Pubertal maturation and classical phenylketonuria.
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Biomedical subjects
Publications and source records attributed to E Riva.
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The effectiveness of an orally administrable thymic derivative (Thymomodulin) for the treatment of the recurrent respiratory infections (RRI) in children has been studied in a double-blind clinical trial with historical comparison. In the Thymomodulin treated group a significant decrease of the monthly frequency of RRI has been observed in comparison with the previous year (P less than 0.05) and with the placebo treated group (P less than 0.002). The evaluation of the laboratory data at the beginning of the study didn't show in the two groups typical alterations of the common hematological and immunological parameters, but at the end of the trial a statistically significant increase of the levels of salivary IgA has been noticed only in the Thymomodulin treated group (P less than 0.02).
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Dihydropteridine reductase deficiency is a rare cause of hyperphenylalaninaemia, characterized by severe and progressive neurological impairment, despite early and accurate dietary control of plasma phenylalanine. We describe two girls, diagnosed at 17 and 14 months of age, respectively, and immediately treated with L-dopa, 5-hydroxytryptophan and carbidopa. In spite of an adequate dietary and pharmacological treatment, the clinical and neurological pictures progressively worsened. Repeated cranial computerized axial tomography scans showed degeneration of the white matter and, in one case, calcification of the basal ganglia. The possible association of this last finding with folate depletion is discussed.
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A 47-year-old woman affected by Cushing's syndrome due to an adrenal adenoma is described. An altered but rhythmometrically apparent cortisol secretory rhythm was detected using the single-cosinor computation. In fact serum cortisol levels and urinary excretion of 17-OHCS were elevated in the PM hours, particularly between 14:00-18.00 h and 18:00-22:00 h, and normal between 02:00-10:00 h. The patient was cured by unilateral adrenalectomy and one year later the circadian rhythm of corticosteroids secretion was investigated again. A normal rhythm of cortisol secretion and of 17-OHCS urinary excretion was found. Though it may be hypothesized that factors intrinsic to the tumoral adrenal cells were responsible for the rhythmic, but phase-shifted, hormonal release, the cause of the persistent and abnormal cortisol secretory rhythm is unknown.
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On the basis of general pharmacological information (blood cells/plasma partition, plasma protein binding) and using HPLC as the principal analytical method, we investigated the kinetics and metabolism of theobromine (a caffeine metabolite) in male rats after a single dose and after a 2 week chronic application. Doses in both conditions varied between 1 and 100 mg/kg. In in vitro and in vivo the fraction of theobromine unbound to plasma proteins averaged 0.90 over a wide range of concentrations. No significant difference was found in the pharmacokinetic profile of the drug after acute or chronic treatment at different doses except for a reduction in the absorption rate constant as the dose increased. AUC values increased in proportion to the dose. The 2 treatment schedules were also similar as regards metabolism, at least 50% of the administered dose of theobromine being excreted unchanged, and 25% as 6-amino-5-[N-methyl- formylamino ]1-methyluracil. Only at the highest doses was there a tendency for theobromine to accumulate at the expense of its major metabolite (a uracil compound).
We studied three healthy volunteers after a single i.v. bolus of amiodarone, during 1 month of chronic oral dosing and after the discontinuation of the drug. Blood concentrations of amiodarone declined rapidly in a bi-exponential fashion after i.v. bolus. The terminal half-life ranged from 10 to 17 h; after discontinuation of chronic treatment the terminal half-lives were 8-21 days. The i.v. data, the trough levels during multiple dosing and the washout phase could be simultaneously fitted using a triexponential equation. The subjects were carefully monitored for cardiac and thyroid function. One subject had to stop taking amiodarone because of profound bradycardia. A reduction of serum TT3 and FT3 concentrations and an increase of serum rT3 and FT4 was found.
The time course and the mode of antiarrhythmic action of Amiodarone was studied after acute i.v. injection of the drug (5 mg/kg in 5 min) to four patients with junctional reciprocating tachycardia. Electrophysiological studies were performed before and 1 and 2 hours after Amiodarone injection. It was impossible or considerably more difficult to induce junctional reciprocating tachycardia after Amiodarone, and the drug's effect was detectable mainly on the AV node. Kinetic analysis of blood levels of Amiodarone during the electrophysiological study did not support a direct association between blood concentration and its effects.
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The effects of the acute administration of sodium-valproate (400 mg po) on plasma ACTH levels were studied in 4 patients with Cushing's disease, 1 with Nelson's syndrome and in 3 with Addison's disease. No significant reduction of corticotropin concentration was observed, as compared to saline infusion. These data do not favor the hypothesis of an inhibitory role of sodium-valproate on ACTH secretion in such patients.