Effect of metoclopramide therapy on arginine vasopressin excretion and renal water handling in premature infants

The role of endogenous dopamine (DA) in regulating arginine vasopressin (AVP) release and renal water excretion was studied in 10 premature infants with a mean birth weight of 1,341 g (range 1,150-1,660 g) and a mean gestational age of 30.2 weeks (28-33 weeks), who were given metoclopramide (MTC), a specific DA antagonist. It was demonstrated that in response to MTC urine flow rate increased significantly from a basal value of 0.90 +/- 0.07 to 1.27 +/- 0.09 ml/min/1.73 m2 (mean +/- SE; p less than 0.01), urinary sodium excretion from 6.10 +/- 1.47 to 11.7 +/- 2.24 microEq/min/1.73 m2 (p less than 0.025) and osmolar clearance from 0.38 +/- 0.044 to 0.600 +/- 0.075 ml/min/1.73 m2 (p less than 0.01). MTC administration did not cause any alterations in free water clearance, whereas urinary AVP excretion fell significantly from 49.38 +/- 10.13 to 32.66 +/- 6.53 ng/min/1.73 m2 (p less than 0.05) after MTC. It is concluded that, contrary to adults, in low birth weight premature infants endogenous DA is enhancing rather than inhibiting AVP release and the MTC-induced water diuresis is independent of the fall of AVP since free water clearance remained unaltered after MTC.     

Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study

The pharmacokinetics of tobramycin in adolescents or young adults with cystic fibrosis and in age-matched controls were prospectively compared. Patients with CF had a higher tobramycin total body clearance (121.2 +/- 14.2 ml/min/1.73 m2) than did controls (102.2 +/- 18.9 ml/min/1.73 m2, P less than 0.05). This was not associated with a higher glomerular filtration rate (iothalamate total body clearance 147.5 +/- 29.2 ml/min/1.73 m2 in patients vs 142.9 +/- 33.3 ml/min/1.73 m2 in controls) or a lower binding of gentamicin to serum proteins (14.3% +/- 2.6% in patients vs 17.4% +/- 3.8% in controls). Tobramycin renal clearance was not significantly different in the two groups (89.5 +/- 17.9 ml/min/1.73 m2 in patients vs 81.0 +/- 15.8 ml/min/1.73 m2 in controls). In the control group, tobramycin total body and renal clearances were highly correlated with iothalamate total body clearance (r = +0.95 and +0.88, P less than 0.01). In patients with cystic fibrosis, the correlation was not significant (r = +0.56, P greater than 0.05 for total body clearance, and r = 0.32, P greater than 0.1 for renal clearance). There was no significant difference in volume of distribution normalized to body surface area or in half-life of elimination. The higher tobramycin total body clearance without an increase in renal clearance, and the lower correlation with glomerular filtration rate indicate that an extrarenal clearance pathway might play a significant role in the elimination of tobramycin from the serum of patients with cystic fibrosis.     

The relationship between carnitine and ketone body levels in diabetic children

Free carnitine was significantly (p less than 0.001) reduced both in the ketotic (29.7 +/- 3.4 nmol/ml) and in the ketoacidotic (24.6 +/- 1.4 nmol/ml) groups when compared to controls (50.0 +/- 2.4 nmol/ml). At the same time, acylcarnitine values in the ketotic (21.2 +/- 2.4 nmol/ml) and ketoacidotic (25.4 +/- 2.3 nmol/ml) groups were significantly above the control value (4.71 +/- 0.6 nmol/ml). There was no significant difference between the two ketotic groups in carnitine derivatives. The abnormal distribution of plasma free and acylcarnitines could be reversed by insulin treatment. There was an inverse correlation between ketone body levels and free carnitine in the ketotic (r = -0.71, p less than 0.02) and ketoacidotic group (r = -0.71, p less than 0.05). However, there was no correlation between ketone bodies and acylcarnitine and between free carnitine and acylcarnitines. We concluded that the increased acylation was only partly responsible for the reduction of free carnitine in diabetic ketosis.     

The effect of assisted ventilation on creatinine clearance and hormonal control of electrolyte balance in very low birth weight infants

Because renal function and electrolyte balance are commonly altered in premature infants, particularly those requiring ventilatory support, we studied the influence of assisted ventilation on renal electrolyte and water excretion in infants with birth weights less than 1501 g during the 2 days after birth. Twenty-two infants receiving assisted ventilation, either as intermittent mandatory ventilation or nasal continuous positive airway pressure, were compared with 21 spontaneously ventilating infants of similar birthweight and gestational age. Mean (and SEM) creatinine clearance was lower (p less than 0.05) in the assisted ventilation group on day 1 (2.9 +/- 0.4 versus 4.1 +/- 0.4 ml/min/1.73 m2) and on day 2 (4.1 +/- 1.0 versus 6.8 +/- 0.8 ml/min/1.73 m2, p = 0.05), and there was a correlation between creatinine clearance and mean blood pressure in both groups. Mean urine vasopressin was higher in the assisted ventilation group on the first day (360 +/- 86 versus 123 +/- 30 pg/mg creatinine; p less than 0.02) and correlated with higher urine osmolality. There were no differences in urine volume, in osmolar or free water clearances, or in the intake and urine excretion of sodium, potassium, and chloride. Plasma renin activity, urine aldosterone, and urine prostaglandin E2 were similar in both groups on both days. Neither the mode of assisted ventilation nor the cause of respiratory failure appeared to affect these results.     

Disposition of oral methotrexate in children with acute lymphoblastic leukemia and its relation to 6-mercaptopurine pharmacokinetics

We studied the disposition pharmacokinetics of methotrexate (MTX) given orally to 16 children with acute lymphoblastic leukemia (ALL) and its relation to the pharmacokinetics of 6-mercaptopurine (6MP) in the same children. There was an eightfold variability in area-under-concentration time-curve (AUC) of MTX achieved by the same dose. Excellent correlation existed between peak concentrations and AUC0----infinity (r = 0.95, P less than 0.001). Elimination T1/2 was between 1.34 and 5 hours (mean 2.16 +/- 0.23 hr, mean +/- SE). A weak correlation existed between AUC achieved by 1 mg/m2 MTX and patients' age or body weight. Weak but significant correlation existed between AUC achieved by 1 mg/m2 of MTX vs. 6MP (r = 0.54, P less than 0.05). In 13/16 patients peak concentrations were achieved at 60 minutes. There was a significantly larger AUC of 6MP achieved by a standardized dose in longer therapy (greater than 15 mo) vs. short therapy (less than 12 mo) (462 +/- 75 and 246 +/- 58 ng.ml-1.min.mg-1.m2, P less than 0.025). No statistical differences in AUC of MTX were found between short and long therapy. The large interpatient variability in MTX pharmacokinetics supports the possibility that differences in absorption and/or clearance of the drug may affect the clinical response. Because of the excellent correlation between peak and AUC of MTX, and because 3 measurements, at 30, 60, and 90 minutes will almost invariably identify the peak, this measurement can be used to estimate AUC for purpose of correlation with clinical outcome.     

Intermittent intravenous cyclophosphamide therapy for lupus nephritis

We carried out a preliminary study to determine whether intermittent intravenous cyclophosphamide therapy could be safely and effectively used in the treatment of childhood lupus nephritis. Sixteen children (4 to 18 years of age) with lupus nephritis were treated with cyclophosphamide monthly for 6 months and then every 3 months. Eight children were treated because of corticosteroid-unresponsive active lupus nephritis, with a fall in their creatinine clearance to less than 100 ml/min/1.75 m2, and eight children were treated because of corticosteroid-dependent nephrotic syndrome or active lupus nephritis with unacceptable corticosteroid-induced side effects. Cyclophosphamide treatment was associated with significant improvement at 1 year in mean levels of hemoglobin (11.3 +/- 0.5 to 13.1 +/- 0.3 gm/dl), C3 (52 +/- 5.9 to 108 +/- 13.7 mg/dl), and C4 (7.6 +/- 0.9 to 15.9 +/- 2.2 mg/dl) (all p less than 0.005), despite a significant reduction in mean prednisone dosage (31 +/- 5 to 14 +/- 2 mg/day; p less than 0.005). There was a decrease in 24-hour urine protein excretion from 3121 +/- 913 to 1016 +/- 364 mg/24 hours (p less than 0.05). For children whose initial creatinine clearance was less than 100 ml/min/1.75 m2, creatinine clearance also improved significantly (57.5 +/- 11 to 121 +/- 24.5 ml/min/1.75 m2; p less than 0.05). The long-term safety of intravenous cyclophosphamide therapy and its long-term efficacy in comparison with prednisone alone remain to be established. In the interim, intravenous cyclophosphamide therapy should be reserved for children with severe, unacceptable corticosteroid side effects or with corticosteroid-resistant and potentially life-threatening disease.     

Renal functional impairment in preterm neonates related to intrauterine indomethacin exposure

Renal function was measured during the first 4 postnatal days in 9 preterm neonates (gestational age 26.2 to 31 wk) exposed to indomethacin during the last 2 days of pregnancy (group I). The data were compared to those obtained from nine control neonates (gestational age 28 to 34.5 wk) (group II). Five of the nine neonates in group I were markedly edematous at birth, none of group II were edematous. Urine production in group I was low (32.2 +/- 16.8 ml/kg.day on day 1 increasing to 68.6 +/- 21.4 ml/kg.day on day 4) and differed significantly from group II [75.2 +/- 26.8 ml/kg.day on day 1 increasing to 84.8 +/- 20.9 ml/kg.day on day 4 (p less than 0.001)]. Fluid intake was adapted to urine production when necessary. A continuous inulin infusion was started directly after admission and continued for 5 days. Renal function was evaluated for 3 consecutive days after at least 48 h of insulin infusion. The values of the inulin clearance, serum creatinine, urine osmolarity, osmolar clearance, and free water clearance were stable in both groups during the study period. Inulin clearance was lower in group I than in group II (p less than 0.001), whereas serum creatinine was higher in group I than in group II (p less than 0.0001). Urine osmolarity was higher in group I (p less than 0.01), whereas osmolar clearance and free water clearance were lower in group I (p less than 0.02, respectively, p less than 0.01). There was no difference in fractional sodium excretion between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect on renal function of essential fatty acid supplementation in cystic fibrosis

Changes in renal hemodynamics, sodium homeostasis, renal acidifying capacity, and aldosterone excretion were studied before and after long-term intravenous essential fatty acid supplementation for a period of 3 years in 11 patients with cystic fibrosis. The mean (+/- SD) glomerular filtration rate was high at the start of the study (133 +/- 18 ml/min/1.73 m2 body surface area) and decreased significantly (p less than 0.05) to within normal values after 1 year of essential fatty acid supplementation. The urinary elimination of an oral sodium load initially was very low (3.6 +/- 2.5 mmol/hr/1.73 m2 body surface area vs control subjects' values of 7.9 +/- 2.0; p less than 0.001) and increased during treatment but was not normalized (p less than 0.05 vs control subjects' values). Free water clearance and distal tubular sodium delivery, which were significantly decreased before treatment (p less than 0.01 and p less than 0.001 vs control subjects' values, respectively) did not increase significantly. The mean urinary aldosterone excretion did not significantly differ from that in control subjects before and after treatment. The acidifying capacity was disturbed, indicating a low renal bicarbonate threshold, and was changed during treatment in only 2 of 10 patients. These data indicate that essential fatty acid deficiency may contribute to the renal disturbances in cystic fibrosis.     

Carnitine status and blood ammonium levels in low birth weight infants

Forty-three low birth weight infants appropriate for gestational age (AGA) were monitored to evaluate carnitine status in relation to blood ammonium levels. The infants were grouped into three depending on blood ammonium level on postnatal day 7: 62.9 +/- 3.8 mumol/L in group 1 (N = 13), 38.9 +/- 8.4 mumol/L in group 2 (N = 23), and 24.5 +/- 2.9 mumol/L in group 3 (N = 9). Plasma free carnitine levels decreased in all three groups (p less than 0.001) and plasma short chain acylcarnitine increased only in group 1 (p less than 0.002), compared to findings in normal infants. The blood ammonium level positively and negatively correlated to plasma short chain acylcarnitine (p less than 0.002) and plasma free carnitine levels (p less than 0.002), respectively. The reabsorption rate of free carnitine in renal tubules (RRFC) was decreased at rates of 37.5, 27.5, and 25% of infants in groups 1, 2, and 3, respectively. The acylcarnitine/free carnitine clearance ratio (RAFCC) was decreased in groups 1 (p less than 0.01) and 2 (p less than 0.05) compared with group 3. Thus, an accumulation of short chain acyl moieties and insufficiency in renal absorption of free carnitine are putative causes of lowered plasma free carnitine in infants with higher blood levels of ammonium. The possibility that the carnitine status regulates blood ammonium levels in low birth weight infants warrants continued investigation.     

Optimization of gentamicin therapy in very low birth weight infants

In order to optimize gentamicin (G) therapy we studied G pharmacokinetics in 48 preterm infants (gest. age 31.6 +/- 3.4, range 25-37 wk; birth weight 1.5 +/- 0.5 kg, range 0.7-2.5 kg). They received IV G twice daily (5.2 +/- 0.6 mg/kg/day). After at least 2 days of treatment trough and peak levels were measured for 2 successive doses. Trough levels were significantly higher in infants less than 1 kg receiving 5 mg/kg/day than in other infants (1-2.5 kg) who received the same dose (3.1 +/- 1.0 vs. 2.3 +/- 0.5 micrograms/ml; p less than 0.01). Mean G t 1/2 was significantly longer in infants under 1 kg than in those weighing 1-2.5 kg (7.9 +/- 1.9 and 6.5 +/- 1.6 hr, respectively; p less than 0.01). These differences could be attributed to lower G clearance in infants less than 1 kg (31 +/- 6 vs. 39 +/- 8 ml/kg/hr; p less than 0.005). There was no difference in G distribution volume between less than 1 kg and 1-2.5 kg infants (0.35 +/- 0.07 and 0.38 +/- 0.13 L/kg, respectively). A correlation was found between clearance and t 1/2 for the total group (r = 0.57, p less than 0.01). No correlation was detected between BUN and clearance or between gestational age and clearance. Our data suggest that G dose in infants less than 1 kg should be reduced to 3.5-4 mg/kg/day in order to avoid excessive levels associated with nephrotoxicity.     

Biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialyzed children

In this study we investigated the value of biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialysis patients. The study was carried out in 22 chronic renal failure patients (mean age: 16.1 +/- 4.5) being treated with chronic dialysis. There were three groups according to intact parathormone (iPTH) levels: Group I (n: 6): iPTH levels were less than 200 pg/ml; Group II (n: 9): iPTH levels were between 201 and 500 pg/ml; and Group III (n: 7). iPTH levels were higher than 501 pg/ml. We investigated iPTH, bone alkaline phosphatase, total serum alkaline phosphatase, osteocalcin, serum type 1 procollagen peptide (PICP) and insulin-like growth factor-1 (IGF-1) levels in all patients. In group III mean bone alkaline phosphatase level (126.0 +/- 10.95) was significantly higher than in both group I and group II (52.16 +/- 22.8, 57.35 +/- 16.21) (p < 0.001). Mean osteocalcin level (35.13 +/- 2.93) in group I was significantly lower than in group III (40.52 +/- 2.83) (p < 0.05). Serum alkaline phosphatase, PICP and IGF-1 levels were not different between the groups (p > 0.05). There was a significant positive correlation between bone alkaline phosphatase and iPTH (r = 0.80, p < 0.0001). Serum osteocalcin correlated with both bone alkaline phosphatase and iPTH (correlation) coefficients were r = 0.44 and r = 0.51 respectively, p < 0.05). It is concluded that bone alkaline phosphatase and osteoocalcin combined with iPTH level seem to be useful noninvasive markers of bone metabolism in dialysis patients.     

Changes of plasma free amino acids and renal clearances of carnitines in premature infants during L-carnitine-supplemented human milk feeding

Eighteen breast-fed infants with a mean post-natal age of 26 days (range 16-41 days) were studied. Following 1 control day, the infants were fed for 7 consecutive days with pooled human milk supplemented with 300 nmol L-carnitine/ml milk. Both plasma fractions of acid-soluble carnitines increased as a consequence of carnitine application. The level of beta-hydroxybutyrate also increased significantly. Of the circulating free amino acids, the levels of alanine (p less than 0.025) and glutamine (p less than 0.01) were found to be lower, with a decreased urea level (p less than 0.005) by the last day of carnitine administration, compared with the control day. The urinary output of total nitrogen also decreased. There were no statistically significant changes in the level of free fatty acids and glucose. On the control day, the renal clearance rate of esterified carnitines significantly exceeded that of free fraction, thus the relative renal reabsorption calculated on the base of creatinine excretion rates was higher for free (mean 98.1%) than for acylated (mean 90.6%) carnitine. In response to enhanced carnitine intake, the clearance rates for each fractions of carnitines significantly exceeded the presupplementary values. The increased clearance rates was more pronounced for free (mean 13.2-fold) than for esterified (mean 8.08-fold) carnitines. Despite the increased clearance rates, considerable relative reabsorption was seen for free carnitines (mean 70.0%) as well as for acylcarnitines (mean 65.3%).     

Comparison of the digitalis receptor in erythrocytes from preterm infants and adults

We compared 86rubidium by erythrocytes of preterm infants and adults as a measurement of their Na+, K+, ATPase enzyme system. In neonates, total uptake (0.92 +/- 0.13 micrograms/10(6) cells) and specific uptake (0.64 +/- 0.076 micrograms/10(6) cells) were significantly higher than in adults (0.52 +/- 0.1 and 0.29 +/- 0.06 micrograms/10(6) cells, respectively; p less than 0.025). The percentage of specific uptake from total uptake was higher in infants (73.3 +/- 2.3%) than in adults (57.9 +/- 4.6%) (p less than 0.005). No differences were found in the affinity constant of 86Rb uptake between infants (4.35 +/- 0.48 ng/ml) and adults (4.85 +/- 0.48 ng/ml). Stratification of infants according to their serum K+ concentrations revealed that levels above 5.4 mEq/liter were associated with a higher specific uptake (0.79 +/- 0.107 micrograms/10(6) cells) than in normokalemic infants (0.54 +/- 0.09 micrograms/10(6) cells) or adults (0.304 +/- 0.061 micrograms/10(6) cells) (p less than 0.05). The difference between hyperkalemic and normokalemic infants persisted after excluding those who received adult packed cells (0.88 +/- 0.1 and 0.6 +/- 0.12 micrograms/10(6) cells, respectively) (p less than 0.05). Infants with serum K+ greater than 5.8 mEq/liter received on average significantly more K+ in previous days (2.46 +/- 0.49 versus 1.13 + 0.34 mEq/kg.day; p less than 0.025). The different K+ level could not be attributed to different creatinine clearance in the two groups.     

Relationship between maturity, electrolyte balance and the function of the renin-angiotensin-aldosterone system in newborn infants.

Simultaneous measurement of plasma renin activity (PRA), plasma aldosterone concentration (PA) and urinary aldosterone excretion (UAE) was made using the RIA method along with determination of Na and K balance in 1-week-old neonates with gestational age of 30-41 weeks (mean 35.9 weeks) and birth weight of 1,160-4,670 g (mean 2,680 g). It was demonstrated that PRA decreased from the value of 36.3 +/- 6.3 ng/ml/h (mean +/- SE) to a level of 10.2 +/- 2.1 ng/ml/h (p less than 0.001), PA did not change and UAE increased from 3.3 +/- 0.8 to 7.8 +/- 1.4 microgram/day (p less than 0.01) as the gestational age advanced from 30-32 to 39-41 weeks. There was no correlation between either PRA and PA and UAE. PRA showed a significant positive correlation with urinary Na excretion (p less than 0.001) and plasma K concentration (p less than 0.05), but it was negatively related to Na balance (p less than 0.001). Significant negative correlations were found between UAE and urinary Na excretion (p less than 0.05), urinary Na/K ratio (p less than 0.01 (and plasma K concentration (p less than 0.05); however, UAE positively correlated with Na balance (p less than 0.01). It is concluded that, in response to renal salt wasting and to the subsequent negative salt balance, premature infants can augment their PRA above values found for full-term infants. Their adrenals, however, failed to respond adequately to this stimulation.     

Peritoneal clearance of biochemical markers of bone turnover in children with end stage renal failure on peritoneal dialysis

Renal osteodystrophy is one of the important complications in children with end stage renal disease. Non-invasive tools for evaluation of bone metabolism have been proposed in recent years. The aim of this study was to investigate the markers of metabolic bone disease and peritoneal clearance of these markers in children treated with continuous ambulatory peritoneal dialysis (CAPD). In this study, serum osteocalcin (OC) levels were found significantly higher in patients (107.98 +/- 99.99 ng/ml) than in the healthy control group (41.94 +/- 12.94 ng/ml; p<0.05). Mean peritoneal clearance (Clp) of OC was 0.87 +/- 0.91 ml/min. There was no correlation between serum OC and Clp-osteocalcin. There was a positive correlation between serum phosphorus (P) and OC (r=0.394, p=0.031), alkaline phosphatase (ALP) and OC (r=0.520, p=0.003), and parathyroid hormone (PTH) and OC (r=0.441, p=0.017), whereas no correlation was found between OC and calcium (Ca) and OC and magnesium (Mg). There was also a significant correlation between serum ALP and PTH (r=0.714, p=0.0001). A positive correlation was found between serum PTH and Clp of PTH (r=0.471, p=0.009). In conclusion, Clp-osteocalcin is of no interest as a non-invasive marker of metabolic bone disease in children treated with CAPD. But significant correlation between serum OC and PTH, P, and ALP shows that serum OC could be used as a valuable non-invasive biochemical marker of metabolic bone disease.     

Control of water balance in infants with bronchopulmonary dysplasia: role of endogenous vasopressin

Babies with chronic bronchopulmonary dysplasia (BPD) can sometimes develop pallor, systemic and pulmonary edema, oliguria, and hyponatremia not attributable to cardiopulmonary or renal impairment. These signs and symptoms might, however, be explained by inappropriate control of vasopressin secretion. To test this hypothesis, we measured plasma vasopressin and osmolality, serum sodium and potassium concentrations, urine output and osmolality, and free water clearance in 26 normoxic infants with BPD aged 1-4 months. All of these infants required supplemental oxygen (FiO2 0.41 +/- 0.03, mean +/- 1 SE) to maintain O2 saturation of greater than 88%, and six infants also required mechanical ventilation. As controls, 10 infants of similar age but without BPD were also studied. None of the infants had been discharged from the nursery and was receiving any medications, and all were clinically stable when studied. Compared to control infants, infants with BPD had significantly elevated plasma vasopressin concentrations (control 5.2 +/- 0.9 pg/ml; BPD 42.4 +/- 5.1; mean +/- SE, p less than 0.05). Moreover, infants with BPD had hyponatremia and hypotonic plasma, and both urine output and free water clearance were significantly reduced. These data suggest that some infants with chronic BPD have elevated vasopressin levels that are functionally significant. We speculate that excessive stimulation of vasopressin secretion may explain some of the pulmonary and nonpulmonary signs and symptoms in infants with chronic BPD.     

Pharmacokinetics of intravenously administered piperacillin in preadolescent children

We studied the pharmacokinetics of piperacillin in 37 preadolescent children (mean age 52 months, range 1 month to 11 years) after 50 mg/kg IV doses. Pharmacokinetic parameters were determined after the initial dose in 18 instances and after subsequent doses in 32 instances. There were no significant differences between the initial doses and the subsequent doses in the plasma piperacillin concentrations at comparable times, the elimination rate constants, the elimination-phase plasma half-lives, the total body clearances, the apparent volumes of distribution, or the areas under the concentration curves. At the end of a 30-minute infusion of the drug, the plasma concentration was 166.2 +/- 42.2 mg/L (mean +/- SD) and ranged from 91.6 to 268.3 mg/L. The mean half-life was 31.0 +/- 9.4 minutes. The half-life of piperacillin in children 1 to 6 months of age (47.2 minutes) was significantly longer than in older children (28.8 minutes) (P less than 0.05). Likewise, the total body clearance of the drug in the younger age group (71.7 ml/min/m2) was significantly lower than in the older children (130.8 ml/min/m2) (P less than 0.05). The mean renal clearance of the drug was only 63% (range 39% to 85%) of the total body clearance, suggesting a variable but substantial nonrenal route of elimination. The intravenous administration of 50 mg/kg piperacillin every four hours results in adequate plasma concentrations for the treatment of most infections caused by gram-negative and gram-positive organisms.     

Fetal arginine vasopressin under basal and hypoosmolal conditions

Blood samples (4 ml) for plasma arginine vasopressin (AVP) measurements were obtained at 3- to 4-hour intervals under basal conditions for 1-2 days from 5 date-bred ewes with chronic maternal and fetal vascular catheters. In addition, 6 chronically catheterized ewes were infused with 2 liters of 0.45% NaCl over 30 min. Fetal and maternal blood samples were obtained before and after the infusion period for measurement of plasma osmolality and AVP concentrations. In the first study, maternal and fetal plasma AVP levels correlated significantly (p less than 0.01, by linear regression analysis) under basal conditions. In the second study, baseline mean (+/- SEM) plasma osmolality was similar for pregnant ewes and fetuses (303 +/- 3.1 and 302 +/- 2.4 mosm/kg, respectively). There was a significant (each, p less than 0.01 by paired t test) decrease from baseline in maternal and fetal osmolality during the 30 min after completion of the hypotonic saline (to 292 +/- 4.7 and 296 +/- 2.4 mosm/kg, respectively). Fetal plasma AVP levels decreased 17 +/- 6% by 30 min following the completion of water loading (1.7 +/- 0.07 to 1.4 +/- 0.16 microU/ml; p less than 0.05). Maternal plasma AVP levels decreased 16 +/- 4% by 30 min after completion of infusion (1.6 +/- 0.14 to 1.38 +/- 0.6 microU/ml; p less than 0.05). These results indicate that maternal and fetal plasma AVP levels correlate under basal conditions and that maternal water loading, which significantly decreases fetal plasma osmolality, significantly suppresses fetal plasma AVP concentrations.     

Persisting glomerular hyperfiltration in short-term diabetic children without microalbuminuria

The renal function in a group of diabetic children (n=29;age;4-17 yr; IDDM duration: 1,5-13 yr) was studied with a 3 year interval. At the first evaluation glomerular filtration rate (GFR) as assessed by inulin clearance was significantly increased compared to control values (167 +/- 32 vs. 124 +/- 18 ml/min/1.73 m2; pl less than 0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR greater than 160). Three years later mean GFR was identical (169 +/- 25 ml/min/1.73 m2) and 16 children were hyperfiltrating. Among them, 11 have had a persisting glomerular hyperfiltration over the 3-year period. Renal plasma flow (RPF) was positively correlated to GFR (r=0.7; p less than 0.01) and remained elevated at both evaluations (794 +/- 163 and 812 +/- 157 ml/min/1.73 m2, p greater than 0.01 vs, control values). When the children were separated into 3 groups according to IDDM duration no significant differences were observed in the results for GFR and RPF, Mean urinary albumin excretion was comparable at the 3-year interval, and not significantly different from the control values (5.2 +/- 3.7 and 8.2 +/- 6.6 respectively vs. 8.65 +/- 4 microgram/min). None of the children demonstrated a persistent microalbuminuria. This study reveals a high proportion of diabetic children with a persisting glomerular hyperfiltration, without any other symptom of incipiens nephropathy, If elevated GFR plays an important role in the development of diabetic nephropathy, this study emphasizes the value of regular evaluation of renal function in diabetic children.     

Abnormal serum phenylalanine-tyrosine ratio and hyperferritinemia in malignant histiocytosis

Nine cases of childhood malignant histiocytosis (MH) showed an abnormally high serum phenylalanine (Phe)/tyrosine (Tyr) ratio (3.47 +/- 1.32) coincident with hyperferritinemia (50,800 +/- 33,600 ng/ml). Lactate dehydrogenase activity was also increased in these patients. These values were compared with data on sera from two groups of patients, acute leukemia cases (n = 14) and measles cases (n = 13), and with control values from normal healthy children (n = 38). The Phe/Tyr ratio was 1.57 +/- 0.54 for the acute leukemia (p less than 0.01) and 2.58 +/- 1.46 for the measles cases (NS), serum ferritin was 245 +/- 124 ng/ml for acute leukemia (p less than 0.01) and 167 +/- 117 ng/ml for measles (p less than 0.01). Accordingly, the concurrence of both abnormalities is considered to be characteristic for MH. It was also found that both serum Phe/Tyr ratio and ferritin levels reflect the disease activity, indicating that these two factors are useful prognostic indicators in the treatment of patients with MH.