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Biomedical subjects

B S Arant

Publications and source records attributed to B S Arant.

At least 37 records · Page 2Linked to original sources
PubMed1987

Prevention of hereditary nephropathies by antenatal interventions. Ethical considerations.

The identification of renal abnormalities in the human fetus has focused attention on considerations for intervening to correct defects in utero as an alternative to abortion. The fervor which has characterized unproven, though seemingly logical measures attempted unsuccessfully thus far to prevent continued renal injury and pulmonary hypoplasia in the fetus with obstructive uropathy, affords an opportunity to discuss ethical issues which will encumber further experimental approaches for treating the defective human fetus. Such uncharted measures must be scrutinized rigorously not only for valid scientific principles, but also for consideration given to ethical concerns.

Ethics, Medical↗
PubMed1986

Urinary arginine vasopressin: pattern of excretion in the neonatal period.

The pattern of arginine vasopressin (AVP) secretion in the immediate neonatal period is unclear. Plasma concentrations of AVP are reflected by its urinary excretion, thus providing a noninvasive method for studying the pattern of AVP release in the neonate. In these studies, we determined the pattern of urinary AVP excretion (microU/mg creatinine) during the first 2-4 days after birth in 78 neonates, 53 of whom had various prenatal and/or neonatal complications. In well term (n = 12) and preterm (n = 13) infants mean urinary AVP excretion decreased gradually during the first 24-36 h after birth. Although term and preterm infants with perinatal asphyxia had highest initial levels of urinary AVP (greater than 200 microU/mg creatinine) and a significant negative correlation with the 1-min Apgar score was obtained, their pattern of excretion was similar to respective controls. After delivery, elevated values for urinary AVP excretion were found among infants with neonatal courses complicated by intracranial hemorrhage, hypoxic encephalopathy, and pneumothorax. Urine osmolality did not correlate linearly with urinary AVP levels, but rather attained a maximum value of approximately 400 mosmol/kg at urinary AVP levels less than 200 microU/mg creatinine and then plateaued. It is concluded that the decrease in urinary AVP excretion observed soon after birth generally reflects diminution of the hypersecretion of AVP during parturition; neonates with evidence of intrapartum asphyxia initially have increased urinary AVP excretion; however, the pattern of excretion is similar to normal infants. During the neonatal period insults such as pneumothorax and intracranial hemorrhage may cause hypersecretion of this hormone.

Amniotic Fluid↗
PubMed1985

Hemodynamic effects of indomethacin in chronically instrumented pregnant sheep.

Indomethacin administration has produced decreases in uteroplacental blood flow in several animal studies; therefore, it has been suggested that the maintenance of uterine blood flow is critically dependent on the continued synthesis of vasodilating prostaglandins. However, vasoconstriction following indomethacin administration may be due to mechanisms other than reduced prostaglandin synthesis. We administered indomethacin (2, 5, or 10 mg/kg) intravenously to seven unanesthetized sheep in late pregnancy and determined the time courses of the uteroplacental and systemic hemodynamic responses, comparing these to the concurrent changes in circulating prostaglandins. Indomethacin administration resulted in rapid increases in systemic and uteroplacental vascular resistance (80% to 100%) and mean arterial pressure (approximately 30%) and in decreases in systemic (approximately 30%) and uteroplacental (0% to 30%) blood flows within 5 minutes. Vasoconstriction was transient, however, and after 60 minutes there was no evidence of uterine or systemic vasoconstriction, although systemic and uterine plasma prostaglandin levels remained reduced for 180 minutes. Thus substantial inhibition of prostaglandin synthesis existed without evidence of concurrent systemic or uteroplacental vasoconstriction, suggesting that uterine blood flow is not directly dependent on maintained prostaglandin synthesis in unstressed pregnant sheep. Furthermore, the transient indomethacin-induced vasoconstriction may not be due to inhibition of prostaglandin synthesis.

Animals↗
PubMed1985

Metabolic clearance of angiotensin II in pregnant and nonpregnant sheep.

Reduced vascular responsiveness to infused angiotensin II (ANG II) has been observed during pregnancy. It has been proposed that infusions produce lower circulating concentrations of ANG II in pregnancy, due to an increase in the metabolic clearance rate of ANG II (MCRangii). We have evaluated the MCRangii and the arterial plasma concentrations of ANG II during constant infusions of 1.15 micrograms ANG II/min into chronically instrumented pregnant (n = 6) and nonpregnant (n = 9) sheep. Although the pressor responses were significantly less in the pregnant than in the nonpregnant sheep (17.5 +/- 0.5 vs. 34.9 +/- 3.2 mmHg, P less than 0.001), the values for MCRangii were not different: 56.2 +/- 6.3 ml X min-1 X kg-1 in nonpregnant and 55.9 +/- 4.3 ml X min-1 X kg-1 in pregnant sheep. The steady-state plasma ANG II concentrations during the infusions were slightly less in pregnant than in nonpregnant sheep (388 +/- 36 vs. 454 +/- 36 pg/ml); however, this difference would be responsible for only a 2-mmHg reduction in the pressor response. We conclude that the reduced pressor response to infused ANG II in pregnancy is not due to an increase in MCRangii nor to lower plasma ANG II concentrations.

Angiotensin II↗
PubMed1984

Urinary potassium excretion in the critically ill neonate.

The possibility that negative potassium balance may occur in critically ill preterm neonates is suggested by factors such as the usual provision of minimal potassium intake, increased plasma aldosterone concentrations, increased prostaglandin synthesis, and the frequent use of diuretic agents. In order to assess the relationship between potassium balance and renal prostaglandins, nine infants with respiratory distress syndrome (mean birth weight 1,264 g, mean gestational age 30.6 weeks) were studied sequentially with timed-urine collections during the first four postnatal days and values were compared with those of 18 preterm infants without respiratory distress syndrome. Mean plasma potassium concentrations decreased significantly from 4.87 +/- 0.19 mEq/L (mean +/- SEM) on day 1 to 3.83 +/- 0.18 mEq/L on day 4, (P less than 0.05), and cumulative potassium balance was -4.07 +/- 0.95 mEq/kg or 10% of estimated total body potassium. Urinary excretion of prostaglandin E2 on day 1 in infants with respiratory distress syndrome was significantly greater than in those without respiratory distress syndrome (22.0 +/- 4.9 v 8.3 +/- 1.6 ng/mg of creatinine) (r = .66, P less than .001). These studies suggest that consideration be given to the importance of providing sufficient potassium to prevent hypokalemia in the stressed preterm infant and that pharmacologic agents that alter prostaglandins or potassium excretion should be used with caution.

Acute Disease↗
PubMed1983

Evolution of renal segmental atrophy (Ask-Upmark kidney) in children with vesicoureteric reflux: radiographic and morphologic studies.

A radiographic and morphologic study of nine patients with renal segmental "hypoplasia," whose kidneys were radiographically normal when first examined, showed the lesion to be a form of localized, progressive renal atrophy. The renal abnormality bears a strong relationship to vesicoureteric reflux, which could be demonstrated in every patient. No evidence of renal scarring or atrophy was observed in initial roentgenographic examinations at a mean age of 2.9 years (range 0.1 to 10 years); however, serial studies during five to 14 years after discovery of vesicoureteral reflux demonstrated both a lack of renal growth and a progressive loss of substance irrespective of infection. Radiographic lengths of scarred kidneys, as measures of renal growth, correlated poorly with the radiographic surface areas of the renal parenchymal outlines. The mean time from discovery of vesicoureteric reflux to appearance of a renal scar was 6.1 years, and to onset of hypertension in six patients was 7.8 years. The renal abnormality consisted of lobar atrophy with variable tubular atrophy and glomerular sclerosis and with parenchymal destruction that in some specimens had proceeded to a complete loss of nephronic elements. The occasional presence of relatively well-preserved glomeruli and tubules and of focal segmental sclerosis within persisting glomeruli was taken as evidence of a progressive renal abnormality, as opposed to a static developmental hypoplasia. These observations indicate that renal scarring, the injury presumably having been initiated by vesicoureteric reflux, can progress despite correction of the reflux and despite prevention of urinary tract infection.

Adolescent↗
PubMed1983

Diuresis and respiratory distress syndrome: physiologic mechanisms and therapeutic implications.

Previous studies have suggested that spontaneous diuresis may be important to the recovery from respiratory distress syndrome in preterm infants. Daily quantification of fluid intake (1) and urine output (O) were recorded, and O/I and alveolar-arterial oxygen gradients (AaDO2) were determined for sequential eight-hour periods in 10 inborn premature infants with RDS. Sequential timed-urine-plasma collections were obtained during the first four days of life to evaluate the role of hormonal and vasoactive factors in the acute phase of RDS. Diuresis (O/I greater than 0.80) occurred at 25 to 32 hours, preceded any significant improvement in AaDO2 (which occurred at 57 to 64 hours), and was associated with a 6.2 +/- 1.4% decrease in body weight. Although there was no significant change in glomerular filtration rate, plasma AVP concentrations, or urinary excretion of AVP in the infants, there were significant decreases in both plasma concentrations and urinary excretion of 6-keto-PGF1 alpha (stable metabolite of prostacyclin) in sequential studies. These results suggest that changes in renal function or AVP may not be of primary importance in the diuresis associated with RDS, and that decreasing levels of prostacyclin, a prostaglandin that increases vascular permeability and lowers blood pressure, may have an important physiologic role.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

The Toronto Western Hospital catheter in a pediatric dialysis program.

Following multiple technical problems with Tenckhoff catheters in children commencing prolonged dwell peritoneal dialysis, we have recently used the Toronto Western Hospital (TWH) catheter with considerable success. Six of the TWH catheters were inserted in children who had experienced either obstruction or leakage with prior use of 1-4 Tenckhoff catheters. Overall, we have used 15 TWH catheters in 12 children and have compared the results to 23 Tenckhoff catheters in 9 children. The rate of obstruction with TWH (7%) has been much less than with the Tenckhoff catheter (45%). We conclude that the TWH catheter represents a significant advance in peritoneal dialysis catheter technology for end-stage renal disease (ESRD) children starting continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD).

Catheters, Indwelling↗
PubMed1983

Renal handling of beta-2-microglobulin in the human neonate.

Glomerulotubular balance for beta-2-microglobulin (beta 2M) in the human kidney has been reported to occur after 34 weeks conceptional age (CA), and fractional tubular reabsorption of beta 2M (T beta 2M) has been suggested as a useful index of renal tubular maturation. To confirm and extend these observations to include still less mature infants, renal handling of beta 2M was investigated during timed-urine collections with corresponding blood samples obtained from 57 infants with CA of 26 to 43 weeks and postnatal ages (PNA) 0.2 to 12 days (study 1); 18 infants were studied a second time 5 to 17 days later (study 2). GFR was measured by endogenous creatinine clearance (CCr). T beta 2M and fractional reabsorption of sodium (TNa) were calculated. Results indicated that while both increased with CA, T beta 2M (r = -0.69, P less than 0.0001) and TNa (r = -0.79, P less than 0.0001) varied inversely with fractional urine flow rate (V/CCr). Moreover, an inverse relationship between changes in T beta 2M and V/CCr was observed in the same infant between study 1 and study 2 (r = -0.47, P less than 0.05). These data suggest that the renal handling of beta 2M in the human neonate is influenced by physiologic variables that are independent of CA, and thus T beta 2M may not be a reliable predictor of renal tubular maturation in the human neonate.

Creatinine↗
PubMed1982

Developmental changes in the mongrel canine brain during postnatal life.

Normal values for changes in brain growth, chemical composition and morphologic features of the mongrel dog between birth and maturity were established in studies of 43 puppies between birth and 6 months of age and 3 adult dogs. Brain weight in puppies increased as the sodium, potassium and chloride contents of brain decreased between birth and 60 days; values similar to the adult were observed in puppies at 3 to 6 months of age. The concentrations of sodium and chloride decreased while the concentration of potassium increased in brain water between birth and 60 days, but the sum of sodium, potassium and chloride concentrations in brain water, an index of brain osmolality, did not change during postnatal development. Total protein (mg/g dry brain) did not change, but DNA (mg/g dry brain) decreased with age; ratios of total protein:DNA increased from birth and were maximal at 90 days. Morphologic changes in the canine brain were characterized by an extensive, densely cellular subependymal germinal zone at birth which, although diminished and focally discontinuous, was present at 30 days and had disappeared by 60 days of age. The gross appearance and histologic changes observed in the mongrel canine brain observed between 1 and 60 days of age are similar to changes described for the human brain between 28 and 40 weeks gestation. We conclude that the mongrel canine brain is a suitable model for studying mechanisms of injury to the neonatal human brain.

Animals↗
PubMed1982

Neonatal hyperbilirubinemia and renal function.

It has been suggested that neonates with hyperbilirubinemia may have impaired renal function. In order to study this problem, creatinine clearance, and fractional tubular reabsorption of sodium and beta-2-microglobulin were measured in 22 jaundiced neonates with gestational ages ranging from 33 to 42 weeks and mean postnatal age of 3.9 days. These data were compared with those obtained from 23 nonjaundiced control infants matched for gestational and postnatal ages. In addition, follow-up studies of renal function were conducted in 18 of 22 study infants when serum bilirubin concentration was less than 11 mg/dl at a mean postnatal age of 7.6 days. No significant differences in CCr, T Na, or T beta 2M were observed. We conclude that when gestational age is greater than or equal to 33 weeks, modification of current management of infants with moderate hyperbilirubinemia is unnecessary to prevent nephrotoxicity.

Creatinine↗
PubMed1982

Adrenal responsiveness in children with steroid responsive idiopathic nephrotic syndrome.

Impaired adrenal cortical responsiveness to ACTH has been reported in children with steroid responsive nephrotic syndrome. Plasma cortisol levels at 8 AM and 2 hours post ACTH stimulation were measured on 42 occasions in 33 children with steroid-responsive nephrotic syndrome. Twenty-two of 42 fasting 8 AM plasma cortisol and 39 of 42 post-ACTH plasma cortisol values were subnormal. Plasma cortisol values were similar in children evaluated prior to, immediately following or 2-24 moths after prednisone therapy. No relationship was observed between 8 AM or post-ACTH plasma cortisol values and serum albumin concentration or the presence of edema. Impaired adrenal responsiveness to ACTH was not helpful in predicting the length of clinical remission. Hydrocortisone replacement therapy given to five children with impaired ACTH-responsiveness did not alter the rate of relapses observed prior to this treatment.

Adolescent↗
PubMed1982

Candida peritonitis in children on continuous ambulatory peritoneal dialysis.

The management, complications and outcome of two small children who developed Candida albicans peritonitis are reported. Both children developed peritonitis while on continuous ambulatory peritoneal dialysis (CAPD) but their fungal infections were treated differently. In one patient, Amphotericin B (1-4 micrograms/ml) was added to the dialysate; infection resolved but an extensive fibrous reaction developed in the peritoneal cavity making subsequent CAPD ineffective. The second patient was treated with a recently introduced oral antifungal agent, Ketoconazole; her catheter was removed. This patient recovered without any identifiable side effects of the drug. This report discusses the clinical course of two different approaches to Candida peritonitis and suggests certain recommendations regarding the treatment of this uncommon, but potentially lethal complication of CAPD.

Amphotericin B↗
PubMed1981

Poststreptococcal crescenteric glomerulonephritis in children: comparison of quintuple therapy versus supportive care.

Crescenteric glomerulonephritis preceded by a streptococcal infection with creatinine clearance CCr of less than 30 ml/minute/1.73 m2 was treated by supportive care plus three months of quintuple therapy (prednisone, azathioprine, cyclophosphamide, dipyridamole, and heparin followed by warfarin) in five children (Group A) or by supportive care alone in five others (Group B). Of the glomeruli examined, 69.8 +/- 11.7% (mean +/- SE) in Group A and 64.4 +/- 10.6% in Group B had crescents which involved 54.0 +/- 10.8% and 60.0 +/- 10.5% of glomerular circumference, respectively. Clinical and histologic findings supported a recent streptococcal infection in every patient. Two patients from Group A had mild proteinuria and normal CCr at 12 months; one died abruptly of pulmonary hemorrhage after maintaining a normal CCr for 25 months. Following a second episode of poststreptococcal acute glomerulonephritis seven months after the first, one patient from Group B had persistent mild proteinuria for 41 months and hypertension through 56 months of follow-up. Nine surviving patients have maintained normal CCr for eight to 60 months (mean 29.5 months). The findings of this study suggest that this quintuple therapy offers no advantage over supportive care in the clinical management and outcome of children with severe crescenteric glomerulonephritis when an antecedent streptococcal infection is confirmed by serologic and histopathologic criteria.

Adolescent↗