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Biomedical subjects

M Preece

Publications and source records attributed to M Preece.

At least 37 records · Page 2Linked to original sources

The relationship of skin temperature to the nasal cycle in normal subjects.

Nasal airway resistance and skin temperature at the cheek, nose and forearm were measured at 30-min intervals over a period of 7 h in six healthy subjects (age 22-25 years). Right and left skin temperature measurements were made with an infrared thermometer, and right and left nasal airway resistance was measured by active posterior rhinomanometry. Three of the six subjects exhibited what has previously been described as a nasal cycle with spontaneous reciprocal changes in nasal airway resistance. There was a highly significant negative correlation between right and left nasal airway resistance in these subjects (r = 0.64 to -0.78). In contrast to the nasal airway resistance the right and left skin temperatures had highly significant positive correlations (r = 0.74 to 0.93), which demonstrates that the skin temperature changes on each side of the body occurred in parallel with no evidence of a reciprocal relationship. The results indicate that in normal healthy subjects there is no relationship between nasal airway resistance and skin temperature despite the fact that both are controlled by sympathetic vasoconstrictor nerves.

Adult↗

The effect of pressure and warmth applied to the axilla on unilateral nasal airway resistance and facial skin temperature.

The effect of pressure, warmth, and control stimuli applied to the axilla and lateral chest wall on unilateral nasal airway resistance and facial skin temperature was investigated in 60 healthy adults. Nasal resistance was measured by posterior rhinomanometry and skin temperature with an infrared thermometer. A significant increase in unilateral nasal resistance ipsilateral to the applied stimulus was seen with both pressure and warmth (p = 0.006, p = 0.02). A decrease in unilateral nasal resistance contralateral to the stimulus was seen in both these groups, but this was not significant (p = 0.45, p = 0.81). The control stimulus showed a non-significant increase in unilateral nasal resistance ipsilateral to the applied stimulus (p = 0.55), and a significant rise in unilateral nasal resistance on the contralateral side (p = 0.008). There were no significant differences between the ipsilateral and contralateral facial skin temperatures before or after the application of a unilateral pressure, warm or control stimulus. A significant bilateral increase in facial temperature was observed during the course of the experiment in all three groups. The mechanisms of induced changes in unilateral nasal resistance are discussed. The results increase our knowledge of the corporo-nasal reflex and demonstrate that the reciprocal changes in sympathetic tone to the nasal capacitance blood vessels are independent from any parallel reflex changes in sympathetic tone to cutaneous blood vessels.

Adolescent↗

The effect of adenoid and tonsil surgery on nasalance.

The change in nasalance following adenoidectomy, tonsillectomy and adenotonsillectomy was studied in 44 children. A subjective assessment of each child's naso-pharyngeal airway was made preoperatively based on a questionnaire completed by the parents. There was no significant change in the nasalance of children following adenoidectomy, but there was a significant increase in the nasalance following tonsillectomy (P = 0.02) and after adenotonsillectomy (P = 0.001). There was no relationship between the change in nasalance and the adenoid volume removed at operation. There was good agreement between the parental subjective assessment of the naso-pharyngeal airway and the preoperative nasalance score, with the best correlation in the adenoidectomy group (r = -0.8) and the adenotonsillectomy group (r = -0.7). Nasalance is more closely related to the size of the naso-pharyngeal airway than to the actual adenoid volume, and measurements of nasalance are of no benefit in predicting adenoid volume. Tonsillectomy had a significantly greater effect on nasalance than adenoidectomy, and adenotonsillectomy had the greatest effect. Further studies are needed to relate nasalance to the size of the naso-pharyngeal airway, but it appears to relate well to the subjective assessment of the airway and may be of use in patient selection for surgery.

Adenoidectomy↗

Growth response to recombinant human growth hormone of mammalian cell origin in prepubertal growth hormone-deficient children during the first two years of treatment.

In five clinical studies performed in Austria, France, the FRG, Italy, Switzerland, the UK and the USA, 304 growth hormone (GH)-deficient children were treated with recombinant human GH (rhGH) of mammalian cell origin. Two hundred and twenty-five patients were previously untreated (naive patients), and 79 were transferred from pituitary hGH after interruption of therapy for at least 6 months (transfer patients). Two treatment protocols, differing in both dose and frequency of injections, were used: (1) a dose of 0.6 IU/kg body weight per week was administered in 3 s.c. injections to 203 patients (178 naive, 25 transfer; group 1); and (2) a dose of 0.45 IU/kg body weight per week was administered in 7 s.c. injections to 101 patients (47 naive, 54 transfer; group 2). After 1 and 2 years of treatment, 143 and 109 naive, and 51 and 46 transfer patients, respectively, were still prepubertal, and their data were analyzed for efficacy. During the 1st year of treatment, both naive and transfer patients on daily injections (group 2) demonstrated better growth than those on 3 injections per week (group 1), with height velocities (HVs) of 10.6 +/- 2.7 cm/year (group 2) versus 8.6 +/- 2.0 cm/year (group 1) for naive patients (p < 0.001), and 9.9 +/- 1.9 cm/year (group 2) versus 7.2 +/- 2.7 cm/year (group 1) for transfer patients (p < 0.001). The corresponding changes in height standard deviation score (delta H SDS) for chronological age (CA) were +1.3 +/- 0.6 (group 2) versus +0.8 +/- 0.5 (group 1) for naive patients (p < 0.01), and +1.1 +/- 0.3 (group 2) versus +0.6 +/- 0.4 (group 1) for transfer patients (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I.

OBJECTIVE: The aim was to study the relationship between growth hormone (GH) and insulin-like growth factor-I (IGF-I) in critically ill patients. DESIGN: Case-control study of critically ill patients admitted to the intensive care unit was carried out. PATIENTS: Six critically ill patients (51-78 years) who required ventilation and parenteral nutrition and six age, weight, height, and sex-matched healthy adults were studied. MEASUREMENTS: The patients and controls were studied for two 24-hour periods; the patients before and after starting parenteral feeding, and the controls during a 36-hour fast and when taking meals equivalent in calories and protein to the patients' parenteral feed. Serum GH was measured at 20-minute intervals and analysed by a pulse detection algorithm (Pulsar) and Fourier transformation. IGF-I was measured at 0, 12, and 24 hours. RESULTS: Patients had low serum IGF-I levels compared with controls, whether fasted or fed, despite having mean GH levels similar to fasted controls. For fasted patients vs fasted controls the mean (+/- 1 SD) GH levels were 4.5 +/- 2.0 vs 4.0 +/- 2.4 mU/l respectively, and IGF-I levels at the end of the fast were 0.17 +/- 0.11 vs 0.78 +/- 0.29 U/ml (P = 0.003). Patients showed elevated baseline GH levels compared with controls when fasted and during parenteral feeding (patients vs controls fasted 3.1 +/- 1.9 vs 0.8 +/- 0.5 mU/l, P = 0.01; patients vs controls fed 4.2 +/- 4.5 vs 0.5 +/- 0.04 mU/l, P = 0.028). Fourier transformation confirmed oscillatory GH levels in the controls, fasted or fed, but this activity was attenuated in the patients. Parenteral feeding had no effect on the GH profiles or IGF-I levels of patients, but controls showed greater mean GH levels during their fast than when fed. CONCLUSIONS: We have demonstrated that critically ill patients have low IGF-I levels associated with augmented baseline GH levels which show reduced oscillatory activity. The results would be compatible with the hypothesis that there is an adaptive change in critically ill patients away from the indirect effects of GH (stimulation of IGF-I production and anabolism) and toward the direct effects (lipolysis and insulin antagonism) which increase the availability of energy substrates. The pattern of GH levels seen in our patients may be important in this adaptation.

Abdomen↗

Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide.

We have treated 16 acromegalic patients for up to 44 months with octreotide in varying doses. Growth hormone levels were suppressed in 14 patients with associated clinical improvement. IGF-1 levels were measured in 12 and fell into the normal range in 10. Prolactin was suppressed in six hyperprolactinaemic patients but was unaltered in normoprolactinaemic acromegalic patients. Post-prandial hyperglycaemia with impaired insulin secretion was noted in all patients, and one patient required oral hypoglycaemic agents. Octreotide did not affect thyroid function. CT scans from before and after six months of treatment demonstrated minimal tumour shrinkage in only two patients. Octreotide was well tolerated with no serious haematological or biochemical disturbance and no evidence of malabsorption. Two patients developed gallstones. Octreotide is effective in acromegaly. The development of gallstones is the only serious adverse event we have encountered.

Acromegaly↗

Variability of urine albumin excretion in normal and diabetic children.

The variability of urine albumin excretion (UAE) was studied in normal and diabetic children and, in addition, the best method of expressing the data was investigated. In 39 timed overnight urine samples from diabetic children, the urine albumin creatinine clearance ratio (CA/CC) was compared with the urine albumin creatinine concentration ratio (UA/UC), the urine albumin excretion rate (UAER) and the urine albumin concentration (UA). UA/UC predicted CA/CC (r = 0.95) better than either UAER (r = 0.83, P less than 0.02) or UA (r = 0.90), 0.1 greater than P greater than 0.05). The within-individual and the between-individual variability in overnight UA/UC in 171 urine samples from 73 normal children was compared with that of 406 urine samples from 119 diabetic children, using a "random effects type 2 nested analysis of variance" model. Geometric mean (range) UA/UC (mg/mmol) in diabetic children, 0.55 (0.04-6.90), was greater than in normal children, 0.33 (0.05-2.10, P less than 0.01), and 18% of diabetics had a value of UA/UC above the normal range. Within-individual variance was the same in normals (0.12) and diabetics (0.12), but between-individual variance in diabetics (0.18) was much greater than in normals (0.03). These data show that within-individual observations for both normals and diabetics are highly but equally variable. Furthermore, from these data, it is possible to infer that a minimum of five estimations are necessary per individual to estimate the true mean value of urine albumin excretion with reasonable confidence.

Adolescent↗

Growth and endocrine function after renal transplantation.

Longitudinal height data and physical development were assessed in 45 boys and 34 girls after renal transplantation. All children received alternate day steroids and either azathioprine or cyclosporin A for immunosuppression. There was a significant increase in growth velocity after transplantation in prepubertal children. Growth velocity declined at the expected age of the normal pubertal growth spurt, however, with delay in the appearance of secondary sexual characteristics. Overnight hormone profiles in 17 adolescent subjects with short stature or maturational delay, or both, showed blunting of growth hormone and gonadotrophin pulsatility. It is likely that long term steroid treatment after renal transplantation induces the clinical and endocrine picture of delayed puberty. Failure of growth to accelerate at this time is a cause of short stature, which may have an effect on adult height.

Adolescent↗

Growth and endocrine function in steroid sensitive nephrotic syndrome.

Longitudinal height data and physical development were assessed in 29 boys and 12 girls taking long term steroid treatment for steroid sensitive nephrotic syndrome. Growth in both boys and girls, assessed by changes in height standard deviation score (delta Ht SDS), worsened significantly with chronological age. There was a significant negative correlation between delta Ht SDS and duration of treatment in boys, but not in girls. There was no correlation between delta Ht SDS and relapse rate or the use of cyclophosphamide. In the boys, Ht SDS decreased significantly only after the age of 10 years and was associated with delay in the appearance of secondary sexual characteristics. Eight adolescent boys were assessed endocrinologically by an overnight hormone profile. Blunting of the pulsatility of growth hormone and gonadotrophins was seen in six. Normal profiles were seen in two subjects who were both off steroid treatment at the time of study. Abnormal endocrine function in adolescent boys treated long term for steroid sensitive nephrotic syndrome corresponded with the clinical picture of delayed onset of puberty, which accounted for severe growth retardation in a substantial proportion of subjects.

Adolescent↗

Effect of thyroxine replacement therapy on plasma insulin-like growth factor 1 levels and growth hormone responses to growth hormone releasing factor in hypothyroid patients.

The aim of this study was to evaluate the effect of T4 replacement therapy on plasma insulin-like growth factor 1 (IGF-1) levels in patients with primary hypothyroidism to see whether recovery of pituitary GH responsiveness to GRF was associated with increased plasma IGF-1 levels. IGF-1 levels and GH responses to GRF (1 microgram/kg) were measured in 21 patients with primary hypothyroidism before and after T4 replacement therapy. T4 increased plasma IGF-1 levels (57.2 +/- 4.4 vs 75.9 +/- 8.8 ng/ml, mean +/- SEM, P less than 0.05) and GH responses to GRF as assessed both by peak GH levels (9 +/- 1.5 ng/ml before treatment vs 16.7 +/- 3 ng/ml after treatment, mean +/- SEM, P less than 0.05) and area under curve (496 +/- 92 before treatment vs 896 +/- 161 after treatment, mean- +/- SEM, P less than 0.05). Linear regression analysis showed a positive correlation between free T3 and IGF-1 levels after treatment (r = 0.37, P less than 0.05) and a negative relationship between plasma IGF-1 levels before treatment and delta IGF following T4 replacement therapy (r = 0.45, P less than 0.025). However, no correlation was found between plasma IGF-1 levels and GH responses to GRF, suggesting that GH responses to GRF are of no predictive value in relation to the recovery of plasma IGF-1 levels following T4 replacement therapy in hypothyroid patients.

Adult↗

Monoclonal antibodies to human growth hormone can distinguish between pituitary and genetically engineered forms.

Monoclonal antibodies (MABs) prepared against human pituitary growth hormone (hGH) have been compared for their binding to pituitary-derived and genetically engineered methionyl growth hormone (met-hGH). The antibodies bind to four non-overlapping epitopes of which two are completely shared with human choronic somatomammotropin (hCS). The determinant defined by MAB NA27 was expressed on met-hGH to a lesser degree than on hGH of pituitary origin. However, another antibody, QA68, which binds to a determinant closely related to NA27, failed to discriminate between hGH and met-hGH. A further two MABs (EB1 and NA71) were similarly ineffective in distinguishing between the two forms of the hormone. The determinant recognized by antibody EB2 was equally represented on hGH and met-hGH when assessed by a liquid-phase radioimmunoassay: however, measurement of the binding in a solid-phase assay resulted in a two-four-fold lower binding to met-hGH. Bioactivity assessed by both an in vitro cell proliferation assay and an in vivo cartilage sulphation bioassay failed to distinguish between the two hormones. It is therefore concluded that the NH2-terminal methionine on bacterially derived growth hormone results in altered antigenicity of the hormone without any measurable effect on bioactivity.

Animals↗

Growth hormone cell antibodies and partial growth hormone deficiency in a girl with Turner's syndrome.

Growth hormone (GH) cell auto-antibodies have been demonstrated in the serum of a girl with an iso-chromosome variant of Turner's syndrome. On two occasions she showed an abnormal response of GH release during insulin induced hypoglycaemia. Her response to GH treatment was poor, but this was commenced at a very late bone-age. It is possible that autoimmunity is a new aetiological factor for GH deficiency in some cases.

Adolescent↗

Immediate response of 5-methoxytryptophol in the circulation to hypoglycaemic stress induced by insulin.

Pineal indoles have been shown to affect the release of anterior pituitary hormones but details of the interrelationships are lacking. Using a new gas chromatography-mass spectrometry (g.c.-m.s.) assay the concentration of 5-methoxytryptophol (ML) was measured in plasma samples obtained from 16 children undergoing investigation of pituitary function for delayed growth. All the children received an insulin tolerance test (ITT) to study their endocrine response to stress. Some children received luteinizing hormone releasing hormone (LH-RH) and/or thyrotrophin releasing hormone (TRH). The change in concentration of ML during an ITT was similar to the change in concentration of blood sugar; a drop at 20 min followed by a rise at 30 min. This was not significantly altered by the administration of LH-RH or TRH, nor was there a different pattern of response in children who were deficient in growth hormone as opposed to those with idiopathic delayed growth. The fall in concentration of ML with stress may mediate the increased secretion of pituitary hormones. Alternatively, the pineal gland may respond directly to insulin.

Adolescent↗