Chromosomes in rheumatoid arthritis.
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Biomedical subjects
Publications and source records attributed to R F Jacox.
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We designed a clinical trial to obtain dose-ranging, efficacy, and aspirin-withdrawal data on tiopinac in patients with rheumatoid arthritis. To accomplish this without exposing the patients to risk of disease exacerbation and avoiding type II error, we used a 3-phase protocol adding tiopinac to current therapy. The 3 phases-open-label dose ranging, double-blind tiopinac versus placebo, and aspirin withdrawal-began after a single-blind run-in period. The manufacturer withdrew tiopinac from investigation because of toxicity at higher doses, but with only 13 patients we found that tiopinac (up to 300 mg/day) decreased walking time, painful joints, and morning stiffness and increased grip strength (p less than 0.05). Both the global evaluation by the investigators and patient ratings of their activity showed superiority of tiopinac (tiopinac: 5 better, 1 worse; placebo: 1 better, 6 worse; p = 0.028 by Fisher's exact test). Complete aspirin withdrawal could be accomplished in only 3 patients, although in 10 of 13 the dose could be reduced 50% of baseline or less. The 3-phase protocol indicated effectiveness, a dose range, and partial aspirin replacement with minimal patient risk.
Cytogenetic studies from the peripheral blood of a patient with malignant lymphoma and rheumatoid arthritis who was treated with intra-articular gold Au 198 revealed mosaicism with a normal female metaphase and a 43-chromosome metaphase. The abnormal cell line showed six missing normal chromosomes and three morphologically abnormal chromosomes. The trypsin-digested G-banding metaphases showed that the marker chromosomes were an isochromosome of the long arm of chromosome 17, a translocated chromosome that involved the long arm of chromosome 4 and a chromosome 16, and a translocated chromosome that involved the long arm of chromosome 4 and a chromosome 5. It is tempting to conclude that these abnormalities were due to the gold Au 198 treatment, but we cannot exclude other possibilities.
A patient who has had three distinct recurrences of disseminated histoplasmosis over 22 years is presented. Measurements of cellular and humoral immune response to histoplasmin antigens were compared with previously reported data. Although initially sulfisoxazole therapy led to regression of disease, over the past 13 years she has required three courses of amphotericin B, each time with resolution of signs and symptoms. Despite minimal evidence of a cellular or humoral immune response to this organism, the patient has done well. Although disseminated histoplasmosis is often a fatal disease, this woman has tolerated the infection well.
Piroxicam (CP 16171), a new nonsteroidal anti-inflammatory agent, decreased pain, stiffness, and inflammation and increased the patient's ability to perform tasks in a double-blind study of patients with active, definite rheumatoid arthritis, poorly controlled despite standard therapy. Clinically and statistically significant improvement occurred in grip strength, walking time, and morning stiffness, and in patient and physician evaluation. Seventy-five per cent of the piroxicam-treated patients increased their daily activities. Three patients treated with the tablet form of piroxicam developed gastrointestinal ulcerations. Another patient developed iron deficiency anemia.
Gonococcal osteomyelitis is a rare complication of gonococcal infections since the advent of antibiotics. It is important that physicians be aware of this potential complication so that it is recognized and appropriate therapy promptly instituted.
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A heavy chain component of gammaG-globulins in normal urines has the characteristics of the proteolytic digestion product, Fc-fragment. This fragment is estimated to compose up to 15% of the gamma globulins present in urines. In contrast to urinary light chains, the urinary Fc-like fragment probably represents a catabolic component in normal gammaG-globulin metabolism. The light chains of the urine constitute more than half the total gamma globulin present. The calculated kappa/lambda ratio of light chains averaged 1.9 in ten urines, but the ratio in individual urines varied widely to either side of this figure. In two adult patients with agammaglobulinemia whose sera contained less than one-hundredth the normal gamma globulin levels, the urinary Fc-like fragment was absent, whereas the light chain levels were only one-tenth the average normal level. Treatment with exogenous gamma globulins resulted in normal or near normal Fc-like fragment excretion, whereas light chain excretion was only modestly affected.