Biomedical subjects
J Sladek
Publications and source records attributed to J Sladek.
Pharmacokinetics and clinical effects of atenolol in therapy of hyperthyroidism.
The pharmacokinetics of atenolol and the effect of the drug on the clinical and laboratory features of hyperthyroidism were studied in 23 patients with hyperthyroidism. In the hyperthyroid state, the time to peak plasma concentration (Tmax) occurred significantly earlier, the elimination half-life was significantly shorter, and the areas under the curve were also significantly less compared to the euthyroid state, but there was no significant difference in peak plasma concentrations (Cmax) between these states. Administration of atenolol once daily resulted in marked clinical improvement in 2 to 4 weeks. The clinical index of thyrotoxic symptoms and signs decreased from 23.2 +/- 10.8 to 8.4 +/- 5.3 (p less than 0.005). Pulse similarly decreased significantly from 93.9 +/- 15.7 to 77.8 +/- 10.5. In contrast to the marked clinical improvement, there was no change in any of the serum concentrations of thyroid hormones T4, free T4, T3 and free T3 at the time of maximal clinical effect compared to pretreatment values. These data show that the beneficial effect of atenolol in hyperthyroidism is not due to changes in thyroid hormone metabolism.
Immunoenzymatic quantification of low concentrations of thyrotropin.
We evaluated an immunoenzymatic assay (Abbott HTSH EIA) for thyrotropin (TSH) as a tool for detecting hyperthyroidism and for monitoring thyroid hormone suppressive therapy in patients with nodular goiter, thyroid carcinoma, and hypopituitarism. We also tested with thyroliberin (TRH), to determine the correlation between peak and basal TSH in suppressed patients. For comparison, we used a nonequilibrium radioimmunoassay optimized for maximum sensitivity (J Clin Endocrinol Metab 1975;41:676). Hyperthyroid patients with values for either or both triiodothyronine and thyroxin above the normal reference interval had Abbott assay values less than or equal to 0.2 milli-int. unit/L, clearly below the Abbott assay normal range, as determined in 116 euthyroid subjects. We detected one-third of the suppressed patients (greater than or equal to 0.3 milli-int. unit/L) with RIA, 69% with the Abbott assay (TSH greater than or equal to 0.04 milli-int. unit/L). Only 20% of patients with undetectable basal TSH values in the Abbott assay responded to TRH with a detectable peak TSH value; the peak TSH value after TRH was proportional to the basal TSH value. A single basal TSH measurement by the Abbott HTSH EIA should be adequate for monitoring the degree of thyroidal suppression in thyroid-hormone-treated patients.
Stimulation of LH fragments with reduced bioactivity following GnRH agonist administration in women.
In eumenorrheic women with endometriosis and in oligo-amenorrheic women with polycystic ovarian disease (PCO), chronic administration of a long-acting GnRH agonist (GnRH-a) reduced the circulating concentrations of estrogens and androgens to levels similar to those of castrated women. The concommittant elevation of LH in both groups suggested that the measured immunoreactive LH had reduced bioactivity. In seven women with endometriosis, bioactive LH (BA LH) measured as the in-vitro secretion of testosterone by dispersed Leydig cells, was significantly (p less than 0.001) reduced from 10.8 +/- 1.2 (SEM) to 4.4 +/- 0.2 mIU/ml at the end of 28 days of GnRH-a therapy. In five women with PCO, BA LH decreased from 44.2 +/- 15.5 to 5.7 +/- 0.6 mIU/ml (p = 0.06). These changes of BA LH appeared to be responsible for the suppression of ovarian androgen secretion during GnRH-a treatment and in turn may have contributed to the profound decreases of estrogen production by reducing the amount of precursor androgen available for aromatization. Free alpha subunit levels increased simultaneously with the decrease of BA LH at the end of therapy, suggesting a post-receptor effect of GnRH-a. Beta subunit levels became undetectable. Cross-reaction of alpha subunit in the RIA for LH was sufficient to only partially account for the LH levels measured. On sephadex G-100 chromatography the excess immunoreactive material was detected at and immediately following the alpha subunit tracer. Further studies will be necessary to elucidate the chemical nature of the immunoreactive LH secreted during GnRH-a therapy.
Histochemical fluorescence after application of neurochemicals to caudate nucleus and septal area in vivo.
The movement of carbachol, norepinephrine, and dopamine from cannula sites in caudate nucleus and septal area of freely moving rats was traced by means of biogenic amine fluorescence. Fluorescent patterns seen after application of carbachol and norepinephrine to brain tissue did not appear to differ from controls. Three types of movement from the cannula site after administration of dopamine were observed. There was a spherical distribution approximately 2 millimeters in diameter. Fluorescence also followed axonal pathways in the orthodromic direction, suggesting that dopamine may have been transported by " axonal streaming " or by some other unknown mechanism in periaxonal spaces. Because fluorescence was present in both the ependymal lining and the choroid plexus, it was inferred that the cerebral ventricles were also involved in the movement of chemical. Any attempt to ascribe anatomical localization to behavioral effects resulting from chemical stimulation of the brain should take into account the widespread movement of chemicals after their local application to brain tissue.