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Biomedical subjects

C Chantler

Publications and source records attributed to C Chantler.

At least 73 records · Page 4Linked to original sources

Bone turnover and 1,25-dihydroxycholecalciferol during treatment with phosphate binders.

The effect of dietary phosphate restriction with high-dose aluminum hydroxide or calcium carbonate on bone disease assessed by histomorphometry and on the plasma levels of 1,25-dihydroxycholecalciferol was investigated in 12 children with chronic renal failure (GFR 8 to 45 ml/min/1.73 m2, age 5 to 15 years) over a one year period. Prior to treatment patients had biochemical and histological hyperparathyroidism with greatly increased bone formation rates. During treatment, plasma phosphate levels decreased from the upper to the lower limit of normal for age (pre, 1.69 +/- 0.06 mmol/liter; 6 months, 1.28 +/- 0.06 mmol/liter; 1 year, 1.34 +/- 0.06 mmol/liter; P less than 0.01). Circulating 1,25-dihydroxycholecalciferol rose to supranormal levels within three months and remained high throughout the period of study (pre, 96 +/- 32 pmol/liter; 6 months, 144 +/- 46 pmol/liter; 1 year, 169 +/- 53 pmol/liter; P less than 0.001). Significant falls in bone formation rate at tissue and cellular levels (P less than 0.005) and in total resorption surface (P less than 0.005) were observed. A mild mineralization defect present before treatment worsened, with a decrease in mineral appositional rate (P less than 0.01) and increase in mineralization lag time (P less than 0.01). Staining for aluminum in post-treatment biopsies was positive in 9 of 11 cases. Phosphate restriction produced suppression of biochemical and histological hyperparathyroidism and sustained elevation of circulating 1,25-dihydroxycholecalciferol. The adverse changes in bone mineralization may be related to aluminum hydroxide therapy; calcium carbonate is therefore recommended.

Adolescent↗

Long term outcome of treatment of end stage renal failure.

The most common causes of end stage renal failure in 46 children (mean age 11 years, range 4-14) treated between January 1972 and June 1977 were: reflux nephropathy (n = 12), cystinosis (n = 7), focal and segmental glomerulosclerosis (n = 6), and Schönlein-Henoch disease (n = 5). The quality of life, degree of renal function, and height attainment of the 31 survivors were assessed in June 1985, when their mean age was 22 years (range 14-27), using hospital records and a questionnaire designed to highlight social and psychological problems. Twenty six patients had a functioning transplanted kidney. Average growth during treatment for all survivors was normal, but most were disappointed with their 'final height'. Though five patients had some form of disabling bone disease, all 31 could walk and 27 could run. Sixteen (67%) were in full or part time employment and nine were living independently. A group of 32 patients with juvenile onset diabetes treated at this hospital for at least five years were also asked to complete the questionnaire and of these, 17 responded. On average, their data could usefully be compared with those of cases of end stage renal failure. More of the diabetics had jobs, but most sexually mature patients with renal disease were concerned about their physical appearance and had not achieved any stable long term sexual relationships. We suggest that a poor body image resulting in low self esteem may be responsible for the deficiency and believe that further study in this group is warranted.

Adolescent↗

Growth and endocrine function after renal transplantation.

Longitudinal height data and physical development were assessed in 45 boys and 34 girls after renal transplantation. All children received alternate day steroids and either azathioprine or cyclosporin A for immunosuppression. There was a significant increase in growth velocity after transplantation in prepubertal children. Growth velocity declined at the expected age of the normal pubertal growth spurt, however, with delay in the appearance of secondary sexual characteristics. Overnight hormone profiles in 17 adolescent subjects with short stature or maturational delay, or both, showed blunting of growth hormone and gonadotrophin pulsatility. It is likely that long term steroid treatment after renal transplantation induces the clinical and endocrine picture of delayed puberty. Failure of growth to accelerate at this time is a cause of short stature, which may have an effect on adult height.

Adolescent↗

Urinary creatinine excretion in the newborn.

We measured the excretion rate of endogenous creatinine in 84 24-hour urine collections obtained from 60 term and preterm newborn infants between the 3rd and the 68th postnatal day, at postconceptional ages 28-42 weeks. The rate was positively correlated with weight, height, and postconceptional age but not with postnatal age; the strongest correlation was that with weight. When the rate was factored by weight it was constant across the range of values studied, with a median and logarithmic mean value of 90 mumol/kg/day (10 mg/kg/day) and a range (2 log SD) of 45-180 mumol/kg/day (5-20 mg/kg/day).

Body Weight↗

Growth and endocrine function in steroid sensitive nephrotic syndrome.

Longitudinal height data and physical development were assessed in 29 boys and 12 girls taking long term steroid treatment for steroid sensitive nephrotic syndrome. Growth in both boys and girls, assessed by changes in height standard deviation score (delta Ht SDS), worsened significantly with chronological age. There was a significant negative correlation between delta Ht SDS and duration of treatment in boys, but not in girls. There was no correlation between delta Ht SDS and relapse rate or the use of cyclophosphamide. In the boys, Ht SDS decreased significantly only after the age of 10 years and was associated with delay in the appearance of secondary sexual characteristics. Eight adolescent boys were assessed endocrinologically by an overnight hormone profile. Blunting of the pulsatility of growth hormone and gonadotrophins was seen in six. Normal profiles were seen in two subjects who were both off steroid treatment at the time of study. Abnormal endocrine function in adolescent boys treated long term for steroid sensitive nephrotic syndrome corresponded with the clinical picture of delayed onset of puberty, which accounted for severe growth retardation in a substantial proportion of subjects.

Adolescent↗

The effect of antenatal dexamethasone administration on glomerular filtration rate and renal sodium excretion in premature infants.

Creatinine clearance (Ccr) and renal sodium (Na+) excretion were measured in 10 premature infants (gestational age less than 34 weeks) whose mothers had received dexamethasone before delivery (group D) and in 11 whose mothers were not so treated (control, group C). Babies were studied twice: on days 2-5 (study 1. all infants) and days 6-10 (study 2, six infants in each group). In study 1, absolute and fractional Na+ excretion were significantly lower (P less than 0.01) and urinary K+:Na+ ratio significantly higher (P less than 0.025) in group D than in group C, while Cr did not differ between groups. In study 2, Ccr in group D had increased compared both with values obtained in the same babies in study 1 (P less than 0.05) and with group C babies in study 2 (P less than 0.05), but significant differences between groups in urinary Na+ excretion and urinary K+:Na+ ratio were no longer found. We conclude that exogenous glucocorticoids accelerate maturation of renal function in immature human infants, probably by inducing tubular Na+. K(+)-ATPase activity. Our findings support the view that endogenous glucocorticoid hormones may play an important part in the normal maturation process.

Adult↗

Long-term suppression of hyperparathyroidism by phosphate binders in uremic children.

Forty-five children with stable chronic renal failure, not on dialysis, were treated conservatively with a regimen of mild dietary phosphate restriction and high-dose phosphate binders for up to 5 years. Both aluminum hydroxide and calcium carbonate were used initially, but almost all patients were taking calcium carbonate towards the end of the period. Serum immunoreactive parathyroid hormone concentrations were significantly decreased and were within the normal range after 1 year and remained normal during treatment. There was no significant change in renal function over the same treatment period. We conclude that calcium carbonate should be used as the phosphate binder of choice in the long-term suppression of hyperphosphatemia and hyperparathyroidism in uremic children.

Adolescent↗

Hyperglycemia with and without glycosuria: effect on inulin and para-amino hippurate clearance.

The response of the clearance of inulin (Cin) and para-amino hippurate (CPAH) to acute hyperglycemia with and without glycosuria was investigated in ten, healthy non-diabetic subjects. Standard methodology (UV/P) was used, with a mean clearance calculated from three, 15-minute urine collection periods. Each subject was studied at three levels of blood glucose (mmol/liter) concentration, mean (SE): Level 1, fasting, 4.5 (0.1); Level 2, hyperglycemia below renal threshold for glucose, 7.2 (0.1); Level 3, hyperglycemia with glycosuria, 12.6 (0.5). There was a significant rise in mean Cin (ml/min/1.73 m2) when changing from Level 1 (112[3]) to Level 2 (121[5]), with no further increase on changing to Level 3 (122[4]). With glycosuria Cin fell in some subjects. Mean CPAH (ml/min/1.73 m2) increased through Level 1 (560[27]) to Level 3 (603[34]), with consequently no change in mean filtration fraction at the three levels of glycemia. Our observations show a rise in glomerular filtration rate with mild hyperglycemia below renal threshold, with no further increase during hyperglycemia sufficient to produce glycosuria.

Adult↗

Hyponatraemia in premature babies and following surgery in older children.

Hyponatraemia implies water retention in excess of sodium with or without increased loss of sodium from the body; extracellular fluid volume may be increased, normal or reduced. It has many causes which are briefly reviewed. Among these is the rare syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is suggested that SIADH is often diagnosed incorrectly because the raised ADH levels are appropriate for the volume status of the child. Precision in the diagnosis is important because whilst water restriction is necessary for the treatment of SIADH, other measures including the administration of extra fluid are often required if the raised ADH is appropriate. Hyponatraemia in the newborn may be caused by prerenal failure, renal failure or renal sodium wasting which is common in premature infants. Careful control of sodium intake as well as water intake is vital in this age group. Surgery is associated with water retention, but recent studies suggest that ADH levels are raised post-operatively because of volume depletion and that present recommendations for fluid therapy during and following surgery are inadequate. The use of electrolyte-free dextrose solutions should be abandoned and more liberal use of physiological saline or colloid is recommended.

Adolescent↗