Pubertal changes in net renal tubular secretion of digoxin.

To evaluate the effect of puberty on the net renal tubular secretion of digoxin, we measured the ratio of digoxin clearance to creatinine clearance in 23 patients aged 4 to 21 yr and correlated this ratio with both sexual maturity (Tanner stage) and chronologic age. All subjects were at steady-state levels for digoxin treatment; all had normal serum creatinine values for age as well as normal serum potassium levels. Mean ratio for immature children (n = 14, Tanner 1 through 3.5) was 1.45 +/- 0.66. Mean ratio for mature adolescents (n = 9, Tanner 4 through 5) was 0.95 +/- 0.28. The difference between the two groups was significant (P less than 0.05). When patients were regrouped by age using either 13 or 15 yr as a cutoff, the difference in ratios was no longer statistically significant. Based on 45 subjects (new and from our previous study) aged 2 mo to 80 yr, there was a significant decrease in the clearance ratio with increasing age, but when the 23 subjects aged 4 to 21 yr were analyzed separately, the correlation between ratio and age was not significant. It appears that the decrease in net renal tubular secretion of digoxin from childhood to adulthood correlates better with full sexual maturation at puberty (Tanner 4 through 5) than with chronologic age. This observation may represent a developmental change in pharmacokinetics with broader significance than for digoxin disposition alone.

Verbal fluency and psychiatric symptoms in geriatric schizophrenia.

Previous studies have demonstrated that negative symptoms are regulated by frontal brain regions. We were interested in the relationship between psychiatric symptoms and performance on a verbal fluency (VF) battery in a population of elderly schizophrenic subjects. Thirty-five elderly schizophrenic subjects were administered a neuropsychological battery which included verbal fluency performance and Positive and Negative Symptom Scale (PANSS). Results showed negative symptoms to be strongly correlated with performance on tasks of VF, which may suggest that negative symptomatology in schizophrenia is related to prefrontal cortical activity.

Changes in salivary antipyrine pharmacokinetics during adolescence, correlated with age, hormonal levels and Tanner stage.

To evaluate the effect of puberty on antipyrine metabolism, we measured antipyrine pharmacokinetics in 17 healthy subjects aged 6-21 years. The subjects received a single oral dose of antipyrine, 18 mg/kg. Salivary antipyrine levels were determined 3, 6, 9, 12 and 24 h after dosing. Age, weight, body surface area and Tanner stage were highly intercorrelated. Volume of distribution (liters) was highly correlated with all of these factors. The weight-corrected clearance of antipyrine declined significantly with age (r = 0.55, p less than 0.025). Patients were classified as immature and other based on serum hormone levels (immature = females with serum estradiol less than 25 pg/ml and males with serum testosterone less than 25 ng/dl). The uncorrected antipyrine clearance was significantly lower in the immature group (mean +/- SD 22.65 +/- 6.04 ml/min) than in others (mean +/- SD 41.30 +/- 13.26; p less than 0.01). This difference disappeared when the weight-corrected antipyrine clearance was compared for these two groups. The change in uncorrected antipyrine clearance with sexual maturation appeared to be due to increased body size, probably related to the adolescent growth spurt.

Pacing in children and young adults with nonsurgical atrioventricular block: comparison of single-rate ventricular and dual-chamber modes.

A prospective comparison of physiologic response to single-rate ventricular and dual-chamber atrioventricular pacing was conducted in 14 pediatric patients (age 1 to 24 years, median 14) with symptomatic nonsurgical second- or third-degree atrioventricular block. All patients were studied acutely during cardiac catheterization before and after 1 hour of both pacing modes. Following pacemaker implant, eight patients were reevaluated after 1 month of each mode with symptom questionnaire, resting ECG, resting echocardiogram, and Doppler cardiac output measurement at rest and at peak treadmill exercise. Cardiac outputs (mean +/- standard error) increased acutely (n = 14) with both ventricular (32 +/- 12%) and dual-chamber (39 +/- 10%) pacing over intrinsic rhythm values (p less than 0.01 in both). During chronic pacing (n = 8), symptoms were reported only with the ventricular mode. Dual-chamber synchronous pacing was associated with improved mean resting shortening fraction and cardiac output, slower mean resting sinus rate (89 +/- 5 compared to 73 +/- 4 bpm (p less than 0.02), and a 23% increase in mean excerise cardiac output (4.2 +/- 0.4 compared to 3.4 +/- 0.3 L/min/m2) compared to single-rate ventricular pacing. Exercise-induced dysrhythmias occurred only with ventricular pacing. This study demonstrates that pediatric patients with nonsurgical atrioventricular block can compensate for loss of atrioventricular synchrony at rest but exhibit improved cardiac function with chronic dual-chamber atrioventricular compared to single-rate ventricular pacing.