We reviewed the records of 42 patients with Wilson's disease participating in a zinc acetate treatment protocol and interviewed 17 of them. Five of the patients studied were asymptomatic. A significant number of symptomatic patients (64.8%) reported psychiatric symptoms at the time of initial presentation. These symptoms were severe enough to warrant psychiatric intervention in almost half of all symptomatic patients before the diagnosis of Wilson's disease was made. Personality changes, particularly irritability and aggression, were most commonly described (45.9%), followed by depression (27%). Cognitive changes, anxiety, psychosis, and catatonia, while less frequent, also occurred. These data underscore the need to include Wilson's disease in the differential diagnosis of psychiatric disorders.

Actinomycin D, an inhibitor of DNA-dependent RNA synthesis, increased the hepatic concentration of a2u globulin, an androgen-inducible protein in the rat. Spayed female rats with a marginally induced state of a2u synthesis showed an approximately 5-fold increase in hepatic a2u globulin within 3-6 hr after treatment with actinomycin D. Initial treatment of these animals with 5a-dihydrotestosterone, followed by actinomycin D, resulted within 2-3 hr in a more than 2-fold increase in hepatic a2u globulin compared to animals treated with the androgen alone. In spite of inhibition of hepatic synthesis of poly(A)containing RNA to less than 25% of control, superinduction with actinomycin D resulted in a parallel increase in the translatable mRNA for a2u globulin. These results showing increase in both a2u globulin and its translatable mRNA after superinduction with actinomycin D support the concept of post-transcriptional repression of a2u synthesis. Actinomycin D, an inhibitor of DNA-dependent RNA synthesis, increases the level of several inducible proteins, a phenomenon termed "superinduction" (1, 2). Because actinomycin D inhibits mRNA synthesis, superinduction by this drug indicates an apparent paradox, the resolution of which may provide important clues concerning the mechanism of gene regulation in the eukaryotic cell. In fact, the post-transcriptional model for the steroidal regulation of gene activity, proposed by Tomkins and coworkers, is based primarily on their interpretation of the superinduction of glucocorticoid-mediated synthesis of tyrosine aminotransferase (TAT) by actinomycin D in hepatoma cells and in rat liver (3). A similar model of translational repression was also suggested by McAuslan (4). The above investigators have proposed that the mRNAs for the inducible proteins are continually being synthesized within the permissive phase of the cell cycle. However, the simultaneous presence of rapidly turning over post-transcriptional repressors prevents the translation of these mRNAs and may lead to their degradation. It is also proposed that, in the presence of inducing steroids, the repressor is inactivated and, because of its short half-life, is preferentially eliminated by actinomycin D, both of which phenomena would favor an accumulation of the inducible mRNA leading to increased synthesis of the inducible protein (3). Due to technical limitations, experimental verification of the McAuslan-Tomkins model has been difficult, and various other interpretations for the phenomenon of superinduction by actinomycin D have been proposed (5-7).In our laboratory we have developed a model system for the study of hormone action in rat liver (8, 9). The system involves androgen-dependent synthesis of a low molecular weight (23,000) protein called a2u globulin (10, 11). We have also identified the mRNA for a2u globulin in rat liver and have established a strong correlation between the androgen-dependent increase in a2u synthesis and the hepatic concentration of the mRNA for this protein (9,12,13 Cyclohexim...

A 27-year-old neuroleptic-stabilised schizophrenic patient presented with a three-day history of psychomotor retardation, disturbed sleep, and social and emotional withdrawal following reduction of his anticholinergic dosage; his symptoms had intensified after an increase in neuroleptic dosage, based on a diagnosis of psychotic decompensation. Recognition of a cholinergic syndrome and institution of appropriate anticholinergic treatment resulted in rapid improvement. The clinical distinction between a cholinergic overdrive state and schizophrenic exacerbation, while sometimes difficult, can be critical in selecting appropriate management.