes are associated with different chromosomal loci. Loci on chromosomes 4 and 6 (Pia2 and Pia3) influence arthritis onset, whereas a locus on chromosome 12 (Pia4) is associated with severity and joint erosion. We found that chronicity is associated with a different set of loci, one on chromosome 4 and the other on chromosome 14 (Pia5, Pia6). These findings demonstrate for the first time that different phases of a chronic self-perpetuative disease which mimics RA are associated with distinct sets of genes.

Animals↗
PubMed1998

Bone scan and serum markers of bone and cartilage in patients with knee pain and osteoarthritis.

OBJECTIVE: To study the relations between knee joint abnormalities, reflected by bone scintigraphy and serum concentrations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP). DESIGN: In a group of 38 individuals aged 37-54 years with chronic knee pain for more than four years, both knees were investigated with bone scan. The bone scans were graded for the extent of abnormalities. Radiographs of both knees were graded for tibiofemoral and patellofemoral osteoarthritis (OA). Serum levels of COMP and BSP were measured by immunoassays. RESULTS: Bone scan abnormalities were detected in 26/38 individuals and radiographic OA in 23/38 individuals. The serum concentrations of COMP and BSP were significantly higher in the individuals with bone scan abnormalities (P = 0.02 and P = 0.004, respectively). In addition, the serum levels of COMP correlated positively with the extent of bone scan abnormalities (N = 38), r = 0.56, P = 0.002. Serum BSP did not correlate to the extent of scan abnormalities. CONCLUSIONS: In individuals with knee pain, serum levels of COMP and BSP differ between those with or without bone scan abnormalities in the knee joints. This suggests that measurements of the serum levels of these markers have potential as means for evaluation of tissue changes in individuals with long standing knee pain in relation to early stages of OA.

Adult↗
PubMed1998

Joint-space width in the axial view of the patello-femoral joint. Definitions and comparison with MR imaging.

PURPOSE: To validate a bony landmark on the dorsal aspect of the patella for measurement of the interbone distance in the axial radiogram of the patello-femoral joint (PFJ); to assess the reproducibility of this radiogram and the minimal joint-space (MJS) width measurements in the medial and lateral compartments of the PFJ in this view; and to relate the MJS of the PFJ to MR-detected cartilage defects in the same joint. MATERIAL AND METHODS: Fifty-seven individuals with chronic knee pain (aged 41-58 years, mean 50 years) were examined with an axial view of the PFJ in the standing position. The MJS was measured with a mm-graded ruler. On the same day, an MR examination was performed with proton density- and T2-weighted turbo spin-echo sequences on a 1.0 T imager. We noted the cartilage defects in the PFJ in axial and sagittal MR images, and the shape of the subchondral cortex of the medial and lateral articular surfaces of the patella in sagittal MR images. RESULTS AND CONCLUSION: The bony landmark was found on all articular surfaces. The axial view of the PFJ and the MJS measurements were reproducible. An MJS of <5 mm showed high specificity for MR-detected cartilage defects. Thus an MJS of 5 mm proved to be a limit in the diagnosis of joint-space narrowing in the PFJ in middle-aged individuals with chronic knee pain.

Adult↗
PubMed1998

Changes in cartilage and bone metabolism identified by serum markers in early osteoarthritis of the knee joint.

Serum concentrations of two extracellular matrix molecules were determined over a 3 yr period in individuals with chronic knee pain to investigate whether sequential serum measurements of cartilage- and bone-derived molecular fragments reflect early stages of osteoarthritis (OA) of the knee joints. Thirty-eight individuals with chronic knee pain (> 3 months at inclusion) with or without radiographic evidence of knee joint OA at the 3 yr follow-up radiographic examination were studied. Serum concentrations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) increased significantly (P < 0.001) in the 23 individuals with radiographic OA at follow-up, while remaining unchanged in the 15 individuals with normal radiographs at follow-up. The baseline concentrations of the two variables did not differ between the groups. These findings suggest that pathological processes in cartilage and subchondral bone coincide in OA, and appear to be reflected by circulating levels of macromolecules released from cartilage and bone. Changes in serum levels of COMP and BSP are potential tools in studies of knee joint OA in subjects with chronic knee pain.

Adult↗
PubMed1998

Serum concentrations of cartilage oligomeric matrix protein and bone sialoprotein in hip osteoarthritis: a one year prospective study.

OBJECTIVE: To evaluate serum concentrations of cartilage oligomeic matrix protein (COMP) and bone sialoprotein (BSP) as predictors of disease progression in hip osteoarthrtitis (OA). METHODS: Forty eight consecutive patients, referred to hospital for symptomatic hip OA, (ACR criteria) were monitored in a one year prospective trial with radiographs and serum samples. The radiographs were graded for joint space narrowing, osteophytes, and sclerosis and the joint space width was measured by a digitised image analyser. Serum COMP and BSP were quantified by immunoassays. RESULTS: The COMP concentrations at baseline correlated with the joint space width at entry and with its yearly mean narrowing (r = 0.38, p = 0.002) but not with joint space narrowing grade progression. The concentrations were higher in patients with bilateral hip OA (p = 0.03). The serum BSP concentrations at baseline were unrelated to OA progression but correlated inversely to the osteophyte grade (r = -0.36, p = 0.004) and sclerosis grade (r = -0.42, p = 0.0004). CONCLUSION: Serum COMP seems to be a surrogate marker of OA and may be of interest for the detection of patients at risk of rapidly progressing disease in hip OA. Serum BSP changes seem to reflect alterations in the subchondral bone turnover in hip OA. Measurement of joint space width using a digitised image analyser is a sensitive way of assessing OA progression that facilitates evaluation of tissue markers in relation to anatomical changes in the joint.

Adult↗
PubMed1997

Postero-anterior radiogram of the knee in weight-bearing and semiflexion. Comparison with MR imaging.

PURPOSE: The purpose was four-fold: to assess the reproducibility of p.a. weight-bearing radiograms of the knee and the minimal joint-space (MJS) width measurements in these radiograms; to compare the MJS with MR-detected cartilage defects; to evaluate the location of these cartilage defects; and to estimate the relation between meniscal abnormalities and joint-space narrowing. MATERIAL AND METHODS: Fifty-nine individuals, aged 41-58 years (mean 50), with chronic knee pain were examined by means of p.a. weight-bearing radiograms in semiflexion with fluoroscopic guidance of the knee joint. The MJS was measured with a standard ruler. On the same day MR imaging was performed with proton-density- and T2-weighted turbo spin-echo on a 1.0 T imager. Meniscal abnormalities and cartilage defects in the tibiofemoral joint (TFJ) were noted. RESULTS AND CONCLUSION: The p.a. view of the knee and the MJS measurements were reproducible. MJS of 3 mm is a limit in diagnosing joint-space narrowing in knees with MR-detected cartilage defects. There was a high proportion (p < 0.001) of meniscal abnormality within the narrowed compartments in comparison with those that were not narrowed. A larger number of the cartilage defects (p < 0.05) was found in the medial femoral condyle than in any of the other condyles of the TFJ. The defects had a dorsal location (p < 0.001) as shown in the weight-bearing radiograms of the knee in semiflexion.

Adult↗
PubMed1997

Tissue-derived macromolecules and markers of inflammation in serum in early rheumatoid arthritis: relationship to development of joint destruction in hands and feet.

We have previously shown that serum concentrations of cartilage oligomeric matrix protein (COMP) are increased early in rheumatoid arthritis (RA) patients who subsequently develop advanced large-joint destruction. A prognostic value for joint damage of serum concentrations of hyaluronan (HA) is also suggested by previous studies. In contrast, serum concentrations of bone sialoprotein (BSP) have not been useful for identifying patients with progressive large-joint destruction. In the present study, we have examined the hypothesis that serum concentrations of these tissue-derived markers are of prognostic value in RA for the development of radiographically detectable joint damage in hands and feet. Serum concentrations of COMP, HA and BSP were quantified in samples obtained from 62 patients within the first year after onset of RA and were related to the development of radiographically detectable damage in these joints after 5 yr. Neither the serum concentrations of COMP nor of BSP at inclusion predicted joint damage in hands and feet after 5 yr, and the concentration of these proteins did not change over the 5 yr period. However, the serum concentration of HA at inclusion correlated with the radiographic score at the 5 yr follow-up (r = 0.425, P < 0.01), but was not a better predictor in this respect than the erythrocyte sedimentation rate or C-reactive protein levels at inclusion. Thus, serum concentrations of the three studied tissue-derived macromolecules were in this study not useful for identifying patients prone to small-joint destruction.

Adult↗
PubMed1997

Increased serum levels of cartilage oligomeric matrix protein and bone sialoprotein in rats with collagen arthritis.

The aim of this study was to investigate whether serum levels of cartilage and bone macromolecules can be used to monitor tissue destruction in experimental arthritis in rats. Serum levels of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) were measured by novel immunoassays in the chronic and destructive arthritis induced in DA rats after immunization with autologous rat native collagen type II in Freund's incomplete adjuvant. Increased serum levels of COMP and BSP were seen on day 21 after immunization, and even higher levels were observed on day 28 at termination of the experiment, paralleling increases in the clinical joint score and histopathological signs of cartilage and bone erosions. Serum analyses of these markers may be a useful non-invasive way of monitoring tissue involvement in experimental arthritis and possibly the effects of therapeutic interventions aimed at retarding tissue destruction.

Animals↗
PubMed1997

HLA DRB1* typing and cartilage oligomeric matrix protein (COMP) as predictors of joint destruction in recent-onset rheumatoid arthritis.

The carriage of a characteristic sequence of amino acids at position 67-72 in the third hypervariable region of the HLA DRB1 chain has been linked to susceptibility to rheumatoid arthritis (RA). Whether this epitope is also a predictor of more severe disease remains controversial. Cartilage oligomeric matrix protein (COMP) is a protein, the serum levels of which have been found to correlate with large joint destructive disease in previous work. In this paper, we compare DRB1* typing and serum COMP levels in a prospectively observed group of RA patients with or without early hip joint destruction. The COMP levels at study inclusion, median 11 months from onset of symptoms, were significantly higher in the patients with early hip joint destruction compared to the patients in the more benign group. There was no difference in the number of disease susceptibility-related epitopes between the groups. DRB1*04, in contrast, was found among 8/8 patients with hip destruction, but also in 5/8 more benign cases. We conclude that in this type of RA patient, COMP serum levels are more informative predictors of aggressive disease than HLA DRB1* typing.

Alleles↗
PubMed1997

Cartilage matrix macromolecules in lavage fluid of temporomandibular joints before and 6 months after diskectomy.

The purpose was to investigate if antigenic fragments of aggrecan and cartilage oligomeric matrix protein (COMP) are detectable by enzyme-linked immunosorbent assay in lavage fluids from the temporomandibular joint (TMJ) and to examine if the relative content of these cartilage markers changes during development of osteoarthrosis (OA) after diskectomy. Lavage fluid was obtained at surgery and 6 months postoperatively in 13 patients. Computed tomography or magnetic resonance imaging was without evidence of hard-tissue changes prior to surgery in all patients. In 9 of the patients, sufficient material for analysis was obtained at both examinations. Aggrecan and COMP were detectable in all but 2 fluids, in which the COMP levels were below detection limit. The aggrecan/COMP ratio increased in all 9 patients during the 6-month period, indicating increased release of aggrecan relative to COMP fragments. The changed aggrecan/COMP ratio possibly reflects increased cartilage turnover during development of OA. Changes compatible with OA were present on computed tomography in all cases at the 6-month follow-up. This study shows that the lavage procedure is feasible for obtaining synovial fluid from the TMJ for immunochemical analyses of tissue-derived macromolecules.

Adolescent↗
PubMed1997

Cartilage markers in synovial fluid in symptomatic knee osteoarthritis.

OBJECTIVE: To investigate if the relative content of aggrecan and cartilage oligomeric matrix protein (COMP) in synovial fluid lavage samples differs between individuals with knee pain with or without evidence of radiological knee osteoarthritis (joint space narrowing). METHODS: In a community based cohort of 204 individuals aged 35-54 years with chronic (> 3 months duration) knee pain, a subgroup of 45 subjects with radiographic osteoarthritis, grade I according to the Ahlbäck classification, was randomly chosen; 45 individuals, age and sex matched from the same cohort with chronic knee pain but with normal radiographs, served as controls, Knee joint fluid was obtained by a standardised lavage procedure. The concentrations of aggrecan core protein epitopes and a cartilage matrix protein (COMP) were determined by immunoassays and the aggrecan/COMP concentration ratio was calculated. RESULTS: The aggrecan/COMP ratio was higher (P < 0.001) in the group with radiographic osteoarthritis than in the control group. CONCLUSIONS: The higher aggrecan/COMP ratios in osteoarthritis could reflect increased cartilage matrix turnover in osteoarthritis with predominant release of aggrecan fragments. Synovial fluid analysis of cartilage markers holds promise as a useful means of monitoring changes in the cartilage turnover in studies of pathogenic mechanisms in osteoarthritis.

Adult↗
PubMed1997

Cartilage macromolecules in knee joint synovial fluid. Markers of the disease course in patients with acute oligoarthritis.

OBJECTIVE: To investigate the development of chronic joint symptoms in patients presenting with acute oligoarthritis including knee joint synovitis with effusion and explore whether prognostic information can be derived from initial synovial fluid concentrations of aggrecan and cartilage oligomeric matrix protein (COMP) for development of chronic joint symptoms. METHODS: Retrospective follow up of 25 patients identified in a bank of knee joint synovial fluids collected consecutively from patients presenting with knee joint synovitis and symptoms from at most three additional joints and in whom no diagnosis could be established at presentation. RESULTS: The 10 patients who developed chronic joint symptoms were characterised by lower knee joint synovial fluid concentrations of aggrecan as well as lower aggrecan/COMP ratios (p < 0.001) than the 15 patients who had a transient arthritis. No other clinical or laboratory differences between the groups were apparent at the time of presentation. CONCLUSIONS: The synovial fluid content of aggrecan is a potential tool in acute arthritis for distinguishing patients with a benign disease course from those who will develop a chronic joint disorder.

Acute Disease↗
PubMed1997

Cartilage and bone macromolecules in knee joint synovial fluid in rheumatoid arthritis: relation to development of knee or hip joint destruction.

OBJECTIVE: To examine the hypothesis that aggrecan, cartilage oligomeric matrix protein (COMP), and bone sialoprotein (BSP) concentrations in synovial fluid could provide information on variations of progression of joint destruction in rheumatoid arthritis. METHODS: Aggrecan, COMP, and BSP were quantified by enzyme linked immunosorbent assays in longitudinally collected knee joint synovial fluid samples of patients rapidly developing destruction in knees or hips, the "'destructive" group, n = 18, and in patients slowly developing destruction, the "non-destructive" group, n = 25. RESULTS: The aggrecan concentrations decreased from initially high levels (P < < 0.001), and the BSP concentrations increased (P < < 0.001) over time in the destructive group, whereas levels of both markers were low and did not change in the non-destructive group. The COMP levels did not change in any of the groups. The aggrecan concentrations were initially highest in the group developing destructions (P < < 0.001), whereas no difference between the groups was found regarding levels of COMP or BSP in the first sample. CONCLUSIONS: A destructive group was characterised by higher initial aggrecan concentrations and rising BSP concentrations in synovial fluid with time. Quantification of cartilage and bone derived macromolecules contributes to the assessment of extent of tissue destruction and may help in the early identification of patients at risk of rapidly progressing destruction.

Adult↗
PubMed1997

Radiographic osteoarthritis of the knee classified by the Ahlbäck and Kellgren & Lawrence systems for the tibiofemoral joint in people aged 35-54 years with chronic knee pain.

OBJECTIVES: To determine the prevalence of tibiofemoral radiographic knee osteoarthritis (OA) in people aged 35-54 years associated with chronic (> 3 months) knee pain using two different radiographic grading systems. METHODS: Population based postal survey in a random sample of inhabitants in a district in southern Sweden followed by clinical examination and plain posteroanterior, weight bearing radiographical examination. The Ahlbäck criteria (focusing on joint space narrowing) and the Kellgren & Lawrence classification for knee OA were used for diagnosing tibiofemoral OA. RESULTS: A questionnaire was sent to 2000 randomly selected people aged 35-54 years. The response rate was 92.6%. Fifteen per cent of these people reported chronic knee pain. This group (n = 279) was offered a clinical and radiographic examination of the knee joint and 204 persons agreed to participate. According to the Kellgren & Lawrence classification 28 subjects had OA of the knee grade 2 or more and 16 grade 3 or more. Radiographically detected OA of the knee according to Ahlbäck was found in 20 cases. The minimum prevalence of radiological tibiofemoral knee OA with knee pain was thus 1.5% for Kellgren & Lawrence grade 2 or more, 0.9% for grade 3 or more, and 1.1% according to the Ahlbäck classification. The agreement between the Kellgren & Lawrence grades 2-3 versus Ahlbäck grade I as well as grade 3-4 versus Ahlbäck grade I-II was good (kappa 0.76 and 0.78 respectively). CONCLUSION: The prevalence of radiographic tibiofemoral OA combined with chronic knee pain in people aged 35-54 years was around 1% as estimated by either the Kellgren & Lawrence or the Ahlbäck classifications systems. Prospective follow up of this cohort should elucidate the significance of knee pain as a sign of developing OA.

Adult↗
PubMed1996

Increased concentrations of bone sialoprotein in joint fluid after knee injury.

OBJECTIVE: To detect evidence for localised changes in bone matrix metabolism after joint trauma and in post-traumatic osteoarthritis by quantification of bone sialoprotein in joint fluid and serum after knee injury in a cross sectional study. METHODS: Samples of knee joint fluid and serum were obtained from volunteers with normal knees (n = 19), patients with rupture of the anterior cruciate ligament isolated or combined with tear of a meniscus (n = 114), and patients with isolated meniscus lesions (n = 80). Concentrations of bone sialoprotein were determined by ELISA. Concentrations of other markers of joint tissue metabolism in these samples were determined in previous investigations. RESULTS: The median concentrations of bone sialoprotein in joint fluid from healthy volunteers was 122 ng ml-1 (range 41 to 183). Concentrations of bone sialoprotein were increased in both injury groups compared with the reference group (median for cruciate ligament injury 146 ng ml-1, range 72 to 339; median for meniscus injury 166 ng ml-1, range 75 to 376). After injury, bone sialoprotein increased quickly and remained increased for six months. Bone sialoprotein in joint fluid was increased only in samples from joints with normal or nearly normal (fibrillated) cartilage, and was within reference range in joints with radiographic signs of osteoarthritis. Bone sialoprotein concentrations in joints with cruciate ligament injury were positively correlated with levels of aggrecan and cartilage oligomeric matrix protein fragments, and with levels of stromelysin-1 and tissue inhibitor of metalloproteinase-1. The ratios between the concentrations of bone sialoprotein in joint fluid and serum were > 1 in the majority of the cruciate ligament injury cases. CONCLUSIONS: The release of significant amounts of bone sialoprotein into joint fluid in connection with acute joint trauma may be associated with injury to, and active remodelling of, the cartilage-bone interface and subchondral bone. The findings are consistent with dramatic shifts in cartilage, bone, and synovial metabolism following joint injury. Bone sialoprotein concentrations in synovial fluid may be a useful marker of subchondral injury and remodelling following joint injury.

Adolescent↗