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Biomedical subjects

E M Hodson

Publications and source records attributed to E M Hodson.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics of cyclosporin in children with stable renal transplants.

Fourteen children, aged between 5 and 17 years, with stable renal graft function and stable cyclosporin A (CSA) trough levels (Cmin) were studied. They had been taking CSA 12-hourly since their transplant 1.5-9 years previously, with the average dose of Neoral being 6.4 (range 4.4-8.4) mg/kg per day. CSA whole blood levels were measured at 0, 20, and 40 min, and at 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h following the morning dose using the Abbott TDx fluorescence polarization immunoassay. The area under the concentration time curve (AUC), clearance adjusted for bioavailability (CL/F), and steady-state volume of distribution adjusted for bioavailability (Vss/F) were determined using model-independent pharmacokinetic analysis. Delay time (Tdel), peak concentration (Cmax), time to peak concentration (Tmax), and Cmin were also determined and correlated with AUC and other parameters. The Tdel in absorption varied from 0.3 to 1.6 (mean 0.73) h, resulting in a similarly variable time to Tmax of 1-2.4 h (mean 1.59). Tmax was related to the age of the patient (Tmax = 0.027 age + 1.41, r2 = 0.56, P < 0.005). The AUC showed good correlation with Cmax (Cmax = 0.25 AUC + 423.32, r2 = 0.96, P < 0.0005). Cmax appears to be a more-suitable measure of exposure to CSA than Cmin. Prediction of Tmax from the age of the child may help to overcome the problem of when to collect blood for peak levels.

Adolescent↗

Corticosteroid therapy in nephrotic syndrome: a meta-analysis of randomised controlled trials.

AIMS: To determine the benefits and toxicity of different corticosteroid regimes in preventing relapse in steroid responsive nephrotic syndrome. DESIGN: Meta-analysis of randomised controlled trials. SUBJECTS: Twelve trials involving 868 children aged 3 months to 18 years. MAIN OUTCOME MEASURE: Frequency of relapse. RESULTS: A meta-analysis of five trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12-24 months (relative risk 0.73; 95% confidence interval 0.60 to 0.89) without an increase in adverse events. There was an inverse linear relation (relative risk 1.382 (SE 0.215) - 0.133 (SE 0.048) duration; r(2) = 0.66; p = 0.05) between the duration of treatment and risk of relapse. CONCLUSIONS: Children in their first episode of steroid responsive nephrotic syndrome should be treated with prednisone for at least three months, with an increase in benefit being shown for up to seven months of treatment.

Adolescent↗

Neonatal Bartter syndrome--use of indomethacin in the newborn period and prevention of growth failure.

Neonatal Bartter syndrome differs from the classical Bartter syndrome in the occurrence of antenatal presentation with polyhydramnios. Nephrocalcinosis and severe growth retardation are common sequelae. Indomethacin has been reported to improve linear growth, but its use in the early newborn period has been infrequently described. In this paper we report normal growth and development and the absence of nephrocalcinosis in an infant now aged 19 months with neonatal Bartter syndrome treated from day 3 of life with indomethacin. With early diagnosis and treatment with indomethacin plus adequate water, calories, and sodium, normal growth can be achieved and nephrocalcinosis may be prevented in children with neonatal Bartter syndrome.

Bartter Syndrome↗

Postnatal diagnosis and outcome of urinary tract abnormalities detected by antenatal ultrasound.

OBJECTIVES: To determine the incidence of urinary tract abnormalities detected by antenatal ultrasound; the value of fetal renal measurements in predicting significant uropathy; and the nature and clinical outcome of fetal uropathy. DESIGN AND SETTING: A retrospective analysis of babies with urinary tract abnormalities detected before birth who were born at or referred to a teaching hospital. PATIENTS: One hundred and twenty-five babies born between June 1989 and November 1992. Sixty-nine babies were born at Westmead hospital and 56 were born elsewhere and referred to Westmead Hospital for investigation. RESULTS: The incidence of uropathy detected before birth among babies born at the teaching hospital was 5.1 per 1000 births. In 60% of these babies, significant abnormalities were confirmed after birth (3.1 per 1000 births). We found a significance of 71% and a specificity of 89% for fetal measurements in predicting significant uropathy. Among all 125 babies the most common abnormalities were pelviureteric junction (PUJ) anomalies (34%), minimal hydronephrosis (26%), ureteric reflux (18%) and multicystic kidney (7%). Pyeloplasty has been performed in 23 (46%) of the 52 kidneys with PUJ anomalies. Renal parenchymal abnormality was detected in four of 22 kidneys with ureteric reflux (18%). Of these four, all were exposed to Grade IV or V ureteric reflux but none had been infected. CONCLUSIONS: Antenatal ultrasound is a sensitive, though nonspecific, tool for the non-invasive identification of congenital abnormalities of the urinary tract, which are common and frequently asymptomatic after birth. Although ureteric reflux may not be predicted from renal measurements, the degree of fetal hydronephrosis indicates the likelihood of obstructive abnormality and, thus, the extent of postnatal investigation required.

Female↗

Phosphate enema poisoning in children.

OBJECTIVE: To report a case of hypocalcaemic tetany occurring in a child secondary to two phosphate enemas administered for faecal retention, and review the literature of phosphate enema toxicity in children. CLINICAL FEATURES: A 23-month-old child with a repaired anorectal malformation and associated unilateral renal hypodysplasia presented with hypocalcaemic tetany (minimum serum calcium level, 1.11 mmol/L), hyperphosphataemia (maximum serum phosphate level, 6.06 mmol/L), hypokalaemia (minimum serum potassium level, 1.9 mmol/L) and dehydration 10 hours after the administration of two phosphate enemas for acute on chronic faecal retention. MANAGEMENT AND OUTCOME: Management consisted of parenteral rehydration, potassium supplementation, calcium gluconate, an enterally administered phosphate binder and saline bowel washouts to evacuate the remaining enema. She was discharged on day eight, with normal biochemical parameters and no neurological sequelae. CONCLUSION: The use of phosphate enemas in children under five years of age is associated with significant morbidity due to hyperphosphataemia, hypocalcaemia, hypokalaemia and dehydration. They should not be used in children under two years of age, and should be used only with extreme caution in children aged two to five years, especially in those with underlying bowel or renal dysfunction.

Child↗

Hypertension associated with diffuse small artery calcification: a case report.

Renal ultrasound examination, performed following a urinary tract infection in a 4.5-year-old girl with triple X syndrome, showed multiple echogenic foci at the corticomedullary junction in both kidneys. She was asymptomatic but had hypertension with echocardiographic evidence of left ventricular hypertrophy. Computerised tomographic scan revealed foci of calcification in the kidneys, spleen and pancreas. On biopsy calcification was found in the internal and external elastic laminae of the superficial temporal artery and in the internal elastic lamina of a renal arcuate artery. Intimal fibrosis was mild and focal. No other arterial calcification was demonstrated radiographically or by ultrasound. Biochemical and hormonal profiles revealed no abnormality except hypercalciuria. The aetiology and prognosis of this child's condition are unknown. Although similar ultrasound and histological appearances have been described in pseudoxanthoma elasticum and in idiopathic arterial calcification of infancy, there is no evidence that the child has either of these conditions.

Calcinosis↗

Insulin-like growth factor-1, growth hormone-dependent insulin-like growth factor-binding protein and growth in children with chronic renal failure.

Insulin-like growth factor-binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) levels were measured by specific radioimmunoassays in children with all degrees of chronic renal failure (CRF). Study group 1 comprised 29 children (10 on dialysis) who had been studied one to four times over 2 years to determine whether IGF-1 and IGFBP-3 levels differed from those in age-matched healthy children and to examine the relationship between these levels and heights. IGF-1 and IGFBP-3 levels did not differ from those in normal children. IGF-1 and IGFBP-3 were significantly correlated, increased with pubertal stage in all children and with age in non-dialysis patients. IGF-1, but not IGFBP-3, correlated with age in dialysis patients. There was no correlation between IGF-1 or IGFBP-3 levels (corrected for age) and height standard deviation score (SDS) in either non-dialysis or dialysis patients. Study group 2 comprised 19 children (7 on dialysis) who were studied prospectively for 1-2 years to examine the relationship between IGF-1 and IGFBP-3 levels, growth rates and nutritional parameters. Mean values of IGF-1 and IGFBP-3 (corrected for age) did not change over 1-year periods, while height SDS fell by -0.38 +/- 0.21 SD/year in dialysis patients and by -0.11 +/- 0.29 SD/year in non-dialysis patients. No significant correlations were found between IGF-1 or IGFBP-3 levels and growth rates or nutritional parameters. Thus growth retardation in children with CRF is not related to circulating levels of IGF-1 or IGFBP-3.

Adolescent↗

Volume expanded diuretic renography in the postnatal assessment of suspected uretero-pelvic junction obstruction.

Controversy surrounds the role of 99mTc-diethylenetriamine pentaacetic acid renography in suspected uretero-pelvic junction obstruction in early life. Accordingly, we retrospectively reviewed 18 patients (28 hydronephrotic kidneys) with a mean age of 2 mo (range: 1 wk-6 mo) who underwent a total of 36 scans using intravenous volume expansion (10 ml/kg) and furosemide diuresis (1 mg/kg). Initial scans were classified as obstructed, not obstructed or indeterminate using differential renal function, furosemide washout T 1/2 and visual assessment of tracer clearance. Those initially classified as obstructed (n = 8) have been surgically confirmed. In the indeterminate (n = 6) and nonobstructed (n = 14) groups, three and two kidneys, respectively, developed obstruction on progress scans. Mean follow-up in the nonsurgical patients was approximately 9 mo (range: 4-17 mo). A total of 13 kidneys had developed obstruction by renographic criteria, and to date 12 have surgical confirmation. Our data indicate that: (1) scans classified as obstructed correlate well with surgery; (2) an initial classification of indeterminate or nonobstructed does not exclude later development of obstruction; and (3) serial scans correctly stratify children with possible uretero-pelvic junction obstruction.

Female↗

Abnormal cortical appearances in pediatric renal allografts.

Renal cortical studies were performed in 19 children with renal transplants. There were 10 normal studies and 9 abnormal studies, 8 of which showed multiple large focal peripheral cortical defects. The following factors showed a positive correlation: (a) the ischemia time of the transplant kidney was significantly shorter in patients with normal studies; (b) cadaver grafts were more likely to have abnormal scan appearances than living related donor grafts; and (c) in four of the five patients with double renal arteries, the scans were abnormal in multiple sites. A possible pathophysiologic mechanism to explain these scan appearances is asymptomatic segmental graft infarction secondary to progressive vascular disease. These infarcts may be a long-term sequela of ischemic insult at the time of or prior to the insertion of the renal allograft.

Child↗

End-stage renal failure in children: 16 years' experience at one Australian centre.

Sixty-five children over one year and under 15 years of age began treatment for end-stage renal failure between 1973 and 1988. Sixty-one renal transplants were performed in 53 children, 39 of these were from living donors (38 were first-degree relatives and one was an emotionally related volunteer). Thirteen children, of whom seven had received transplants and six had not, died, including three children with functioning transplants; nine deaths occurred in the first eight years of the programme. Cumulative five-year and 10-year patient survival rates were 78% and 75%, respectively. Eighteen transplants failed, 12 as a result of rejection, five as a result of disease recurrence and one due to primary non-function. Cumulative five-year and 10-year transplant survival rates for first grafts were 66% and 53%, respectively. For living donor transplants these rates were 85% and 68%, respectively. Growth rates fell by 0.4 +/- 0.05 standard deviation score (SDS) per year in children undergoing dialysis, were normal in children with renal transplants receiving prednisone (change in SDS per year, -0.02 +/- 0.08) and increased by 0.36 +/- 0.07 SDS per year in children with transplants receiving cyclosporin A alone. Currently, 32 (82%) of 39 transplant recipients and 7 (58%) of 12 patients undergoing dialysis attend school or work full time. Although both dialysis and transplantation are acceptable therapies for children with end-stage renal failure, successful transplantation provides the best opportunity for satisfactory growth and development.

Actuarial Analysis↗

Treatment of childhood renal osteodystrophy with calcitriol or ergocalciferol.

Quantitative bone histology, biochemistry and height velocities were studied in 18 children suffering from chronic renal failure. Eight received calcitriol, 7 ergocalciferol and 3, though alloted to a treatment group, failed to comply with therapy. A histochemical stain for aluminum showed heavy deposition at the calcification front in 3 patients; 2, in the calcitriol group had severe osteomalacia which worsened during treatment, and 1 in the ergocalciferol group had osteomalacia which did not improve. One had never undergone hemodialysis. Bone histology improved markedly in the remaining 12 patients, whichever vitamin D preparation was used; it was unchanged in 3 non-compliant children. Plasma calcium levels rose while parathyroid hormone and alkaline phosphatase levels fell following both treatments, and were unchanged in non-compliant children. Hypercalcemia occurred more frequently following calcitriol therapy (11 episodes) than following ergocalciferol therapy (3 episodes). Height velocities, studied in 11 children, increased in 5 (3 on ergocalciferol and 2 on calcitriol) and were unchanged in 6 (1 on ergocalciferol, 5 on calcitriol). Improved bone histology did not correlate with increase in height velocity. As ergocalciferol and calcitriol had similar therapeutic effects and as side-effects were more common with calcitriol, it is concluded that calcitriol provides no advantage over ergocalciferol in the treatment of renal bone disease in children.

Alkaline Phosphatase↗

Growth retardation and renal osteodystrophy in children with chronic renal failure.

Height, expressed as standard deviation scores for chronological age and for bone age, was studied in relation to glomerular filtration rate, bone age delay, and bone histology in 47 children with chronic renal disease and GFR less than 80 ml/min/1.73 m2. In multiple regression in all 47 patients, only GFR and bone age delay significantly affected height; 40% of children were short (height standard deviation score less than -2) for chronological age, and 9% were short for bone age. Renal osteodystrophy, which only occurred at GFR less than 30 ml/min/1.73 m2, significantly affected height only in children with congenital renal disease and GFR less than 20 ml/min/1.73 m2. Although radiological and biochemical changes of renal osteodystrophy were seen more often in short children, histological bone disease occurred just as frequently in tall children as in short children. Thus much of the observed height retardation in chronic renal failure is associated with delayed skeletal maturation. In addition, although severe renal osteodystrophy may contribute to growth retardation in advanced renal failure, our data suggest that milder degrees of bone disease evident only on histological study cannot be implicated in the etiology of growth failure in chronic renal impairment.

Adolescent↗

Quantitative bone histology in children with chronic renal failure.

Quantitative bone histology (on undecalcified sections following double tetracycline labeling), radiographs, and biochemistry were studied in 47 children, ages 1 to 17 years, with glomerular filtration rates (GFR) below 80 ml/min/1.73m2. The earliest histologic change was an increased osteoid surface accompanied by increased osteoblast and tetracycline surfaces. However, significant bone disease (increased osteoclastic surface, fibrosis, increased osteoid area, increased mineralization lag time, and reduced tetracycline uptake at osteoid surfaces) occurred only at GFR below 30 ml/min/1.73m2. Radiographs and alkaline phosphatase were normal in 25% of children with significant bone disease; parathyroid hormone was increased in 48% of children without bone disease. Thus, these noninvasive investigations were poor predictors of disease presence. GFR was the most sensitive indicator because bone disease occurred only at GFR below 30 ml/min/1.73m2 and was present in all children with GFR below 20 ml/min/1.73m2. It was concluded that bone histology is required for early detection of bone disease and is an essential tool in experimental studies of renal osteodystrophy. However, because the level of GFR will indicate the presence or absence of bone disease in most children, bone biopsy can be avoided generally in clinical practice.

Adolescent↗

The diagnosis of renal osteodystrophy: a comparison of Technetium-99m-pyrophosphate bone scintigraphy with other techniques.

In order to determine the place of Technetium-99m-pyrophosphate bone scintigraphy in the assessment of renal osteodystrophy, 17 patients with chronic renal failure requiring hemodialysis underwent bone scans and these were compared to results of biochemical, radiological and histologic studies. Bone histology was abnormal in all patients with most having evidence of osteomalacia and hyperparathyroid bone disease. Using semi-quantitative scan scores and regional bone-standard ratios, isotope uptake was increased in 16 patients, while 15 had elevated alkaline phosphatase levels and 7 had X-ray changes. An osteoid-osteoclast index combining histological osteomalacia and hyperparathyroid disease was derived and was found to correlate more closely with alkaline phosphatase and parathyroid hormone levels than with scan parameters. It was concluded that bone scans did not provide therapeutically useful information that could not be obtained from biochemical and radiological studies. It appeared that only bone histology could differentiate osteomalacia and hyperparathyroid bone disease.

Adult↗