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Biomedical subjects
Publications and source records attributed to C A Pierach.
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The effect of bilateral carotid sinus denervation (CSD) on the ECG and on the monophasic ventricular action potential (MAP) was studied in 28 and 4 rats, respectively. After CSD, T wave changes, similar to those seen in man after carotid endarterectomy, were observed and mean Q-T prolongations of 19 ms were recorded (P less than 0.001). Mean MAP increased by 10 ms (P less than 0.02). P-QRS and heart rate remained stable. Propranolol, 10 mg/kg iv, before CSD and 10 mg.kg-1.day-1 iv for 2 days prevented all ECG abnormalities. Atropine, 1 mg/kg iv, before CSD and 2.5 mg.kg-1.day-1 iv for 2 days had no effect. Isoproterenol, 0.02-0.06 microgram iv, after CSD produced further lengthening of the MAP and Q-T interval. Blood gases and electrolytes remained unchanged, and cardiac histology was unremarkable. These results suggest that CSD produces alterations in cardiac sympathetic activity in the rat leading to MAP and Q-T prolongations and to changes in the T wave form. Similar mechanisms may be operative after carotid endarterectomy in man.
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In rats after i.v. porphobilin, blood pressure and pulse rate remained stable, the animals were calm and moved freely with no symptoms or signs of nervous effect. Porphobilin was rapidly excreted in the urine.
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There is compelling, indirect evidence of hepatic heme deficiency due primarily to the respective genetic errors of the three inducible hepatic porphyrias, acute intermittent porphyria, porphyria variegata, and hereditary coproporphyria. The induction is enhanced by exogenous inducers such as barbiturate, estrogens and other "porphyrogenic" chemicals and factors, including glucose deprivation. The newer knowledge of the induction of delta-aminolevulinic acid synthetase [delta-aminolevulinate synthase; succinyl--CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] in relation to inadequate heme, and repression by heme, stimulated early trials of hematin infusions to overcome the acute relapse in the foregoing inducible porphyrias. Recently this experience has been considerably expanded, 143 infusions of hematin having been given in 22 cases. Studies of the effect on the serum concentrations of delta-aminolevulinic acid and porphobilinogen have shown a highly significant decline, often to 0, especially of delta-aminolevulinic acid. A distinct relationship to the clinical severity of the attack has been evident in the frequency and magnitude of decline of serum delta-aminolevulinic acid and porphobilinogen. This was regularly associated with objective clinical improvement.
Early, intravenous administration of hematin in a patient with acute intermittent porphyria and severe quadriparesis may have produced partial but remarkable improvement of neuropathy, and resulted in simultaneous decline of porphyrin precursors in the blood. Intermittent, biweekly hematin infusions given 1 month after the onset of the porphyric relapse had no effect on recovery of the residual neuropathy. We believe hematin may be effective in the treatment of porphyric neuropathy, if administered before irreversible neuronal damage has occured.
A comparison of the Hoesch and the Watson-Schwartz tests shows that the latter, although slightly more complicated, generally yields more concise results and is superior in sensitivity and specificity for porphobilinogen. The recommendation of the Hoesch test for use as a "bedside screening" method seems unrealistic. Before the diagnosis of an "inducible" porphyria is made, a positive Hoesch test requires that indoles, indoleacetic acid, methyldopa, end-stage alcoholic malnutrition, and phenazopyridine HCl be excluded, to avoid misinterpretation.