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Biomedical subjects

G M Addison

Publications and source records attributed to G M Addison.

At least 37 records · Page 2Linked to original sources

Nocturnal urinary growth hormone excretion in growth hormone-deficient children on and off growth hormone treatment.

Non-compliance has been reported as a major issue in growth hormone (GH) therapy. We explored the use of urinary GH (uGH) measurements to monitor the GH treatment of 18 children (aged 5-16 years) diagnosed as GH deficient on the basis of history, phenotype, auxology and peak GH concentration during 2 provocation tests of < 15 mU/l. Each child collected 5 consecutive overnight urine samples while on GH replacement schedules, then discontinued treatment for 2 days and collected a further 5 urine samples. The mean mass of uGH excreted on treatment (8.6 ng, range 3.6-13.0 ng) was significantly greater than that off treatment (1.2 ng, range 0.6-2.7 np; p < 0.01). All uGH values on treatment exceeded the mean nocturnal uGH excretion of normal age- and sex-matched children. The clear distinction between uGH levels on and off GH treatment indicates that uGH measurement would determine whether two or more GH injections had been missed. A series of uGH estimates over a 2-week period may provide a realistic perspective on injection frequency.

Adolescent↗

Urinary growth hormone excretion in the assessment of children with disorders of growth.

OBJECTIVE: We wished to evaluate the use of urinary GH measurements when compared to conventional GH provocation tests in the assessment of short children. DESIGN: Children presenting for the first time to a regional growth clinic were assessed clinically by one observer. Investigations comprising standard GH provocation tests and measurement of urinary GH were undertaken to exclude GH deficiency. PATIENTS: Fifty-eight children aged 5.8-16 years were enrolled. Ten were diagnosed on clinical assessment as GH deficient, 43 had delayed growth and/or familial short stature, and five had idiopathic short stature; the 48 children in the last two groups were defined as short normal. MEASUREMENTS: GH secretion was evaluated by two standard provocation tests and by the measurement of GH in five overnight urine collections. A normal peak GH concentration was defined as > 16 mU/l. The values for urinary GH excretion were compared to normal ranges (+/- 2 standard deviations from the mean), established in healthy schoolchildren of normal stature. RESULTS: All children considered GH deficient on clinical grounds had low peak GH concentrations on provocation tests, while 8/10 had low values of urinary GH excretion. All short normal children with normal peak GH concentrations (n = 36) on provocation tests and 11/12 children with low peak GH concentrations had urinary GH excretion within the normal range. There was therefore a significant difference in the classification of 'normal' GH secretion in the two tests. If the clinical diagnosis was used as the standard by which GH tests were judged, the predictive value of a positive urinary GH test in the diagnosis of GH deficiency was 89% compared with 45% for GH provocation tests.

Adolescent↗

Variability in the urinary excretion of growth hormone in children: a comparison with other urinary proteins.

As a basis for assessment of the clinical validity of urinary GH (uGH) measurements in children, the day-to-day variability in renal handling of GH has been compared with that of albumin, N-acetylglucosaminidase (NAG) and creatinine. Five overnight urine specimens were collected over a 2-week period from 78 healthy children (aged 5-16 years), 20 of normal stature and 58 with growth disorders; ten children were classified as GH-deficient (GHD) and 48 were designated short normal (SN). The variability of excretion of each substance was expressed as a coefficient of variation (C.V.) which was not influenced by expressing the urine results as total mass excreted, concentration, excretion rate or as a ratio to creatinine. There was considerable night-to-night variability in the excretion of all substances (mean C.V. values for all groups: 56% for albumin, 41% for GH, 33% for NAG and 27% for creatinine). No differences were found in the variability of GH excretion between males and females, nor between prepubertal and pubertal subjects. The mean C.V. for uGH excretion ranged from 37% in normal and 35% in SN children to 52% in those with GHD (P < 0.05). Assay variation rather than a change in renal protein handling accounted for the large variations in uGH concentrations of < 5 pg/ml, thus contributing to the high uGH C.V. of the GHD group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

A novel variant of growth hormone (GH) insufficiency following low dose cranial irradiation.

OBJECTIVE: We aimed to investigate the effect of low dose (1800 cGy) prophylactic cranial irradiation on physiological growth hormone secretion. DESIGN: We performed an analysis of 24-hour serum GH profiles using 20-minute sampling. PATIENTS: Forty-four children were studied, of whom 21 were long-term survivors of acute lymphoblastic leukaemia and 23 were normal children. They were further subdivided into prepubertal, pubertal and post-pubertal groups. MEASUREMENTS: GH profiles were analysed by autocorrelation, Fourier transformation and spectral analysis of stationarized data, and peak detection using the Pulsar peak detection program. RESULTS In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups (62 (11-124) and 137 (142-158) IU/I/h respectively, (P less than 0.01)). There was also a change in the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post-pubertal groups but sharply focused in the pubertal group. In the cranially irradiated children there was no significant increase in AUC between the prepubertal (62(13-110) IU/I/h) and pubertal groups (92 (14-163) IU/I/h). The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranially irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. CONCLUSIONS: A novel form of GH insufficiency has been observed after low dose irradiation in childhood in which an abnormality of periodicity and a quantitative reduction in GH secretion appears restricted to puberty.

Adolescent↗

Relationship between urinary and serum growth hormone and pubertal status.

Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty.

Adolescent↗

The influence of age, size, pubertal status and renal factors on urinary growth hormone excretion in normal children and adolescents.

Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 years) whose heights and weights were between the third and 97th centiles. Urinary GH increased significantly with age, reaching a maximum in boys at 15-years-old and in girls at 13-years-old. Peak levels were five and three times higher in boys and girls respectively than in 4-year-olds. Maximum urinary GH excretion was seen at breast stages 3 and 4 in girls and at genital stage 4 in boys followed by a decline in both sexes at stage 5. Boys excreted more GH than girls during prepubertal and pubertal years. During prepubertal years there were fluctuations of urinary excretion of GH with age. Height, weight and pubertal status predicted 31% of the variability of urinary excretion of GH, and urinary excretion of creatinine, albumin and N-acetylglucosaminidase (NAG) predicted 52% of the variability. The importance of establishing sound age and sex-related reference ranges for urinary growth hormone is stressed before application of this test to children with growth disorders.

Adolescent↗

Increase in urinary growth hormone excretion in puberty.

During the pubertal years the overnight urinary excretion rate of growth hormone (hGHu) increases to three to four times the prepubertal rate, reaching a peak in girls at 13 years and in boys at 15 years. After puberty the mean rate of overnight hGHu is twice that before puberty.

Adolescent↗

Growth and growth hormone responses to oxandrolone in boys with constitutional delay of growth and puberty (CDGP).

Thirteen boys with constitutional delay in growth and/or development aged 7.6 to 16 years received 2.5 mg/day of oxandrolone for 3 months. Their growth response on treatment and in the subsequent 3 months was compared to that of 14 age-matched untreated controls. Growth rates were analysed in groups arbitrarily defined by testicular volume at entry (less than 4 ml prepubertal, greater than 4 ml pubertal). Growth velocities increased on oxandrolone (prepubertal, mean 4.4 to 7.5 cm/year, P = 0.05: pubertal, mean 4.7 to 8 cm/year, P less than 0.05). Over the next 3 months, the pubertal boys grew at 9.3 cm/year, while the prepubertal group decelerated to 6.2 cm/year. Both control groups showed no significant change in velocity over 6 months. GH responses to arginine and GRF, and to sleep in prepubertal boys, were unchanged throughout the study. However, in pubertal boys the mean GH levels ('area under the curve') during sleep at 3 and 6 months, had increased over baseline values, associated with a significant increase at 6 months in basal somatomedin-C (140 to 214 ng/ml, P less than 0.05). Oxandrolone does not alter the GH status of prepubertal boys, and thus probably promotes growth by a direct action at the growth plate. In contrast, the persistent growth acceleration of pubertal boys may be associated with increased GH and somatomedin-C levels: in this group, oxandrolone has proved a useful stimulus to growth.

Adolescent↗

Congenital hypothyroidism: increased incidence in Asian families.

Screening in the North West health region of England showed a significantly higher incidence of congenital hypothyroidism in Asian families--1/918 compared with 1/3391 in non-Asians. This could only in part be explained by consanguinity. No differences were found in birth order, season of birth, gestational age, or birth weight between normal infants and those with congenital hypothyroidism. There was a significantly higher incidence of additional congenital abnormalities (9%) and a significantly increased mortality (5%) in infants with congenital hypothyroidism compared with unaffected infants.

Asia↗

Neuroblastoma--when are urinary catecholamines and their metabolites 'normal'?

The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.

Adolescent↗

Prevention of cisplatin-induced hypomagnesemia.

Twenty-eight children were treated for various cancers with protocols that included dichlorodiamine platinum (cisplatin). Sixteen children were given intravenous magnesium after the administration of cisplatin, and 12 were given intravenous magnesium before and after administration of cisplatin. Serum magnesium concentration levels were monitored before, during, and after the full course of treatment and found to be lower in the first group of patients than in the second group. We recommend that magnesium supplements be given to patients receiving cisplatin during the precisplatin hydration period to prevent hypomagnesemia.

Adolescent↗

Neutropenia associated with dual antimalarial chemoprophylaxis--use of bone-marrow culture as an aid in further drug management.

Bone-marrow culture in soft agar was used to determine the cause of neutropenia in a visitor to Tanzania who had been taking both amodiaquine and proguanil for antimalarial prophylaxis. Desethyl-amodiaquine, a major metabolite of amodiaquine (but not amodiaquine itself, proguanil, cycloguanil or chloroquine) was implicated. Supplementary studies using amodiaquine binding techniques supported the notion that the parent compound, amodiaquine, was not the cause of the neutropenia. The bone-marrow culture technique proved useful in deciding further anti-malarial prophylaxis and in formulating the choice of curative antimalarial therapy, should this have proved necessary. The procedure may help in the managing other such patients with presumed drug-induced blood dyscrasias when the choice of appropriate and effective antimalarial drugs is limited.

Adult↗

Effects of fasting and oral premedication on the pH and volume of gastric aspirate in children.

The pH and volume of gastric aspirate were measured immediately after the induction of anaesthesia in 224 healthy children to determine the effects of decreasing the period of fasting and of giving oral premedicants before anaesthesia. Fasting for less than 4 h was found to increase the volume of gastric aspirate and the risk of developing pulmonary aspiration syndrome. Trimeprazine syrup was found to increase the pH of the gastric contents, and decrease the likelihood of the pulmonary aspiration syndrome. There was a significant increase in gastric volume in patients premedicated with temazepam elixir which did not occur in patients given temazepam capsules. These results support the custom of fasting patients for at least 4 h before anaesthesia and indicate that oral premedicants and their vehicles can have significant effects on the stomach.

Administration, Oral↗