Comparison of urinary acylglycines and acylcarnitines as diagnostic markers of medium-chain acyl-CoA dehydrogenase deficiency.
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Biomedical subjects
Publications and source records attributed to L V Miller.
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The present study was designed to study the interaction of propionic acid and carnitine on oxidative metabolism by isolated rat hepatocytes. Propionic acid (10 mM) inhibited hepatocyte oxidation of [1-14C]-pyruvate (10 mM) by 60%. This inhibition was not the result of substrate competition, as butyric acid had minimal effects on pyruvate oxidation. Carnitine had a small inhibitory effect on pyruvate oxidation in the hepatocyte system (210 +/- 19 and 184 +/- 18 nmol of pyruvate/60 min per mg of protein in the absence and presence of 10 mM-carnitine respectively; means +/- S.E.M., n = 10). However, in the presence of propionic acid (10 mM), carnitine (10 mM) increased the rate of pyruvate oxidation by 19%. Under conditions where carnitine partially reversed the inhibitory effect of propionic acid on pyruvate oxidation, formation of propionylcarnitine was documented by using fast-atom-bombardment mass spectroscopy. Propionic acid also inhibited oxidation of [1-14C]palmitic acid (0.8 mM) by hepatocytes isolated from fed rats. The degree of inhibition caused by propionic acid was decreased in the presence of 10 mM-carnitine (41% inhibition in the absence of carnitine, 22% inhibition in the presence of carnitine). Propionic acid did not inhibit [1-14C]palmitic acid oxidation by hepatocytes isolated from 48 h-starved rats. These results demonstrate that propionic acid interferes with oxidative metabolism in intact hepatocytes. Carnitine partially reverses the inhibition of pyruvate and palmitic acid oxidation by propionic acid, and this reversal is associated with increased propionylcarnitine formation. The present study provides a metabolic basis for the efficacy of carnitine in patients with abnormal organic acid accumulation, and the observation that such patients appear to have increased carnitine requirements ('carnitine insufficiency').
The reaction of verapamil with concentrated sulfuric acid was studied. It was found, in disagreement with a published report, that the reaction did not hydrolyze the nitrile group of the drug to the corresponding carboxylic acid, but, instead, produced a sulfonated derivative. Analysis of the product using several spectroscopic techniques indicated that the sulfonic acid moiety was introduced into the verapamil molecule at the 6-position of the 3,4-dimethoxyphenyl ring distant to the chiral center.
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A study was conducted on the use of radiographic studies by 138 medical residents. They ordered an initial chest film on 88% of their patients and averaged a 34% yield. Though the range of other radiographic studies ordered per patient varied by a factor of 15, more than half the resident physicians ordered an average of less than one for every two patients. These physicians experienced overall yields between 0 and 100%, with half the residents averaging between 33 and 57%. This data base was then used to derive empirical norms of radiographic study utilization that can be employed to evaluate physicians' utilization in providing care to comparable populations.
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