Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis.

Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.

The effect of lead on tetrahydrobiopterin metabolism. A possible mechanism for neurotoxicity.

The use of low levels of lead in vivo in rats has been found to inhibit dihydropteridine reductase and cause an apparent increase in tetrahydrobiopterin biosynthesis. At higher dose levels inhibition of tetrahydrobiopterin biosynthesis has been observed. At low levels the disruption of tetrahydrobiopterin metabolism has been found to give an increase in the total level of biopterin derivatives but a movement away from the fully reduced form to the oxidised species in a manner consistent with dihydropteridine reductase inhibition. Lead has been found to inhibit dihydropteridine reductase in man.

Pseudotumor cerebri--a complication of tetracycline treatment of acne.

A female adolescent on tetracycline therapy for a dermatologic condition developed pseudotumor cerebri resulting in impaired visual acuity and papilledema. The therapy of pseudotumor cerebri is discussed.

Neonatal staphylococcal scalded skin syndrome: massive outbreak due to an unusual phage type.

A massive outbreak of the staphylococcal scalded skin syndrome due to an organism with an unusual phage pattern, occurred during a 115-day period and involved 68 newborns. Generalized exfoliative dermatitis was seen in 24 babies, and Staphylococcus aureus was isolated from 23. Fourteen isolates were phage typed, with 13 reported as the epidemic strain 29/79/80/3A/3C/54/75. Eight babies had generalized scarlatiniform eruption without exfoliation (staphylococcal scarlet fever). Cultural data were available from six, all positive for S aureus. Four organisms were typed and reported as the epidemic strain. Of 34 infants with bullous impetigo 20 had cultures that were positive for S aureus, and four were phage typed, revealing the epidemic strain. Illness was mild in all patients; there were no deaths and no invasive forms of staphylococcal infection. The male to female ratio of generalized exfoliative disease was 5:1. The concept of a neonatal staphylococcal scalded skin syndrome, comprised of a triad of skin disorders induced by an exotoxin elaborated by certain strains of coagulase positive S aureus, is confirmed.