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D R Matthews

Publications and source records attributed to D R Matthews.

At least 91 records · Page 5Linked to original sources

The effect of changing gonadotropin-releasing hormone pulse frequency on puberty.

We have examined the effect of using different pulse frequencies of exogenous GnRH to induce puberty and the time relationship among LH, FSH, sex steroids, and GH in these individuals. Five girls and three boys with delayed puberty received exogenous GnRH at either 3-h frequency (slow) or every 45 min (fast). Treatment was initially given overnight and increased to 24 h when breast stage 3 in girls or testicular volume of 10 mL in boys was attained. Twenty-four-hour gonadotropin profiles were performed after 5 days, 1 month, 3 months, 6 months, and 1 yr of treatment. Temporal relationships among LH, FSH, and estradiol; LH and testosterone; GH and estradiol; and GH and testosterone were examined by cross-correlation. There was no difference in the rate of pubertal progress between the groups. Mean serum gonadotropin and sex steroid levels did not differ. LH was correlated with estradiol for both groups at 240 min (slow group, r = 0.54; fast group, r = 0.50). Estradiol correlated with LH at 300 min in the slow group (r = -0.41) and 200 min in the fast group (r = -0.37). FSH correlated with estradiol at 140 min in the slow group (r = 0.62) and 160 min in the fast group (r = 0.50). A rise in estradiol occurred 140-160 min after a rise in FSH and 240 min after a rise in LH. A rise in estradiol was followed 200-300 min later by a fall in LH. LH was correlated with testosterone at 60 min in the slow group (r = 0.73) and at 40 min in the fast group (r = 0.55). Testosterone correlated with LH at 420 min in the slow (r = -0.67) and 460 min in the fast group (r = -0.40). A rise in LH was followed 40-60 min later by a rise in testosterone. A rise in testosterone was followed by fall in LH 420-460 min later. GH correlated with estradiol at 320 min in the slow group (r = 0.37) and 380 min in the fast group (r = 0.38). A rise in GH was followed, after 320-380 min, by a rise in estradiol. There was a correlation between GH and testosterone in the slow group after 280 min (r = 0.44). A rise in GH was followed by a rise in testosterone after 280 min. The pituitary-gonadal axis is sufficiently robust to allow puberty to progress with different fixed pulse frequencies. There is a temporal relationship among LH, FSH, and estradiol secretion and between LH and testosterone secretion. We have demonstrated the feedback effect of sex steroids at the level of the pituitary and the time course of the effect of GH on gonadal function.

Adolescent↗

Changes in gonadotrophin secretion during childhood and puberty.

The changes in gonadotrophin secretion in childhood and puberty involve changes in the pulsatile pattern as well as mean concentration. We have examined pulsatile secretion using 24-h LH profiles in 78 children aged 4.2-15.6 years and six adult men. The profiles were analysed by a method which gives an estimate of peak and baseline levels and by spectral analysis. Prepubertal children were divided into groups by age and pubertal children by pubertal stage. Baseline LH levels in children aged 4.2-6.9 years were higher than in those aged 7.1-9.8 years. Pulse frequency in both groups was slow (periodicities 140-200 min). In the oldest prepubertal group there was an increase in peak levels with increased spectral power at periodicities of 100-120 min. Pulse frequency did not change in puberty (periodicity 120-160 min). Girls demonstrated an increase in both peak and baseline LH concentrations in early puberty. Boys had an increase in only peak levels in early puberty; there was no increase in baseline concentrations until a testicular volume of 10 ml was attained. In conclusion, these data show that LH levels do not reach a nadir until 8 years of age. We have detected a sex difference in the pattern of LH secretion seen in early puberty, and this mirrors clinical findings. The mature pattern attained by the end of puberty in both sexes is probably important for fertility.

Adolescent↗

Effects of learner-centered laboratory activities on achievement and students' preferences in two high school biology courses.

The effects of two types of teaching procedures in two sections of high school biology on 46 students' achievement and preferences were examined using a pre-posttest comparison-group design. The 19 students in the lab group were taught a unit in cell biology through lecture and a guided laboratory approach. The comparison group of 27 were students in 12th grade biology who were taught the same material by lecture and nonexperimental learner-centered activities. Pre- and posttest scores on an examination requiring formal operational reasoning and a teacher-designed questionnaire were analyzed. Students in the laboratory group scored significantly higher at posttest, but no significant differences in students' preferences were found. In high school biology instruction, use of guided laboratory activities may be advantageous.

Adolescent↗

The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with type 1 (insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s.c. dose of recombinant insulin-like growth factor I (40 micrograms/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1 +/- 28.2 ng/ml, mean +/- SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4 +/- 4.0 compared with 33.6 +/- 5.8 mU/l; p = 0.01), as were the insulin requirements for euglycaemia (0.25 +/- 0.02 compared with 0.31 +/- 0.04 mU.kg-1.min-1; p = 0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9 +/- 2.7 compared with 67.9 +/- 16.0 mU/l; p = 0.001) but no significant differences in ketone or lactate levels were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prednisolone enhances beta-cell function independently of ambient glycemic levels in type II diabetes.

This study examined the changes in beta-cell response and insulin sensitivity induced by a single overnight dose of 15 mg prednisolone in eight type II diabetic subjects, seven nondiabetic normal controls, and eight subjects with a first-degree type II diabetic relative who were therefore at risk of developing diabetes. beta-Cell secretion was assessed by use of the hyperglycemic clamp technique, and insulin sensitivity was assessed with the clamp and the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique. Subjects were studied in random order on two occasions, after placebo and after prednisolone administration. Normal subjects showed an increase of median fasting glucose level from 4.7 to 5.2 mmol.L-1 after prednisolone (P < .02) and at-risk subjects showed an increase from 4.8 to 5.5 mmol.L-1 (P < .005), whereas diabetic subjects showed no significant increase in median fasting plasma glucose level (7.0 mmol.L-1 after placebo and 6.3 mmol.L-1 after prednisolone). Six of these eight diabetic subjects showed a paradoxical decrease of fasting plasma glucose level after prednisolone therapy. All three groups showed a significant elevation of clamp steady-state plasma insulin levels following prednisolone, with a median percentage elevation of 46%, 66%, and 31% for normal, at-risk, and diabetic subjects, respectively. All three groups showed significant reduction in insulin sensitivity measured by CIGMA following prednisolone of 51%, 41%, and 25% of pre-prednisolone levels in normal, at-risk, and diabetic subjects, respectively, with a significantly greater reduction in normal subjects than in diabetics (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The relationship between endogenous testosterone and gonadotrophin secretion.

OBJECTIVE: The secretion of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone in the adult male was studied by means of 48-hour profiles. The aim of the study was to examine the effects of the endogenous circadian variation in serum testosterone concentration on LH pulsatility, and to determine the temporal relationships between FSH and LH, and between LH and testosterone by cross-correlation, and the pulse frequency of these hormones by spectral analysis, as revealed by extended sampling periods. DESIGN: Hormone profiles were obtained by 20-minute sampling over 48 hours. SUBJECTS: Six healthy adult males, aged between 21 and 23 years. MEASUREMENTS: LH and FSH were measured using an immunoradiometric assay and testosterone with a solid-phase radioimmunoassay. RESULTS: The profiles showed pulsatile secretion of all three hormones, and a circadian rhythm with levels highest between 0200 and 0600 h. Cross-correlation analysis: There was a significant relationship between LH and FSH (r = 0.5; P = 0.001) at 0 minutes (i.e. no time lag). A pulse of testosterone followed on average 60 minutes after a pulse of LH (r = 0.26; P = 0.001). Fourier transformation: Spectral analysis showed the dominant period for LH and FSH pulsatility to be 200 minutes. The dominant period for testosterone pulsatility was 400 minutes. The effect of endogenous variations in serum testosterone concentrations: The LH profiles were divided into periods when the serum testosterone concentration was high or low, and Fourier transformation carried out on these shorter periods. These transforms showed that the dominant period during high serum testosterone concentration was 180 minutes, and during low serum testosterone was 120 minutes (P < or = 0.025). CONCLUSIONS: FSH and LH are co-secreted, and a pulse of testosterone follows a pulse of LH by 60 minutes. The physiological changes in serum testosterone concentration that occur during the day result in changes in the pulse frequency of LH. Testosterone concentrations thus have rapidly acting feedback activity at hypothalamic level.

Adult↗

The frequency and amplitude of growth hormone secretory episodes as determined by deconvolution analysis are increased in adolescents with insulin dependent diabetes mellitus and are unaffected by short-term euglycaemia.

OBJECTIVE: High overnight plasma growth hormone (GH) levels in insulin-dependent diabetes mellitus (IDDM) are reflected in both an increase in the GH pulse amplitude and elevated baseline GH concentrations. To determine whether these are a result of an increase in GH secretory episodes, we undertook deconvolution analysis of overnight GH profiles using previously determined half-life data. DESIGN: Deconvolution of overnight GH profiles (2000-0800 h) was undertaken from normal and diabetic adolescents (either on their usual insulin regime (n = 15), during overnight euglycaemic clamp using a variable rate insulin infusion (n = 29), or during clamp plus 100 mg pirenzepine to suppress endogenous GH (n = 7)). PATIENTS: Thirty-five normal and 29 diabetic adolescents of both sexes at all stages of puberty. MEASUREMENTS: GH secretory rates were calculated from deconvolution analysis, and Fourier transformation was increased mean overnight GH secretion when analysed by sex and by puberty stage compared to normal subjects; overnight GH secretion median (range) of diabetic group 1.88 (0.56-3.81) mU/min; control group 0.62 (0.32-1.92) mU/min (P < 0.001). Fourier transform analysis of these secretory episodes showed greater pulse frequency in the diabetics with dominant pulse periodicity of 90 minutes compared with 135 minutes in normal subjects. During overnight euglycaemia, mean +/- SEM overnight GH secretory rates were comparable to subjects' usual regime night (1.82 +/- 0.33 vs 1.91 +/- 0.37 mU/min) and there was no change in the dominant pulse periodicity of 90 minutes. Pirenzepine administration in diabetic subjects significantly reduced overnight GH secretion from 1.57 +/- 0.19 to 0.71 +/- 0.80 mU/min (P < 0.001) showing a median (range) reduction of 63 (9.3-82.8)% when compared to the subjects' clamp night. However, dominant pulse periodicity was not altered by pirenzepine administration, and remained at 90 minutes. CONCLUSION: In patients with insulin-dependent diabetes mellitus there is an increase in both the amplitude and frequency of pulsatile GH secretion compared to normal subjects, which is not affected by maintenance of overnight normoglycaemia. The anticholinergic drug pirenzepine appears to suppress the amplitude of GH pulse secretion but has no effect on frequency.

Adolescent↗

Short-term endocrine consequences of total body irradiation and bone marrow transplantation in children treated for leukemia.

We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation (group 1) and fourteen of whom had not (group 2), before and 6-12 months after total body irradiation (TBI) for bone marrow transplantation in leukaemia. Fourier transformation demonstrated that group 1 children had a faster periodicity of GH secretion before TBI than group 2 children (160 vs 200 min) but the amplitude of their GH peaks was similar. There were no differences between the groups in circadian cortisol rhythm, serum concentrations of insulin-like growth factor-I (IGF-I), sex steroids and basal thyroxine (T4). The peak serum GH concentrations observed after insulin-induced hypoglycaemia were similar between the two groups but the majority of patients had blunted responses. TBI increased the periodicity of GH secretion in both groups (group 1 vs group 2; 140 vs 180 min), but the tendency to attenuation of amplitude was not significant. There were no significant changes in the peak serum GH concentration response to insulin-induced hypoglycaemia which remained blunted. Serum IGF-I, sex steroid, cortisol or T4 concentrations were unchanged. Low-dose cranial irradiation has an effect on GH secretion affecting predominantly frequency modulation leading to fast frequency, normal amplitude GH pulsatility. This change is accentuated by TBI. In patients with leukemia, there is a marked discordance between the peak serum GH response to insulin-induced hypoglycaemia compared with the release of GH during 24-h studies, irrespective of the therapeutic regimen used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evidence for a role for insulin and growth hormone in overnight regulation of 3-hydroxybutyrate in normal and diabetic adolescents.

OBJECTIVE: To determine the relative effects of growth hormone and insulin on ketogenesis during puberty. RESEARCH DESIGN AND METHODS: We studied overnight changes in plasma ketones--3-hydroxybutyrate and acetoacetate--in 35 normal and 26 IDDM adolescents at different stages of puberty. The diabetic adolescents either were on their normal insulin regimen or were studied during an overnight euglycemic clamp with or without suppression of endogenous growth hormone release. RESULTS: Total ketone body and 3-hydroxybutyrate concentrations in the normal adolescents rose significantly from 2000 (29 +/- 5 microM), reaching a peak at 0200 (103 +/- 16 microM, P < 0.001 vs. 2000). After a brief fall, a further rise occurred before breakfast. Fasting 3-hydroxybutyrate concentrations showed a negative correlation with fasting insulin levels (r = -0.46, P = 0.005) and decreased with advancing puberty, while insulin concentrations increased. In the diabetic patients on their usual insulin regimen, free insulin levels waned overnight, and an exaggerated rise in ketones was observed before breakfast. During the euglycemic clamp studies, ketone levels were higher than normal throughout the night. Mean overnight growth hormone and free insulin levels also were higher than in the normal control subjects. The addition of the anticholinergic drug pirenzepine reduced growth hormone secretion and obliterated the early-night peak of 3-hydroxybutyrate. CONCLUSIONS: We conclude that the early-night peak of ketone concentrations is related to growth hormone release, whereas the fasting levels are largely determined by insulin concentration. Inadequate insulin delivery in the presence of the high growth hormone concentrations characteristic of diabetic adolescents could lead to rapid decompensation and ketoacidosis.

3-Hydroxybutyric Acid↗

Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine.

OBJECTIVE: To compare the efficacy and safety of cholestyramine, an anion exchange resin, and pravastatin, a new hydrophilic specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in the treatment of heterozygous familial hypercholesterolaemia. DESIGN: Double blind, double dummy, placebo controlled study with three parallel groups. SETTING: Six specialist lipid clinics in the United Kingdom. PATIENTS: 128 patients aged 18-70 with heterozygous familial hypercholesterolaemia diagnosed on strict biochemical and clinical findings. MAIN OUTCOME MEASURES: Total plasma cholesterol, triglyceride, and lipoprotein subfractions and biochemical and haematological safety parameters. RESULTS: Pravastatin (40 mg/day) led to a 25% reduction in total plasma cholesterol concentration and a reduction in low density lipoprotein cholesterol concentration of 30%. Cholestyramine (24 g/day) led to similar reductions in concentrations of total cholesterol (23%) and low density lipoprotein cholesterol (31%). No consistent changes occurred in high density lipoprotein cholesterol values with either compound. Plasma triglyceride concentrations showed a small rise (18%) on resin therapy. No serious adverse drug reactions occurred during the study. CONCLUSIONS: Pravastatin seems to be a highly effective, well tolerated drug for severe hypercholesterolaemia. Patients chosen for this study were recruited on the basis that they could tolerate a full dose of cholestyramine, and in this situation cholestyramine was also highly effective in lowering plasma low density lipoprotein cholesterol concentrations.

Adolescent↗

Contrasting metabolic effects of continuous and pulsatile growth hormone administration in young adults with type 1 (insulin-dependent) diabetes mellitus.

Plasma growth hormone profiles in adolescents with Type 1 (insulin-dependent) diabetes mellitus are characterized by both increases in pulse amplitude and higher baseline concentrations. To determine which of these abnormalities adversely affect metabolic control, we studied six young adults overnight on three occasions. On each night somatostatin (50-100 micrograms.m2-1.h-1) and glucagon (1 ng.kg-1.min-1) were infused continuously and 18 mU/kg of growth hormone was given as either: three discrete pulses of 6 mU.kg-1.h-1 at 180-min intervals or a 12-h infusion (1.5 mU.kg-1.h-1) or buffer solution only on a control night. Euglycaemia was maintained by an insulin-varying clamp. Blood samples were taken every 15 min for glucose and growth hormone and every hour for intermediate metabolites and non-esterified fatty acids. Comparable normoglycaemic conditions were achieved on all three nights. Growth hormone levels achieved (mean +/- SEM) on study nights were: 32.8 +/- 2.2 mU/l (peak level during growth hormone pulses); 9.8 +/- 0.8 mU/l (continuous growth hormone) and 1.1 +/- 0.3 mU/l (control level). Pulsatile growth hormone administration led to an increase in insulin requirements (mean +/- SEM: 0.17 +/- 0.03 vs control 0.09 +/- 0.01 mU.kg-1.min-1, p less than 0.05) whereas insulin requirements following continuous growth hormone administration were unchanged. Cross-correlation confirmed an increase in insulin requirements occurring 135 min after a growth hormone pulse (r = 0.21, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

Loss of regular oscillatory insulin secretion in islet cell antibody positive non-diabetic subjects.

Basal insulin secretion was compared in nine islet-cell antibody positive, non-diabetic first-degree relatives of children with Type 1 (insulin-dependent) diabetes mellitus and nine normal control subjects matched for age, sex and weight. Acute insulin responses to a 25 g intravenous glucose tolerance test were similar in the two groups (243 (198-229) vs 329 (285-380) mU.l-1 x 10 min-1, mean (+/- SE), p = 0.25). Fasting plasma insulin was assayed in venous samples taken at one min intervals for 2 h. Time series analysis was used to demonstrate oscillatory patterns in plasma insulin. Autocorrelation showed that regular oscillatory activity was generally absent in the islet-cell antibody-positive group, whereas a regular 13 min cycle was shown in control subjects (p less than 0.0001). Fourier transformation did, however, show a 13 min spectral peak in the islet-cell antibody positive group, consistent with intermittent pulsatility. We conclude that overall oscillatory patterns of basal insulin secretion are altered in islet-cell antibody positive subjects even when the acute insulin response is within the normal range.

Activity Cycles↗

Rate of change (modulation) of serum growth hormone concentrations is a more important factor in determining growth rate than duration of exposure.

OBJECTIVE: To determine whether duration of exposure to GH and/or rate of change of serum GH concentration are important factors in determining the growth rate of short children. DESIGN: An analysis of parameters of occupancy percentage and rate of change of serum GH concentration was performed as part of a prospective study investigating the relationship between growth and GH in childhood. PATIENTS: Sixty-four short prepubertal children (48 male, 16 female) aged between 4.7 and 11.9 years were studied. Thirty-one children were growing with a height velocity standard deviation score between 0 and -0.8 and were defined as short normal. Thirty-three children were growing with a height velocity standard deviation score less than -0.8 and were defined as short slowly growing. MEASUREMENTS: Twenty-four hour serum GH concentration profiles were constructed by withdrawing samples at 20-minute intervals. Analysis of occupancy percentage was performed on each data array by determining cumulative distributions and plotting these as linear probits against log serum GH concentration. Estimates of peak (OC95), intermediate (OC50) and trough (OC5) occupancies were calculated. A first-order derivative of the concentration-time data array was determined for each profile as a measure of rate changes. RESULTS: First-order derivative values were significantly greater in the short normal group than in the short slowly growing children (short normal median 1.41 mU/l/min; short slowly growing median 0.72 mU/l/min; P less than 0.001). OC95 values were significantly higher in the short normal group (median 19.31 mU/l) than the short slowly growing group (median 7.69 mU/l) (P less than 0.001). There was no difference in OC50 values. OC5 values were lower in short normal children (median 0.20 mU/l) than in the short slowly growing children (0.55 mU/l) (P less than 0.003). The most important factor in determining growth rate was the rate of change in serum GH concentration (FOD). Occupancy percentage played no part in the relationship. The regression equation was Height velocity SDS = 1.16 (In FOD) - 1.03; r = 0.75; P less than 0.001 CONCLUSIONS: These data suggest that the pattern of presentation of GH in the circulation is an important factor in determining target organ response. Although occupancy percentages at differing serum GH concentrations differ between short slowly growing and short normal children, it is the rate of change of the hormone in the circulation which appears to be the more important 'signal' in terms of modulating growth.

Child↗

Half-life of exogenous growth hormone following suppression of endogenous growth hormone secretion with somatostatin in type I (insulin-dependent) diabetes mellitus.

OBJECTIVE: To estimate the half-life of growth hormone in young adult patients with type I (insulin-dependent) diabetes mellitus following bolus injection and prolonged exposure for the purpose of deconvolution analysis of plasma growth hormone profiles to determine growth hormone secretory rates. DESIGN: In the bolus study, an intravenous bolus injection of 100 mU of biosynthetic human growth hormone was given while endogenous growth hormone was suppressed by a continuous infusion of somatostatin under three different glucose clamp conditions: normoglycaemia (5 mmol/l) with normoinsulinaemia (65 pmol/l); hyperglycaemia (12 mmol/l) with normoinsulinaemia; and normoglycaemia with hyperinsulinaemia (360 pmol/l). In the infusion study, the effect of prolonged and repeated growth hormone exposure upon the growth hormone half-life was estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two hours apart under euglycaemic somatostatin suppression were applied. PATIENTS: Six young adult patients with type I (insulin-dependent) diabetes mellitus were studied in both the bolus and the infusion study. RESULTS: Mean GH half-lives by mono-exponential analysis were not significantly different remaining unaltered by the short-term metabolic changes of hyperglycaemia and hyperinsulinaemia. Data were therefore pooled yielding an overall mean GH half-life of 13.6 minutes (range 11.9-19.4). Applying a bi-exponential model mean GH half-lives were 3.1 minutes (range 2.5-5.9) for the rapid phase of distribution of the hormone and 13.8 minutes (range 9.6-16.9) for the decay of GH from the circulation. The GH half-life during the infusions studies did not vary with repeated exposure but was significantly longer (mean half-life of 25.7 minutes; range 19.4-37.1) than during the bolus studies (P less than 0.001). CONCLUSIONS: The half-life of exogenous r-hGH is not affected by glucose or insulin concentrations but increases after prolonged GH exposure in young adults with type I (insulin-dependent) diabetes mellitus.

Adolescent↗

Analysis of trough serum growth hormone concentrations: comparison of an immunoradiometric assay and a sensitive ELISA for growth hormone.

OBJECTIVES: We compared a sensitive assay for GH (ELISA) with a conventional immunoradiometric (IRMA) assay with particular reference to the oscillatory activity detected by Fourier transformation and the estimation of trough concentrations using occupancy analysis. DESIGN: Eight healthy adult male volunteers underwent 24-hour profiles during which samples were drawn at 20-minute intervals. Samples were analysed by an ELISA and an IRMA system. MEASUREMENTS: The 24-hour serum GH concentration profiles were subjected to Fourier transformation and to occupancy analysis. RESULTS: No additional GH periodicities could be determined in the ELISA data other than the well documented 180-200-minute periodicity. Median observed concentrations (OC) at 5% occupancy were 0.035 mU/l (range 0.004-0.22) for the ELISA and 0.035 mU/l (range 0.001-0.50) for the IRMA. For all OC parameters, 5, 50 and 95%, there was a good correlation between the ELISA and IRMA systems. The mean difference (bias) between the ELISA and IRMA were -0.05, -0.28 and -1.40 mU/l at OC values of 5, 50 and 95% respectively and the standard deviations of the difference at the same OC values were 0.10, 0.50 and 1.61 mU/l. CONCLUSION: Although there is a qualitative improvement on visual inspection of individual 24-hour serum GH profiles obtained using the ELISA system, there is little additional information gained in terms of pulse periodicity or occupancy analysis.

Adult↗

Fate of research studies.

A retrospective survey was conducted of 720 research protocols, approved by the Central Oxford Research Ethics Committee between 1984 and 1987, to determine the fate of research studies from inception. Forty-five per cent were clinical trials, 23% were observational studies and 32% were laboratory-based experimental studies. Further information was obtained on 487 studies, of which 287 (59%) had been completed, 100 (21%) had never started, 58 (12%) had been abandoned or were in abeyance and 42 (9%) were still ongoing, as of May 1990. Forty-three per cent of the original 487 studies were subsequently published or presented. The most frequent reason for not starting a study was failure to obtain funding (40%). The main reason for abandoning a study was difficulty in recruiting study participants (28%). Departure of one of the investigators from the institution and a variety of logistical problems were also common reasons for either not starting or abandoning a study. A thorough review of the pragmatic as well as the scientific aspects of a planned research project is important to minimize the initiation of studies that are unlikely to succeed.

Biomedical Research↗