Eimar Munthe

Dermatomyositis Associated With BCG Vaccination

Two young boys developed serious forms of dermatomyositis following BCG vaccination. Possibilities of a causal relationship between the disease and the vaccination are discussed. Extensive immunological tests, however, including in vitro stimulation of lymphocytes with PPD, gave no decisive evidence of abnormalities. It is concluded that in cases of dermatomyositis there is an absolute indication for a full anamnesis with regard to previous vaccination, to obtain clarification of the practical and theoretically important questions of a possible connection in this respect.

Gold and Thiol Compounds in the Treatment of Rheumatoid Arthritis

Double isotope-labelled auro thiomalate (Au195-C14-thiomalate) has been administered to mice and rats, and the excretory fate and tissue distribution have been studied. The results show that the gold and the thiomalate separate in vivo resulting in protein-bound gold and release of free thiomalate. About half of this thiol is excreted in the urine during the first day and the remaining half is taken up by the tissues. Thiomalate penetrates cellular membranes poorly, but is able to interact slowly with proteins (mixed disulphide formation). Part of the thiomalate which remains in the body is membrane bound. In contrast to penicillamine little thiomalate remains in circulation a few hours after administration. Gas chromatography--mass spectrometry has been used to search for the presence of free thiomalate in rheumatoid arthritis patients on Myocrisin (auro thiomalate) therapy. Thiomalate was found in their urine, but not in serum and synovial fluid 20 hours after administration. As thiomalate is released in the body after administration of Myocrisin. the question arises whether this thiol, like penicillamine, may have a beneficial effect in the treatment of rheumatoid arthritis.

Capillary column gas chromatography--mass spectrometry in studies on rheumatoid arthritis.

A method is described for determining the organic acid profile of synovial fluid. The method requires 50--100 microgram of sample and involves ion exchange for isolation of the acids followed by combined capillary column gas chromatography--mass spectrometry. Normal synovial fluid and synovial fluid from patients with rheumatoid arthritis show a similar qualitative pattern of acids (mainly fatty acids) resembling the pattern found in serum. The concentrations of the organic acids in the abnormal synovial fluids are 5--10 times higher than those in the fluid from the normal joints. In patients receiving treatment with gold thiomalate, free thiomalate was excreted in the urine. The release of this thiol upon gold therapy is of consequence for the further understanding of the mechanism of action of certain drugs against rheumatoid arthritis.

THE EFFECT OF PENICILLAMINE AND 2,3-DIMERCAPTOSUCCINIC ACID ON URINARY EXCRETION AND TISSUE DISTRIBUTION OF GOLD

In order to study interactions in vivo between Au+ and SH-containing agents, groups of mice were given 35 mumol/kg of radiolabelled [195Au] thiomalate (Myocrisin) intramuscularly. The administration of Myocrisin is known to result in protein-bound gold and free thiomalate (mercaptosuccinate). High doses of dimercaptosuccinate (1 mmol/kg daily) increased the urinary excretion of radiolabelled gold [195Au] for several days. Treatment for 7 days with 1 mmol/kg of penicillamine or dimercaptosuccinate reduced the blood and kidney levels of gold to 30--50% of the controls. The oral administration of penicillamine in high doses, 1--10 mmol/kg, increased significantly the urinary excretion of [195Au] the first day after the Myocrisin injection, but on the subsequent days the radio-metal excretion was unaffected by the treatment. A lower dose level of penicillamine (0.3 mmol/kg daily) gave rise to only a small and insignificant increase in the urinary excretion of gold. The present results indicate that penicillamine at low clinical doses is an inefficient chelator of gold, while high doses (presumably comparable to about 1 200 mg daily in humans) may mobilize certain amounts of the metal deposits.

Biochemical and Clinical Effects of Penicillamine and Other Thiols Used in the Treatment of Rheumatoid Arthritis

Several years ago it was shown that rheumatoid factor molecules were split in vitro by the thiol penicillamine1. This was the rationale behind the original attempts to use penicillamine in the treatment of rheumatoid arthritis2. Although later studies have clearly shown that this simple mechanism does not operate in vivo, it was found that penicillamine was an antirheumatic drug3 which offers an alternative to gold compounds which, despite their high toxicity, have been used in the treatment of rheumatoid arthritis for over 50 years. In clinical laboratories and rheumatological centres there has consequently been an increasing interest in the biological effects of thiols in general and of penicillamine in particular. Recently another thiol, thiopyridoxin4,5 has been shown to posses antirheumatic properties. From the numerous scientific articles published during the last years, it appears that the thiol group may play important roles in the unlocking of the pathogenesis of rheumatoid arthritis.