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Biomedical subjects

Johannes W J Bijlsma

Publications and source records attributed to Johannes W J Bijlsma.

At least 19 recordsLinked to original sources
PubMed2007

Exposure of human cartilage tissue to low concentrations of blood for a short period of time leads to prolonged cartilage damage: an in vitro study.

OBJECTIVE: Joint bleeding, or hemarthrosis, leads in time to severe joint damage. This study was carried out to test the in vitro thresholds of exposure time and concentration that lead to irreversible joint damage, to add to the discussion on the usefulness of aspiration of the joint after a hemorrhage. METHODS: Explants of healthy human articular cartilage tissue were cultured in the presence or absence of 50% (volume/volume) blood for 1, 2, 3, or 4 days or in the presence of 0%, 5%, 10%, 20%, 30%, or 50% (v/v) blood for 4 days, followed by a 12-day period of recovery after withdrawal of blood. The effect of blood exposure on cartilage was determined by measuring the rate of proteoglycan synthesis as well as the release and content of cartilage matrix proteoglycans and the activity of matrix metalloproteinases. RESULTS: Exposure of cartilage to 50% (v/v) blood led to adverse changes that were largely independent of the exposure time. The adverse effects persisted after an initial exposure of up to or exceeding 2 days. Exposure of cartilage to increasing concentrations of blood for 4 days led to concentration-dependent adverse changes. These effects persisted when the concentration equaled or exceeded 10% (v/v) blood. Moreover, after 2 days of exposure to a blood load of 10% (v/v), the adverse effects on cartilage were not reversible. CONCLUSION: A 2-day exposure of cartilage in vitro to 10% (v/v) blood leads to prolonged impairment of joint cartilage. This suggests that aspiration of blood from the joint within 2 days after hemarthrosis should be considered to prevent blood-induced joint damage in the long term.

Blood↗
PubMed2006

Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha blockade in patients with rheumatoid arthritis.

OBJECTIVES: To identify the mechanism of interleukin (IL)7-stimulated tumour necrosis factor alpha (TNFalpha) production and to determine the relationship between intra-articular IL7 and TNFalpha expression levels in patients with rheumatoid arthritis (RA). In addition, the effect of TNFalpha blockade on IL7 activity and on IL7 levels was studied. METHODS: The effect of IL7 on isolated CD4 T cells and CD14 monocytes/macrophages was studied. IL7 and TNFalpha levels were measured in the synovial fluid of patients with RA. In RA synovial tissue, IL7 and TNFalpha expression was assessed in addition to IL1beta, numbers of inflammatory cells and adhesion molecule expression. The extent to which TNFalpha blockade could prevent IL7-induced lymphocyte responses was studied in vitro. In addition, regulation of serum IL7 levels on anti-TNFalpha therapy (adalimumab) was studied. RESULTS: IL7 induced cell contact-dependent TNFalpha production by cocultures of T cells and monocytes, but not by T cells and monocytes cultured separately. IL7 and TNFalpha levels in RA synovial fluid and synovial tissue significantly correlated. IL7-stimulated lymphocyte responses were not inhibited by TNFalpha blockade. Circulating IL7 levels were significantly reduced in patients who successfully responded to anti-TNFalpha treatment. However, IL7 levels persisted in non-responders. CONCLUSION: The present data suggest that IL7 is an important inducer of T cell-dependent TNFalpha production in RA joints. This may contribute to the correlation of intra-articular IL7 and TNFalpha in these joints. Furthermore, the persistence of IL7-induced inflammatory activity on TNFalpha blockade in vitro and persistence of IL7 levels and disease activity in anti-TNFalpha non-responders suggest that IL7 might additionally promote TNFalpha-independent inflammation.

Adalimumab↗
PubMed2006

Effectiveness of behavioral graded activity in patients with osteoarthritis of the hip and/or knee: A randomized clinical trial.

OBJECTIVE: To determine the effectiveness of a behavioral graded activity program (BGA) compared with usual care (UC; exercise therapy and advice) according to the Dutch guidelines for physiotherapy in patients with osteoarthritis (OA) of the hip and/or knee. The BGA intervention is intended to increase activity in the long term and consists of an exercise program with booster sessions, using operant treatment principles. METHODS: We conducted a cluster randomized trial involving 200 patients with hip and/or knee OA. Primary outcome measures were pain (visual analog scale [VAS] and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), physical function (WOMAC), and patient global assessment, assessed at weeks 0, 13, 39, and 65. Secondary outcome measures comprised tiredness (VAS), patient-oriented physical function (McMaster Toronto Arthritis Patient Preference Disability Questionnaire [MACTAR]), 5-meter walking time, muscle strength, and range of motion. Data were analyzed according to intent-to-treat principle. RESULTS: Both treatments showed short-term and long-term beneficial within-group effects. The mean differences between the 2 groups for pain and functional status were not statistically significant. Significant differences in favor of BGA were found for the MACTAR functional scale and 5-meter walking test at week 65. CONCLUSION: Because both interventions resulted in beneficial long-term effects, the superiority of BGA over UC has not been demonstrated. Therefore, BGA seems to be an acceptable method to treat patients with hip and/or knee OA, with equivalent results compared with UC.

Aged↗
PubMed2006

Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis.

BACKGROUND: Treatment with glucocorticoids is associated with bone loss starting soon after therapy is initiated and an increased risk of fracture. METHODS: We performed a randomized, double-placebo, double-blind clinical trial of 18 months' duration among patients with a rheumatic disease who were starting glucocorticoids at a daily dose that was equivalent to at least 7.5 mg of prednisone. A total of 201 patients were assigned to receive either alendronate (10 mg) and a placebo capsule of alfacalcidol daily or alfacalcidol (1 microg) and a placebo tablet of alendronate daily. The primary outcome was the change in bone mineral density of the lumbar spine in 18 months; the secondary outcome was the incidence of morphometric vertebral deformities. RESULTS: A total of 100 patients received alendronate, and 101 received alfacalcidol; 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1 percent in the alendronate group (95 percent confidence interval, 1.1 to 3.1 percent) and decreased by 1.9 percent in the alfacalcidol group (95 percent confidence interval, -3.1 to -0.7 percent). At 18 months, the mean difference of change in bone mineral density between the two groups was 4.0 percent (95 percent confidence interval, 2.4 to 5.5 percent). Three patients in the alendronate group had a new vertebral deformity, as compared with eight patients in the alfacalcidol group (of whom three had symptomatic vertebral fractures) (hazard ratio, 0.4; 95 percent confidence interval, 0.1 to 1.4). CONCLUSIONS: During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced bone loss than was alfacalcidol. (ClinicalTrials.gov number, NCT00138983 [ClinicalTrials.gov].).

Aged↗
PubMed2006

The cost effectiveness of behavioural graded activity in patients with osteoarthritis of hip and/or knee.

OBJECTIVE: To evaluate whether exercise treatment based on behavioural graded activity comprising booster sessions is a cost-effective treatment for patients with osteoarthritis of the hip and/or knee compared with usual care. METHODS: An economic evaluation from a societal perspective was carried out alongside a randomised trial involving 200 patients with osteoarthritis of the hip and/or knee. Outcome measures were pain, physical functioning, self-perceived change and quality of life, assessed at baseline, 13, 39 and 65 weeks. Costs were measured using cost diaries for the entire follow-up period of 65 weeks. Cost and effect differences were estimated using multilevel analysis. Uncertainty around the cost-effectiveness ratios was estimated by bootstrapping and graphically represented on cost-effectiveness planes. RESULTS: 97 patients received behavioural graded activity, and 103 patients received usual care. At 65 weeks, no differences were found between the two groups in improvement with respect to baseline on any of the outcome measures. The mean (95% confidence interval) difference in total costs between the groups was -euro773 (-euro2360 to euro772)--that is, behavioural graded activity resulted in less cost but this difference was non-significant. As effect differences were small, a large incremental cost-effectiveness ratio of euro 51,385 per quality adjusted life year was found for graded activity versus usual care. CONCLUSIONS: This study provides no evidence that behavioural graded activity is either more effective or less costly than usual care. Yielding similar results to usual care, behavioural graded activity seems an acceptable method for treating patients with osteoarthritis of the hip and/or knee.

Cost of Illness↗
PubMed2006

Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo.

OBJECTIVE: In a previous clinical trial of patients with early rheumatoid arthritis (RA), it was determined that patients who received 10 mg of prednisone per day for 2 years had less radiographic joint damage compared with those who received placebo. Our goal was to investigate whether this beneficial effect persisted after the end of the trial. METHODS: A blinded assessment of radiographic joint damage was performed approximately 3 years after the end of the original 2-year study. Twenty-four patients from the original prednisone group (60%) and 28 patients from the original placebo group (68%) participated in this followup study. At the end of the original trial, prednisone dosages were tapered down in the prednisone group and stopped, if possible. Patients from the original prednisone group took prednisone during 35% of the followup period (approximately 1 year) at a mean daily dose of approximately 5 mg. Two patients from the original placebo group started taking prednisone during followup. Radiographs of the hands and feet were scored according to the van der Heijde modification of the Sharp method. RESULTS: During 3 additional years of followup, radiographic scores showed significantly less progression in the original prednisone group than in the original placebo group. Radiographic damage in the original prednisone group did not show an accelerated rate of progression during the followup period. CONCLUSION: The inhibition of radiographic joint damage in patients with early active RA treated with 10 mg of prednisone per day for 2 years seems to persist after the end of prednisone therapy.

Arthritis, Rheumatoid↗
PubMed2006

Diversity of regulatory T cells to control arthritis.

During follow-up of the suppressive functions of CD4+ T helper (Th) 2 cells in recent years, the suppressive capacities of newly recognised CD4+ Th cells with more widespread suppressive potential have been extensively investigated. These Th cells, collectively termed regulatory T cells, are characterised by the secretion of specific cytokines, such as interleukin (IL)-10 (Tr1 Th cells), transforming growth factor (TGF)beta (Th3 cells) or the constitutive expression of CD25 (naturally occurring T regulatory cells, nTregs). The balance of these regulatory T cells with pro-inflammatory effector T cells, such as Th1 (interferon (IFN)gamma secreting), Th17 (IL-17 secreting) and CD25- Th cells, has been shown to be of pivotal importance for the development and persistence of autoimmune diseases. The high potential of regulatory T cells (in particular nTregs), to efficiently suppress several arthritic responses both in humans and in animal models of arthritis, make them therapeutic targets of interest in arthritic conditions such as rheumatoid arthritis.

Animals↗
PubMed2006

Active involvement and long-term goals influence long-term adherence to behavioural graded activity in patients with osteoarthritis: a qualitative study.

QUESTION: Why do some patients who have received a behavioural graded activity program successfully integrate the activities into their daily lives and others do not? DESIGN: Qualitative study. PARTICIPANTS: 12 patients were selected according to the model of deliberate sampling for heterogeneity, based on their success with the intervention as assessed on the Patient Global Assessment. INTERVENTION: Behavioural graded activity. OUTCOME MEASURES: Data from 12 interviews were coded and analysed using the methods developed in grounded theory. The interviews covered three main themes: aspects related to the content of behavioural graded activity, aspects related to experience with the physiotherapist, and aspects related to characteristics of the participant. RESULTS: Interview responses suggest that two factors influence long-term adherence to exercise and activity.First, initial long-term goals rather than short-term goals seem to relate to greater adherence to performing activities in the long term. Second, active involvement by participants in the intervention process seems to relate to greater adherence to performing activities in the long term. CONCLUSION: Although involvement of patients in the intervention process is already part of behavioural graded activity, it would be beneficial to emphasise the importance of active involvement by patients right from the start of the intervention. Furthermore, to increase the success of behavioural graded activity, physiotherapists should gain a clear understanding of the patient's initial motives in undergoing intervention.

Activities of Daily Living↗
PubMed2006

Differential direct effects of cyclo-oxygenase-1/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitro study.

Treatment of osteoarthritis (OA) with nonsteroidal anti-inflammatory drugs (NSAIDs) diminishes inflammation along with mediators of cartilage destruction. However, NSAIDs may exert adverse direct effects on cartilage, particularly if treatment is prolonged. We therefore compared the direct effects of indomethacin, naproxen, aceclofenac and celecoxib on matrix turnover in human OA cartilage tissue. Human clinically defined OA cartilage from five different donors was exposed for 7 days in culture to indomethacin, naproxen, aceclofenac and celecoxib--agents chosen based on their cyclo-oxygenase (COX)-2 selectivity. As a control, SC-560 (a selective COX-1 inhibitor) was used. Changes in cartilage proteoglycan turnover and prostaglandin E2 production were determined. OA cartilage exhibited characteristic proteoglycan turnover. Indomethacin further inhibited proteoglycan synthesis; no significant effect of indomethacin on proteoglycan release was found, and proteoglycan content tended to decrease. Naproxen treatment was not associated with changes in any parameter. In contrast, aceclofenac and, prominently, celecoxib had beneficial effects on OA cartilage. Both were associated with increased proteoglycan synthesis and normalized release. Importantly, both NSAIDs improved proteoglycan content. Inhibition of prostaglandin E2 production indirectly showed that all NSAIDs inhibited COX, with the more COX-2 specific agents having more pronounced effects. Selective COX-1 inhibition resulted in adverse effects on all parameters, and prostaglandin E2 production was only mildly inhibited. NSAIDs with low COX-2/COX-1 selectivity exhibit adverse direct effects on OA cartilage, whereas high COX-2/COX-1 selective NSAIDs did not show such effects and might even have cartilage reparative properties.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

The impact of stressors on health status and hypothalamic-pituitary-adrenal axis and autonomic nervous system responsiveness in rheumatoid arthritis.

The hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are critically involved in inflammation and are activated by stress. This suggests that stressful circumstances may affect the chronic inflammation of rheumatoid arthritis (RA). Fifty-six scientific publications of the past 15 years were reviewed to get insight into the possible impact of stressors (grouped in five categories) on the health status and HPA axis and ANS functioning of adult patients with RA. Our findings in this review were: (1) In response to mental and physical effort and applied physiological stressors, patients demonstrate ANS hyporesponsiveness and "too normal" HPA axis responsiveness considering the elevated immune activity. A premorbid defect, past and current inflammatory activity, past and current stress, and physical deconditioning may explain disturbed physiological responses. (2) After brief naturalistic stressors, self-perceived and clinician's ratings of disease activity are increased; inflammation parameters have been insufficiently examined. (3) Major life events do not univocally affect disease status, but appear able to modify disease activity in a positive or negative way, depending on the nature, duration, and dose of the accompanying physiological stress response. (4) Enduring (e.g., work-related or interpersonal) stressors are associated with perceived health. Because this stressor category mingles with personality variables, the mere observation of a correlation does not prove that chronic stressors provoke health changes, although this might be the case. (5) Not one study rigorously examined the prospective hypothesis that past stressors (e.g., childhood victimization or pre-onset stressful incidents) may trigger RA or aggravate existing RA, which is a realistic belief for some patients.

Acute Disease↗
PubMed2006

Are glucocorticoids DMARDs?

Disease modifying antirheumatic drugs (DMARDs) are drugs used in rheumatoid arthritis (RA) to control the disease and to limit joint damage and improve long-term outcome. The last decade evidence has accumulated that suggests that low dosages of glucocorticoids are indeed able to control the disease and limit the destruction. This role is especially present in early disease and in combination with other drugs. The evidence is carefully evaluated and discussed. The ultimate conclusion is that indeed glucocorticoids are DMARDs and are especially useful in early RA.

Antirheumatic Agents↗
PubMed2006

Revisiting the toxicity of low-dose glucocorticoids: risks and fears.

We have recently participated in a careful literature search and critical evaluation of glucocorticoids, and we have revised the side-effects data of four recent controlled trials of low-dose glucocorticoids (GCs) in rheumatoid arthritis. The toxicity profile stands out as remarkably more benign than expected from most textbook recommendations. Data regarding low-dose therapy are scarce and of low quality, as no controlled trials have been designed to specifically address toxicity. Common fears of GC toxicity seem to originate from an excessive weight on anecdotal data and observations with high doses, as in organ transplantation. There is now evidence that mechanisms of action of GCs vary considerably according to the dose, thus allowing the possibility of a different toxicity profile. Data from recent controlled trials are quite reassuring, overall. Certainly, risks and benefits of GCs need to be carefully weighed in every patient. But we need to make a clear distinction between established risks and unchecked fears while trying to get the best result for our patient. Clearly, there is a need for studies that are appropriately designed to address the toxicity of GCs and to avoid the risk of "throwing out the baby with the bath water."

Arthritis, Rheumatoid↗
PubMed2005

Influence of various recruitment strategies on the study population and outcome of a randomized controlled trial involving patients with osteoarthritis of the hip or knee.

OBJECTIVE: To examine the effect of 2 different recruitment methods on the characteristics of participants with osteoarthritis (OA) of the hip or knee and on the efficacy of an exercise program. METHODS: In a clinical trial on the effectiveness of exercise therapy in OA of the hip or knee, 2 groups of patients were recruited: one group through referrals by physiotherapists (PT group, n = 110) and one group invited by newspaper articles (NP group, n = 90). At baseline, demographic, clinical, and psychosocial data were collected and compared between the 2 groups using chi-square and Student's t-tests. After 13 weeks of exercise therapy and followup assessments at weeks 39 and 65, the main outcome measures (pain, physical function, and global perceived effect) were assessed and compared by multiple regression analysis. RESULTS: The NP group reported less pain and tiredness at baseline, although more joints were affected with osteoarthritis. The PT group scored higher on the scale 'powerful-others' of locus of control. After adjusting for baseline differences, the effect of treatment after 13, 39, and 65 weeks was comparable for both groups for all outcome measures. CONCLUSION: Recruitment method affects clinical characteristics and physical functioning of patients recruited for the study. A mix of recruitment strategies does not seem to affect treatment outcome, on the condition that adjustments are made for baseline differences.

Exercise Therapy↗