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Biomedical subjects

M A Preece

Publications and source records attributed to M A Preece.

At least 73 records · Page 4Linked to original sources
PubMed1990

A longitudinal study of total and free thyroid hormones and thyroxine binding globulin during normal puberty.

Thyroid hormones are essential for normal pubertal growth, yet the changes in total and, especially, free thyroid hormones and thyroxine-binding globulin during puberty have not been adequately defined. Serum from 39 normal children (20 girls, 19 boys) between the ages of 10 and 15 years were assayed for total T4, free T4, free T3 and thyroxine-binding globulin at 6-monthly intervals; the free hormone assays were valid, non-analogue methodologies. In the girls, free T4 levels fell from 15.7 +/- 0.6 pmol/l at 10 years to 13.0 +/- 0.6 (p less than 0.001) at 12.5 years before rising to 15.9 +/- 0.7 at 15 years; this nadir occurred at puberty stages 3-4. Changes in total T4 followed a similar pattern with a slight delay in the nadir (13 years, puberty stage 4). In the boys, free T4 fell from 16.3 +/- 0.6 pmol/l at 10 years to 14.3 +/- 0.3 at 13.5 years, then rising to 15.4 +/- 0.5 at 15 years; the nadir again occurred at puberty stages 3-4. The corresponding nadir in total T4 which occurred at puberty stages 4-5 was not apparent by age analysis. Thyroxine-binding globulin concentrations remained unchanged in the girls, but fell slightly in the boys during later puberty. Free T3 concentrations in the girls showed a progressive fall after 12.5 years which was significant by the age of 14 when most had been in puberty stage 5 for more than 1 year. The boys showed no change of free T3 concentration throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Ovarian ultrasound appearances in Turner syndrome.

We performed pelvic ultrasound assessment in 104 patients with Turner syndrome aged 0.2 to 17.4 years; 69 had the 45,X karyotype and 35 had variant karyotypes. Ovarian appearances were classified as "streak" (n = 70, including 30 patients in whom no ovary could be seen) or "nonstreak" (n = 34). The nonstreak ovaries ranged from small glands, sometimes containing minute cysts, to ovaries indistinguishable from those which are normal for age. Nonstreak ovaries retained a range of function, as evidenced in some cases by spontaneous breast development and uterine enlargement. The proportion of nonstreak ovaries followed a U-shaped pattern, with a nadir from 4 to 10 years; this follows the known biphasic pattern of luteinizing hormone and follicle-stimulating hormone secretion. Only those patients with karyotype variants in which the long arm of the X chromosome was retained fared better than those with the 45,X karyotype.

Adolescent↗
PubMed1989

Antigenicity and efficacy of authentic sequence recombinant human growth hormone (somatropin): first-year experience in the United Kingdom.

Twenty-one children were treated for GH deficiency with authentic sequence biosynthetic human GH (somatropin), 60 micrograms/kg body weight, subcutaneously, three times weekly for 1 year or longer. The magnitude of growth response and rise in serum insulin-like growth factor I levels were similar to those expected from experience with pituitary GH and somatrem. Three patients developed serum antibodies to GH with a binding capacity greater than 0.02 mg/l, but in only one patient was the GH binding capacity greater than 1.0 mg/l and he showed no attenuation of growth response. Escherichia coli polypeptide antibodies did not rise significantly and no clinically important side-effects occurred. Somatropin is safe, effective and of low immunogenicity in the treatment of GH deficiency.

Adolescent↗
PubMed1989

Changes in skeletal muscle after discontinuation of growth hormone treatment in young adults with hypopituitarism.

Skeletal muscle strength and size were measured for 1 year following discontinuation of human growth hormone (hGH) treatment in 11 patients with hypopituitarism. Quadriceps and forearm flexor maximum voluntary isometric strength and size were measured. At the end of the study, endocrine status was reassessed by an insulin tolerance test. Three of the 11 subjects were found to have normal hGH secretion and were not included in the analysis. At 12 months, quadriceps strength, size and fibre areas were 94.0 +/- 8.5%, 94.5 +/- 6.3% and 85.6 +/- 17.7% (mean +/- SD), respectively, of baseline values. Forearm flexor strength and size were 101.4 +/- 7.9% and 92 +/- 9.2% of control values. Although these changes are relatively small, they suggest a role for growth hormone in the maintenance of muscle in the adult.

Adolescent↗
PubMed1989

Physiological growth hormone secretion and response to growth hormone treatment in children with short stature and intrauterine growth retardation.

Physiological growth hormone (GH) secretion was examined in 31 children (8 girls, 23 boys) with short stature secondary to intrauterine growth retardation (IUGR). Seventeen (4 girls, 13 boys) had dysmorphic features of Russell-Silver syndrome. Four of the 31 children had GH insufficiency with peak GH levels of less than 20 mU/l during the night. Nine of the patients (8 of whom had Russell-Silver syndrome) had a single nocturnal GH pulse. Twenty-three children (6 girls, 17 boys) were randomized into two groups treated with either 15 or 30 U/m2/week of GH by daily subcutaneous injections. Age, sex distribution, pretreatment height velocity SD score (SDS), and distribution of dysmorphic and non-dysmorphic children were similar in both groups. The group treated with 15 U/m2/week for a mean of 0.82 years showed an increase in mean height velocity SDS from -0.61 to +1.09, and the group treated with 30 U/m2/week for a mean of 0.92 years showed an increase in mean height velocity SDS from -0.69 to +3.48. The results suggest that physiological GH insufficiency is probably common in children with Russell-Silver syndrome and that both dysmorphic and non-dysmorphic children with short stature secondary to IUGR will respond to GH treatment. Initial evidence suggests that the increase in short-term growth velocity does not result in an improved final height prognosis.

Body Height↗
PubMed1989

Egg and breast milk based nitrogen sources compared.

A nitrogen source based on egg protein (Vamin 9 glucose) and an alternative with an amino acid profile more similar to breast milk (Vaminolact), were compared in 14 parenterally fed infants. Subjects were randomly allocated to receive one or other amino acid solution, but were otherwise given identical diets. At the start of the study the two groups did not differ significantly in postconceptual age, postnatal age, or weight. Over a six day study period on a stable intake of intravenous nutrients there was no significant difference in growth or nitrogen retention between the two groups. Plasma amino acid profiles in those receiving Vamin 9 glucose, however, were frequently abnormal. Notably, mean concentrations of potentially neurotoxic phenylalanine and tyrosine were significantly higher (140% and 420%, respectively) in patients fed Vamin 9 compared with those given Vaminolact. An amino acid solution based on the composition of breast milk protein therefore brings plasma amino acid profiles during parenteral nutrition closer to those found in breast fed infants, and reduces in particular, the risks of hyperphenylalaninaemia and hypertyrosinaemia.

Amino Acids↗
PubMed1989

Growth in atopic eczema: a controlled study by questionnaire.

The parents of 128 children with atopic eczema and 117 healthy control children responded to a questionnaire that included measurement of their own and their children's heights at home after standardised instructions. When cases and controls were compared there was no significant difference in parental height but the children with eczema were significantly shorter than the healthy control group. This difference remained significant when children with associated asthma were excluded from the analysis.

Adolescent↗
PubMed1989

Growth hormone secretion in Turner's syndrome and influence of oxandrolone and ethinyl oestradiol.

We investigated 24 hour growth hormone secretion by intermittent 20 minute blood sampling in 34 prepubertal patients with Turner's syndrome, aged 4.3-12.4 years. Growth hormone profiles were analysed by the PULSAR programme and results expressed as the sum of growth hormone pulse amplitudes. Six patients had abnormal growth hormone pulse frequencies. In the remaining 28, growth hormone pulse amplitudes declined significantly with increasing age, but there was no correlation between growth hormone pulse amplitudes and growth rates. Concentrations of insulin like growth factor-1 (IGF-1) rose with age but did not correlate with either growth rates or growth hormone secretion. Fifteen patients were given oxandrolone and 11 low dose ethinyl oestradiol. Both agents increased height velocity without increasing growth hormone secretion. We conclude that the relation between growth hormone secretion and growth in Turner's syndrome is less certain than in normal children. End organ resistance is probably due to a skeletal dysplasia. Both oxandrolone and low dose ethinyl oestradiol improve the growth of girls with Turner's syndrome, but their mechanism of action remains uncertain.

Body Height↗
PubMed1989

Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty, and adult life.

The relationships between plasma insulin, insulin-like growth factor I (IGF-I) and dehydroepiandrosterone sulfate (DHEAS) concentrations in normal subjects have not been defined. We performed iv glucose tolerance tests on 102 normal subjects, aged 5-20 yr. The subjects were divided into 4 groups according to pubertal stage (Tanner): A, stage 1 (n = 22); B, stages 2 and 3 (n = 17); C, stages 4 and 5 (n = 20); and D, adult, greater than 17 yr (n = 43). The basal plasma IGF-I and insulin concentrations and incremental 0-60 min insulin areas in response to glucose rose significantly throughout puberty (P less than 0.001 for all parameters) and declined to prepubertal levels by the third decade of life. There was a strong positive correlation between log fasting plasma insulin vs. log plasma IGF-I (r = 0.625; P less than 0.001) and log incremental 0-60 min insulin areas vs. log plasma IGF-I (r = 0.572; P less than 0.001). Plasma DHEAS concentrations were measured in groups A-C (n = 59); these also rose throughout puberty. There was strong correlations between log plasma DHEAS and log basal or stimulated (incremental 0-60 min areas) insulin responses (P less than 0.001). To assess the relationship between plasma DHEAS and insulin before puberty, we analyzed the data from group A separately. Plasma DHEAS concentrations tended to be higher in children 9 yr of age or older than in those less than 9 yr old, whereas basal and stimulated plasma insulin levels were similar. We found no correlation between log plasma insulin (fasting or stimulated responses) and log plasma DHEAS concentrations in group A (P greater than 0.05). In conclusion, we found a strong relationship between plasma insulin and IGF-I throughout childhood and puberty and during adult life. This finding suggests that insulin may be important for normal growth during childhood. There was no correlation between plasma insulin and DHEAS concentrations in prepubertal children, which suggests that adrenarche does not influence insulin levels.

Adolescent↗
PubMed1989

Pulsatile gonadotropin secretion in pubertal children with chronic renal failure.

We have examined physiological nocturnal secretion of gonadotropins in 6 boys and 2 girls with end-stage renal disease, who had either delayed or disturbed puberty. The 5 patients treated by dialysis had reduced gonadotropin pulsatility for their stage of pubertal maturation, whereas the 3 patients with successful kidney grafts demonstrated a higher nocturnal rise and increased amplitude of gonadotropin pulsatility. It is suggested that the improved gonadotropin pulsatility of transplanted patients is due to their restored renal function.

Adolescent↗
PubMed1989

A monoclonal antibody to human insulin-like growth factor-I: characterization, use in radioimmunoassay and effect on the biological activities of the growth factor.

A monoclonal antibody (BPL-M23) to insulin-like growth factor-I (IGF-I) was obtained following immunization of BALB/c mice with human IGF-I conjugated to ovalbumin. The affinity constant of BPL-M23 for IGF-I was 10.5 litres/nmol and the cross-reactivities of IGF-II, multiplication-stimulating activity III-2 and insulin were 0.8, 0.03 and less than 0.0001% respectively. Porcine, bovine, ovine and rabbit sera, but not rat or mouse sera, showed substantial reactivity with the antibody. Comparison of radioimmunoassay analyses of 54 human serum samples from normal subjects and acromegalic and GH-deficient patients using BPL-M23 and a polyclonal rabbit antiserum (R557A) to human IGF-I showed a high correlation, indicating the usefulness of the monoclonal antibody in radioimmunoassay. Monoclonal antibody BPL-M23 was capable of abolishing the sulphation, mitogenic and insulin-like activities of IGF-I in in-vitro bioassays, suggesting that these activities may rely upon the same receptor-binding site which is near to the antibody-binding site.

Animals↗
PubMed1988

Insulin like growth factor-I, protein kinase-C, calcium and cyclic AMP: partners in the regulation of chondrocyte mitogenesis and metabolism.

The possible role of protein kinase-C (PKC), calcium and cyclic AMP (cAMP) in mediating the metabolic and mitogenic effects of insulin-like growth factor-I (IGF-I) on chondrocytes was investigated using a PKC activator (phorbol ester 12,13-dibutyrate, PDBU), a PKC inhibitor (compound H7), a calcium channel blocker, (verapamil) and a cAMP analogue (dibutyryl cAMP). IGF-I and PDBU stimulated sulphate and thymidine incorporation by chondrocytes. Both of these effects were inhibited by compound H7. Verapamil inhibited IGF-I- and PDBU-stimulated sulphate incorporation, but contrastingly stimulated basal and enhanced IGF-I and PDBU stimulation of thymidine incorporation. Dibutyryl cAMP increased basal and IGF-I-stimulated sulphate incorporation but inhibited but inhibited both basal and IGF-I stimulation of thymidine incorporation. These results suggest a harmonic overlap between the activities of PKC and cAMP-dependent PKA enzyme systems, and calcium balance in the mitogenic and metabolic process of the chondrocyte.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Gonadotrophin, growth hormone and prolactin secretion in children with primary hypothyroidism.

We have studied eight children with primary hypothyroidism (6F, 2M) aged 6.7 to 14.2 years. The girls were prepubertal and the boys had early normal pubertal development. Overnight secretion of LH, FSH, TSH, PRL and GH, and ovarian ultrasound morphology were assessed before and up to 9 months after commencing thyroxine treatment. Serum FSH concentrations in all the girls were increased above LH levels and severe hypothyroidism was associated with reduced GH secretion. These abnormalities reversed with thyroxine treatment. The boys had less severe hypothyroidism and did not demonstrate abnormal gonadotropin or GH secretion. We conclude that primary hypothyroidism in childhood is associated with widespread disturbance of pituitary function, including increased FSH secretion often without signs of early sexual maturation.

Adolescent↗
PubMed1988

Physiological growth hormone (GH) secretion during the recovery from psychosocial dwarfism: a case report.

We describe a 6.4 year old boy who had reversible GH insufficiency secondary to psychosocial dwarfism. On removal to a more favourable environment we observed the recovery of physiological GH secretion by progressive increase in GH pulse amplitude. These observations are relevant to our understanding of the control of GH secretion in that GH pulse frequency appears invariable and alteration in GH secretion is by pulse amplitude modulation.

Child↗