The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment.

OBJECTIVE: Recent in vitro studies showed that celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, protects human osteoarthritic cartilage tissue from degeneration. The objective was to substantiate these beneficial effects in an in vivo (clinical) study with celecoxib treatment of patients with severe knee osteoarthritis (OA) and subsequent evaluation of cartilage tissue ex vivo. METHODS: Patients with knee OA were treated 4 weeks prior to total knee replacement surgery with either celecoxib 200mg b.d., indomethacin 50mg b.d., or received no treatment. During surgery cartilage and synovium were collected and analyzed in detail ex vivo. RESULTS: When compared to non-treated patients, patients treated with celecoxib showed significant beneficial effects on proteoglycan synthesis, -release, and -content, confirming the in vitro data. In the indomethacin group, no significant differences were found compared to the control group. On the contrary, a tendency towards a lower content and lower synthesis rate was found. In the treated groups prostaglandin-E(2) levels were lower than in the control group, indicating COX-2 inhibition. Ex vivo release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha by synovial tissue was decreased by treatment with celecoxib, whereas in the indomethacin group only IL-1 beta release was decreased. CONCLUSION: Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.

Polyarticular heterotopic ossification complicating critical illness.

A patient with generalized heterotopic ossification (HO) complicating critical illness due to necrotizing pancreatitis is described; data on two other cases with HO are briefly presented. The clinical features, prevention and therapy of HO are discussed. The effect of surgical therapy of the HO in our three patients was good.

Haemophilic arthropathy resembles degenerative rather than inflammatory joint disease.

AIMS: To investigate the pathogenetic mechanisms of haemophilic arthropathy (HA) by comparing end-stage arthropathy with osteoarthritis (OA; a degenerative joint disorder) and rheumatoid arthritis (RA; an inflammation-mediated joint disease). METHODS AND RESULTS: Cartilage and synovium from patients with HA (n=10), RA (n=8), OA (n=14) and normal control subjects (n=6) were examined morphologically, biochemically and histochemically. Cartilage in HA exhibited characteristics of degenerative joint disease (OA), as evidenced by morphological, histochemical (Safranin-O fast green-iron haematoxylin, Mankin grade) and biochemical (proteoglycan synthesis, glycosaminoglycan content and DNA content) changes, whereas synovium in HA showed characteristics of inflammation-mediated joint disease (RA), as evidenced by histochemical (inflammation, haematoxylin and eosin (H&E) and iron deposition, Perls' blue) and biochemical changes (interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)alpha and catabolic properties). CONCLUSION: Haemophilic arthropathy shows characteristics of both inflammatory and degenerative joint disease. On the basis of these results and published information, it appears that degenerative cartilage changes have a dominant role in HA and are augmented by relatively mild inflammation of the synovium.

Iron deposits and catabolic properties of synovial tissue from patients with haemophilia.

Haemophilic arthropathy is characterised by iron deposits in synovial tissues. We investigated the suggestion that iron plays an important role in synovial changes. We obtained synovial tissue from six patients with haemophilia during arthroplasty, finding that brown haemosideritic tissue was often adjacent to tissue with a macroscopically normal appearance in the same joint. Samples from both types of synovial tissue were analysed histologically and biochemically to determine catabolic activity. Macroscopically haemosideritic synovium showed a significantly higher inflammatory activity than that with a normal appearance. Cultures of abnormal synovial tissue gave a significantly enhanced production of IL-1, IL-6 and TNF alpha compared with cultures of synovial tissue with a normal appearance. In addition, the supernatant fluids from the cultures showed greater catabolic activity from haemosideritic tissue, as determined by the inhibition of the synthesis of articular cartilage matrix. We conclude that in patients with haemophilic arthropathy, local synovial iron deposits are associated with increased catabolic activity.

Synovium in haemophilic arthropathy.

Synovium is an essential component of the joint and plays a critical role in maintaining a balance between physiological processes and pathological changes in the joint. Recurrent intra-articular bleeding as occur in haemophilia induce pathological synovial changes in the joint. From a certain point on, synovitis inevitably plays a major role in joint destruction, although in the early phase of haemophilic arthropathy its role may be secondary to cartilage damage as a result of the direct effects of blood on cartilage. The changed haemosiderotic, synovial tissue produces catabolic cytokines and enzymes harmful for cartilage.

Periarticular aneurysm formation in haemophilia.

BACKGROUND: Spontaneous bleeding into the joints is common in haemophilia. Recurrent intra-articular bleeding leads to joint destruction. In the past 4 years we have carried out sixteen total knee replacements for haemophilic arthropathy. In three patients there was persistent bleeding with haemarthrosis, manifest skin discolouration, severe pain, and swelling, which was caused by a periarticular aneurysm. METHODS: Using angiography as part of the preoperative preparation, we initiated a prospective study. Ten angiographic examinations (six preoperative, two postoperative, one both) were carried out in seven patients without major complications. FINDINGS: In seven of the ten angiographic examinations, three preoperative and four postoperative, we found aneurysms around the knee. Since the patients with a positive postoperative finding did not have preoperative studies, we do not know whether the aneurysms existed before surgery. INTERPRETATION: Aneurysms can cause increased bleeding and other complications. The occurrence of spontaneous periarticular aneurysms in haemophilia has not been explored. In these cases, the resultant bleeding led to serious clinical symptoms that were not responsive to conservative measures. This new finding is relevant to those who surgically treat haemophilia patients. Angiography--and, when indicated, embolisation--before total knee replacement proved simple and effective as a diagnostic and therapeutic procedure.

The diameter of the distal abdominal aorta and the aetiology of local atheroma.

In our patients it was found that small sized prostheses were usually implanted to replace obliterated aortic bifurcations. Consequently, the question was considered whether the haemodynamic processes involved in the lysis of the aortic wall at the bifurcation and in the succeeding atherosclerotic lesions were related to the small diameter of the aorta in these cases. In an extensive angiographic and ultrasonic study on men without atherosclerotic lesions, the diameter of the abdominal aorta was determined (control group). Aortic diameter appears to depend on age as well as body length. We also found a difference between the average diameters for women and for men. Of our patients who were operated on, over 35% had an aortic diameter below the 95% population lower boundary line of the control group, while for over 90%, the diameter was below the average of the control group. On analysis of our data the explanation for the aetiology of atheromatosis at the aortic bifurcation must be much more complicated than current hemodynamic theories suggest.