Renzo Okamoto

Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells.

Recent studies have shown that cyclooxygenase exists in two isozyme forms. Since differences in the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs) might be accounted for by varying degrees of selectivity for these isozymes, cyclooxygenase-1 and -2, the relative potency of various NSAIDs in inhibiting their activities was examined in intact human cells. We used human platelets cyclooxygenase-1 and interleukin-1beta-stimulated human synovial cell cyclooxygenase-2 for measuring cyclooxygenase selectivity. The presence of the enzymes was confirmed by immunoblotting and immunoprecipitation analysis, and by the reverse transcriptase-polymerase chain reaction. Mean IC50 values (microM) for human platelet cyclooxygenase-1 and interleukin-1beta-stimulated human synovial cell cyclooxygenase-2 and cyclooxygenase-1/-2 IC50 ratio of various NSAIDs were as follows: aspirin, 3.2, 26, 0.12; diclofenac, 0.037, 0.00097, 38; etodolac, 122, 0.68, 179; ibuprofen, 3.0, 3.5, 0.86; indomethacin, 0.013, 0.044, 0.30; loxoprofen (active metabolite), 0.38, 0.12, 3.2; NS-398, 12, 0.0095, 1263; oxaprozin, 2.2, 36, 0.061; zaltoprofen, 1.3, 0.34, 3.8; respectively. Our bioassay system employing intact human cells to assess the cyclooxygenase selectivity of NSAIDs may provide clinically useful information.

Gradual low riding of the patella during postoperative course after total knee arthroplasty in osteoarthritis and rheumatoid arthritis

Patellar height in the lateral view of radiograms was measured on 94 knees of 61 women before and after total knee arthroplasty in order to study postoperative changes of position. The mean age of patients at surgery was 58.4 years (range, 30-77 years). Eighty-one knees were rheumatoid and 13 osteoarthritic. Inserted prostheses were Kinematic anteriorly joined type in 49 knees, Kinematic posterior cruciate retention type in 19, and UCI type in 26. The observation period ranged from 6 months to 9 years, with an average of 2.6 years after surgery. The ratio of length of the patellar ligament to that of the patella (Insall-Salvatis ratio) decreased by more than 10% of preoperative value in 61 knees, remained unchanged in 31, and increased in only 2. The average ratio was 0.93 +/- 0.16 before surgery and 0.75 +/- 0.20 at the final follow-up examination (P less than .01).

15-year follow-up study of total knee arthroplasty in patients with rheumatoid arthritis

In 25 patients with rheumatoid arthritis, 36 cases of cemented Kinematic total knee arthroplasty were reviewed clinically and radiographically at 13 to 19 years after surgery. The mean age at the time of surgery was 51.6 +/- 8.9 years. According to the follow-up results evaluated with the Hospital for Special Surgery knee scoring system, 28 knees (77.7%) were classified as good or excellent. The mean flexion angle at follow-up evaluation was 99 degrees +/- 24 degrees (10 degrees -140 degrees ). At the tibial or femoral bone-cement interfaces, a radiolucent line was seen in 10 of 36 knees (27.8%) at follow-up evaluation. The survival rate of prostheses with revision as the endpoint was estimated to be 93.7% at 15 years. Kinematic total knee arthroplasty in rheumatoid arthritis patients provided a good long-term outcome.

Radical synovectomy with muscle release for the rheumatoid elbow.

Twenty-three synovectomies of the elbow with concomitant muscle release at the humeral epicondyles were performed in 21 patients with rheumatoid arthritis. Ten elbows were classified as anatomical Stage 2, 12 as Stage 3, and one as Stage 4. The patients were followed from 1 to 8 years. Postoperative clinical results showed improved relief of pain, and range of motion, and activities of daily living. Increased range of motion with improvement of flexion contracture was obtained in most cases by releasing the muscle insertions around the humeral epicondyles and by resecting the radial head and bony spurs of the coronoid and the olecranon. The operation was beneficial even at advanced stages.

Resection of painful shelf (plica synovialis mediopatellaris) under arthroscopy

In a series of 3,250 patients with knee disorders, a painful shelf was diagnosed and resected in 39 knees of 32 patients. Thirty of them were done by arthroscopy and nine by arthrotomy. There were 10 men and 22 women whose ages ranged from 4 to 55 years, with an average of 19 years. The follow-up period ranged from 1 to 6 years. Postoperatively, the pain was relieved in 26 knees and diminished in 13. A cord-like mass, palpable in 30 knees, disappeared in 25 postoperatively. Clicks were noted in 34 knees; 28 of these were not audible or palpable postoperatively. The provocation test 1 result was positive in 23 of 28 knees preoperatively, negative in 21, and diminished in 2 postoperatively. The provocation test 2 was performed in 23 knees; it produced pain and/or palpable click in 14 preoperatively, and was negative in 12 and diminished in 2 postoperatively.

Up-regulation of CD44 in rheumatoid chondrocytes.

The adhesion molecule CD44 is thought to play an important role in the inflammatory process. To identify the expression of CD44 in articular chondrocytes in rheumatoid arthritis (RA), monoclonal anti-CD44 antibodies were immunohistochemically used to react with articular cartilage specimens of 15 patients with RA, 9 with osteoarthritis (OA), and 6 with femoral neck fracture (FF). The proportion of CD44-positive chondrocytes in RA was 93±2% (N=16), which was significantly higher than that in OA (59±7%, N=9, p<0.001) and FF (46±5%, N=6, p<0.001). Among CD44 isoforms examined, the hemopoietic form was dominant in chondrocytes in RA. Therefore, up-regulation of CD44 on chondrocytes may play a significant role in cartilage degeneration in RA.The adhesion molecule CD44 is thought to play an important role in the inflammatory process. To identify the expression of CD44 in articular chondrocytes in rheumatoid arthritis (RA), monoclonal anti-CD44 antibodies were immunohistochemically used to react with articular cartilage specimens of 15 patients with RA, 9 with osteoarthritis (OA), and 6 with femoral neck fracture (FF). The proportion of CD44-positive chondrocytes in RA was 93 +/- 2% (N=16), which was significantly higher than that in OA (59 +/- 7%, N=9, p<0.001) and FF (46 +/- 5%, N=6, p<0.001). Among CD44 isoforms examined, the hemopoietic form was dominant in chondrocytes in RA. Therefore, up-regulation of CD44 on chondrocytes may play a significant role in cartilage degeneration in RA.

Pain reduction after anteromedial displacement of the tibial tuberosity:5-year follow-up in 21 knees with patellofemoral arthrosis

We performed anteromedial displacement of the tibial tuberosity in 21 knees of 16 patients having patellofemoral arthrosis with lateral subluxation. The mean age of the patients was 53 (47-65) years and they were followed for 5(2-13) years. Preoperatively, all knees were painful on descending or ascending stairs; pain was relieved after operation in 20. Retropatellar crepitations disappeared in 2 of 20 knees, but retropatellar pain when squeezing the patella against the femur disappeared in 16 of 17 knees. Patellar subluxation diminished in all knees.

Radiologic evaluation of the rheumatoid hand after synovectomy and extensor carpi radialis longus transfer to extensor carpi ulnaris

PURPOSE In this study we radiologically evaluated the effects of extensor carpi radialis longus (ECRL) tendon transfer on the stability and deformity of joints of rheumatoid hands in cases with a postoperative period of more than 5 years. METHODS Synovectomy concomitant with tendon transfer of the ECRL to the extensor carpi ulnaris (Claytons procedure) was performed in 28 wrists of 23 patients with rheumatoid arthritis. The follow-up period was 8.8 +/- 2.8 years. Pre- and postoperative x-rays were reviewed and measured. Follow-up evaluation included Steinbrockers classification of the radiocarpal joints, Larsens grade of the third metacarpophalangeal (MCP) joint, radial angulation of the wrist, ulnar translocation of the carpus, and ulnar drift of the fingers. RESULTS Nineteen of 28 wrists (68%) were ankylosed (radius-proximal carpal row fusion or radiolunate limited fusion). Radial angulation of the wrist was reduced from 131 degrees +/- 8.8 degrees before surgery to 121 degrees +/- 7.9 degrees after surgery. Dislocation and ulnar translocation of the carpus (UTC) were prevented by surgery (UTC: 1.05 +/- 0.10 before and 1.07 +/- 0.09 after surgery). The mean ulnar drift of the fingers was maintained at the preoperative level (UDF: 14 degrees +/- 5.7 degrees before and 14 degrees +/- 12.9 degrees after surgery). The incidence of alteration (increase and decrease) of UDF of more than 5 degrees between pre- and postoperative evaluation was significantly higher in the group with worsening of Larsen grade of MCP joints than in the group without worsening (with worsening: 7 of 8 MCP joints, without worsening: 8 of 20 MCP joints). CONCLUSIONS ECRL tendon transfer (Claytons procedure) provided effective stabilization at more than 5 years (mean, 8.8 y) after surgery. In addition, this method may help to prevent ulnar drift of the fingers if combined with correction of local factors at the MCP joints.

Isolation and differential secretion of metalloproteinase by superficial chondrocytes in articular cartilage

Summary. Chondrocytes from superficial layers of articular cartilage have distinct phenotypic properties which are different from those of cells obtained from the deeper areas. We describe a method that isolates highly purified articular cartilage chondrocytes from the superficial layers. When the superficial cells are stimulated in vitro with a source of cytokines, they secrete greater amounts of metalloproteinase compared to chondrocytes obtained from a deeper area.Résumé. Des études récentes ont démontré que les chondrocytes originaires des couches superficielles du cartilage articulaire possèdent des caracteristiques phénotypiques differentes des caracteristiques des cellules provenant de la région profonde du tissu. Nous décrivons une nouvelle méthode qui permet l’isolement d’une population des chondrocytes superficiels de haute pureté. Nous montrons aussi que quand les chondrocytes superficiels sont stimulés in vitro avec des cytokines, on peut constater une sécrétion plus importance de caséinase par rapport au niveau de sécrétion des cellules profondes.

CD44 expression in synovial lining and cartilage of rat knees induced by intraarticular injection of synthetic lipid A

Abstract To study the effect of synthetic lipid A on the expression of the adhesion molecule CD44 in synovium and cartilage, synthetic lipid A (10 μg/ml, 0.5 ml) diluted in 0.025% triethylamine (TEA) was injected into the left knee of male Wistar rats. The equivalent volume of 0.025% TEA was injected simultaneously into the right knee of the same rat as a control. The numbers of infiltrating neutrophils and mononuclear cells in the synovium were counted, and the expression of CD44 was detected immunohistochemically. Infiltration of neutrophils in the synovium of the knee reached a maximum at 12 h after intraarticular injection of lipid A (78.4 ± 5.6 cells/400× field), and had subsided at 7 days after injection (2.1 ± 0.6). CD44 expression in the lining cells of the synovium was detected 24 h after injection (2.5 ± 0.3 cell layers), and it lasted 7 days after injection (2.6 ± 0.4 cell layers). CD44 expression in cartilage started at 24 h (69.0% ± 4.6% positive area of specimen) and lasted 7 days after injection (27.3% ± 3.3%). Intraarticular injection of lipid A was proven to induce acute arthritis and CD44 expression in the synovial lining layers and articular cartilage.