No abstract

Summary: Purpose: We wished to determine the incidence of first provoked and nonprovoked epileptic seizures in the canton of Geneva, Switzerland.

Binding sites for AVP and for OT were studied by in vitro autoradiography in sections from the brain of rat fetuses, neonates and infants; their distribution was compared to that of the brain of adults. Specific binding sites were first detected in the vagal complex for OT and in the reticular formation for AVP at E14 and E16 respectively. In the perinatal period, other areas become labeled. Approximately one week after birth, a "stable" pattern of distribution is established for AVP binding sites, and a different "stable" pattern obtained for OT binding sites. For both types of sites and in many areas, the density of labeling increases during the next two weeks to reach adult levels, whereas labeling decreases concomitantly in other areas of the brain. The distribution of AVP binding sites is of the adult pattern by the time of weaning. In contrast, the adult pattern of distribution of OT binding sites is only established after puberty, when new OT receptors appear in some regions of the hypothalamus and basal forebrain. "Transient" binding sites for AVP and OT, i.e. sites located in areas which were labeled in neonates but not in weanlings, were shown to have the same ligand affinity than the binding sites present in the adult. Electrophysiological studies suggest that at least some of these "transient" binding sites represent authentic receptors and may be involved in neuronal signaling.

During the period of life that precedes weaning, the facial nucleus of the newborn rat is rich in 3H-vasopressin binding sites, and exogenous arginine vasopressin (AVP) can excite facial motoneurons by interacting with V1 (vasopressor-type) receptors. We have investigated the mode of action of this peptide by carrying out single-electrode voltage-clamp recordings in coronal brainstem slices from the neonate. Facial motoneurons were identified by antidromic invasion following electrical stimulation of the genu of the facial nerve. When the membrane potential was held at or near its resting level, vasopressin generated an inward current whose magnitude was concentration related; the lowest peptide concentration still effective in eliciting this effect was 10 nM. The vasopressin-induced current, IAVP, was resistant to tetrodotoxin (TTX) and was insensitive to a reduction in extracellular calcium concentration. It was sustained, was inward at all potentials tested (-120 to -25 mV), and increased in magnitude during depolarization. IAVP was not generated by the blockade of a potassium current, because it did not reverse at hyperpolarized potentials, was not affected by a two-fold increase in the transmembrane potassium gradient, and was not modified by the potassium channel blockers tetraethylammonium bromide (TEA), 4-aminopyridin (4-AP), barium, cesium, quinine, glibenclamide, and apamin. Also, IAVP was not affected by changes in the transmembrane chloride gradient. In contrast, it could be reduced by partially substituting extracellular sodium with equimolar N-methyl-D-glucamine or Tris. Our results suggest that vasopressin increases the excitability of facial motoneurons by generating a persistent sodium-dependent membrane current that is voltage gated and TTX resistant.

We have compared the dose of levothyroxine (L-T4) required to suppress serum TSH to given levels in two clinical groups: 1) 44 patients with thyroid cancer whose thyroid glands had been ablated by surgical thyroidectomy and 131I treatment, and 2) 113 patients with thyroidal failure due either to spontaneous primary hypothyroidism (31 patients) or after 131I treatment for Graves' hyperthyroidism (82 patients). The dose of L-T4 needed to attain serum TSH levels in the euthyroid range (0.5-6.2 microU/mL) was significantly greater (P less than 0.01) in patients with thyroid cancer (2.11 micrograms/kg.day) than in the patients with primary hypothyroidism associated with nonmalignant disease (1.63 micrograms/kg.day). Similarly, patients with thyroid cancer required a higher dose of L-T4 to suppress serum TSH to a given subnormal level. These findings suggest that the secretion of hormone from residual thyroid tissue in patients who have not been subjected to near-total thyroid ablation contributes substantially to the circulating levels of serum T4 and T3. We, therefore, infer that residual thyroidal secretion in the patients with hypothyroidism due to benign causes is relatively independent of TSH stimulation. Further subdivision of patients with benign hypothyroidism revealed that patients with Graves' who developed hypothyroidism after 131I treatment showed a lower mean dose requirement than patients with spontaneous hypothyroidism. This raises the possibility that continued secretion of thyroid-stimulating immunoglobulin in such patients might account for the lower dose requirement in the combined group with hypothyroidism. Our studies also have allowed us to make serial observations in 4 patients with thyroid cancer who exhibited elevated levels of serum thyroglobulin. In this limited series, maximal suppression of serum thyroglobulin was produced by doses of L-T4, which reduced circulating TSH to 0.4 mU/L.