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Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study.

Low dose corticosteroids are effective in suppressing synovitis in rheumatoid arthritis (RA), but there remains concern about their side effects, particularly osteoporosis. To examine the effects of low dose corticosteroids on bone loss in RA bone mineral density (BMD) was measured in the lumbar spine and hip for up to two years in 15 patients treated with these agents (mean dose prednis(ol)one 6.6 mg/day). 15 patients not receiving them, and 15 age matched controls. The initial BMD at both skeletal sites was significantly reduced in both patient groups compared with controls. The mean change in bone density was 0.2, 0.1, and -0.1% a year in the spine and -2.0, -1.9, and -1.0% a year in the hip respectively for the three groups. These rates of bone loss were not significantly different between groups at either site. These findings suggest that low dose corticosteroid treatment in RA is not associated with an increased risk of osteoporosis.

Patterns of plasma concentrations and urinary excretion of salicylate in rheumatoid arthritis

lntersubject differences in the volume of distribution, whole body clearance, and steady‐state plasma concentrations of salicylic acid (SA) were studied in a series of patients with rheumatoid arthritis and healthy control subjects. The measurement of the plasma concentration of SA 12 hr after an oral dose of 1.2 gm aspirin appears predictive of the success of long‐term dosage of aspirin. Concentrations below 5 u‐g/ml in this single‐dose test were associated with failure to achieve therapeutic plasma concentrations of SA (above 150 u‐g/ml) during long‐term therapy with approximately 4.8 gm aspirin per day. Conversely, plasma concentrations above 10 u‐g/ml in the single‐dose test were associated with levels above 150 u‐g/ml during long‐term therapy. The volume of distribution of SA correlated poorly with body weight (r = 0.51, P < 0.01) and did not correlate significantly with plasma albumin levels. Corticosteroids appear to induce the metabolism of SA and most subjects dosed with oral corticosteroids and aspirin 4.8 gm/day did not attain plasma levels of SA above 150 u‐g/ml. The clearance of SA was greater in male than in female patients. The difference appears to be of clinical significance since fewer men than women achieved therapeutic plasma concentrations of SA.

The effect of cyanide on the uptake of gold by red blood cells.

Cyanide markedly increased the rate of uptake of gold by red blood cells when incubated with sodium aurothiomalate, a polymeric gold complex. Thiocyanate had no significant effect on gold uptake. The effect of cyanide was demonstrated to be due to the conversion of aurothiomalate to the complexion, aurocyanide, which is rapidly taken up by red blood cells. At a low ratio (1:20) of cyanide to aurothiomalate, cyanide appeared to act as a shuttle to carry gold into red blood cells. Tobacco smoking is known to increase the concentrations of gold in red blood cells in patients treated with aurothiomalate. The present data indicate that this effect of smoking is most likely due to cyanide inhaled in tobacco smoke and not to thiocyanate, a circulating metabolite of cyanide. An effect of cyanide on the uptake of polymeric gold complexes to target cells such as polymorphonuclear leukocytes and monocytes is suggested.

The activation of gold complexes by cyanide produced by polymorphonuclear leukocytes—I: The effects of aurocyanide on the oxidative burst of polymorphonuclear leukocytes

It has been suggested that the antiarthritic gold complex, aurothiomalate (Autm), is activated by its conversion to aurocyanide by polymorphonuclear leukocytes (PMN) which generate cyanide from thiocyanate. In an examination of this hypothesis, a study has been conducted on the effects of aurocyanide on the oxidative burst of polymorphonuclear leukocytes (PMN) and monocytes activated by phorbol myristate acetate (PMA). Aurocyanide produced delayed inhibition of the oxidative burst as shown by its effect on both lucigenin and luminol-dependent chemiluminescence and on the production of superoxide. It was a more potent inhibitor of luminol-dependent chemiluminescence than free thiomalate and other by-products of the reaction between Autm and cyanide. Aurocyanide had a biphasic effect on the PMA-stimulated hexose monophosphate shunt of PMN, with enhancement at 0.1 microM and inhibition at 10 and 100 microM. The activity of aurocyanide was also compared with that of auranofin, an orally active gold complex, which inhibits a variety of functions of PMN and monocytes. At low concentrations, auranofin produced delayed inhibition of chemiluminescence in a similar fashion to aurocyanide but at high concentrations was an immediate inhibitor of the oxidative burst.

The effect of non-steroidal anti-inflammatory drugs on adenosine triphosphate content and histamine release from rat peritoneal cell suspensions rich in mast cells.

1 Non‐steroidal anti‐inflammatory drugs (NSAID) suppressed compound 48/80‐induced histamine release from rat peritoneal cells in vitro in a dose‐dependent manner. 2 NSAID suppressed the adenosine triphosphate (ATP) content of rat peritoneal cells in vitro and this correlated strongly with the suppression of compound 48/80‐induced histamine release. 3 The correlation demonstrated suggests that the mechanism of action of NSAID in the rat peritoneal cells is via depletion of cellular ATP.

Fibromyalgia in the workplace.

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