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When performing total hip arthroplasty (THA) for a rheumatoid arthritis patient with protrusio acetabuli, we made an acetabular model by computerized reconstruction of CT scan data. Using this model, a graft of dense hydroxyapatite plus tricalcium phosphate was made to fit the defect in the acetabular roof. Surgery was relatively easy and the graft fitted well. This method appears useful for THA when there is a large acetabular roof defect.

A double-blind comparative study among 9 medical centers was conducted in order to investigate the optimal daily administration schedule of UHAC62 (Generic name: Meloxicam), a kind of non-steroidal anti-inflammatory oxycam agent. The daily 10 mg of UHAC62, which had been considered as an optimal dose, was administered either once daily, immediately after supper (Group O), or given twice a day divided into 5 mg immediately after breakfast and supper (Group T), both for weeks to patients with rheumatoid arthritis.Out of the total 52 patients, 1 patient was excluded from the analyses; and 41 patients (Group O: 23 cases, Group T: 18 cases), 51 patients (Group O: 27 cases, Group T: 24 cases) and 44 patients (Group O: 24 cases, Group T: 20 cases) were subjected to the ratings of Final Global Improvement, Overall Safety, and Usefulness, respectively. The results showed the following:(1) The ratio of the patients who showed a better than “Moderate Improvement” in the Final Global Improvement Rating was 30.4 % and 27.8 % in the Group O and Group T, respectively.(2) The ratio of the patients on whom the test drug was shown to be “Completely Safe” in the Overall Safety Rating was 88.9% and 91.7% in the Group O and Group T, respectively. All of the adverse drug reactions which were seen in the patients of Group O and the 2 patients of the Group T were assessed as “mild”.(3) The ratio of the patients on whom the test drug was rated as better than “Useful” was 29.2% and 25.0 % in the Group O and Group T, respectively.There was no significant difference in the overall evaluations and the improvement rating of the symptoms between the groups.According to these results, it was considered that the once daily administration of UHAC62 might be more promising for materializing a higher compliance in the patients who need long-term administration, although both regimens, the once and the twice daily administrations are applicable.

The expression of human inducible NO synthase (iNOS) and membrane-bound interleukin (IL)-6 receptor (mIL-6R) were investigated immunohistologically in relation to the abnormal activation and infiltration mechanism of macrophages in interface tissues surrounding the femoral component of failed cementless total hip arthroplasty (THA). Gene expression of these cytokines at the lesion site was investigated using the reverse transcription-polymerase chain reaction (RT-PCR) method, and mRNAs for iNOS and mIL-6R were found to be expressed in the interface tissue surrounding the femoral component of failed cementless THA. Immunohistochemical investigation revealed the presence of iNOS and mIL-6 R. These results suggest that iNOS and mIL-6R play a role in the focal osteolysis observed in patients with failed cementless hip prostheses. Moreover, iNOS and mIL-6R were expressed in almost identical cells in an autocrine manner, indicating that when iNOS expression is enhanced, mIL-6R expression is also enhanced.

The multiple dose Phase I study was performed on SA96 in 5 healthy volunteers.300 mg/day and 600 mg/day of SA96 were administered t. i. d. after meals for 6 days consecutively after 2 weeks washout.The following results were obtained.1) No remarkable subjective complaint was registered except for belching.2) No significant anomaly was noted in clinical symptoms or laboratory values.3) The changes in blood concentration of SA96 followed the same pattern as the single dose study, that is the drug was rapidly absorbed in the blood and rapidly excreted without accumulation.4) Little difference was noted in urinary excretion pattern between day 1 and day 6, and 39-46% of the amount administered was excreted into the urine by 24 hours after the first administration on each day. SA96 was not detected in the urine on the day after finishing the administration, but trace amou ts of SA679 was found for 2 days thereafter.Since the Phase I studies confirmed the safety of SA96 in the range of single doses at 200 mg and 6 consecutive days of doses at 600 mg/day, it is adjudged possible to proceed to a Phase II study to evaluate the effectiveness, safety, and usefulness of the drug on rheumatoid arthritis.

A single dose Phase I study was performed on the newly developed antirheumatic, N (2-mercapto-2-methylpropionyl)-L-cysteine (SA 96)Five healthy volunteers were administered 200 mg and 400 mg of SA 96 in a singledose after breakfast, after which the safety and pharmacokinetics of the drug were studied with the following results.1) No remarkable subjective complaints were registered except for belching.1) No significant anomaly was noted in clinical signs or laboratory examination values.3) The average concentration of SA 96 in the blood reached highest concentration by about 1 hour after administration and repidly disappeared thereafter . About 40% of the SA96 was excreted into the urine in 24 hours.Based on the above results, we plan to proceed to a multiple dose study in order to further evaluate the safety of SA96.

We evaluated halopredone acetate in basic and clinical aspects. Halopredone acetate is a highly topical corticosteroid. When it is used for intraarticular injections, the effects last longer than any other steroids which have been used, and it has less general effects. We applied halopredone acetate for RA and OA patients. For RA patients, mean dose for a wrist is 12.5 mg and that for a knee is 25 mg. About 90% cases showed effectiveness and in about 45% cases the duration of effect is longer than 4 weeks. More than half cases of OA showed also improvements.