A. Avinoam Kowarski

Correlation of Urinary Excretion of C-Peptide with the Integrated Concentration and Secretion Rate of Insulin

The secretion rate of insulin (SR-I) of 50 normal subjects was calculated from the 24-h integrated concentration of insulin (IC-I), the peripheral metabolic clearance of insulin (pMCR-l), and the mean fractional hepatic insulin extraction (fhMCR-l) that was derived from our data. fhMCR-l was determined as the difference in the molar secretory rate of C-peptide (SR-C) and the molar peripheral clearance of insulin (pMCRI × IC-I) divided by SR-C. The IC-I in our 50 subjects was 1.19 ± 0.38 ng/ml and the IC-C was 2.93 ± 0.58 ng/ml. Based on these data, the fhMCR-l was 0.40 and the SR-I was estimated to be 54.8 ± 18.0 U/24 h. The 24-h urinary C-peptide excretion (U-C), 44.9 ± 20.4 μg/24 h, had a statistically significant correlation with SR-I (r = 0.838, P < 0.0001), while the IC-I correlated significantly with the 24-h urinary C-peptide/g of creatinine (r = 0.823, P < 0.0001). The U-C may thus serve as a practical method for estimating the SR-I.

The pharmacokinetics of amikacin in children

The pharmacokinetic variables of amikacin were measured in 20 children and adolescents, four to 16 years of age. The mean plasma clearance of amikacin was 120 ml/minute/1.73 m 2 . The major route of elimination was renal (82%). Simultaneously measured inulin clearance showed that a majority (64%) of the drug filtered by the kidneys was excreted in the urine. The mean volume of distribution of amikacin was 32% of body weight; half-life during the final (pseudoequilibrium) phase averaged 1.6 hours. No significant accumulation of the drug was seen when four doses were given intravenously at 420 mg/m 2 every 8 hours; the plasma concentration just before injection of the fourth dose averaged 2.4±1.1 μg/ml. The mean plasma concentration at 60 to 75 minutes after injection of the drug was 28.7 μg/ml with little interpatient variation (SD 3.5 μg/ml). When the dose was expressed in terms of milligrams per kilogram, it was found that children often needed 50 to 100% more of the drug, compared to adults, to achieve equivalent plasma concentrations; this larger requirement was primarily due to a higher clearance of amikacin in proportion to body weight. Dosages based on surface area, however, resulted in uniform requirements and predictable plasma concentrations in all patients studied.

Pituitary function in adult males receiving medroxyprogesterone acetate

The pituitary, adrenal, and gonadal functions of nine males (six XY, two XYY, and one XY/XYY) were studied after at least 6 months of medroxyprogesterone acetate (MPA) therapy for antisocial or sex-offending behavior. Five were studied both before and during therapy, four only during therapy. MPA was effective in decreasing serum gonadotropin and plasma testosterone concentrations. MPA caused no change in the 24-hour rhythm or total integrated concentration of growth hormone. The plasma cortisol circadian rhythm was suppressed but not obliterated by MPA therapy. Although a significant decrease (P less than 0.001) in 24-hour integrated concentrations of plasma cortisol was also found, the rise in the plasma cortisol level after insulin-induced hypoglycemia was unchanged.

The in vivo stability of the tritium label in 1,2-H3d-aldo-sterone when used for measurement of aldosterone secretion rate by the double isotope dilution technique.

Abstract The in vivo stability of the tritium label in 1,2-H3- d -aldosterone has been demonstrated in two totally adrenalectomized patients. It is concluded that this radioactive preparation is suitable for the measurement of aldosterone secretion rate in man. It is suggested that when using the method of Kliman and Peterson, two paper chromatographies should be carried out after pH 1 hydrolysis, acetylation and oxidation.

Are Constitutional Delay of Growth and Familial Short Stature Different Conditions

Children between 2 and 4 standard deviations below the mean height for age with no specific cause to account for their short stature are usually considered to represent either constitutional delay of growth (CDG) or familial short stat ure (FSS). This study was undertaken to determine whether 167 patients who were referred to our clinic for short stature could be divided into two distinct populations that fit the criteria of CDG and FSS. When the patients were arti ficially divided into 2 subgroups based on skeletal age greater or less than 2 standard deviations below the mean, no significant difference in growth rates or midparental heights could be found between them. Height ages were sig nificantly more delayed in the group with greater skeletal age delay. Mid parental height of our total population of short children was less than the mean midparental height of normal American children. It was concluded that our patients did not distribute into these two clear-cut entities. Whether they repre sented one continuum or two largely overlapping populations could not be decided on the basis of our data.

Persistence of the enzymatic block in adolescent patients with salt-losing congenital adrenal hyperplasia.

The 24-hour integrated concentration of aldosterone, plasma renin activity, and 17-hydroxprogesteronewas measured simultaneously in 12 patients with congenital virilizing adrenal hyperplasia due to 21-hydroxylase deficiency. Eight were salt-losers and four nonsalt-lowers. Seven normal children served as control subjects. All patients were receiving glucocorticoid replacement therapy (32 mg/m 2 /day). All but one of the SL-CVAH patients were also being treated with 9α-fluorocortisol. The mean (±SD) IC-PRA of the control subjects was 1.6±0.7 ng/ml/hour and in the NSL-CVAH patients was similar (1.6±0.7 and 2.2±1.0 ng/ml/hour). The IC-PRA of the SL-CVAH patients (21.1±28.8 ng/ml/hour) was significantly ( P P