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Biomedical subjects

I A Jaffe

Publications and source records attributed to I A Jaffe.

At least 37 records · Page 2Linked to original sources
PubMed1986

Adverse effects profile of sulfhydryl compounds in man.

Many of the adverse reactions produced by penicillamine and other compounds with an active sulfhydryl group form a distinctive pattern when viewed as a class. Alterations in taste perception, mucocutaneous lesions, proteinuria due to immune-complex membranous glomerulopathy, and pemphigus are adverse reactions that have been encountered with all of the compounds discussed herein. Hematologic reactions such as neutropenia and thrombocytopenia occur rarely and with variable frequency. The angiotension converting enzyme inhibitor captopril has an active sulfhydryl group. When it was first given in high doses to patients with severe hypertension, adverse effects similar in pattern to those just outlined were reported. With reduced doses and more careful patient selection, the more serious reactions are no longer found, but disturbances of taste perception, rash, and oral mucosal ulcers are still encountered.

Anemia, Aplastic↗
PubMed1983

Penicillamine: an anti-rheumatoid drug.

Penicillamine is now established as a useful disease remittive drug in the treatment of rheumatoid arthritis. Improvement during a successful course of treatment may be found in a decrease in the degree of synovitis, which is associated with a reduction in the level of rheumatoid factor and immune complexes in serum and synovial fluid. Vasculitic lesions also resolve. There is roentgenographic evidence of healing of the erosive lesions after two to three years of treatment. The multiplicity of adverse effects caused by the drug limits its usefulness, although with increasing experience more patients are being treated successfully. The induction of autoimmune side effects in a small number of patients treated with penicillamine has elicited particular interest since this may represent a clue to its mechanism of action on the immune system. The over-all approach to the use of the drug, including currently accepted methods of dosing and safety monitoring, is reviewed.

Antigen-Antibody Complex↗
PubMed1982

Penicillamine-induced myasthenia gravis: effects of penicillamine on acetylcholine receptor.

Autoimmune diseases, including myasthenia gravis, occur in patients treated with D-penicillamine. Because D-penicillamine might induce autoantibodies by the mechanism of antigenic alteration, we studied the reaction of D-penicillamine with purified acetylcholine receptor from Torpedo californica. We found that brief exposure to D-penicillamine resulted in its covalent attachment to two receptor subunits, alpha (40,000 daltons) and gamma (59,000 daltons), presumably by reduction and formation of mixed disulfides. Furthermore, D-penicillamine treatment resulted in a dramatic modification of the equilibrium acetylcholine binding properties of both purified receptor and receptor-rich membrane fragments.

Acetylcholine↗
PubMed1981

Penicillamine-associated pemphigus: is it really pemphigus?

Penicillamine-associated bullous eruptions share with spontaneously occurring pemphigus intraepidermal acantholysis, epidermal intercellular deposition of immunoglobulin, and circulating serum antibody against the intercellular regions of the epidermis. We report the case of a penicillamine-associated bullous eruption in which there were some of the histologic features of pemphigus, but none of the immunofluorescent features. Instead, the immunofluorescent findings of bullous pemphigoid were demonstrated. Review of the literature reveals that clinical and histologic features of penicillamine-associated bullous eruptions differ in important respects from those of spontaneously occurring pemphigus. Our report adds immunologic data to evidence that the penicillamine-associated bullous eruptions may not be the same disease as spontaneously occurring pemphigus.

Arthritis, Rheumatoid↗
PubMed1980

5-Thiopyridoxine in rheumatoid arthritis: clinical and experimental studies.

Twelve patients with rheumatoid arthritis who had failed to respond to or developed side effects preventing further use of penicillamine were given 5-thiopyridoxine (5-TP). These patients were compared with 48 patients with similar indications randomly assigned to placebo or penicillamine. Both 5-TP and penicillamine were superior to placebo, and the effectiveness of the two active drugs was similar. Both produced a gradual amelioration of symptoms and signs of the disease accompanied by reduction in erythrocyte sedimentation rate, rheumatoid factor titer, and immunoglobulins. Nine patients on 5-TP were able to continue treatment with good control of the disease for at least 18 months. Toxic effects included rashes, proteinuria, loss of taste, and mouth ulcers. Patients who had developed a particular side effect with penicillamine did not necessarily do the same with 5-TP. This is the second mercaptan compound which has suppressive effects on the clinical and laboratory features of rheumatoid arthritis. Because of their similarities, 5-TP and penicillamine were studied in various experimental systems in an attempt to find some common biochemical or pharmacologic action. Among the properties studied were the effects on copper, vitamin B6 metabolism, dermal collagen, and mixed disulfide formation. Results with animal models of inflammation were also examined. The only common action was enhancement of the secondary lesions of adjuvant arthritis.

Animals↗
PubMed1979

Penicillamine in rheumatoid arthritis: clinical pharmacology and biochemical properties.

The current status of the clinical pharmacology of penicillamine was reviewed. Its indications in the therapy of RA were defined, and current principles of dosage were presented. The autoimmune side effects were discussed in the light of their possible implication with regard to a locus of action of the drug on the immunological system. A comparison was presented of the biochemical properties of penicillamine and 5-thiopyridoxine, another mercaptan compound which appears to demonstrate a penicillamine-like action in patients with RA. It was found that 5-thiopyridoxine did not possess copper chelating properties, it failed to form a mixed disulfide with cystine, it did not induce dermolathyrism in the weanling rat, and it was not a vitamin B6 antagonist. If both of these compounds do work by a common mechanism in RA, then the aforementioned biochemical properties of penicillamine must be presumed to be not relevant to its fundamental action in this disease.

Arthritis, Rheumatoid↗
PubMed1978

[Pyrithioxine a new basic treatment of rheumatoid polyarthritis: initial study of 72 cases with a 6-month follow-up].

Pyrithioxine has certain chemical resemblances to penicillamine and is used as original treatment in a series of 72 cases of rheumatoid arthritis over a period of six months in a dose of 600 mgs daily. Results were favourable in 63% of cases with important lowering of the articular index, return to normal of the sedimentation rate and less frequently a reversal of the Waaler-Rose reaction. Secondary complications were essentially muco-cutaneous, sometimes gastric and necessitated stopping treatment in 15% of cases. No other serious side effect has been observed. When compared with penicillamine pyrithioxine would appear less efficacious but better tolerated. The usefulness of this new medicament in the treatment of rheumatoid arthritis needs to be further explored.

Adult↗
PubMed1977

[Pyrithioxine: a new basic treatment of rheumatoid arthritis. Open study of 60 cases with a follow-up of 6 months].

Pyrithioxine, a chemical compound with several points in common with penicillinamine, was used for six months as the basic treatment in a series of 60 cases of rheumatoid arthritis, in a dose of 600 mg per day. The results were favourable in 60 per cent of cases, with a marked fall in articular index, a return to normal of sedimentation rate and, less commonly, negativisation of the Rose-Waaler reaction. Side effects were essentially cutaneo-mucosal (pruitus, rash) and necessitated the interruption of treatment in 16.5 per cent of cases. No complications were seen. Compared with penicillinamine, pyrithioxine appears to be less effective but better tolerated. The place of this new basic drug in the basic treatment of rheumatoid arthritis remains to be precisely determined.

Adult↗