Search

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 FU. 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.

Mitogen-stimulated normal human lymphocytes were exposed to d-penicillamine (d-pen) at various concentrations and different time intervals. d-Pen inhibited-lymphocyte response to mitogen stimulation and was also inhibitory to the mixed lymphocyte reaction. The inhibition was found to be partial and dose dependent. The inhibition of lymphocyte transformation was not due to nonspecific inhibition of protein, RNA, or DNA synthesis. The drug was inhibitory only when it was present during the first 20 hr of culture. The inhibitory effect seemed to be related to some process prior to the initiation of the replicative phase. It is suggested that d-pen may block the signal for the initiation of DNA replication, or partially inhibit the activation of enzymes required for the above process.

We report the clinical and pathologic features of a patient with peripheral neuropathy that was the first clinical expression of cholesterol emboli syndrome (CES). Biopsy of skeletal muscle and peripheral nerve revealed cholesterol clefts in lumens of small arteries, necrotizing arteritis, and severe degeneration of peripheral and intramuscular nerves. At autopsy, the peripheral nervous system was extensively affected by similar changes. We conclude that (1) peripheral neuropathy may be the initial manifestation of CES. Presumably, deposition of cholesterol leads to arteritis. (2) The underlying pathology of CES neuropathy is chronic axonal degeneration, possibly due to chronic ischemia of epineurial arteries. (3) Muscle biopsy is important in the antemortem diagnosis of CES. Nerve biopsy may show involvement of epineurial vessels. (4) CES may resemble polyarteritis nodosa clinically and pathologically. (5) CES may be under-recognized and should be included in the differential diagnosis of any neuropathy of uncertain cause, particularly when there is a history of vascular catheterization, or severe aortic atherosclerosis.

The tetragonal polymers (III) with stacked layer (Rh(I)...Rh(I) 3.31‐3.41 Å) structures are prepared by the 1:4 molar reactions shown in the scheme.