Short-term effect on growth of two doses of GRF 1-44 in children with growth hormone deficiency: comparison with growth induced by methionyl-GH administration.

In a double-blind study 12 prepubertal children with idiopathic growth hormone (GH) deficiency were treated with growth hormone releasing factor (GRF) 1-44 in a dosage of 7.5 or 15 micrograms/kg body weight, administered once a day subcutaneously. With 7.5 micrograms/kg the average growth velocity increased from 2.5 to 4.6 cm/year, an insufficient response. With the higher dosage the average growth velocity increased from 2.7 to 7.0 cm/year, a similar increase as observed with GH therapy in subsequent periods. In 3 of the 6 children treated with the higher dose appropriate catch-up growth was observed. The growth response of the lower leg length was not always consistent with the statural growth response.

[Efficacy and kinetics of chlorazepate administered to anxious patients in a single daily dose]. / Efficacité et cinétique du clorazepate administré en une dose unique quotidienne chez des anxieux.

Twelve patients of both sexes (5 women, 7 men; mean age = 39,9) suffering from marked anxiety as defined by DSM III for generalised anxiety (score greater than 20 on the Hamilton-A scale) but in good physical health, were given 15 mg of clorazepate daily at 8 p.m. for a period of 28 days. Desmethyldiazepam, the active metabolite of clorazepate was measured in blood samples on day 1, 14 and 28 of the experiment as well as the level of anxiety on the Hamilton scale. Anxiety decreased significantly between day 1 and day 14 (mean score declining from 33,9 to 18,4) and from day 14 to day 28 (mean score 18,4 to 14,7). Desmethyldiazepam reached its maximum blood concentration 2 hours after the first intake of clorazepate. A plateau had been reached at day 14 and remained stable up until day 28, indicating the absence of cumulating effects. The dosage remained the same for all patients during the 28 days of the experiment. There were no drop outs and no undesirable effects.

Pemoline pharmacokinetics and long term therapy in children with attention deficit disorder and hyperactivity.

The pharmacokinetic behaviour of pemoline was studied in 28 children, aged 5 to 12 years, diagnosed as having the attention deficit disorder with hyperactivity. The mean elimination half-life of pemoline in these children was approximately 7 hours, which is considerably shorter than the half-life of 11 to 13 hours previously reported in adults. The tendency of the half-life to increase with age may be explained by the statistically significant decrease in total body clearance with age. The increasing half-life of pemoline with age should be considered during long term drug therapy. In this study no tolerance to the beneficial effects of pemoline was observed over 6 months. The apparent therapeutic serum concentration range for these children was attained after doses of 37.5 to 131.25 mg pemoline daily. Since the optimum serum concentration shows wide variation, the dosing regimen must be determined individually. Routine monitoring of the pemoline serum concentrations is not useful because of this apparent variation in optimum serum concentration and because of the linear relationship between dose and concentration.

Plasma estrone sulfate levels in postmenopausal women.

Estrone sulfate levels were measured in the plasma of 63 postmenopausal women. The assay method involved prior extraction of the free estrogens, enzyme hydrolysis of the estrone sulfate with sulfatase and radioimmunoassay of the estrone liberated. The plasma levels ranged from 37 to 320 pg/ml (expressed as free estrone) with a mean value of 178 +/- 79 pg/ml. As observed in premenopause, estrone sulfate is quantitatively the most important circulating estrogen in postmenopausal women.

Analysis of pemoline in serum by high performance liquid chromatography: clinical application to optimize treatment of hyperactive children.

The analysis of pemoline (2-imino-5-phenyl-4-oxazolidine) by a rapid, sensitive, and specific high performance liquid chromatographic assay using ultraviolet detection is described. Only 100 microliters of plasma or serum is required. Analytical recoveries of 88% for pemoline and 93% for the internal standard (4-methylprimidone) are obtained by this procedure. Between-day precision studies of serum controls containing 10.2, 2.0, and 0.5 mg pemoline/liter produce coefficients of variation of 6.2, 9.4, and 16.2%, respectively. A clinical study of 28 children treated with pemoline demonstrated a linear relationship between drug dose and serum concentrations with an apparent therapeutic range falling between 1.7 and 7.0 mg/liter. These serum concentrations were achieved at drug dosages between 37.5 and 112.5 mg/day.

The responses to synthetic luteinizing hormone-releasing hormone in patients with primary selective pituitary deficiency in gonadotropins.

Fifteen patients, 11 female and four male, with primary selective pituitary deficiency in gonadotropins were submitted to the subcutaneous administration of 100 to 400 mcg. of luteinizing hormone-releasing hormone (LH-RH). When compared to the effect of LH-RH in eight normal female subjects, two types of responses were observed: there were either small increments in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or increases comparable to those observed in normal subjects. Five patients received 100 mcg. of LH-RH daily over four consecutive days. No additive nor depleting effects could be observed. The responses in seven patients given 400 mcg. were not significantly different from those obtained with 100 mcg. Our results indicate two possible etiologies of primary hypogonadotropic hypogonadism. A normal response in LH and FSH after administration of LH-RH assesses a selective hypothalamic deficit in releasing hormones, whereas a negative or low response suggests a dysfunction of the pituitary gonadotropic cell.

Pituitary responsiveness to gonadotrophin releasing factor (GnRH) in puerperium.

Administration of a single dose of Gondotrophin Releasing Factor (GnRF) failed to induce an increase in serum FSH immediately postpartum suggesting pituitary refractoriness. However, multiple injection of GnRF resulted in significant FSH increments but these were less than the FSH responses to a single injection of GnRF in normal menstruating women.

Survival and growth in a woman with untreated hypothalamic panhypopituitarism of 21 years' duration.

A 29-year-old woman with evidence of a craniopharyngioma and documented panhypopituitarism is described. Clinical and laboratory evaluation revealed deficiencies of follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, growth hormone, prolactin, adrenocorticotropic hormone and antidiuretic hormone. Prompt release of several pituitary hormones was noticed after administration of the hypothalamic releasing hormones FSH/LH-RF and thyrotropin-releasing hormone, whereas insulin-induced hypoglycemia, levodopa, chlorpromazine and clomiphene citrate, all of which act at the level of the hypothalamus, did not alter basal pituitary secretion. The patient's height of 60 inches, despite panhypopituitarism, and the interpretation of the above data are discussed in the light of current concepts regarding the dynamics of the hypothalamic-hypophyseal system.