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Biomedical subjects

M A Preece

Publications and source records attributed to M A Preece.

At least 37 records · Page 2Linked to original sources
PubMed1991

Laron-type dwarfism with apparently normal high affinity serum growth hormone-binding protein.

OBJECTIVE: Normal serum contains a high affinity GH-binding protein, which appears to be identical with the extracellular domain of the GH receptor. It is normally absent from the serum of patients with Laron-type dwarfism. We wished in this study to define the serum GH-binding protein status of a family with Laron-type dwarfism. DESIGN AND PATIENTS: We performed an open case study of an Asian family in which three sisters (aged 3 to 15 years) had the phenotype of Laron-type dwarfism. Sera from a fourth, unrelated girl with Laron-type dwarfism and subjects without endocrine disorders were used as control samples. MEASUREMENTS: Laron-type dwarfism was confirmed by demonstration of elevated serum GH levels and low serum IGF-I levels on immunoassay, with serum IGF-I levels failing to rise during treatment with GH. Serum GH-binding proteins were characterized using gel chromatography on Sephacryl S-100HR following incubation of serum with 125I-GH, Scatchard analysis of ligand binding, and by polyacrylamide gel electrophoresis after covalent cross-linking to 125I-GH. RESULTS: All members of the family had high affinity serum GH-binding protein activity similar in size, circulating levels and apparent affinity for GH to that of normal subjects. This contrasted with the very low serum GH-binding protein activity in the unrelated child with Laron-type dwarfism and previous reports of serum GH-binding protein levels in this disorder. CONCLUSIONS: The affected patients may possess a novel biochemical defect which results in GH-resistance and reduced production of IGF-I in the presence of normal serum GH-binding protein levels.

Adolescent↗
PubMed1991

Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children.

OBJECTIVE: The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone in normal children at various stages of puberty. DESIGN: Blood samples were taken at 15-minute intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). PATIENTS: Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1-20.9 years). They were of normal height, non-obese, and covered the range of puberty. MEASUREMENTS: Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed in a subgroup of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. RESULTS: Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive luteinizing hormone concentrations were higher than immunoreactive luteinizing hormone levels in all the girls studied (n = 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase in the bioactive: immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4-5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bioactive than immunoreactive luteinizing hormone levels and overall bioactive and immunoreactive luteinizing hormone and testosterone concentrations increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an increase in the bioactive: immunoreactive ratio was observed in the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data in the girls, testosterone secretion always followed luteinizing hormone pulsatility overnight. CONCLUSION: We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than immunoreactive luteinizing hormone in both sexes, but there is very little discordance between immunoreactive and bioactive luteinizing hormone pulsatility. The bioactive: immunoreactive ratio increases with the occurrence of pulsatility overnight in early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion.

Adolescent↗
PubMed1991

Does growth hormone treatment improve final height attainment of children with intrauterine growth retardation?

Twenty four children (five girls, 19 boys) who had intrauterine growth retardation were treated with daily subcutaneous biosynthetic human growth hormone, initially in a dose of either 15 or 30 U/m2/week for the first year and in the latter dose for the next two years. Six patients (one girl, five boys) had no dysmorphic signs and 18 (four girls, 14 boys) had signs of Russel-Silver syndrome. All had birth weights below the third centile when adjusted for gestation age and all the children were below the third height centile at the start of treatment. Mean age was 6.3 years (range 2.1-9.7) when growth hormone treatment was started. All had normal growth hormone secretion to either a pharmacological or physiological test. In the first year of treatment, height velocity SD score increased from -0.75 to +3.6 in the group treated with 30 U/m2/week, and from -0.77 to +1.4 in the lower dose group. After three years of treatment, mean height velocity SD score was +1.1, irrespective of which initial treatment dose had been administered during the first year. There was no difference in the growth response of children with or without dysmorphic features. However, despite the sustained increase in growth rate, there was no significant change in height for bone age SD score, pointing to an unaltered final height outcome.

Age Determination by Skeleton↗
PubMed1991

Growth prognosis and growth after menarche in primary hypothyroidism.

The long term growth of 20 girls and nine boys with juvenile primary hypothyroidism was studied until they reached final height. At diagnosis the girls had a mean age of 8.8 years (range 3.0-13.0); mean bone age was 5.4 years. The mean age of the boys at diagnosis was 9.5 years (range 3.7-14.2); mean bone age was 6.3 years. The patients were treated with thyroxine 100 micrograms/m2/day and serum thyroxine concentrations were maintained in the normal range. During treatment the rate of skeletal maturation exceeded the change in chronological age. Initial mean height SD score for bone age before treatment in the girls was +0.59 and after 11 years of treatment fell to -0.55 Mean height SD score for bone age in the boys decreased from +1.6 to -0.87 during treatment. In the girls the onset of puberty was 1.2 years later than the normal population but the duration of puberty was reduced. Mean age (SD) of menarche was 13.8 (1.7) years. The pattern of growth in girls with treated hypothyroidism was abnormal as growth continued after menarche, at a time when normal girls have almost stopped growing. During the second year after menarche our patients still had a mean growth velocity of 4.1 cm/year. Our data suggest that juvenile primary hypothyroidism results in a permanent height deficit. In addition, there is a loss of the normal harmony between growth and sexual maturation in girls, despite adequate treatment, in that growth continues for much longer after menarche than in normal girls.

Adolescent↗
PubMed1991

Treatment of constitutional growth delay in prepubertal boys with a prolonged course of low dose oxandrolone.

Forty six prepubertal boys who had constitutional growth delay were treated with oxandrolone. Mean age at the onset of treatment was 11.9 years (range 9.0-14.0) and bone age delay was 1.9 'years'. The dose of oxandrolone used was a mean of 0.05 mg/kg (range 0.03-0.18) for a mean of 0.9 years (range 0.2-3.6). Height velocity increased from a mean (SD) before treatment of 4.0 (1.0) to 7.5 (1.2) cm/year with oxandrolone. Growth rate was sustained at 7.6 (2.2) cm/year in the period after treatment. Those boys who attained a testicular volume of 4 ml or greater at the end of the treatment period had the most pronounced sustained growth acceleration. Height for bone age SD score did not alter significantly from a mean of -1.0 before treatment to -1.2 after treatment. Oxandrolone is a safe and effective treatment for prepubertal boys with constitutional growth delay.

Adolescent↗
PubMed1991

Evidence for temporal coupling of growth hormone, prolactin, LH and FSH pulsatility overnight during normal puberty.

The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00-08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9.1-20.9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization. The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150-180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30-75 min (r = 0.32; P less than 0.001) and 30 min (r = 0.47; P less than 0.0001) respectively. Generally, LH and prolactin pulses were in phase (r = 0.42; P less than 0.0001) and there was a highly significant correlation (r = 0.64; P less than 0.0001) between FSH and LH pulsatility. Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150-180 min was established and there was remarkable temporal coupling of pulsatility.

Adolescent↗
PubMed1990

Evaluation of the nutritional status of 1st-year school children in Campinas, Brazil.

We present findings from a study of nutritional status amongst 1st year primary school children in Brazil. The study was based on a 10% stratified random sample of children in Campinas, Sao Paulo State. The primary schools in the city were grouped into four socio-economic strata (high, medium, low and very low) based on the type of school maintenance (private or maintained by the local or by the State government) and the socio-economic characteristics of the school's catchment area. The nutritional status of 1942 children was assessed by looking at the distributions of z-scores of weight-for-age, height-for-age and weight-for-height in relation to growth charts of the National Center for Health Statistics reference population. In the overall population, 22% of the children were found to be stunted (z-score of height-for-age less than -1.0), 15% wasted (z-score of weight-for-height less than -1.0), 22% underweight (z-score of weight-for-age less than -1.0) and 5% overweight (z-score of weight-for-height greater than 2.0). These figures represent an excess of 6% of stunted children and also 6% of underweight children in comparison with the expected values in the NCHS reference population, and an excess of 2% overweight. The data were analysed by age, sex, ethnic group and socio-economic level. Both stunting and low weight-for-age were observed in 32% of children from the very low socio-economic level, with the highest percentages amongst the oldest children. A total of 11.6% of children from the high socio-economic stratum were obese. These results emphasize the need for different programmes to deal with nutritional problems in different groups of the population.

Age Factors↗
PubMed1990

The growth hormone independent insulin-like growth factor-I binding protein BP-28 is associated with serum insulin-like growth factor-I inhibitory bioactivity in adolescent insulin-dependent diabetics.

The relationship between the growth hormone independent insulin-like growth factor binding protein (BP-28) and serum insulin-like growth factor-I (IGF-I) inhibitory bioactivity observed in diabetic serum was investigated in five poorly controlled adolescent type I diabetics. We have measured the in-vitro effects of purified BP-28 from amniotic fluid on serum IGF-I stimulated and basal cartilage sulphation and compared serum IGF-I bioactivity obtained from 24-h serum profiles from each diabetic subject with serum concentrations of BP-28 and IGF-I measured by specific radioimmunoassays. Purified BP-28 inhibited serum IGF-I stimulated and basal cartilage sulphation in vitro, in a dose-dependent manner. Serum IGF-I bioactivity of diabetic sera showed a change in activity over the 24-h period, with peak inhibitory bioactivity observed in each subject between 0800 and 1000 h. BP-28 concentrations in each individual showed a marked circadian rhythm with maximum peak levels occurring at 0800 h. Long-acting insulin administered in the evening in two of the diabetic subjects blunted the maximum peak level attained compared to the three diabetics who had long-acting insulin administered in the morning. IGF-I concentrations did not change over the 24-h period in each individual. The data shows that BP-28 inhibits serum IGF-bioactivity on cartilage in vitro. The changes in inhibitory bioactivity observed in diabetic serum are associated with similar changes in serum concentrations of BP-28. We propose that BP-28 is one of the IGF-I inhibitors observed in diabetic serum and that it may play a role in retarded growth and delayed puberty often seen in the adolescent diabetic.

Adolescent↗
PubMed1979

Melatonin, the pineal gland and human puberty.

Animal experiments have suggested that the pineal gland produces an anti-gonadotropic hormone. The hamster, for example, undergoes reproductive collapse when kept in short-day periods, an effect which is abolished by pinealectomy. Although there is little direct evidence about the endocrine role of the pineal gland in man, it has been noted that tumours of the pineal gland in young boys are associated with precocious puberty and the human pineal gland has been suggested to produce a substance that holds sexual maturation in check. This observation has been extended by Kitay, who has shown that destructive tumours are associated with precocious puberty whereas hyperactive tumours are associated with delayed puberty. However, no studies have described any change of pineal function with normal puberty. Because two pineal indoles, melatonin and methoxytryptophol, have been shown to be antigonadotropic when administered to animals, we have now measured them in schoolchildren. Our findings show that in young boys there is an abrupt fall in the concentration of melatonin with advancing development suggesting that it may play an important physiological role in the control of human puberty.

Adolescent↗
PubMed1979

Experience with human growth hormone in Great Britain: the report of the MRC Working Party.

The Working Party on human growth hormone (hGH) has during the past decade developed a system for the evaluation and treatment of patients suffering from hGH lack. Today there are nineteen measurement centres in the United Kingdom at which patients are assessed and where the effects of therapy are monitored. The current supply of hGH, which is prepared from pituitary glands collected by pathologists in the National Health Service, is just enough to meet demand, but research conducted on behalf of the Working Party suggests that hGH deficiency is more common than has been thought and that the prevalence may be as high as one in 10 000. If, as is hoped, patients are diagnosed younger and more patients with partial deficiency are recognized, demand may soon outstrip supply. Work is in progress to define better methods of hGH production and optimal dose regimens, both of which will help to minimize the problem of supply and demand. A few children have anti-hGH antibodies, which block growth as a result of treatment. Improved hGH production techniques may result in a less antigenic product and the resolution of this problem. Many of the Working Party's activities began as research and have evolved into service. Because of this shift in emphasis, and although much research is still to be done, responsibility for provision of treatment with hGH transferred from the Medical Research Council to the Department of Health and Social Security in July 1977.

Adolescent↗
PubMed1978

A new family of mathematical models describing the human growth curve.

A new family of mathematical functions to fit longitudinal growth data is described. All members derive from the differential equation dh/dt = s(t). (h1-h) where h1 is adult size and s(t) is a function of time. The form of s(t) is given by one of many functions, all solutions of differential equations, thus generating a family of different models. Three versions were compared. All were superior to previously described models. Model 1, in which s(t) was defined by ds/dt = (s1 - s)(s - s0) was especially accurate and robust, containing only five parameters to describe growth in stature from age two to maturity. Derived "biological" parameters such as Peak Height Velocity were very consistent between these three members of the family but, in some cases, differed signficantly from previous estimates.

Body Height↗
PubMed1978

Analysis of the human growth curve.

Mathematical techniques are well suited to analysis of growth data. In the past there has been much emphasis on the mathematical description of shape and changes of shape as exemplified by the allometric equation. More recently these methods have been less popular and shape analysis has been handled largely by modern multivariate statistical methods. In contrast, there has been an increasing interest in fitting models to size data, related to time. Many such functions have been described; some for small parts of the growth curve and others for the whole growing period. More recently single, non-linear functions have been developed and their properties and use are now described.

Adolescent↗
PubMed1977

Growth-hormone deficiency in congenital rubella.

Two boys with congenital rubella and concomitant growth-hormone deficiency responded to human-growth-hormone replacement and have already (over a period of 18 mo) achieved a significant increase in height. The association of these two diagnoses requires recognition so that treatable endocrine disorders, which are becoming recognized more often in congenital rubella, are always positively excluded when affected children with inexplicable short stature are seen.

Anthropometry↗
PubMed1977

Dextrostix-Eyetone in the insulin hypoglycaemia test.

The Ames Dextrostix-Eyetone system was evaluated for monitoring the blood glucose concentration during insulin-induced hypoglycaemia. The results agreed well with laboratory values for plasma glucose, obtained by an orthotoluidine method, and the method was practicable as a bedside technique. In two cases quick results obtained with the Eyetone enabled the insulin tolerance test to be interrupted to prevent severe hypoglycaemia before the clinical indications were obvious. The extra time and effort required were minimal, and its value seems to far outweigh the disadvantage of the extra work entailed. Nevertheless, care in using the system was important, and the operator must familiarise himself with the system before the most reliable results can be obtained.

Adolescent↗