Study of the synovial fluids of nine patients suffering from rheumatoid arthritis before and four weeks after the injection of thiotepa, showed a significant drop in the total white cell count, a reversion to a more normal differential count and significant reduction in the synovial fluid/serum protein ratio, total proteins and gammaglobulin levels.
Esseva studiate le liquidos synovial de novem patientes con arthritis rheumatoide, ante e quatro septimanas post le injection de thiotepa, con el constatation de un significative declino del numeration total de leucocytos, de un reversion a un plus normal numeration differential, e de significative declinos del proportion de proteinas inter liquid0 synovial e sero, del proteinas total, e del nivello de globulinas gamma.
H E USE OF alkylating agents in the treatment of rheumatoid arthritis T was first described by Diaz and co-workers,l who used nitrogen mustard intravenously. They reported temporary clinical improvement and likened the results to those of ACTH. Subsequent reports by Phillips and co-workers2 and by Paul et aL3 noted temporary clinical improvement and a tendency fcr the serum proteins to shift towards normal. Scherbel and Schuchter4 first used nitrogen mustard intra-articularly in dogs, observing that the synovium returned to normal in about 30 days. In 1960, Vainio and Julkunen5 compared the iise of intra-articular nitrogen mustard in patients suffering from rheumatoid arthritis with the use of hydrocortisone. They reported that in the less severe cases of rheumatoid arthritis, nitragen mustard was more effective than hydrocortisone, but in late cases nitrogen mustard was actually harmful.
More recently Flatt6 reported the use of another alkylating agent, Thiotepa, in the small joints of the fingers and noted clinical improvement. Wenley' compared the effect of Thiotepa and hydrocortisone injected into the knee joints of patients suffering from rheumatoid arthritis. He found that a dose of 15 mg. of Thiotepa was as effective as 100 mg. of hydrocortisone and suggested that 30 mg. of Thiotepa would be more effective. Several authors have found that the synovial fluid of rheumatoid arthritic patients has a high globulin content; Oldhagen, B.,s Perlman and co-workers.R Schmid and McNairl" concluded that the synovial proteins were identical with plasma proteins. Wilkinson and JonesT1 showed that the ratio of gamma globulin in synovial fluid to gamma globulin in plasma was higher in rheumatoid arthritis than in patients suffering from other forms of joint disease. The Ieucocytes in synovial fluid have been investigated by Ropes and Bauer12 and they showed that in rheumatoid arthritis the total white cell count is usually above 10,000 cells per cubic mm.; the differential count usually shows 80 per cent or more of polymorphic leucocytes and 20 per cent or less of lymphocytes. In 1962 the authors decided to investigate the effect of Thiotepa on the white cell counts