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Biomedical subjects

M A Preece

Publications and source records attributed to M A Preece.

At least 199 records · Page 11Linked to original sources

Growth hormone treatment in children with craniopharyngioma: final growth status.

Twenty-seven out of thirty craniopharyngioma patients treated with human growth hormone (hGH) for 2 years or more (average 4.5 years) reached final adult heights above the population third centile, though none was above the fiftieth centile. However, only twelve of twenty-eight patients had final heights above the lower limits to be expected from their parents' heights. All patient eventually had long legs relative to sitting height (final mean subischial leg length SDS = + 0.2, final mean sitting height SDS = -3.0). Twenty-nine patients were TSH-deficient, twenty-two were ACTH-deficient, thirteen were deficient in ADH and all had total (85%) or partial (15%) gonadotrophin deficiency. Following the administration of testosterone or hCG the boys had, on average, only half the normal adolescent growth spurt. This may have been due to the lateness of starting androgens in these patients and we recommend, when considering height, that testosterone or hCG should be started when a bone age of 13.0 "years' is reached or when a lower bone age has remained unchanged for a year. The girls showed adolescent height spurt; the average increase after oestrogen treatment commended was 1.7 cm.

Adolescent↗

Calf hypertrophy and asymmetry in female carriers of X-linked Duchenne muscular dystrophy: an over-diagnosed clinical manifestation.

The height, weight and calf sizes of 19 carriers of X-linked Duchenne muscular dystrophy were compared with 32 normal female controls of comparable age. Whereas the regression of the sum of right and left calf sizes on weight was highly significant in both groups, the difference between right and left calf size showed no significant association with weight, height or age. There was no significant difference between carriers and controls in the sum of calf sizes either before or after correction for weight by Analysis of Covariance and no significant difference between the two groups in the degree of asymmetry of right and left calf size.

Adolescent↗

Gonadotrophin response to LH-RH in boys with delayed growth and adolescence.

Plasma luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations were measured before and after intravenous luteinising hormone-releasing hormone (LH-RH) in 33 boys with growth delay. Eighteen were prepubertal and 15 pubertal. Basal LH and FSH levels were low in both groups with mean increments after LH-RH of 3.2 +/- 0.8 U/l (mean +/- SEM) and 2.6 +/- 0.4 U/l respectively in the prepubertal and 7.4 +/- 0.7 U/l and 2.0 +/- 0.3 U/l in the pubertal boys. The LH increment showed a positive correlation with increasing bone age (r = 0.71, P less than 0.001); FSH did not. The LH-RH response thus appeared normal in relation to the stage of maturity.

Adolescent↗

Effect of bovine growth hormone and a partially pure preparation of somatomedin on various growth parameters in hypopituitary dwarf mice.

The growth-promoting effects of a partially purified preparation of somatomedin (12.7 units/mg) were compared with those of various doses of bovine GH (5, 20 and 80 micrograms/day) when injected into hypopituitary dwarf mice. Growth parameters studied were body-weight and tail-length velocities (calculated as the slope of a regression line fitted to daily measurements against time), uptake of 35SO4(2-) into costal cartilage in vivo and organ weights (heart, liver and kidney). In the first experiment somatomedin (6.4 units/day), bovine GH and 0.9% NaCl were injected once daily in a volume of 0.1 ml for 10 days. Treatment with bovine GH promoted a significant dose-dependent increase in body-weight and tail-length velocities and 35SO4(2-) uptake into costal cartilage in vivo. Somatomedin also promoted a significant increase in body-weight velocity and 35SO4(2-) uptake, both responses were between that observed with the lowest dose of bovine GH and control values. Somatomedin did not promote increase in tail-length velocity. Organ weights did not differ significantly between any of the treatment groups when expressed as mg/g body weight. In the second experiment somatomedin (a daily total of 21.6 units/day) and 0.9% NaCl were injected three times per day in a volume of 0.033 ml, bovine GH was again injected once daily in a volume of 0.1 ml, and the treatment period was 12 days. As in the first experiment all doses of bovine GH and somatomedin promoted a significant increase in body-weight velocity. These results are consistent with the somatomedin hypothesis.

Animals↗

Effect of glucocorticoids, butanol extraction of serum and adrenalectomy on somatomedin levels in the rat.

Serum from adrenalectomized rats was equipotent with serum from non-adrenalectomized animals when measured in a rat cartilage somatomedin bioassay. Extraction with butanol of sera from normal or adrenalectomized rats reduced their potency in the somatomedin bioassay rather than increasing it as has been previously reported. Butanol-soluble inhibitors of cartilage metabolism were found in sera from both normal and adrenalectomized rats. Cortisol and corticosterone, up to mildly supraphysiological levels, were found to have no effect on basal cartilage metabolism. These results suggest that physiological levels of glucocorticoids do not exert an inhibitory effect on the uptake of 35SO4(2-) into immature rat cartilage. Since butanol-soluble inhibitors of cartilage metabolism were found in adrenalectomized rat serum it is unlikely that these substances are glucocorticoids.

Adrenalectomy↗

Short stature as the primary manifestation of coeliac disease.

Thirty-four patients with short stature of undetermined cause and no gastrointestinal symptoms underwent jejunal biopsy for exclusion of coeliac disease. Eight had subtotal or severe partial villous atrophy and seven showed a significant acceleration in height and weight velocity after the introduction of a gluten-free diet. Short stature by itself, in the complete absence of gastrointestinal symptoms, is an indication for jejunal biopsy, particularly if bone age is delayed by more than 4 years and/or there are associated haematological abnormalities.

Adolescent↗

Effect of naloxone in a previously undescribed hypothalamic syndrome. A disorder of the endogenous opioid peptide system?

A syndrome of disordered hypothalamic function with abnormal control of temperature, appetite, and thirst, hyperprolactinaemia, and inappropriate vasopressin release is described in a 13-year-old boy who, in addition, had insensitivity to pain and a more general disorder affecting mood, sleep, and control of respiration. A disturbance of the opioid peptide system is postulated. Naloxone reversed central analgesia, altered urine fluid and electrolyte excretion, modified the hormonal response to gonadotrophin-releasing and thyrotrophin-releasing hormones, and improved the auditory and visual reaction times. Specific opioid antagonists may have a therapeutic role.

Adolescent↗

Familial male pseudohermaphroditism due to deficiency of 5 alpha-reductase.

Two brothers of Greek Cypriot origin, karyotype 46 XY, aged 17 and 19 years were brought up as females because of predominantly female external genitalia with clitoromegaly and urogenital sinus. At puberty there was genital masculinization with testicular enlargment and descent and development of male musculature and body habitus without gynaecomastia. Both subjects acquired male gender identity and changed from a female to a male gender role. The internal genitalia were normally formed with an ejaculate containing mature spermatozoa. In both subjects plasma testosterone levels were slightly elevated, dihydrotestosterone was in the low normal range and the plasma testosterone to dihydrotestosterone ratio was markedly elevated. Plasma oestrogens were normal whereas SHBG binding capacity was elevated. The urinary 5 beta-aetiocholanolone to 5 alpha-androsterone ratios were elevated compared with normal subjects. Basal plasma LH was normal but, the LH response to LHRH was exaggerated and basal and peak plasma levels of FSH were elevated. 5 alpha-reductase activity in genital skin homogenates was higher when androstenedione was used as a substrate, compared with testosterone, suggesting a decreased affinity of the enzyme for testosterone. The clinical and hormonal features in the two siblings are consistent with an impaired peripheral conversion of testosterone to dihydrotestosterone due to deficiency of the enzyme 5 alpha-reductase.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Growth in height compared with advancement in skeletal maturity in patients treated with human growth hormone.

Height growth and skeletal maturation were compared in 201 patients treated for between 1 and 15 years with growth hormone (GH) supplied by the Medical Research Council. 107 patients had isolated GH-deficiency, 30 had panhypopituitarism, and 64 craniopharyngiomata. The mean rate of skeletal maturation did not differ between the first year and the total period of treatment, averaging 1 'year'/year in the patients with isolated GH-deficiency or panhypopituitarism, and 0.6 'years'/year in those with craniopharyngioma. No association was observed between the rate of skeletal maturation and the bone age or the bone age deficit (chronological minus bone age) at the start of treatment. Mean height standard deviation score for bone age was negative in all three diagnostic groups at the start of treatment, but became less negative as treatment progressed in patients with isolated GH-deficiency or craniopharyngioma. In patients with panhypopituitarism there was no significant change in height standard deviation score for bone age as a result of treatment. The findings do not support the suggestion that treatment with GH(UK) causes ultimate stunting due to greater osseous maturation than growth in height.

Adolescent↗

Controlled trial of intermittent aerosol therapy with sodium 2-mercaptoethane sulphonate in cystic fibrosis.

Twenty-seven patients with cystic fibrosis completed a controlled trial comparing the effects of an inhaled mucolytic drug, sodium-2-mercaptoethane sulphonate (Mistabron, UCB Pharmaceutical Division, Brussels, Belgium), with inhaled iso-osmolar hypertonic saline. As a group the 22 patients with chronic sputum production showed small but statistically significant improvement in pulmonary function tests after Mistabron therapy, both when compared with a control period, and with iso-osmolar saline results. Subjective measurements by diary card failed to show any changes. No significant changes were found in five patients with no measurable sputum production. The inhalations were given after physiotherapy and were well tolerated. There were no significant side effects. The results suggest that Mistabron has a beneficial therapeutic effect unrelated to its high osmolality, and the intermittent inhalation of Mistabron may have a role in the treatment of selected patients with cystic fibrosis.

Adolescent↗

Short-term effects of chest physiotherapy on pulmonary function in children with cystic fibrosis.

In a short-term controlled study of 20 patients with cystic fibrosis and chronic sputum production, chest physiotherapy resulted in a significantly improved peak flow over a whole day, with no significant difference in other forced expiratory flows, when compared to a control day. This suggests that physiotherapy may be effective in enhancing clearance of sputum from central large airways, but it has little obvious effect on more peripheral airways. A bronchodilator given before physiotherapy had no added effects. It is important that we examine ways of improving physiotherapy to aid clearance of secretions from the more peripheral airways.

Adolescent↗

Effects of growth hormone, prolactin and thyroxine on body wegith, somatomedin-like activity and in-vivo sulphation of cartilage in hypopituitary dwarf mice.

Hypopituitary dwarf mice were found to have reduced levels of serum somatomedin-like activity compared with normal mice of the Snell strain. Treatment with bovine growth hormone for 3 and 7 days resulted in growth without significantly increased levels of serum somatomedin-like activity, as detected by in-vitro uptake of 35SO4(2-) into normal rat cartilage; only after treatment for 14 days was somatomedin activity significantly raised. However, treatment for 2 days with bovine growth hormone, bovine prolactin or thyroxine resulted in a dose-dependent increase in in-vivo uptake of 35SO4(2-) into dwarf mouse costal cartilage; growth hormone and thyroxine did not act synergistically. Ten days of treatment with growth hormone promoted a dose-dependent increase in both growth (increased weight gain and tail length) and in-vivo of 35SO4(2-). Increase in tail length was correlated with uptake of 35S04(2-). Thus, in-vivo uptake of 35SO4(2-) into dwarf mouse costal cartilage provides a sensitive method for detecting a dose-related effect of growth hormone.

Animals↗

Age-related changes in the degradation of thyrotrophin releasing hormone by human and rat serum.

Changes in the rate of in-vitro degradation of thyrotrophin releasing hormone (TRH) in serum as related to age have been investigated in the rat and man. In rats, no inactivation was found up to the age of 15 days but therafter an age-related increase in inactivation was detected with approximately 75% inactivation in 60 min at 40 days and reaching a maximum of 88-93% inactivation in adult male and female animals. The human serum samples studied (both male and female) showed a similar but less clear-cut pattern of inactivation of TRH compared with that found in the rat. A physiological role for these age-related changes in the degradation of TRH remains to be established but it has been concluded that the changes observed in both rat and man may be associated with growth and development, possibly by facilitating feedback control of thyrotrophin secretion through the degradation of TRH.

Adolescent↗

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↗

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↗