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Biomedical subjects

M van Oosterhout

Publications and source records attributed to M van Oosterhout.

8 recordsLinked to original sources

Comparison of efficacy of arthroscopic lavage plus administration of corticosteroids, arthroscopic lavage plus administration of placebo, and joint aspiration plus administration of corticosteroids in arthritis of the knee: A randomized controlled trial.

OBJECTIVE: To compare the efficacy of arthroscopic lavage plus administration of corticosteroids (ALC), arthroscopic lavage plus administration of placebo (ALP), and joint aspiration plus administration of corticosteroids (JAC) in knee arthritis, and to evaluate whether clinical or histologic characteristics determine outcome. METHODS: Patients with knee arthritis (not due to gout, osteoarthritis, or septic arthritis) were randomized over 3 treatment arms: ALC, ALP, and JAC. The primary end point was event-free survival, with events defined as 1) recurrence or persistence of symptomatic knee swelling necessitating local re-treatment, or 2) nonimprovement of the knee joint score. Synovial tissue specimens were collected and analyzed histologically to identify predictive factors of responsiveness. RESULTS: A total of 78 patients were enrolled; 3 patients did not receive their allocated therapy and 3 were lost to followup. The median time until recurrence was 9.6 months after ALC, 3.0 months after JAC, and 1.0 month after ALP, corresponding to a relative risk (RR) of arthritis recurrence of 2.2 for JAC (95% confidence interval [95% CI] 1.2-4.2, P = 0.02) and 4.7 for ALP (95% CI 2.3-9.4, P < 0.0001) compared with ALC. A high versus low synovial extent of fibrosis conferred an RR for recurrence of 5.7 (95% CI 1.6-20.5, P < 0.01) after ALC. CONCLUSION: Arthroscopic lavage plus administration of corticosteroids was more effective than arthroscopic lavage plus administration of placebo or joint aspiration plus injection of corticosteroids. The absence of fibrosis was a histologic predictor of a beneficial response.

Adrenal Cortex Hormones↗

Intracellular free radical production in synovial T lymphocytes from patients with rheumatoid arthritis.

OBJECTIVE: To investigate the cellular and molecular sources of oxidative stress in patients with rheumatoid arthritis (RA) through analysis of the production of reactive oxygen species (ROS) in synovium. METHODS: Cytochemical procedures based on the 3,3'-diaminobenzidine (DAB)-Mn2+ deposition technique were used on unfixed cryostat sections of synovium from RA patients and rheumatic disease controls. For immunophenotyping, sections were incubated, fixed, and stained with fluorescein isothiocyanate-labeled antibodies. Fluorescence-activated cell sorter analysis of the ROS-reactive dye 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate-di(acetoxymethyl ester) was used to measure intracellular ROS in T lymphocytes from peripheral blood and synovial fluid. To determine which enzymes produced ROS, different inhibitors were tested. RESULTS: Large quantities of DAB precipitated in the majority of RA synovial T lymphocytes, indicative of intracellular ROS production. These ROS-producing T lymphocytes were observed throughout the synovium. Polymerization of DAB was observed to a lesser extent in other forms of chronic arthritis, but was absent in osteoarthritis. DAB staining of cytospin preparations of purified RA synovial fluid T cells confirmed the presence of ROS-producing cells. One of the ROS involved appeared to be H2O2, since catalase suppressed intracellular ROS production. Superoxide dismutase, which uses superoxide as a substrate to form H2O2, diphenyleneiodonium (an inhibitor of NADPH oxidase), N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthesis), nordihydroguaiaretic acid (an inhibitor of lipoxygenase), and rotenone (an inhibitor of mitochondrial ROS production) failed to suppress ROS production. CONCLUSION: Our findings show that chronic oxidative stress observed in synovial T lymphocytes is not secondary to exposure to environmental free radicals, but originates from intracellularly produced ROS. Additionally, our data suggest that one of the intracellularly generated ROS is H2O2, although the oxidase(s) involved in its generation remains to be determined.

Arthritis, Rheumatoid↗

Clinical efficacy of infliximab plus methotrexate in DMARD naive and DMARD refractory rheumatoid arthritis is associated with decreased synovial expression of TNF alpha and IL18 but not CXCL12.

BACKGROUND: Tumour necrosis alpha (TNF alpha) blocking agents lead to pronounced clinical effects and reduced synovial infiltrate in rheumatoid arthritis. Laboratory and clinical studies suggest that TNF alpha independent pathways play a role in the disease. OBJECTIVES: To evaluate the immunopathological effects of combination therapy on rheumatoid synovial tissue in order to identify TNF alpha independent mechanisms. METHODS: 12 rheumatoid patients, including four DMARD (disease modifying antirheumatic drug) naive patients with early disease, were studied for the effect of combination therapy with infliximab and methotrexate on the synovial infiltrate. Biopsies and clinical assessments (DAS28) were carried out before the first and after the third infusion of infliximab. Synovial inflammation was scored semiquantitatively. Co-expression of CD38(+) cells was studied by an immunofluorescent double labelling technique. RESULTS: Marked clinical responses were associated with a global reduction in the synovial infiltrate and expression of cytokines, notably interleukin 18 and TNF alpha, but low grade disease activity persisted. There was no effect on the expression of CXC chemokine ligand (CXCL12), and germinal centre-like structures were still detectable in synovial tissue in two patients after treatment. CD38(+) activated T cells were more resistant to treatment than CD38(+) plasma cells. No differences in clinical response or effects on synovial infiltrate were observed between DMARD refractory and DMARD naive patients. CONCLUSIONS: Persistent expression of CXCL12 and incomplete resolution of lymphocytic infiltrates after infliximab plus methotrexate indicates that TNF alpha independent mechanisms are operative in rheumatoid arthritis. This may contribute to low grade disease activity, even in DMARD naive patients with early disease.

Adult↗

High dose chemotherapy and syngeneic stem cell transplantation in a patient with refractory rheumatoid arthritis: poor response associated with persistence of host autoantibodies and synovial abnormalities.

BACKGROUND: Immunoablative therapy combined with haematopoietic stem cell transplantation (SCT) is a possible treatment for patients with severe rheumatoid arthritis (RA). CASE REPORT: A patient with rheumatoid factor positive, progressively erosive RA, refractive to treatment, was treated with high dose cyclophosphamide, followed by reinfusion of an unmanipulated peripheral blood graft derived from her identical twin sister. The clinical response was unsatisfactory, necessitating reinstitution of treatment with disease modifying antirheumatic drugs, which was associated with persistence of host serum autoantibodies and a cellular infiltrate in synovium, notably of plasma cells. DISCUSSION: The effectiveness of syngeneic SCT may be critically dependent on the degree of immunoablation achieved or on the composition of the graft.

Adult↗

Superior effect of arthroscopic lavage compared with needle aspiration in the treatment of inflammatory arthritis of the knee.

OBJECTIVES: To compare the duration of symptom relief after arthroscopic lavage versus needle aspiration in gonarthritis. METHODS: A retrospective chart analysis was performed in 50 patients with non-septic inflammatory arthritis of the knee who underwent arthroscopic lavage because of relapsing or persisting arthritis after needle aspiration. The primary outcome measure was the time until symptomatic recurrence of knee synovitis. RESULTS: Needle aspiration was associated with a 3.0 times greater risk of recurrence of arthritis compared with arthroscopic lavage within 12 months (P<0.001, 95% confidence interval 2.1-4.4). Patients with longer disease duration and who had used more disease-modifying anti-rheumatic drugs (DMARDs) had a significantly lower risk of recurrence of arthritis compared with patients with shorter disease duration and a lower number of previous DMARDs (P=0.04 and 0.02 respectively). Corticosteroids augmented the effect of both interventions. CONCLUSIONS: Our results indicate that arthroscopic lavage is an effective therapeutic modality in the treatment of inflammatory arthritis of the knee refractory to joint aspiration, especially in patients with longstanding disease.

Administration, Topical↗

Cross-talk between the lungs in piglets.

HYPOTHESIS: During alternating ventilation (AV) (i.e. differential ventilation (DV) of both lungs with a phase difference of half a ventilatory cycle) volume expansion of the inflated lung will occur partly by compression of the opposite lung. OBJECTIVE: We studied whether and how large an undulating flow would occur out of and into the non-ventilated lung during unilateral ventilation. DESIGN: In 20 anaesthetized, paralysed piglets (11.0 +/- 1.0 kg) DV was applied at a rate of 10 breaths per minute (bpm). In 6 animals, 15 and 20 bpm were also applied with the tidal volume adapted no normocapnia. As the measure of interaction (cross-talk) served the volume change in the non-ventilated lung, found by integration of the low signal, in percentage of the tidal volume to the other lung. RESULTS: In all pigs, tidal volume to the left lung. (VT,l = 7.33 +/- 1.06 ml kg-1) caused a volume change in the right lung of about 21% of VT,l at 10 bpm. The right-to-left cross-talk was significantly lower and about 15% of VT,r (9.07 +/- 1.21 ml kg-1). At higher ventilatory rates, the l-to-r and the r-to-l cross-talk did not change. CONCLUSION: During unilateral ventilation, volume expansion of the inflated lung occurs partly by compression of the opposite lung. The lower mean lung volume during AV compared to synchronous differential ventilation can be explained by such compression. The mechanism of compression is similar at different ventilatory rates.

Animals↗

Haemodynamic and respiratory conditions during alternating and synchronous ventilation of both lungs.

OBJECTIVE: We tested the hypothesis that mean thoracic expansion (and mean lung volume) is lower during alternating ventilation (AV), i.e. ventilation of both lungs with a phase shift of half a ventilatory cycle, compared to synchronous ventilation (SV) of both lungs. As a consequence, intrathoracic pressure will be lower, causing lower, central venous pressure and higher cardiac output. DESIGN: In eight anaesthetized and paralysed piglets, differential ventilation was established by fixation of an endobronchial tube in the left main bronchus. SV and AV were sequentially applied for four and three periods, respectively, of 10 minutes each. Minute ventilation was the same during AV and SV and adapted to normocapnia. Two series of observations were performed: series 1 with intact thorax and monitoring of oesophageal pressure; series 2 after perforation of the sternum, airtight closure of the thorax and monitoring of pericardial pressure. RESULTS: In both series, mean lung volume was 16 +/- 4% lower and central venous, oesophageal (series 1) and pericardial pressures (series 2) were 0.5-0.7 mmHg lower during AV compared to SV (all p < 0.001). In series 1, aortic pressure was 5 mmHg and cardiac output 8% higher (both p < 0.001). In series 2, cardiac output was 5% higher during AV (p < 0.001), but aortic pressure did not change (p = 0.07). CONCLUSION: Our data verified the hypothesis. The lower oesophageal (series 1), pericardial (series 2) and central venous pressures during AV compared to SV could be explained by the smaller thoracic expansion due to the lower mean lung volume, which was attributed to compression of the opposite lung by the, expansion of the inflated lung.

Animals↗