Pediatr. Res. 15: 1248Res. 15: -1255 one can speculate that a decrease in glomerular vascular resistcatheterized fetal lambs between 106 and 140 days of gestation ance is a major determinant in the postnatal increase in glomerular (term, 145 days) and in six newborn lambs between 3 and 19 days perfusion rate and GFR. of age. The present study demonstrates for the first time in lambs that the nephrogenic zone disappears around 130 days of gestation and that the total glomerular counts per kidney in fetuses over Previous studies (5,13,14,16) have demonstrated that the 130 days (4682% + 41173 glomeruli per kidney) is not significantly cortical blood flow is distributed preferentially to the juxtameduldifferent than in newborn lambs (433704 + 21553). Glomerular lary area of the cortex during early postnatal life, and with density, determined in four cortical zones (zone I being the out-maturation, the development of cortical flow follows a centrifugal ermost portion of the cortex) did not show any significant changes pattern. Spitzer and Brandis (26) also demonstrated that the during fetal life; however, significant decreases in glomerular maturation of glomerular filtration rate (GFR) closely follows the density were observed in each cortical zone after birth. The relative developmental pattern of cortical blood flow, M~~~ recently, distribution of glomeruli during fetal life decreased in the outer ~~~~i~ and ~~~i~ (31, studying factors modulating the changes in portion (zones I and 11) and increased in the inner Portion (zones GFR during maturation, have suggested that glomerular perfusion 111 and IV) of the cortex as fetuses matured and approached term. rate (GPR) is an important determinant of the increase in GFR After birth, this difference became even more prominent; the outer during postnatal life, cortical fraction (zone I) decreased from 49.6 + 2.9% in fetuses of studies from our laboratory have demonstrated that during less than 120 days 37-8 * (P < Oeo5) in lambs, fetal life G F R increases at the same rate as the fetal body weight whereas the fraction found in zone 111 increased from 14.9 + 1.3% and kidney weight (18, 21). ~h~~~ observations are contrary to to 20.8 + 0.7% ( P < 0.05). Small but significant increases in what occurs after birth, where the increase in G F R is disproporglomerular filtration rate (GFR) ( P < 0.01) and total renal blood tionately higher than the concomitant rise in body weight and flow (P < 0.05) were observed during fetal life: GFR and total kidney weight (1 1, 20). Factors responsible for the difference in renal blood flow increased, respectively, from 1.84 2 0.11 and 37 the developmental patterns of fetal and newborn G F R have not f 2 ml/min in fetuses I30 days gestation. During the same period, filtration important factor responsible for the development of GFR in fraction (FF) did not increase significantly whereas a significant newborn rats (31, the pre...

The renal and adrenal responses to a continuous infusion of the angiotensin-converting enzyme (ACE) inhibitor captopril were studied in 27 chronically catheterized sheep fetuses (less than 120 days gestation, n = 15, and greater than 130 days gestation, n = 12; term being 145 days) and in 12 newborn lambs between 8 and 21 days of age. Total renal blood flow did not change during ACE inhibition. However, the renal vascular resistance decreased significantly in newborn lambs (-21.8 +/- 5.7%) and in fetuses greater than 130 days (-21.7 +/- 4.7%) but not in fetuses less than 120 days. A significant decrease in filtration fraction (-19.2 +/- 6.5%) was observed in newborn lambs. No changes in urinary kallikrein and prostaglandin excretion rate were observed during ACE inhibition in any group of animals. ACE inhibition produced similar declines in blood pressure in both groups of fetuses (-10.2 +/- 3% in fetuses less than 120 days and -9.5 +/- 4.6% in fetuses greater than 130 days) and in newborn lambs (-13.4 +/- 2.1%). The percent changes in plasma renin activity were similar in all groups of animals. However, a significant decline in plasma aldosterone concentration was observed only in newborn lambs (from 130 +/- 31 to 64 +/- 9 pg/ml). These results suggest that the renin-angiotensin system might have physiological significance during maturation, but that this role seems to be more important in near-term fetuses (greater than 130 days) and postnatally than early in gestation.

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The role of normocapnic hypoxemia (arterial PO2 33 +/- 7 torr for 30 minutes) in asphyxial renal failure and its modification by maturation of renal function was studied in 50 chronically catheterized, unanesthetized lambs of 2-38 days postnatal age. Arterial pH and PCO2 did not change significantly in response to hypoxemia in these lambs. Normocapnic hypoxemia was associated with (1) significant percent increases in arterial serum osmolality (1.82 +/- 2.96%, P = 0.0001), arterial blood lactate concentration (1009 +/- 2092%, P = 0.0018), arterial blood hematocrit (6 +/- 12%, P = 0.0016), arterial hemoglobin concentration (4.6 +/- 6.5%, P = 0.0004), arterial plasma vasopressin (2370 +/- 3340%, P = 0.0001), arterial plasma renin activity (153 +/- 230%, P = 0.0001), arterial plasma aldosterone (91.3 +/- 143%, P = 0.0001), and fractional sodium excretion rate (120 +/- 240%, P = 0.007); and (2) significant percent decline in glomerular filtration rate (-22.6 +/- 32.6%, P = 0.0003). Several responses to hypoxemia correlated significantly with postnatal age, including (1) positive correlation of postnatal age with percent change in blood osmolality (r = 0.36, P = 0.010), hematocrit (r = 0.48, P = 0.0005), hemoglobin (r = 0.59, P = 0.0004), and lactate (r = 0.72, P = 0.0001), suggesting greater water movement from the intravascular compartment in response to hypoxemia in more mature lambs; and (2) positive correlation of postnatal age with change in urinary flow rate (r = 0.66, P = 0.0001), urinary sodium excretion rate (r = 0.65, P = 0.0001), and osmolar clearance rate (r = 0.60, P = 0.0002), suggesting a greater effect of hypoxemia on the renal tubules to decrease sodium reabsorption in more mature kidneys. Thus, normocapnic hypoxemia may play a role in asphyxial renal failure, and the immature kidney does not have increased susceptibility to this condition.

Three cases of severe mercury toxicity occurring within a family are reported. Two cases of thrombocytopenia occurred in this family and represent the second such report in the literature of an association between elemental mercury toxicity and thrombocytopenia. Three of the children presented with a combination of dermatologic and neurologic manifestations reminiscent of acrodynia or pink disease. Each of the four children in this family were treated with dimercaptosuccinic acid. The hazard of vacuuming spilled mercury and appropriate clean-up procedures are described.

During the past 20 years, advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regimen and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless.12 Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravenous access, which is a particular benefit for children. This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients, especially factors that could lead to drug-related toxicity or adverse responses, are emphasized.

The ontogeny of the renal kallikrein-like activity and the interrelationships between this enzyme and the renin-angiotensin-aldosterone and prostaglandin systems were studied in 43 chronically catheterized sheep fetuses between 104 and 142 days of gestation (term, 145 days) and in 8 chronically catheterized newborn lambs between 5 and 23 days of age. Urinary kallikrein (UKall) excretion rate expressed in absolute values (mEU/hr) or corrected for kidney weight (mEU X hr-1 X gKW-1) or glomerular filtration (mEU X hr-1 X ml GFR-1) increased significantly during fetal maturation and after birth. The rise in UKall during fetal and newborn life was not dependent on an increase in urinary flow rate (r = 0.06). The increase in fetal UKall (mEU X hr-1 X gKW-1) correlated closely with the rise in plasma aldosterone concentration for values above 35 pg/ml (r = 0.72, P less than 0.001). A significant negative correlation was found between UKall (mEU X hr-1 X gKW-1) and log of individual urinary sodium excretion values (r = -0.78, P less than 0.001). No correlation was found between UKall and urinary prostaglandins (PGE, PGF2 alpha) excretion during fetal and newborn life, but UKall correlated closely with the rise in renal blood flow during maturation (r = 0.87, P less than 0.001). The present data suggest that aldosterone is an important regulator of UKall release early during development. It is also suggested that conceptional age is an important factor which may modulate the renal sensitivity to aldosterone-stimulated UKall excretion.