Search PubMed⌕ Search

Biomedical subjects

D R Matthews

Publications and source records attributed to D R Matthews.

At least 73 records · Page 4Linked to original sources
PubMed1997

The use of an automated microsampling system for the characterization of growth hormone pulsatility in newborn babies.

To overcome the difficulties of studying hormone pulsatility in the newborn, we have developed an automated microsampling system that permits the measurement of hormones in small prediluted samples of blood (40 microL) taken at 10-min intervals over 12 h. The system has been validated in adult volunteers, and the error attributable to the dilution was <4%. Using this method in 10 preterm babies, we have been able to describe pulsatile changes in GH and have demonstrated a clear postprandial elevation in GH levels peaking 60 min after a feed. Fourier transform analysis indicated a pulse periodicity of 180 min in babies who were appropriate for gestational age (n = 6), but faster, co-dominant pulse periodicities of 90-100 and 140 min in babies who were small for gestational age (weight and length below the 10th centile) (n = 4). There was no significant difference between mean, peak, and baseline GH levels between the two groups.

Adult↗
PubMed1997

Approach to maintaining comparability of biochemical data during long-term clinical trials.

Our objective was to design a structured approach to maintaining comparability of biochemical data during a long clinical trial. Maintaining the comparability of clinical and biochemical data obtained in long-term studies is essential, even though analytical methods in the laboratory may be changed, conventions on specimen handling and storage revised, calibration procedures updated, quality-control systems replaced, and secular changes may occur. The United Kingdom Prospective Diabetes Study (UKPDS), a large randomized control trial investigating therapy for type 2 diabetes, was the setting for the study. Data were collected from 5102 subjects randomized since 1977. Our techniques included quality control, external quality assurance, direct comparison of laboratory methods when updating assays and statistical techniques for the detection of unsuspected changes in assay bias, laboratory comparisons of new with old assay methodologies, the realigning of data to current methods, the use of a suitable reference population for long-term monitoring, and rules to aid decision-making about clinical vs statistical significance. Procedures by which comparability of data is assured should be specified for all long-term trials and, where possible, comparison with reference methods should be detailed to allow results from different laboratories to be compared.

Diabetes Mellitus, Type 2↗
PubMed1996

Brain serotonin (5-HT) neuroendocrine function in patients taking cholesterol-lowering drugs.

Brain serotonin (5-HT) neuroendocrine function, plasma tryptophan, and platelet 5-HT content were examined in 20 patients treated in a lipid clinic for hypercholesterolaemia with combined drug and diet therapy and in 20 healthy matched controls. Treatment had produced a substantial decrease in total cholesterol concentrations in the patients, but they still had higher cholesterol and triglyceride levels than control subjects. The patients were somewhat more depressed than controls but did not differ from them in degree of hostility, free or total plasma tryptophan, or prolactin response to 30 mg of d-fenfluramine. This study does not reveal evidence of abnormal brain 5-HT neuroendocrine function in hypercholesterolaemic patients receiving cholesterol-lowering medications and diet.

Analysis of Variance↗
PubMed1996

The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity.

OBJECTIVE: Hexarelin is a synthetic six-amino-acid compound capable of releasing GH in animals and in man. Its mechanism of action is not understood and little is known about the GH response after repeated administration. The aim of this study was to determine the GH response to the administration of two intravenous boluses of hexarelin, growth hormone releasing hormone (GHRH) or hexarelin with GHRH. DESIGN: Single boluses of hexarelin (1 microgram/kg), GHRH-(1-29)-NH2 (1 microgram/kg) or hexarelin with GHRH-(1-29)-NH2 were administered intravenously. Each study was performed on two further occasions, with a second bolus being administered 60 or 120 minutes after the first. A control study was performed giving saline intravenously. Studies were performed in a random order. SUBJECTS: Six healthy adult males (25.4-34.1 years) were studied. MEASUREMENTS: Serum GH was measured by radioimmunoassay. GH secretion rates were derived from the measured serum GH concentrations using the technique of deconvolution analysis. RESULTS: The peak GH secretion rate following the first intravenous bolus of hexarelin was greater than that following the first bolus of GHRH-(1-29)-NH2 (P < 0.001), and was greatest following the administration of hexarelin with GHRH-(1-29)-NH2 (P < 0.001). The coadministration of the two secretagogues resulted in peak GH secretion rates significantly greater than the arithmetic sum of those following their isolated administration (P = 0.001), demonstrating synergism. Compared to saline, the administration of a second bolus of hexarelin, GHRH-(1-29)-NH2 or both resulted in significant further GH secretion (P = 0.02, P = 0.002, P = 0.03, respectively). The administration of a second bolus of hexarelin or hexarelin with GHRH-(1-29)-NH2 120 minutes after the first bolus resulted in lower peak GH secretion rates (P = 0.03). The reductions in peak GH secretion rates following the 60-minute boluses were not statistically significant. The peak GH secretion rates following the first GHRH-(1-29)-NH2 boluses were similar to those following the 60 and 120-minute GHRH-(1-29)-NH2 boluses (P = NS). Irrespective of the interval between the boluses of hexarelin with GHRH-(1-29)-NH2, the peak GH secretion rates following the second boluses were not significantly different from the arithmetic sum of those following the administration of the second boluses of hexarelin or GHRH-(1-29)-NH2, indicating loss of synergism on repeated administration. CONCLUSION: This study shows that hexarelin is a potent GH secretagogue active after two successive doses; the magnitude of the GH response to the second dose was influenced by the dosing interval. Hexarelin and GHRH-(1-29)-NH2 are synergistic, a property which is lost after repeated administration. These findings may help our understanding of GHRPs and may have implications for the potential use of hexarelin and other GHRPs as therapeutic agents.

Adult↗
PubMed1996

Is the growth hormone concentration regulated by the morning rise in the plasma cortisol concentration?

Exogenous steroids affect plasma growth hormone (GH) concentrations and hypothalamic somatostatin levels either directly, by stimulating the anterior pituitary gland, or indirectly by partially inhibiting the response of the pituitary gland to stimuli. The effect of the circadian rhythm of cortisol on plasma GH concentrations is unknown. In normal subjects, highest plasma GH concentrations are recorded within the first two hours of onset of sleep. During the early morning the plasma GH concentration decreases and the plasma cortisol concentration increases. We investigated the effect of the early morning rise in plasma cortisol concentration on plasma GH concentrations. We studied 12 healthy volunteers on two occasions. On one occasion the early morning rise in plasma cortisol concentrations was reduced by administering metyrapone (750 mg, 4 hourly from 03.00), while on the other occasion no intervention was made. Plasma GH and cortisol concentrations were measured every 30 and 60 minutes respectively from 22.00 until 14.00. Metyrapone caused a significant reduction in the rise of plasma cortisol concentration, but the GH concentration was identical on both occasions. We conclude that the morning rise in cortisol concentration has no acute regulatory effect on the plasma GH concentration.

Adult↗
PubMed1996

The effect of glimepiride on pancreatic beta-cell function under hyperglycaemic clamp and hyperinsulinaemic, euglycaemic clamp conditions in non-insulin-dependent diabetes mellitus.

The comparative effects of glimepiride (Amaryl; HOE 490) and glibenclamide on insulin and glucose metabolism under hyperglycaemic and hyperinsulinaemic, euglycaemic clamp conditions were studied in a double-blind, placebo-controlled, cross-over trial. Patients with sulfonylurea-controlled non insulin-dependent diabetes were allocated in random order to placebo, glimepiride (5 mg) or glibenclamide (5 mg) and received one week treatment of each with no wash-out period. At the end of each treatment week a clamp study was performed. Two protocols were used. Protocol 1 used a 5 h hyperglycaemic clamp at 10.9 mmol/l whole blood glucose concentration and Protocol II used a 3 h hyperinsulinaemic, euglycaemic damp at 3.5 mmol/l whole blood glucose concentration. Both glimepiride and glibenclamide exhibited a hypoglycaemic effect. A significant reduction in fasting whole blood glucose concentration was observed after one-week treatment of each active agent (fasting glucose: glimepiride v. placebo, 9.3 +/- 0.7 v. 10.7 +/- 0.8 mmol/l, p < 0.02; glibenclamide v. placebo, 8.9 +/- 0.9 v. 10.7 +/- 0.8 mmol/l, p < 0.005). This hypoglycaemic action of both preparations administered in equivalent daily dose appeared comparable. Glimepiride and glibenclamide stimulated beta-cell secretion and in the basal state both beta-cell secretory products insulin and C-peptide, were elevated in the plasma (basal C-peptide concentration: glimepiride v. placebo, 0.79 +/- 0.08 v. 0.68 +/- 0.07 nmol/l, p < 0.01; glibenclamide v. placebo, 0.79 +/- 0.07 v. 0.68 +/- 0.07 nmol/l, p < 0.004). This insulinotropic effect appeared to be comparable with no demonstrable difference in the efficacy of the two preparations. Under steady-state hyperglycaemic conditions both agents promoted insulin release (stimulated C-peptide concentration; glimepiride v. placebo, 1.39 +/- 0.16 v. 1.11 +/- 0.20 nmol/l, p < 0.006; glibenclamide v. placebo. 1.60 +/- 0.18 v. 1.11 +/- 0.20 nmol/l, p < 0.001) and there was no statistically significant difference between active treatments. Under steady-state euglycaemia both preparations continued to stimulate insulin release as evidenced by the mean plasma C-peptide concentrations (glimepiride v. placebo, 0.69 +/- 0.10 v. 0.28 +/- 0.06 nmol/l, p < 0.01; glibenclamide v. placebo, 0.76 +/- 0.12 v. 0.28 +/- 0.06 nmol/l, p < 0.01). Both glimepiride and glibenclamide had a comparable and significant enhancing effect on glucose metabolism (Protocol II: M: glimepiride v. placebo 4.4 +/- 1.3 v. 1.3 +/- 0.7 mg/kg.min, p < 0.05; glibenclamide v. placebo 4.7 +/- 1.3 v. 1.3 +/- 0.7 mg/kg min, p < 0.03) and improved tissue sensitivity to the action of insulin as determined by the quantity of glucose metabolised per unit insulin (Protocol II: M/l ratio: glimepiride v. placebo, 0.09 +/- 0.03 v. 0.03 +/- 0.01 kg.min per mU/l, p < 0.02; glibenclamide v. placebo, 0.1 +/- 0.03 v. 0.03 +/- 0.01 kg.min per mU/l, p < 0.01). In conclusion, glimepiride is a "second-generation" sulfonylurea agent which stimulates pancreatic beta-cell insulin secretion, lowers blood glucose and improves tissue insulin sensitivity in non-insulin-dependent diabetic subjects. Its insulinotropic effect is comparable with that of glibenclamide but may diminish in the presence of normoglycaemia. The magnitude and hence, the clinical relevance of a selective beta-cytotropic action, determined by blood glucose concentration, remains to be demonstrated.

Blood Glucose↗
PubMed1996

Postprandial lipemia: the origin of an early peak studied by specific dietary fatty acid intake during sequential meals.

Previous studies have noted the presence of an early postprandial peak in plasma triacylglycerol concentration, particularly when successive meals have been consumed. We tested the hypothesis that fat from a previous meal contributes to this early postprandial lipemia. We investigated the effect of consuming a lunch containing 61 g fat 5 h after a breakfast containing 54 g fat. The predominant fatty acids in the first meal, expressed as % by wt of total fatty acids, were 18:2 (linoleic acid), 68%, and 18:1 (oleic acid), 19%. The main fatty acids in the second meal were 18:1 (75%) and 18:2 (8%). After lunch, the early peak (at 50-60 min) in chylomicron triacylglycerol was found to contain a large proportion of 18:2, the main constituent of the first meal, whereas at later time points the chylomicron triacylglycerol fatty acid profile more closely resembled that of the second meal. Control studies in three subjects showed the complete absence of the early peaks in plasma and chylomicron triacylglycerol concentrations when either the lunch was omitted or the first meal was low in fat. The plasma nonesterified fatty acid profile also showed a corresponding peak in 18:2 at 50-60 min, which may represent the release into the plasma of fatty acids arising from the hydrolysis of chylomicron triacylglycerol by adipose tissue lipoprotein lipase.

Adult↗
PubMed1996

Effects of morning rise in cortisol concentration on regulation of lipolysis in subcutaneous adipose tissue.

Cortisol has a well-defined circadian rhythm. The aim of the study was to examine the effect of the morning rise in cortisol concentration on lipolysis in adipose tissue. Ten healthy subjects were studied on two occasions, and six of these were studied on three occasions. During the first two occasions, either a control or cortisol suppression study was performed by using metyrapone, and on the third occasion exogenous cortisol replacement was given in addition to metyrapone. Lipolysis in the subcutaneous adipose tissue of the anterior abdominal wall was studied by measurement of arteriovenous differences. Reduction in the early morning rise in cortisol led to significantly decreased venoarterialized differences for nonesterified fatty acids (P < 0.05) and glycerol (P < 0.01), attributable in part to decreased hormone-sensitive lipase (EC 3.1.1.3) action (P < 0.05) in adipose tissue. At the same time the arterialized plasma triacylglycerol concentration increased (P < 0.005) with a significant reduction in the adipose lipoprotein lipase (EC 3.1.1.34) rate of action (P < 0.05). In the replacement study, values were identical to those of the control study, showing that metyrapone had no nonspecific effects on lipolysis. We conclude that the morning rise in plasma cortisol concentration plays an important role in the regulation of lipolysis in adipose tissue in normal healthy adults.

Adipose Tissue↗
PubMed1996

Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study.

To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1.5-11.8 years, with brain tumours in the posterior fossa (n = 25) or cerebral hemispheres (n = 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR (n = 9); Group 2: > or = 30 Gy DXR only (n = 22); Group 3: > or = 30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children. Compared with SN children, children with brain tumours had faster GH pulse periodicities (200 min vs 140 min) and attenuated peak GH responses to ITT (24.55 (19.50-30.20) vs 8.32 (4.57-15.14) mU/l) after neurosurgery, before radiotherapy. However, spontaneous GH peaks (19.05 (15.49-23.44) vs 14.13 (9.12-21.38) mU/l), 24 h mean GH (5.01 (4.37-5.62) vs 3.98 (2.63-5.89) mU/l) and FODs (1.43 (1.17-1.69) vs 1.22 (0.88-1.56) mU/l per min) were similar. The abnormalities present before radiotherapy persisted in group 1 children at 1 year when 24 h mean GH (2.45 (1.17-5.01) mU/l) and FODs (0.73 (0.26-1.20) mU/l per min) were additionally suppressed, although partial recovery was evident by 2 years. With time from radiotherapy, there was a progressive increase in GH pulse periodicity (Group 2: 200 min at 1 year, 240 min at > or = 2 years; Group 3: 140 min at 1 year, 280 min at > or = 2 years) and a decrease in 24 h mean GH (Group 2 vs Group 3 at > or = 2 years: 2.45 (1.70-3.47) vs 1.86 (1.32-2.69) mU/l) and FODs (Group 2 vs Group 3 at > or = 2 years; 0.56 (0.44-0.69) vs 0.44 (0.27-0.61) mU/l per min). Initial discrepancies between measures of spontaneous and stimulated (ITT) GH peaks were lost by 2 or more years (spontaneous vs ITT; Group 2: 7.76 (5.89-9.77) vs 3.80 (0.91-15.84) mU/l; Group 3: 6.03 (4.27-8.32) vs 3.80 (0.31-46.77) mU/l). After cranial irradiation, a number of changes evolved within the GH axis: faster GH pulse periodicities and discordance between physiological and pharmacological tests of GH secretion before irradiation gave way to a slow GH pulse periodicity, decreased GH pulse amplitude and rate of GH change (FOD) and, with time, eventual concordance between physiological and pharmacological measures. The evolution of these disturbances may well reflect differential pathology affecting hypothalamic GH-releasing hormone and somatostatin.

Brain Neoplasms↗
PubMed1996

Oscillatory insulin secretion: a variable phenotypic marker.

Oscillatory secretion of endocrine hormones is a widely recognized phenomenon. In man, as well as other species (dog, monkey), during the basal state insulin secretion is oscillatory and, on average, regular with a 13-min periodicity. In NIDDM there is a loss of regular oscillatory activity, being shorter in duration and irregular in nature. First-degree relatives of NIDDM subjects with normoglycaemia and obese normal subjects also exhibit this change, reverting to the regular oscillatory characteristic following weight loss in the latter group. The regular insulin secretory oscillations seen in the fasting stage in normal subjects are completely lost by raising the basal glucose concentration only marginally to about 6 mmol l-1. Thus, regular oscillations reflect a 'contented' beta-cell. Also, in states of hyperglycaemia, pulsatile exogenous insulin is more effective than continuous administration. Additional studies indicate that it is the periodicity of the insulin secretory oscillations and the rate of rise of the first phase insulin secretion in response to a glucose challenge which are the main candidates for successful signalling. Irregular oscillations of insulin can be used as an early marker of beta-cell under stress, but not as a fixed phenotypic marker.

Activity Cycles↗
PubMed1995

UK prospective diabetes study (UKPDS) 14: association of angiotensin-converting enzyme insertion/deletion polymorphism with myocardial infarction in NIDDM.

The deletion allele of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene has been suggested to be an independent risk factor for myocardial infarction, particularly in subjects judged to be "low-risk" by the criteria of lipid status and body mass index. In a prospective, matched case-control study, we have investigated the role of this polymorphism as a risk factor for myocardial infarction in 173 newly-diagnosed British Caucasian non-insulin-dependent diabetic subjects taken from the United Kingdom Prospective Diabetes Study who subsequently developed myocardial infarction and 297 control subjects from the same study population matched for known cardiovascular risk factors including age at diagnosis of diabetes, gender, blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride and smoking habit. A trend towards increased risk conferred by homozygosity for the deletion allele was observed in cases (odds ratio 1.63, p = 0.09). When the population was stratified according to the matched risk factors, the deletion allele was associated with myocardial infarction in those with low plasma low-density lipoprotein cholesterol (odds ratio 3.67, p = 0.002), or low triglyceride (odds ratio 3.14, p = 0.005). The strongest association of the deletion allele with myocardial infarction was observed in subjects with both low low-density lipoprotein cholesterol and low triglyceride levels (odds ratio 9.0, p < 0.001). These results show that the deletion allele is a risk factor for myocardial infarction in non-insulin-dependent diabetic patients who have a favourable lipid profile.

Case-Control Studies↗
PubMed1995

Growth and the growth hormone axis in prepubertal children with asthma.

To determine the influence of asthma and its treatment with inhaled corticosteroids on growth, linear growth velocity, and the growth hormone axis in prepubertal children, we performed a longitudinal study for 12 months in 56 children with asthma, aged between 4.4 and 11.7 years. Height, weight, skin-fold thickness, and lung function were measured every 3 months and bone age at entry to and exit from the study. A 24-hour serum growth hormone concentration profile and fasting insulin-like growth factor I levels were measured halfway through the year. Seventy-four percent of boys and 62% of girls had heights below the 50th percentile. Growth velocity in the nonsteroid-treated control group (n = 13) was normal; 10 of 20 children taking beclomethasone grew slowly (14/20 used a dry powder device), and 4 of 19 children taking budesonide grew slowly (15/19 used a spacer). Three of four children using inhaled steroids and prednisolone grew slowly. In none of the treatment groups were measures of growth hormone secretion or levels of radioimmunoassayable serum insulin-like growth factor I affected. We conclude that slow growth in steroid-treated children with asthma does not appear to be associated with major perturbations in the growth hormone axis.

Administration, Inhalation↗
PubMed1995

Evaluation of a second-generation electrochemical blood glucose monitoring system.

One hundred and ninety-five diabetic patients attending hospital clinics gave blood samples to test the accuracy and precision of a second generation glucose sensor (satellite G, MediSense Inc., Abingdon, UK) with particular emphasis on its performance with venous blood. Sensor results correlated closely with a standard laboratory method; analysis of residuals showed no deviation from zero slope. Mean percentage difference was low (< +/- 6.0%) and the 95% limits of agreement were < +/- 30% with both capillary and venous blood. Error Grid Analysis showed that none of the measurements would have led to serious management errors. Precision of the system was good with coefficients of variation (CV) between 2.8% and 7.1% for glucose concentrations ranging from 3.0 to 24.0 mmol l-1. The mean CV for duplicate measurements was 5.4% with capillary and 4.4% with venous blood. We conclude that the electrochemical glucose method gives accurate and precise measurements of venous and capillary blood glucose.

Analysis of Variance↗
PubMed1995

Clinical comparison of patient-side fibrinogen assay and common laboratory analyzer in pediatric cardiopulmonary bypass.

The coagulation status of infant and pediatric patients can be severely compromised during the course of cardiopulmonary bypass due primarily to hemodilution and hypothermia. Fibrinogen level is one source of information necessary to assess the coagulation status of a patient. An accurate and expedient method to determine the fibrinogen level would allow for earlier initiation of coagulation therapy to prevent excessive postoperative bleeding. The purpose of this study was to compare two methods of determining fibrinogen level: a patient-side assay and a common laboratory analyzer. The patient-side test utilized the HemoChron Fibrinogen Assay and was performed in the operating room. The MLA 1000C was the laboratory method utilized in the hospital's coagulation laboratory. Simultaneous testing was conducted prebypass and intraoperatively on 26 infant and pediatric patients undergoing cardiopulmonary bypass for palliation and correction of congenital heart defects. The resulting values were compared using paired t-test, regression and correlation analysis, and descriptive analysis. The values obtained by the two methods were significantly different (p < .05) at each collection time. Further analysis revealed that other variables, such as hematocrit and platelet count, affected the differences between the results of the methods. The HemoChron Fibrinogen Assay may not be a viable tool for the assessment of fibrinogen level on infant and pediatric patients undergoing cardiopulmonary bypass surgery. Further studies should be done in this patient population incorporating other confounding variables.

Analysis of Variance↗
PubMed1994

The effects of recombinant human insulin-like growth factor I on growth hormone secretion in adolescents with insulin dependent diabetes mellitus.

OBJECTIVE: It has been proposed that low IGF-I levels and reduced IGF-I bioactivity may lead to elevated GH levels in adolescents with insulin dependent diabetes (IDDM). We have therefore studied the effects of human recombinant insulin-like growth factor I (rhIGF-I) administration on GH levels and GH secretion in adolescents with IDDM. PATIENTS: Nine late pubertal adolescents (four male and five female) with IDDM. DESIGN: A double-blind placebo controlled study of rhIGF-I administered subcutaneously in a dose of 40 micrograms/kg body weight at 1800 h. MEASUREMENTS: IGF-I and GH concentrations were measured at regular intervals throughout the study. Twenty-two hour GH secretory rates were calculated by deconvolution analysis. Overnight GH profiles were analysed by distribution analysis, and Fourier transformations were performed on both overnight GH concentrations and GH secretory rates. RESULTS: Mean IGF-I levels over the 22-hour study period were significantly elevated following rhIGF-I administration (350 +/- 26 vs 205 +/- 21 micrograms/l (mean +/- SEM), P < 0.01). Mean 22-hour GH levels were reduced following rhIGF-I administration (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; P = 0.01). Distribution analysis demonstrated that the reduction in GH levels was due to changes in the proportion of values at both high and low concentrations. Deconvolution analysis also revealed a significant overall reduction in GH secretory rate following IGF-I administration (1.81 +/- 0.30 vs 2.98 +/- 0.47 mU/min, P = 0.01) which was still apparent during the final 5.5 hours of the study period (1.51 +/- 0.30 vs 2.76 +/- 0.61 mU/min, P = 0.02). The dominant periodicity of GH secretory episodes as determined by Fourier transformation was between 120 and 180 minutes after both IGF-I and placebo. CONCLUSIONS: In late pubertal adolescents with IDDM the rise in IGF-I levels following rhIGF-I administration in a subcutaneous dose of 40 micrograms/kg body weight leads to a significant reduction in GH levels and GH secretory rate. The reduction in GH secretion is due to changes in pulse amplitude rather than frequency. A reduction in GH secretion was apparent at the beginning and also towards the end of the 22-hour study period.

Adolescent↗
PubMed1994

Reversibility of physiological growth hormone secretion in children with psychosocial dwarfism.

OBJECTIVE: Reversibility of GH insufficiency with a change of environment is characteristic of psychosocial dwarfism, and excludes an organic endocrinopathy. However, the change in GH pulsatility has not previously been described. We therefore wished to study spontaneous GH secretion before and after change to a more favourable environment in 11 children with psychosocial deprivation and short stature in order to evaluate if separation from the families can modify their patterns of GH secretion. PATIENTS AND DESIGN: We describe 11 prepubertal children (6 M and 5 F; 2.2-13.5 years of age) who had growth failure and psychosocial deprivation. They were diagnosed by a multidisciplinary team as having environmental growth failure after admission to hospital for 3 weeks. Six of them were discovered to have been sexually abused. During the uninterrupted hospital admission parental access was restricted. Three sets of 18-hour GH profiles were performed on each child, except one child who had only two, during the 3-week admission. MEASUREMENTS: Pulse analysis of GH profiles was by Fourier transformation. RESULTS: On the first day of admission spontaneous GH secretion demonstrated a spectrum of abnormalities in the pattern of basal values, pulse frequency and pulse amplitude. Such GH insufficiency showed reversibility during the 3 weeks in hospital. Indeed, there was a significant increase in GH secretion which was amplitude modulated without any significant modification in pulse frequency. CONCLUSION: Our data indicate that there is abnormal physiological GH secretion in children with psychosocial deprivation, which is associated with growth failure. Despite a pathological situation, each child retained his own characteristic pattern of GH pulsatility. The pattern of reversibility of abnormal GH pulsatility provides information for the mechanism of the control of GH secretion.

Adolescent↗
PubMed1994

Nursing as a career choice for women in Pakistan.

This paper reports on semi-structured interviews with 114 Pakistani nurses. This sample comes from a larger long-term study examining the impact of advanced training in Canada on the lives and careers of nurses and lady health visitors from Pakistan. The data reported here were drawn from the first interview with all nurses, and focuses on how and why they chose a career in nursing. Demographically, the respondents (Rs) were more urban and more highly educated than the average Pakistani woman. Compared to the national population, Ismailis and Christians were over-represented and non-Ismaili Muslims under-represented in our sample. Although these ratios are also true of Pakistan's nursing population, the bias has been exaggerated by the convenience nature of our sample drawn primarily from the Aga Khan University Medical Centre. Most Rs found out about nursing through a relative or friend who was also a nurse. Eighty per cent of Rs (n = 92) reported having made the decision to pursue nursing by themselves, illustrating the increasing ability of women to control their own lives in this traditionally patriarchal society. 'Professionalism' was the predominant reason why Rs (or others) decided on nursing, followed by 'Altruism'. These findings are compared to other studies on the career choice of nurses done in non-Islamic societies. Over 90% of Rs reported receiving support from at least one friend or relative for their decision to enter nursing. Nonetheless, over half (58%) also reported that someone, most often a male relative, had opposed their career choice. Our results are discussed in terms of the status of women and nursing in Pakistan.

Adult↗