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Biomedical subjects

E G John

Publications and source records attributed to E G John.

At least 19 recordsLinked to original sources

Significance of fractional excretion of sodium and endothelin levels in the early diagnosis of renal failure in septic neonatal piglets.

PURPOSE: This experiment was designed to help understand the cascade of events that end in renal impairment in septic animals. METHODS: Twenty 3- to 8-day-old piglets were anesthetized and the femoral artery, jugular and femoral veins, and bladder were catheterized. After stabilization under anesthesia with ventilatory support, they were divided into a control group and three groups that received endotoxin (ETX) in doses of 0.01 mg/kg, 0.025 mg/kg, and 0.05 mg/kg. Blood pressure and blood gases were monitored continuously. Blood and urine samples were obtained before (B), 1 hour (E1), and 3 hours (E3) after the bolus of ETX to determine glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tumor necrosis factor (TNF), and endothelin-1 (ET-1) levels. RESULTS: Incremental doses of ETX induce greater release of ET-1 with an early proportionate increase in FENa (P< .05) and late decrease in GFR (P< .05). TNF release is dose and time dependent after ETX injection (P < .05). CONCLUSION: ET-1 and FENa are the best tests to evaluate renal failure during early sepsis in neonatal piglets.

Acute Kidney Injury

Pharmacokinetics of once-daily dosing of gentamicin in neonates.

In a prospective, randomized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group, respectively, had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7 micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic effects were identified in any group. Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve. Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates.

Ampicillin

The effect of prostaglandin E1 analog misoprostol on chronic cyclosporin nephrotoxicity.

Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

Aldosterone

Vasoactive factors in the immature kidney.

The newborn infant is in a state of renal insufficiency with a glomerular filtration rate (GFR) as low as 20 ml/min per 1.73 m2 at term, and 10 ml/min per 1.73 m2 at 28 weeks of gestation. While the immature "insufficient" kidney can cope with most of the normal demands, its reserve is limited, and often overwhelmed by commonly occurring neonatal stresses. Various vasoactive systems such as the renin-angiotensin system, intrarenal adenosine, the prostaglandins and the atrial natriuretic peptide, are hyperactive in the neonatal period. Some of these systems appear crucial for the maintenance of GFR. Overstimulation of both angiotensin II and adenosine by an hypoxaemic stress can further impair the GFR, eventually leading to established renal failure. Inhibition of angiotensin II formation by the administration of angiotensin converting enzyme inhibitors can, on the other hand, also lead to renal failure. Prevention of these renal risks requires a precise knowledge of the newborn kidney physiology, physiopathology and pharmacology.

Adenosine

The effect of low-dose dopamine infusion on cardiopulmonary and renal status in premature newborns with respiratory distress syndrome.

To study the effects of infusion of low doses of dopamine hydrochloride on cardiopulmonary and renal status in premature newborns with respiratory distress syndrome, 49 newborns were randomly assigned to three groups: group 1 (18 patients) received no dopamine and was the control group; group 2 (16 patients) was infused with a dose of dopamine measuring 1.0 micrograms/kg of body weight per minute for 72 hours; and group 3 (15 patients) was infused with a dose of dopamine measuring 2.5 micrograms/kg of body weight per minute for 72 hours. Birth weights, gestational ages, post-natal ages, and cardiopulmonary status of all groups at the start of the study were comparable. Continuous infusion of these low doses of dopamine for 3 days after birth did not significantly improve levels of blood gases, acid-base balance, or clinical outcome. In newborns with systemic hypotension, dopamine improved cardiovascular status and caused early return of blood pressure to the normal range. Infusion of low doses of dopamine produced mild to moderate natriuresis and insignificant increases in glomerular filtration rate and urine volume.

Acid-Base Equilibrium

Acute hypertensive encephalopathy in minimal change nephrotic syndrome.

A 3-year-old child with minimal change nephrotic syndrome (MCNS) developed an acute hypertensive encephalopathy characterized by coma, focal seizures, right hemiparesis, global aphasia and cortical blindness. Episodic hypertension and seizures persisted for 24 h despite intervention with antihypertensive and anticonvulsant therapy. Clinical suspicion of cortical blindness was confirmed by visual-evoked potential studies. CT scans performed 14 and 21 days after the acute episode demonstrated symmetric occipital white matter lucencies compatible with ischemia and/or associated edema. Hypertensive encephalopathy with cortical blindness and symmetric white matter hypodense lesions visualized on CT scan have recently also been described in eclampsia of pregnancy. This report documents an unusual acute hypertensive encephalopathy in childhood MCNS, unassociated with membranoproliferative glomerulonephritis, or progressive focal glomerulosclerosis.

Blindness

Digitalis, digitalis antibodies, digitalis-like immunoreactive substances, and sodium homeostasis: a review.

Most pharmacokinetic and biologic attributes of digitalis are age dependent. They are determined in great measure by the chemical structure of the specific cardiac glycoside being used. These effects differ in the intact normal circulation and in heart failure because of the altered autonomic nervous system and hormonal control that exist in the latter. Digitalis is effective only in the presence of myocardial dysfunction, but in a clinical setting, cardiac performance may be difficult to gauge; improved tools are needed for this purpose. The dosages of digoxin recommended for infants and children have been steadily reduced in the past decade, and there is no good evidence that more favorable risk-to-benefit ratios are achieved when higher doses are used or when higher plasma concentrations are sought. Massive digitalis toxicity is a serious, often fatal, complication in young infants, especially when the drug is given parenterally; it may be difficult to diagnose early. The only reliable deterrent for this complication is the adoption of careful safety standards whenever the drug is employed. Experience with digoxin antibodies is still scarce in children, especially in infancy, but their use generally has been associated with a favorable outcome. Endogenous substances that interfere with the digoxin radioimmunoassay (DLIS) occasionally yield clinically relevant, erroneously high, plasma digoxin concentration readings in neonates. An interesting hypothesis currently being investigated is the physiologic and pathologic role of these compounds in sodium hemostasis; they may be part of a putative endogenous NaK-ATP-ase inhibitor involved in the pathogenesis of hypertension and renal diseases.

Cross Reactions

Effect of tolazoline on renal function in newborn puppies.

Tolazoline is used in pulmonary hypertension and hypoperfusion syndrome during the neonatal period. Some of the side effects of tolazoline are hypotension, bleeding disorders and renal dysfunction. The present study was designed to investigate the effect of hypoxia and tolazoline on renal function in newborn puppies. The data in normal animals administered tolazoline alone did not reveal any statistically significant changes in blood pressure or in renal function. In the hypoxia group changes in renal function were noticed in spite of normal blood pressure. When tolazoline was administered to the hypoxic animals, a marked decrease in blood pressure resulted. Indeed, changes in renal function were more profound in the hypoxic animals receiving tolazoline than in hypoxic animals not receiving tolazoline, even though some of the renal functional values did not reach statistical significance.

Animals

Renal function in the tiny, premature infant.

This article discusses the adaptation of the immature kidneys to extrauterine life and targets some of the clinical problems arising from the renal immaturity of the very low birth weight infant.

Calcium

Beta 2-microglobulin clearance in neonates: index of tubular maturation.

Serum and urinary beta 2-microglobulin (beta 2M) were studied by enzyme immunoassay in 28 normal neonates at day 1 and day 4 of life in relation to gestational age (GA) and postnatal age (PNA). The infants were grouped according to GA; 10 with GA ranging from 32 to 35 weeks (mean 33.5 weeks) and 18 with GA ranging from 36 to 41 weeks (mean 38.3 weeks). Serum beta 2M varied directly with both GA and PNA. When values for serum beta 2M were related to conceptional age (CA), a significant positive correlation was present for all the infants studied (r = 0.68, P less than 0.01). Fractional excretion of beta 2M (FE beta 2M) decreased as a function of both GA and PNA. When a comparison of FE beta 2M was made in infants of all CA, a significant inverse correlation was noted for infants with CA less than or equal to 35 weeks (r = -0.89, P less than 0.001). The fall in FE beta 2M reached a plateau by 36 weeks. The highest FE beta 2M (33%) was observed in infants of 32 weeks CA who had the lowest filtered beta 2M (F beta 2M). No statistically significant relationship between changes in FE beta 2M and fractional urine flow rate was observed within each of the CA categories (infants less than or equal to 35 weeks, r = 0.21, P = 0.28; infants greater than or equal to 36 weeks, r = 0.25, P = 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Gestational Age

Effect of peritoneal dialysis on serum concentrations of three drugs commonly used in pediatric patients.

The use of peritoneal dialysis in young infants bears the theoretical advantage that the relative size of their peritoneal surface area is twice that of adults. The movement of drugs across the peritoneum is affected by the physiochemical properties of the drug molecules and the pathophysiologic condition of the patient. It is observed that the peritoneal dialysis clearances of phenobarbital, amikacin and cefazolin in infants were 1.07-1.33, 0.54-0.86 and 0.40-1.02 ml/min, respectively. The dosage determination in the dialysis patients receiving these drugs is discussed.

Amikacin

Hypouricemia in neonates with syndrome of inappropriate secretion of antidiuretic hormone.

A prospective study of serum levels of uric acid in 23 hyponatremic neonates was performed. Infants on diuretic medications or with renal failure were excluded. The infants were separated into two groups: group I consisted of 11 neonates with clinical evidence of syndrome of inappropriate secretion of antidiuretic hormone (SIADH), (mean +/- SD serum sodium 127 +/- 1.36 mEq/liter). Group II included 12 infants with hyponatremia (mean serum sodium 128 +/- 1.10 mEq/liter) associated with decreased effective vascular volume manifest by a fractional sodium excretion less than 1%. The groups were similar for gestational and postnatal ages, birth weight, clinical conditions, and concurrent use of drugs. The serum urate concentration in neonates with SIADH was 2.46 +/- 0.54 mg/dl; serum urate concentration in group II infants was 8.49 +/- 2.45 mg/dL (p less than 0.001). Water restriction in the group I infants with SIADH resulted in a rise in mean serum urate concentration (p less than 0.001). Fractional excretion of urate was elevated during hyponatremia in the group I infants (to 78 +/- 0.13%) and fell to 51 +/- 0.08% after correction (p less than 0.001). In group I infants, a direct correlation was found between fractional excretion of urate and sodium (r = 0.7667, p less than 0.001). These results indicate that hypouricemia is common in infants with suspected SIADH and seems to be due to increased urate clearance secondary to volume expansion.

Humans

Intravenous indomethacin and changes of renal function in premature infants with patent ductus arteriosus.

Selected parameters of renal function were studied in premature infants with a significant patent ductus arteriosus who were treated with intravenous indomethacin according to a specific protocol. Urine volume, glomerular filtration rate, urine sodium, and the fractional excretion of sodium were analyzed in 17; osmolar, sodium, and free water clearances in 8; and indomethacin pharmacokinetics in 7 premature infants. All renal function parameters analyzed decreased during indomethacin therapy: urine volume and glomerular filtration rate returned to normal, while urine sodium, fractional excretion of sodium, and the osmolar, sodium, and free water clearances remained low 24 hours after cessation of therapy. The water retention, shown by the reduced free water clearance, had no apparent deleterious effects, probably because of the infants' low fluid intake. Indomethacin pharmacokinetic parameters (clearance, area under the curve) may account in part for the variability of the fractional excretion of sodium, glomerular filtration, and urine flow rate.

Ductus Arteriosus, Patent