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Biomedical subjects

J W Balfe

Publications and source records attributed to J W Balfe.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of puberty on markers of glomerular hypertrophy and hypertension in IDDM.

Epidemiological data implicate puberty as a factor in the initiation of diabetic nephropathy. However, the mechanism remains unclear. We hypothesized that puberty would result in an increase in glomerular hypertrophy and hypertension; these two early concomitant events are seen as pivotal to the pathophysiology of diabetic nephropathy. We studied the effect of pubertal duration on three surrogate markers of glomerular hypertrophy/hypertension: kidney volume (KV), microalbuminuria (MA), and Na-Li countertransport (CT). We recruited 177 subjects (87 female and 90 male; aged 6.2-22.1 years) with IDDM of 5 to 10 years' duration (6.8 +/- 1.6 years) into three groups with different pubertal duration: prepubertal since IDDM diagnosis; prepubertal at diagnosis, now pubertal; or early puberty at diagnosis, now postpubertal. KV was measured by ultrasound and corrected for body surface area; MA was defined as urinary albumin excretion of 15-200 micrograms/min in two of three 24-h samples, and Na-Li CT was measured in erythrocytes. As pubertal duration increased, there was a disproportionate increase in mean KV (prepubertal, 247 +/- 6 [SE] ml/1.73 m2; pubertal, 282 +/- 7/1.73 m2; postpubertal, 295 +/- 7/1.73 m2, P = 0.001), prevalence of nephromegaly (KV > 300 ml/1.73 m2) (14, 31, and 45%, respectively, P = 0.001), and prevalence of MA (0, 9.7, and 20.5%, respectively, P = 0.003). Subjects with KV > 300 ml/1.73 m2 were eight times more likely to have MA than those with KV < 300 (odds ratio 8.1, 95% confidence interval 2.4-27.4, P = 0.0001). There was no effect of pubertal duration on Na-Li CT. Multiple regression with KV as the dependent variable found an association with pubertal duration, MA, Na-Li CT, and current HbA1c (P < 0.0001). Our findings indicate that pubertal duration is an important determinant of both KV and MA and suggest that nephromegaly precedes microalbuminuria. We postulate that these effects are attributable to the influence of the pubertal milieu on glomerular hypertrophy/hypertension.

Adolescent↗
PubMed1995

A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension.

In a crossover design, control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension. Compliance with once daily felodipine was higher than with nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine, at 77.6 (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age) was lower for felodipine than for nifedipine: 43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though this did not reach statistical significance. These data suggest that once a day felodipine is effective in children with hypertension. This may be because of improved compliance.

Adolescent↗
PubMed1994

Penoscrotal transposition: a case report and review.

We report on a boy born with complete penoscrotal transposition, normal scrotum, twisted penile shaft with hypoplastic penile urethra, meatal stenosis, normal bladder, and bilateral cystic dysplastic kidneys. The patient died of renal failure at 2.5 months. This is the 13th reported case of complete penoscrotal transposition with normal scrotum. The possible pathogenesis is discussed and the literature is reviewed.

Abnormalities, Multiple↗
PubMed1994

Pediatric clinical use of the ketoconazole/cyclosporin interaction.

Ketoconazole is known to inhibit the metabolism of cyclosporin through inhibition of cytochrome P-450. This pharmacological interaction was used in an 8-year-old renal transplant patient to successfully achieve therapeutic cyclosporin blood concentrations. The addition of ketoconazole to the cyclosporin regimen should be considered when difficulties are encountered in attaining satisfactory cyclosporin levels.

Child↗
PubMed1994

Plasma prorenin as an early marker of nephropathy in diabetic (IDDM) adolescents.

We studied a group of 50 adolescents, average age 16 years, with diagnosed IDDM present for about seven years. Twenty-five had microalbuminuria (MA) averaging 111.0 +/- 34.0 (SEM) micrograms/min albumin excretion rate versus 6.7 +/- 7.4 micrograms/min in the 25 without MA. In other respects, such as sex ratio, age, body mass index, duration of IDDM, hemoglobin A1c, and normotensive systolic, diastolic and mean blood pressures (BP), these subgroups were closely matched. We compared them with a control group of 39 normotensive adolescents, of whom 18 were carefully matched siblings of the IDDM subjects with MA and 21 were similarly matched siblings of the IDDM non-MA subjects. Plasma renin concentration was determined by a direct radioimmunoassay method (Sanofi-Pasteur) and found to be virtually the same in the control and IDDM adolescents as a whole. There was also no real difference between the MA and non-MA subgroups. In contrast, plasma prorenin was significantly higher in the combined IDDM group (197.5 +/- 9.3 vs. control, 134.0 +/- 7.9 pg/ml, P < 0.0001). It was also higher in the MA subgroup than in the non-MA subgroup (226.4 +/- 13.6 vs. 168.5 +/- 10.1 pg/ml, P < 0.001). Interestingly, the 18 control siblings matching the MA subgroup had higher plasma prorenin than the 21 control siblings matching the non-MA subgroup (P < 0.001), suggesting a familial predisposition that precedes detectable diabetes and nephropathy. Our findings confirm and extend reports by other workers that elevated plasma prorenin is associated with incipient nephropathy, manifested by MA. The exclusive renal origin of this prorenin, its role in plasma, and the mechanism responsible for its elevation in IDDM with MA, are yet to be demonstrated, as is the general applicability of these findings to different populations of diabetics, with a higher incidence and severity of complications.

Adolescent↗
PubMed1994

Sodium-lithium transport in adolescents with IDDM. Relationship to incipient nephropathy and glycemic control.

OBJECTIVE: The aims of this study were to examine genetic and environmental influences in the development of early diabetic nephropathy and to assess the value of measuring membrane sodium transport as a marker for early nephropathy. RESEARCH DESIGN AND METHODS: We measured erythrocyte sodium-lithium (Na-Li) countertransport, blood pressure (BP), HbA1c, and microalbuminuria (MA) in 84 adolescents with insulin-dependent diabetes mellitus (IDDM), 29 of whom had MA. Twenty-nine non-MA patients were selected and matched for age, sex, and IDDM duration with the 29 diabetic subjects with MA. The 84 diabetic adolescents were also compared with 85 nondiabetic siblings. RESULTS: The erythrocyte Na-Li countertransport was significantly greater in the IDDM group than in the sibling group (mean +/- SD, 0.41 +/- 0.14 vs. 0.30 +/- 0.11 mmol Li.liters of erythrocytes-1.h-1, respectively, P < 0.0001), but a significant correlation was noted between the results in IDDM subjects and their siblings (r = 0.42, P < 0.0008). Na-Li countertransport was not different in the diabetic subjects with or without MA (0.43 +/- 0.13 vs. 0.37 +/- 0.13 mmol Li.liters of erythrocytes-1.h-1, respectively). There was a significant correlation in the IDDM group between recent diabetic control (HbA1c) and Na-Li countertransport (r = 0.37, P < 0.003). Diastolic BP was significantly higher in the IDDM group with MA than in those without MA (60 +/- 6 vs. 55 +/- 6 mmHg, respectively, P < 0.03). CONCLUSIONS: These results suggest that erythrocyte Na-Li countertransport is influenced by the diabetic milieu. However, there was also evidence in our subjects of a genetic contribution to Na-Li countertransport as seen by the correlation between levels in the IDDM subjects and their siblings. Using Na-Li countertransport, we were not able to segregate those IDDM adolescents with and without early nephropathy.

Adolescent↗
PubMed1994

Comparisons between oral and intraperitoneal 1,25-dihydroxyvitamin D3 therapy in children treated with peritoneal dialysis.

Recent studies in adults have suggested that parenteral 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may have advantages over oral therapy in the management of renal osteodystrophy. The purpose of this study was to determine whether there were clear differences between oral and IP 1,25(OH)2D3 treatments in children who did not pose a treatment problem. Seven children (5 males, 2 females, aged 1.8 to 16 years, median 4.8 years) undergoing peritoneal dialysis were initially treated with oral 1,25(OH)2D3 for a one month equilibration period They were randomly assigned to 3 months of either oral or intraperitoneal (IP) therapy with 1,25(OH)2D3 followed by 3-months-treatment using the alternative route. No significant differences in serum creatinine, phosphate, or parathyroid hormone concentrations were found between the different routes of administration in the patients. No significant differences in height standard deviation scores or renal osteodystrophy scores were found over the six-month study. Paired oral and IP pharmacokinetic studies were performed on these 7 patients and 2 other children who had been treated for at least 2 months using either oral or IP 1,25(OH)2D3. Serum was taken prior to one of the usual 1,25(OH)2D3 doses and 0.5, 1.5, 3, 6, and 24 h afterward. The highest measured concentrations of 1,25(OH)2D3 were found at 1.5 h for both oral and IP treatments (mean Cmax [SD]: oral 116 [23] pmol/l, IP 121 [24] pmol/l, p > 0.05). The AUC's for oral and IP therapy were similar (1701 [276] and 1645 [301] pmol/h/l, respectively). In the paired pharmacokinetic studies no significant differences were found between oral and IP treatments for the serum half life (27.4 [11.6] h and 19.2 [8.1] h, respectively) and total body clearance (15.3 [2.1] h and 18.4 [3.3] h, respectively) of 1,25(OH)2D3. In children who respond appropriately to oral 1,25(OH)2D3 there is no biological advantage to the use of IP 1,25(OH)2D3.

Administration, Oral↗
PubMed1994

Peritoneal dialysis in the prune belly syndrome.

OBJECTIVES: To describe our experience with chronic ambulatory peritoneal dialysis in children with the prune belly syndrome (PBS). DESIGN: From our peritoneal dialysis (PD) program we were able to review the medical records of 6 boys with PBS. Data were collected on potential complications such as infections, hernias, growth, and problems encountered with PD catheter insertion. RESULTS: The ages of the 6 boys ranged from 10 months-17 years. The dialysis duration was from 9-22 months, with a total of 76 patient-months on PD. There was one death, possibly as a complication of an exit-site infection. Five received a renal transplant, and 4 have functioning grafts. Peritonitis occurred once in every 10.8 patient-months, and exit-site or tunnel infection was diagnosed every 7.6 patient-months. Four patients required PD catheter replacement because of tunnel infection in 2, persistent exit-site infection in 1, and fluid leakage in 1. Of a total of nine catheters, three were inserted using a laparoscopic technique. There were no leaks in these three; however, there was one exit-site infection. Two patients had inguinal hernias that required surgery. CONCLUSION: Deficiency of abdominal musculature in PBS poses potential problems for the use of PD, in particular, catheter anchorage, exit-site healing, and leakage. In our patients the most serious complications were infections of the exit site or catheter tunnel. Our experience suggests that a laparoscopic technique may provide improved catheter placement. PD offers a potentially successful form of dialysis for patients with PBS.

Abdominal Muscles↗
PubMed1994

Mass transfer area coefficients in children.

OBJECTIVE: Measurement of mass transfer area coefficients (MTAC) in children of different sizes to determine if solute transport varies with age and to compare with published adult values. DESIGN: Mass transfer area coefficients calculated from prospectively collected data in 28 selected patients. PARTICIPANTS: All children starting maintenance peritoneal dialysis at the Hospital for Sick Children. Selected patients were also studied if hospitalized for unrelated reasons. RESULTS: Mean MTAC values for creatinine and glucose were 4.0 and 4.5 mL/min, respectively, both considerably lower than adult values. When scaled per 70 kg body weight, these results were greater, and when scaled per 1.73 m2 surface area, they were lower than reported adult values. The MTAC/kg body weight was inversely correlated to age. CONCLUSIONS: Solute transport in children is directly related to age and does not approach adult values until later childhood. However, more rapid transport per unit body weight is observed in children and may reflect an increased effective peritoneal surface area.

Adolescent↗
PubMed1994

Effects of 3-month amino acid dialysis compared to dextrose dialysis in children on continuous ambulatory peritoneal dialysis.

OBJECTIVES: To compare the nutritional and biochemical effects of amino acid dialysis to dextrose dialysis in children receiving continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective randomized crossover study. SETTING: Pediatric Nephrology Unit in a tertiary care, teaching hospital of the University of Toronto. PATIENTS: Seven children aged 0.7-16.5 years receiving CAPD. All patients had poor linear growth, with 5 patients showing evidence of energy deficit. INTERVENTIONS: Each patient received either amino acid or dextrose dialysate for 3 months, then crossed over to the alternate regimen for a subsequent 3 months. MAIN OUTCOME MEASURES: Nutritional and biochemical data were obtained on each patient during each dialysis regimen. RESULTS: Analysis of the patients' nutritional data showed comparable weight gain with both regimens but no significant improvement in lean body mass with either regimen. Appetite improved in most patients during amino acid dialysis. Biochemical data during amino acid dialysis showed a tendency to higher plasma potassium and urea levels with no clinical side effects or worsening of acidosis; however, there was a reduced anion gap and increased total plasma protein, due mostly to a rise in plasma albumin and a smaller increase in immunoglobulins. With the exception of tryptophan, fasting amino acid levels at the start and end of amino acid dialysis did not show any significant change. An interesting phenomenon of early blunting of the rise in amino acid levels, following a single amino acid dialysate exchange, was noticed at the end of the amino acid dialysis period. This newly described phenomenon could have been due to tolerance or hepatic enzyme induction. CONCLUSIONS: Overall amino acid dialysis was comparable to dextrose dialysis with no additional proven nutritional benefit, was equally effective in ultrafiltration and creatinine clearance, and produced no adverse clinical or biochemical effects.

Acid-Base Equilibrium↗
PubMed1993

The use of alternative peritoneal dialysis solutions in pediatric patients.

Changes in the formulation of peritoneal dialysis solutions will continue. For the present, dextrose dialysis will remain the osmotic solute of choice. How amino acids and glucose polymers as solute replacements for glucose fit into the dialysis prescription remains to be seen. The lower concentration of calcium and magnesium appears to be gaining acceptance in many centers. It is feasible that in the next few years the challenge of adding bicarbonate to the peritoneal dialysis solution will be circumvented, because there appears to be a real clinical need for such an improvement. Pediatric modifications will be necessary, appreciating that such changes will have an economic penalty, and thus must have proven value.

Amino Acids↗
PubMed1993

Initial hypoalbuminemia and hyperlipidemia persist during chronic peritoneal dialysis in children.

OBJECTIVE: To document serum lipid values in pediatric peritoneal dialysis (PD) patients, particularly the very young, and investigate relationships with serum albumin levels. DESIGN: Retrospective review of all PD patients seen in the first 11 years of the PD program at our institution. PATIENTS AND METHODS: Any pediatric PD patient was eligible for inclusion if at least four simultaneous measurements of serum lipids and albumin were recorded over a minimum of 90 days of PD. RESULTS: Thirty-nine continuous ambulatory peritoneal dialysis (CAPD) patients (9, aged < 5 years) and 14 continuous cycling peritoneal dialysis (CCPD) patients (7, aged < 5 years) were followed for 90-1200 days. Hypoalbuminemia, present in 43% of initial recordings, did not alter significantly during PD in any group; it was most marked in the CAPD < 5 year (mean 30.7 g/L) and CCPD > 5 year groups (mean 31.4 g/L). Average serum cholesterol levels were 27% higher, and triglyceride 122% higher, than the maximum accepted 18-year-old level and did not change significantly during PD. Similarly, 33% of high-density lipid recordings were below normal and remained unaltered during PD. CONCLUSIONS: Our results confirm the high incidence of hypoalbuminemia, hypertriglyceridemia, and hypercholesterolemia and associated low levels of high-density lipids, even in young PD patients, and demonstrate that these remain unchanged during PD. Such results have not previously been reported in PD patients as young as ours. Abnormal lipid profiles are a neglected cardiovascular risk factor in children with renal failure; therapeutic interventions should therefore be seriously considered.

Blood Proteins↗
PubMed1992

Inherited WT1 mutation in Denys-Drash syndrome.

Patients with the Denys-Drash syndrome (Wilms' tumor, genital anomalies, and nephropathy) have been demonstrated to carry de novo constitutional mutations in WT1, the Wilms' tumor gene at chromosome 11p13. We report three new cases, two carrying a previously described WT1 exon 9 mutation and one with a novel WT1 exon 8 mutation. However, unlike patients in previous reports, one of our three patients inherited the affected allele from his phenotypically unaffected father. This observation indicates that the WT1 exon 9 mutation affecting 394Arg demonstrated in over one-half of the patients with the Denys-Drash syndrome may exhibit incomplete penetrance. Consequently, familial studies in patients affected by this syndrome are recommended.

Adolescent↗
PubMed1992

Captopril test in children with reflux nephropathy.

We studied the plasma renin activity (PRA) and blood pressure (BP) responses to a single oral dose of captopril in children with renal scarring due to vesicoureteral reflux. The test was performed on 19 children, of whom 13 were normotensive and 6 hypertensive. Basal PRA was within the normal range for age for all except 1 patient. Mean basal PRA values for normotensive and hypertensive patients were not significantly different. At 90 min post captopril, the mean PRA increase was 3.61 ng/l per second (SD = 7.07) in the normotensive group but only 0.77 ng/l per second (SD = 0.83) in the hypertensive group. In 11 patients the average systolic BP 60-90 min post captopril was 0.9%-12.4% lower than the basal value. Diastolic BP decreased after captopril administration in 10 patients and increased in 9. The changes in mean arterial pressure and PRA between 0 and 90 min post captopril were inversely correlated (r = 0.605, P less than 0.01). Because of the PRA responsiveness in the normotensive patients with renal scarring, we suggest that there was activation of the renin-angiotensin axis in this group. However, it is not apparent whether such patients are more at risk of developing hypertension at a later time.

Adolescent↗
PubMed1992

Ambulatory blood pressure monitoring and left ventricular mass and function after successful surgical repair of coarctation of the aorta.

Late cardiovascular morbidity and mortality remain significant despite apparently successful surgical repair of aortic coarctation. Alterations in cardiac function have been reported in normotensive patients who have had successful repair, the reasons for which remain unclear. This study addresses the relation between ambulatory blood pressure measurements and alterations in left ventricular performance in 20 patients with normotension at rest after successful repair of aortic coarctation. Exercise testing, ambulatory blood pressure monitoring and two-dimensional echocardiographic studies in 13 boys and 7 girls (mean age 14.2 +/- 2.31 and 14.7 +/- 3 years, respectively) who had no evidence of recoarctation were compared with the findings in 20 matched control subjects. No difference was found in systolic blood pressure at rest or peak exercise between patients and control subjects. Male patients developed a significant arm/leg gradient at peak exercise. Systolic ambulatory blood pressure was higher throughout the day in the male group. In the female group, systolic blood pressure was higher only during sleep. No difference was found in diastolic blood pressure or heart rate. The transverse aortic arch was smaller and the left ventricular mass greater in all patients. The relation of wall stress to rate-corrected velocity of shortening was 2 SD above normal in 8 of the 20 patients, suggesting that some have enhanced contractility. The E/A ratio on the atrial echocardiogram was significantly reduced in the patient group. Successfully treated patients who are normotensive at rest after operation are still at risk for developing end organ damage, which is probably explained by incipient mild hypertension documented by ambulatory blood pressure monitoring.

Adolescent↗