Biomedical subjects
M A Preece
Publications and source records attributed to M A Preece.
Catch-up growth.
We describe the phenomena of catch-up and catch-down growth. These are normal physiological responses in both endocrine and non-endocrine diseases of childhood. Evidence suggests that catch-up growth is controlled by a centre in the central nervous system and that it is not dependent on increased growth hormone secretion.
Biosynthetic growth hormone: whom to treat?
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Nocturnal adrenal suppression in asthmatic children taking inhaled beclomethasone dipropionate.
Plasma cortisol was measured every 20 min and sleep was monitored in nineteen asthmatic children, twelve of whom were receiving various doses of inhaled beclomethasone dipropionate (BDP). Children receiving inhaled BDP had lower cortisol secretion during the night than those who were not taking inhaled BDP, a delayed rise from the nocturnal nadir, and low early morning levels. Inhaled BDP produces a dose-dependent adrenal suppression.
The growth of children with chronic paediatric disease.
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Diabetes insipidus and occult intracranial tumours.
We describe four patients with intracranial tumours who presented with diabetes insipidus and subsequently developed an evolving anterior pituitary endocrinopathy. The delay in imaging the tumours varied between 2.1 and 11.2 years (mean 5.4 years).
Somatomedin C/insulin-like growth factor I: simplified purification procedure and biological activities of the purified growth factor.
Human somatomedin C has been purified from Cohn fraction IV paste by a simplified procedure using chromatofocusing, hydroxylapatite chromatography and reverse-phase high performance chromatography. The purified material has a specific activity by somatomedin C radioimmunoassay of 9160 units/mg (1 unit is defined as the amount of somatomedin present in 1 ml normal adult male human serum), representing a 650,000-fold purification, and possesses sulphation, mitogenic and insulin-like activities (specific activities of 3388 units/mg, 832 units insulin equivalents/mg and 1122 units/mg respectively). Somatomedin C is shown to be a potent stimulator of DNA synthesis (50% maximum stimulation at 150 fmol/ml) in isolated chondrocytes derived from costal cartilage, a major physiological target tissue.
Potentiation of the somatogenic and lactogenic activity of human growth hormone with monoclonal antibodies.
Monoclonal antibodies of certain epitope specificity have been shown to produce a marked dose-dependent enhancement of the somatogenic and lactogenic activity of human GH (hGH). Two antibodies (EB1 and EB2), binding to distinct antigenic determinants and expressed on both hGH and human chorionic somato-mammotrophin (hCS), significantly enhanced the hGH-stimulated uptake of 35S-labelled sulphate into cartilage. Similarly, these antibodies enhanced the lactogenic activity of both hGH and hCS in the pigeon crop sac test. Two hGH specific monoclonal antibodies (QA68 and NA71), defining a further two epitopes, exhibited only modest enhancing or inhibitory activity in these assays, whereas the binding of certain combinations of monoclonal antibodies resulted in either reversal of enhancement or inhibition of hormone activity. Univalent antibody fragments derived from EB1 were as enhancing as the intact antibody indicating that bivalency dependent mechanisms were not involved in the phenomenon. Enhancing monoclonal antibodies were relatively poor inhibitors of 125I-labelled hGH binding to liver microsomal receptors, which is in contrast with their previously described property of potent suppression of hGH interaction with lymphoid cell receptors. It is tentatively concluded that 'restriction' of hormone binding to particular hGH receptors, relevant to somatic growth or lactogenic activity, may play a role in the enhancement phenomenon of hGH in vivo.
Creutzfeldt-Jakob disease after administration of human growth hormone.
A 2-year-old girl had a craniopharyngioma removed in 1964. She received human growth hormone (HGH) twice a week from July, 1972, until July, 1976. In March, 1984, a subacute dementing illness developed with neurological signs that included pronounced cerebellar ataxia. A clinical diagnosis of Creutzfeldt-Jakob disease (CJD) was made. The patient died in February, 1985. Necropsy revealed a spongiform encephalopathy compatible with the transmissible form of CJD. HGH administration may be implicated in the transmission of the disease in this case.
Lack of thirst, osmoreceptor dysfunction, early puberty and abnormally aggressive behaviour in two boys.
Two unrelated boys (C.C. 13 years; J.W. 18 years) presenting with early puberty and episodes of aggressive behaviour were found to have hypernatraemia and hypodipsia. Plasma vasopressin (AVP) levels were inappropriately low in relation to plasma osmolality, but the patients did not have diabetes insipidus since 24 h urinary volumes were less than 1 litre and the maximal urinary osmolality was 1232 in C.C. and 950 in J.W. Plasma renin activity was elevated (greater than 2000 mg AI/1/h) although aldosterone concentrations were normal. Excretion of a water load (20 ml/kg) was delayed, but plasma renin and aldosterone fell with increased naturesis. An infusion of 0.85 mol/l saline produced a rise in AVP in C.C. but not in J.W. Insulin and hypotension resulted in the release of AVP in both boys suggesting a selective defect of osmoreceptor function. Hyperprolactinaemia and an exaggerated PRL response to TRH were also noted but no intracranial lesion was demonstrable on CT scan. These boys appear to have a hypothalamic syndrome with early puberty, hyperprolactinaemia, hypodipsia and osmoreceptor dysfunction which may be associated with aggressive behaviour.
Growth curve for girls with Turner syndrome.
A growth chart for girls with Turner syndrome has been prepared using data from four published series of European patients, and evaluated using retrospective data on the heights of girls with Turner syndrome seen at this hospital. The results indicate that calculation of height standard deviation score from this chart allows a reasonable prediction of adult stature in any patient with Turner syndrome. In addition, the results indicate that while oestrogen treatment causes an initial acceleration of growth, it has no significant effect on adult height.
Oxandrolone in low dose for constitutional delay of growth and puberty in boys.
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The use of growth hormone-releasing hormone in the diagnosis and treatment of short stature.
We have assessed the role of growth hormone-releasing hormone (GHRH) as a diagnostic test in 40 children and young adults with growth hormone deficiency (GHD), principally using the GHRH(1-29)NH2 analogue. Following 200 micrograms GHRH as an acute intravenous bolus, serum GH rose to normal or just subnormal levels in 13 out of 17 children with structural lesions, and in 8 of 14 patients with idiopathic GHD or panhypopituitarism. Of 9 children (mean age 12 years) with GHD following treatment with cranial irradiation for nonendocrine tumours, all responded acutely to GHRH. 12- and 24-hour infusions with GHRH(1-29)NH2, and 1- and 2-week treatments with twice-daily subcutaneous GHRH(1-29)NH2, showed persistent stimulation of GH release. It is concluded that many children with GHD of diverse aetiology will respond both acutely and chronically to treatment with GHRH.
Monoclonal antibody-mediated enhancement of growth hormone activity in vivo.
This work demonstrates that complexing hGH with monoclonal antibody EBl (MAB-EBl) can produce a striking potentiation of the somatogenic actions of hGH in vivo in Snell dwarf mice. In short-term experiments significant increases in cartilage metabolism and body weight were noted; these responses were dose-dependent for both MAB-EBl and hGH concentration. Increased growth was also observed in long-term experiments. In marmosets where MAB-EBl cross-reacts with endogenous GH, MAB-EBl alone enhanced the actions of endogenous GH. A new perspective may be necessary to incorporate these results into the current concept of antibody action.
Responses to analogues of growth hormone-releasing hormone in normal subjects, and in growth-hormone deficient children and young adults.
Three analogues of growth hormone-releasing hormone (GHRH) have been compared in normal subjects. GHRH(1-29)NH2 is equipotent to GHRH(1-40); increasing doses from 10-200 micrograms per subject augments the duration of stimulated growth hormone (GH) release, but the peak serum GH shows only a poor correlation with dose. The derivative D-Ala2-GHRH(1-29)NH2 is no more potent than the unsubstituted GHRH(1-29)NH2. In 20 children and young adults with growth hormone deficiency by conventional criteria, eight showed normal or only slightly subnormal peak serum GH responses to GHRH(1-40) or GHRH(1-29)NH2. These included two patients with tumours of the hypothalamus, as well as six with idiopathic isolated growth hormone deficiency or panhypopituitarism. A poor response to GHRH was generally seen in patients on long-term GH therapy. Priming with GHRH, in either a single bolus or a continuous infusion, did not increase the GH response to GHRH. It is concluded that GHRH(1-29)NH2 is a useful analogue in the testing of GH reserve in patients with growth hormone deficiency, and has considerable potential for long-term therapy.
Body proportions in precocious puberty.
Sitting height (SH) and sub-ischial leg length (SLL) were measured in 10 boys and 16 girls with precocious puberty; the patients were aged from 1.5 to 13.4 years at the time. Standard deviation scores (SDS) calculated for chronological age and bone age showed higher scores for SH than for SLL in all but two patients, both girls: the differences between the SDS for SH and SLL were more marked in the boys. The findings indicate that growth of the trunk is usually greater than growth of the legs in precocious puberty, particularly in boys.
Hypoplastic optic nerves and pituitary dysfunction. A spectrum of anatomical and endocrine abnormalities.
Fourteen children with optic nerve hypoplasia associated with either mid-brain abnormalities or pituitary dysfunction, or both, are described. All patients were either partially sighted or blind. One case is reported in detail. The importance of hypoglycaemia in the neonatal period and later in childhood is emphasised in relation to diagnosis and developmental delay. Pituitary dysfunction is variable and may be progressive. Forty percent of the patients had a septum pellucidum and its presence or absence cannot be used as a radiological marker for the condition. Long term endocrine follow up of these patients is required.