Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function. Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction, controversy exists regarding the effects of increased concentrations of phenylalanine in older patients. We have studied ten older, treated, phenylketonuric patients using a triple-blind, multiple trials, crossover design. Each patient was tested at the end of each of three 1-wk periods of high or low phenylalanine intakes. Tests included a repeatable battery of neuropsychological tests, analysis of plasma amino acids, and measurement of urine amino acids, phenyl organic acids, dopamine, and serotonin. In all 10 patients, plasma phenylalanine rose (9004,000 AM). In 9 of 10 patients there was an inverse relationship between plasma phenylalanine and urine dopamine excretion. When blood phenylalanine was elevated, these patients had prolonged performance times on neuropsychological tests of higher but not lower integrative function. Urinary serotonin fell during phenylalanine loading in six patients. The concentration of phenylacids in the urine was not proportional to the plasma phenylalanine at concentrations below 1.5 mM. In one patient, neither performance time nor dopamine excretion varied as blood phenylalanine rose or fell. We interpret these data as follows: blood phenylalanine above 13 mM impairs performance on neuropsychological tests of higher integrative function, this effect is reversible, and one mechanism may involve impaired biogenic amine synthesis.

A 75-year-old man suffered a cardiac arrest and severe anoxic encephalopathy. A serial study of electroencephalograms during 4 days showed sequential changes from periodic approximately 2 Hz spike activity to absence-like status (ALS) and then into a suppression-burst pattern. Intravenous administration of phenytoin had no effect on ALS. A small dose of intravenous diazepam reduced a suppression-burst pattern. We speculate that the ALS originates in the midline structures, spreading bilaterally and synchronously to the "dysfunctional" cortex; the sustained discharges were a manifestation of associated reticular lesions, and we believe that intravenous diazepam suppressed the spread of ALS to the "dysfunctional cortex," leading to the appearance of the suppression-burst pattern. The only limitation for definitive conclusions may be a lack of postmortem verification. Autopsy findings, however, could not have confirmed the dynamic changes that occurred during the 5 days before the patients death.

In this new method for estimating free thyroxine concentration in serum by use of polyacrylamide gel filtration, the prolonged incubation that is characteristic of equilibrium dialysis is obviated. Although the values so obtained for the percentage of free thyroxine are severalfold higher than those obtained by dialysis, the results of the two procedures correlate well over a wide range of thyroid states. In addition, the precision of the polyacrylamide method compares well with that for equilibrium dialysis. The method is convenient for use in clinical laboratories and values for free thyroxine in serum of patients with metabolic thyroid disorders are diagnostically discriminatory.

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