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Biomedical subjects

C T Cowell

Publications and source records attributed to C T Cowell.

65 records · Page 4Linked to original sources
PubMed1989

Insulin and variation in glucose levels modify the secretion rates of the growth hormone-independent insulin-like growth factor binding protein-1 in the human hepatoblastoma cell line Hep G2.

The plasma level of the GH-independent insulin-like growth factor binding-protein-1 (IGFBP-1) is regulated inversely by insulin. In this study the effect of insulin and changes in the glucose concentration on in-vitro IGFBP-1 secretion by the Hep G2 cell line was studied. Media from confluent cells in 12 replicates were collected for consecutive periods: initial control (20 h), study (6 h) and recovery (20 h). Insulin suppressed IGFBP-1 secretion maximally at 100 mU/l (-32%) within 6 h. The secretion of IGFBP-1 was stimulated by a decrease in the glucose concentration in the medium, maximally (+25%) with a decrease from 24 to 6 mmol/l. Stimulation by varying glucose levels and suppression by insulin of IGFBP-1 secretion persisted on return to control conditions after the removal of physiological concentrations of glucose (4-12 mmol/l) and insulin (50-500 mU/l). The findings in the Hep G2 cell line that a variation in the physiological concentrations of glucose and insulin each independently regulate IGFBP-1 secretion suggest that this cell line may be a suitable model for further in-vitro studies of the regulation of secretion of IGFBP-1.

Carcinoma, Hepatocellular↗
PubMed1988

Growth and growth hormone therapy of children treated for leukaemia.

A total of 37 children (24 male, 13 female) who had been treated for leukaemia with chemotherapy and 24 Gy cranial irradiation, and who were disease free for at least 18 months, were commenced on somatrem at a mean of 7.6 years (range, 4.8-12.1 years) after leukaemia diagnosis because of growth rate below the 25th centile for bone age. Peak GH response to provocation (exercise, arginine, insulin hypoglycaemia) was less than 20 milliunits/litre in 27 children (deficient group) and 20 milliunits/litre or more in 10 children (non-deficient group). The mean height SD decrease from diagnosis of leukaemia to commencement of somatrem was 1.98, 86% of the children decreasing by more than 1 SD. Those who were tall for age at leukaemia diagnosis and females were more severely affected. Mean (+/- SD) height velocity increased on somatrem from 2.7 +/- 1.1 to 6.6 +/- 2.2 cm/year during the first 6 months (n = 25), and to 6.0 +/- 1.7 cm/year during the first 12 months (n = 19). No difference in growth response was seen between the sexes or between the deficient and non-deficient groups. Catch-up growth occurred for the first 6 months only. It is concluded that children with a low growth rate after treatment of leukaemia should be considered for GH therapy irrespective of the results of GH provocative tests.

Adolescent↗
PubMed1988

Regulation of the growth hormone-independent growth factor-binding protein in children.

Regulation of the diurnal variation of the GH-independent insulin-like growth factor-binding protein (BP-28) was studied in 53 children who underwent various investigations for possible endocrine abnormalities. The plasma BP-28 levels increased 12-fold from 8 +/- 2 (+/-SE) micrograms/L at 2100 h to a peak level of 109 +/- 15 micrograms/L between 0600 and 0800 h. This rise was inversely related to plasma insulin levels and was unrelated to plasma cortisol levels. The overnight rise of plasma BP-28 was significantly altered in children who ate a light meal at 0130 h; in them BP-28 levels started to fall after 0300 h, reached nadir levels at 0400 h, began to rise again by 0700 h, and returned to control levels by 0800 h. Such changes did not occur in children given water alone. From the peak early morning level, plasma BP-28 fell to basal levels in children given oral glucose at 0800 h; the t1/2 of the fall was 55 +/- 9 (+/-SE) min. In children who continued to fast, plasma BP-28 did not fall but, rather, increased from 144 +/- 12 micrograms/L at 0800 h after 10 h of fasting to 239 +/- 30 micrograms/L by 1600 h. The induction of hypoglycemia by insulin given at 0945 h after an overnight fast caused a similar but more rapid rise in plasma BP-28 to 668 +/- 317 micrograms/L (range, 208-1763 micrograms/L) by 1230 h. These results suggest that the diurnal variation of plasma BP-28 concentrations in children is not due to an intrinsic rhythm, but is regulated by the metabolic status of the child.

Adolescent↗
PubMed1987

Growth failure and growth-hormone deficiency after treatment for acute lymphoblastic leukaemia.

In a study of 77 children who had been treated for acute lymphoblastic leukaemia (ALL) with an LSA2L2 (Memorial Sloan-Kettering) chemotherapy protocol plus radiotherapy (24 Gy) as cranial prophylaxis, growth was examined 3.0-9.5 years after diagnosis. The children's growth slowed and they crossed height percentiles towards the end of or after treatment. The Z-score, which reflects the deviation of height measurements from the population mean, was used to assess height change. The mean Z-score was 0.16 at diagnosis, -0.30 2 years later, -0.71 4 years later, and -1.37 6 years later. Height for age had fallen by more than 1 standard deviation of the population mean in 32% of survivors 4 years after diagnosis and in 71% 6 years after diagnosis. Younger children and those tall for age at diagnosis were more severely affected. Growth-hormone (GH) response to standard provocation tests was measured in 46 patients; 30 had partial or complete GH deficiency. Mean pulsatile GH secretion was low in the 34 patients tested. Cranial irradiation is probably the most important causative factor in the development of GH deficiency in survivors of ALL.

Adolescent↗
PubMed1987

Diurnal rhythm of growth hormone-independent binding protein for insulin-like growth factors in human plasma.

An antibody raised against the major insulin-like growth factor (IGF)-binding protein in amniotic fluid (BP-28) was used to measure the levels of a cross-reacting protein in human plasma by RIA. Plasma BP-28 immunoreactivity had an apparent mol wt of 35,000 by high performance permeation chromatography. Sampled hourly for 12- or 24-h periods in 15 children with a wide range of GH secretory activity, plasma BP-28 levels showed a marked diurnal cycle, rising 10- to 20-fold between 2400 and 0600 h to a peak of 50-500 micrograms/L, then falling to basal levels (0-40 micrograms/L) by 1200 h. Plasma GH levels were measured at 20-min intervals in the same subjects. Neither peak nor basal BP-28 levels were significantly associated with chronological age, bone age, mean or peak nocturnal GH secretion, relative height, or relative growth velocity in tall, normal, short, or GH-deficient children. Plasma proteins measured in a RIA for 53,000 mol wt GH-dependent IGF-binding protein (BP-53) did not vary diurnally. The IGF-binding activity of plasma BP-28, measured by incubating plasma with IGF tracer and precipitating the BP-28-IGF complex with anti-BP-28 antiserum, closely paralleled the morning rise in BP-28 immunoreactivity. Immunoprecipitable BP-28 bound both IGF-I and IGF-II tracers, with a clear preference for IGF-I, and unlabeled IGF-I was more effective than IGF-II in displacing either tracer IGF. We conclude that plasma BP-28 levels in children have a marked diurnal rhythm which is unrelated to GH secretory activity.

Adolescent↗
PubMed1986

First morning urinary albumin concentration is a good predictor of 24-hour urinary albumin excretion in children with type 1 (insulin-dependent) diabetes.

Twenty-four hour urinary albumin excretion was measured in 97 children with Type 1 (insulin-dependent) diabetes and found to have a geometric mean of 6 mg/day (range 1-38 mg/d). The same geometric mean of 6 mg/day (range 1-45 mg/d) was found in 120 normal children. The relationship of 24-h urinary albumin excretion to the albumin concentration (mg/l) and to the ratio of albumin: creatinine (mg:mmol) on first morning urine samples in 64 patients was highly significant (r = 0.93 and r = 0.62 respectively, p less than 0.001). In 41 patients, the relationship between 24-h urinary albumin excretion and albumin concentration upon urine samples at various times was assessed. The correlation was highest on the first morning sample (r = 0.86); 09.00 h to 13.00 h, 0.51; 13.00 h to 18.00 h, 0.68; 18.00 h to 23.00 h, 0.32. High sensitivity and moderate specificity was obtained using a first morning albumin concentration of greater than 20 mg/l to detect increased albumin excretion. These results show that the measurement of albumin concentration on the first morning urine sample can be used for a screening test for microalbuminuria in children.

Adolescent↗
PubMedDate not supplied

DXA for bone density measurement in small rats weighing 150-250 grams.

The present study evaluated the use of a small animal total body software of dual energy x-ray absorptiometry (DXA) in the assessment of total body and regional bone mineral content (BMC) and bone mineral density (BMD) in small rats. Twenty-three rats, with weights ranging from 146 to 246 g, were included in the study. All were scanned using the same software version and same scan procedure (speed and scanned area). Total body BMD, BMC, and body weight were measured by DXA in each rat. Femoral BMC and BMD were analyzed by using regional analysis facilities. The repeatability (precision) of this software version was assessed prior to the study and the coefficients of variation (CV) were 2.9% for total body BMC, 0.8% for total body BMD, 1.2% for body weight, and 2.2% for mean femoral BMD. DXA measurements were compared with the measurements obtained by using established standards, namely weight and bone ash content. Total body ash content and femoral ash content were measured separately in all rats. There was a strong linear correlation between BMC and ash content in total body (r2 = 0.98, p = 0.0001) and in femur (r2 = 0.94, p = 0.0001). There was also an excellent linear association between body weight measured by DXA and scale weight (r2 = 0.99, p = 0.0001). We conclude that this software version is suitable for study on small animals and is a useful tool for assessment of regional as well as total body bone mineral status.

Absorptiometry, Photon↗
PubMedDate not supplied

Adverse events during growth hormone therapy.

The aim of this study was to ascertain the frequency of adverse events occuring during GH therapy in Australia and New Zealand since 1988. Data for children receiving GH has been collected prospectively on a national database, OZGROW, after informed consent has been given. Adverse events were coded by clinicians and have been analysed in relation to the nature of the event and the underlying diagnosis. There were 2922 subjects analysed, representing 9004 years of GH therapy. 151 subjects reported a total of 210 adverse events giving an overall frequency of 2.3% adverse events/patient treated year. Events that were probably related to GH therapy included peripheral oedema, injection site problems and increased frequency of kyphoscoliosis and slipped epiphysis in some groups. Adverse events were more frequent in growth hormone deficient children who had previously been treated for leukaemia, 8.1%, and in children previously treated for craniopharyngioma, 5.6%. A lower frequency was found for those with a diagnosis of idiopathic short stature, 1.6%, and familial short stature, 0.9%. Kyphoscoliosis was more frequently seen in Turner's syndrome, and slipped epiphyses in adolescent individuals with growth hormone deficiency, especially following treatment for leukaemia. There were no de novo tumours reported but the frequencies of recurrence/patient year for leukaemia, solid cranial tumours and craniopharyngioma were 1.1%, 2.2% and 3.8% respectively. A low frequency of adverse events has been reported on the OZGROW database but subsets of patients may be at increased risk of musculoskeletal abnormalities during GH therapy. The frequency of tumour recurrence during therapy is not different from known rates of recurrence in individuals not treated with GH.

Adolescent↗
PubMedDate not supplied

Prevention and treatment of osteoporosis in chronically ill children.

Osteoporosis secondary to chronic disease in children has emerged as a major health issue. As the severity of a child's illness increases, so too does the number of factors affecting their bone health. Determinants of bone health in children include level of mobility, exposure to osteotoxic medication, nutritional status, calcium and vitamin D intake, chronic inflammation and pubertal development.

Adolescent↗