The New England journal of medicine
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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. ⋯ 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.
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Randomized Controlled Trial Clinical Trial
Inhibition of mediator release in allergic rhinitis by pretreatment with topical glucocorticosteroids.
Patients with allergic rhinitis often have immediate symptoms after antigen challenge (the early-phase response), followed several hours later by a recurrence of symptoms (the late-phase response). Systemic glucocorticosteroids are known to inhibit the late-phase but not the early-phase response. We studied the effect of one week of pretreatment with topical (rather than systemic) glucocorticosteroids on the response to nasal challenge with antigen in a double-blind, randomized, placebo-controlled crossover study of 13 allergic patients who had previously had a dual response to nasal challenge. ⋯ Topical glucocorticosteroids significantly reduced both the symptoms and the levels of histamine, TAME-esterase activity, and kinins in the early, late, and rechallenge allergic reactions. The fact that, in contrast to treatment with systemic glucocorticosteroids, prolonged pretreatment with topical glucocorticosteroids inhibited the early-phase response to antigen suggests that the route and duration of administration affect the mechanisms of action of the steroids. We conclude that inhibition of the early-phase as well as the late-phase response by topical glucocorticosteroids may provide an advantage over treatment with systemic glucocorticosteroids in patients with allergic rhinitis.
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Whether human coronary arteries undergo compensatory enlargement in the presence of coronary disease has not been clarified. We studied histologic sections of the left main coronary artery in 136 hearts obtained at autopsy to determine whether atherosclerotic human coronary arteries enlarge in relation to plaque (lesion) area and to assess whether such enlargement preserves the cross-sectional area of the lumen. The area circumscribed by the internal elastic lamina (internal elastic lamina area) was taken as a measure of the area of the arterial lumen if no plaque had been present. ⋯ The lumen area did not decrease in relation to the percentage of stenosis (lesion area/internal elastic lamina area X 100) for values between zero and 40 percent but did diminish markedly and in close relation to the percentage of stenosis for values above 40 percent (r = -0.73, P less than 0.001). We conclude that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area. The preservation of a nearly normal lumen cross-sectional area despite the presence of a large plaque should be taken into account in evaluating atherosclerotic disease with use of coronary angiography.