No abstract

Limited extension of the small joints of the hand in association with tight, waxy overlying skin has been described in up to 30% of juveniles with insulindependent diabetes.'`3 This condition, termed juvenile diabetic cheiroarthropathy, has been described only infrequently in adults. The pathogenesis of diabetic cheiroarthropathy is poorly understood. In children it is most commonly associated with microvascular disease, at times predating the onset of microangiopathy of the eyes or kidneys. This suggests that the vascular abnormality characteristic of diabetes may be an important factor also in the development of limited joint mobility. In addition in poorly controlled insulin-dependent diabetic children enhanced cross-linking of connective tissue collagen may further contribute to the development of the lesion.3 Indeed the thickened skin and bowed fingers in cheiroarthropathy are remarkably similar to the appearance of the skin and fingers of individuals with early systemic sclerosis, where the development of bowed fingers appears to be secon-

No abstract

Among 31 patients with parkinsonism three investigations were performed by injecting apomorphine hydrochloride or placebo: (1) to 17 patients with or without orally administered levodopa, (2) to 14 patients receiving levodopa during episodes of tremor, hypokinesia or involuntary movements, and 3 to 10 patients three to 6 times a day for 2 to 43 days. With or without levodopa, apomorphine diminished tremor and rigidity. It decreased bradykinesia in patients receiving levodopa. The respective side effects were not additive: the "awakening effect", involuntary movements, and nausea induced by levodopa were antagonized by apomorphine, whereas the sedative effect and the nausea of apomorphine were antagonized by levodopa. The dichotomy between synergistic and antagonistic effects may be explained by the molecule of apomorphine, part of which resembles dopamine and the other resembles phenylethylamine, which can displace neurotransmitters from cellular sites. (27:474-480, 1972) Increased cerebral content of dopamine is assumed to explain the therapeutic effects of levodopa1 in parkinsonism2 and in chronic manganese poisoning,3 but this assumption cannot be proven by giving dopamine. Since dopamine is both a primary amine and a catechol, it is readily inactivated by both monoamine oxidase4 and catechol O-methyl transferase,1 and therefore it cannot enrich the brain after systemic administration. The weak tertiary catecholamine, apomorphine, must be less labile because tertiary amines are poor substrates for monoamine oxidase.4 Schwab et al5 showed that apomorphine injections can bring about short-lived but marked improvement of parkinsonism. Al¬ though we were unaware of this discovery we confirmed it in a double-blind study6 and so have others.7·8 Questions arose whether the symptoms of parkinsonism respond dif¬ ferently to injected apomorphine than to orally administered levodopa and whether improvement and side effects are increased or decreased when both drugs are adminis¬ tered together. Tests addressed to these questions are reported here. ProceduresPatients.-Thirty-one patients with parkin¬ sonism were studied as inpatients in a metabol¬ ic ward. They were injected subcutaneously with apomorphine (a) without orally adminis¬ tered levodopa (patients 1 to 11 and 26 to 31); (b) with orally administered levodopa (7 to 26); (c) both with and without orally adminis¬ tered levodopa (7-11 and 26). Seven patients (8, 10 to 13, 25, and 26) participated in more than one of three experiments detailed below and in the Tables.

No abstract