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Biomedical subjects

D R Matthews

Publications and source records attributed to D R Matthews.

At least 109 records · Page 6Linked to original sources
PubMed1992

The effect of changing somatostatin tone on the pituitary growth hormone and thyroid-stimulating hormone responses to their respective releasing factor stimuli.

Somatostatin (SS) inhibits GH and TSH secretion, but its role in modulating their pulsatility is unclear. We studied GH and TSH responses to GH-releasing hormone (GHRH) and TRH stimulation upon a variable background infusion of saline, SS-(1-14) at 20 and 100 micrograms/m2.h, and oral pyridostigmine (30 and 60 mg) in six adult males. Basal GH levels were unaffected by SS-(1-14). Deconvolution analysis of serum GH values demonstrated that the pituitary responded to two GHRH stimuli 90 min apart without attenuation of the second response. The higher dose of SS-(1-14) significantly blunted the first GH response; second GH responses were further attenuated by both SS-(1-14) doses. Maximum GH release and "switch-off" rates for both stimuli were reduced without changes in the 50% secretion time. Pyridostigmine enhanced the first GH response to GHRH with an increase in the GH release rate; second GH responses were not augmented. GH secretion was prolonged by pyridostigmine, although the 50% secretion time remained unchanged. Peak stimulated serum TSH was attenuated by both SS-(1-14) doses, but pyridostigmine had no effect. All other TSH parameters examined were unaffected. We conclude that the GH response to GHRH is dependent on SS tone, but that the thyrotroph is not tonically inhibited by SS. SS attenuates the rate of GH release without changing the duration of secretion and appears important in terminating GH secretion.

Adult↗
PubMed1992

Growth hormone secretion in patients with Turner's syndrome as determined by time series analysis.

Twenty-four-hour growth hormone (GH) profiles in 26 girls with Turner's syndrome were compared with those of 26 normally growing short children and 24 slowly growing short children. All children were prepubertal and below 12 years of age. A subgroup of 13 girls was treated with ethinyl estradiol and a 24-h GH profile was reassessed. In an additional group of 45 girls with Turner's syndrome (aged 6.7-18.9 years) the effect of age, spontaneous breast development and ethinyl estradiol treatment was studied. The profiles were assessed by Fourier analysis. The oscillatory activity and the mean 24-h GH concentration were similar in children with Turner's syndrome and the normally growing short children, in contrast to lower levels in the slowly growing short children. The periodicity of GH secretion was similar in all groups. In the longitudinal study, ethinyl estradiol treatment resulted in a significant increase in pulse amplitude, but not in periodicity. In the cross-sectional study there was no significant difference between the subgroups of girls with either presence or absence of breast development or ethinyl estradiol treatment. GH secretion was not significantly related to age, height in standard deviation score or height velocity. These data imply that there is no abnormality in GH secretion in girls with Turner's syndrome.

Aging↗
PubMed1992

The management of hyperlipidaemia: are specialist lipid clinics needed?

A survey of all general practitioners in Oxfordshire was undertaken to determine what use they wanted to make of a district lipid clinic, and to assess how effectively it met their needs. The response rate was 85% (288/340) but some respondents failed to answer each section of every question. One hundred and eighty-five general practitioners (64%) had previously referred patients to the clinic. Most respondents selectively asked for blood cholesterol measurements in patients with major cardiovascular risk factors (94%, 266/283), and few routinely asked for cholesterol as part of a health check (17%, 43/258). Most thought that referral to a clinic was appropriate for children (65%, 149/229), for patients aged 20 to 39 (85%, 209/247), and for older patients aged up to 60 (77%, 186/243). Ninety-four per cent (260/277) wanted access to specialist advice for patients with a cholesterol concentration exceeding 8.0 mmol l-1, and 73% (197/270) wanted specialist advice before starting treatment with a lipid-lowering drug. Although most respondents rated the service provided by the clinic favourably, more than half would have liked more information on prognosis, drug treatment, long-term follow-up, and screening of family members. We conclude that general practitioners would like access to specialist advice for the management of severe hyperlipidaemias, and that cardiovascular screening programmes in primary care have important resource implications for specialist services.

Adult↗
PubMed1991

Publication bias in clinical research.

In a retrospective survey, 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987, were studied for evidence of publication bias. As of May, 1990, 285 of the studies had been analysed by the investigators, and 52% of these had been published. Studies with statistically significant results were more likely to be published than those finding no difference between the study groups (adjusted odds ratio [OR] 2.32; 95% confidence interval [Cl] 1.25-4.28). Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor. An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results, and with increasing sample size. The tendency towards publication bias was greater with observational and laboratory-based experimental studies (OR = 3.79; 95% Cl = 1.47-9.76) than with randomised clinical trials (OR = 0.84; 95% Cl = 0.34-2.09). We have confirmed the presence of publication bias in a cohort of clinical research studies. These findings suggest that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies. Improved strategies are needed to identify the results of unpublished as well as published studies.

Bias↗
PubMed1991

No glucotoxicity after 53 hours of 6.0 mmol/l hyperglycaemia in normal man.

In vitro and in vivo studies have suggested that metabolic deterioration can be induced by hyperglycaemia per se. The effect of 53 h of 2.2 mg glucose.kg ideal body weight-1.min-1 was examined in four normal male subjects. This produced overnight hyperglycaemia of 6.0 mmol/l on the two nights of the study compared with 4.7 mmol/l on the control night (p less than 0.05). In response there was a sustained, two-fold increase in basal plasma insulin (p less than 0.005) and C-peptide (p less than 0.05) levels. After two days of hyperglycaemia an increased Beta-cell response was demonstrated in response to an additional glucose infusion stimulus (estimated Beta-cell function median of 84% on the control day to 100% after two days glucose infusion). Plasma insulin and C-peptide responses to a 10.0 mmol/l hyperglycaemic clamp increased over the two days of the study (insulin from median 48 mU/l to 73 mU/l and C-peptide from median 2.0 pmol/ml to 2.6 pmol/l). Glucose tolerance to the additional glucose infusion stimulus improved, suggesting that the increased insulin response during hyperglycaemia was enhancing peripheral glucose uptake. The calculated peripheral insulin sensitivity was unchanged during the hyperglycaemic clamp. Thus, in response to the two days of basal hyperglycaemia, both the basal and stimulated Beta-cell responses were enhanced and there was no evidence for 'glucose toxicity' to the Beta-cells.

Adult↗
PubMed1991

Simple empirical assessment of beta-cell function by a constant infusion of glucose test in normal and type 2 (non-insulin-dependent) diabetic subjects.

The plasma insulin or C-peptide response to a 90-min constant glucose infusion 5 mg.kg ideal body weight-1.min-1 provides Beta-cell assessment comparable to more intensive methods. In 14 diet-treated Type 2 (non-insulin-dependent) diabetic subjects and 12 non-diabetic subjects, plasma insulin and C-peptide concentrations gave near linear plots against simultaneous glucose values. The 'glucose-insulin and glucose-C-peptide vectors' (G-I and G-C vectors), could be extrapolated to predict insulin and C-peptide levels during a 12 mmol/l hyperglycaemic clamp. Predicted concentrations correlated with clamp concentrations, r = 0.94 and r = 0.98 respectively, p less than 0.001, validating the vectors as empirical glucose dose-response curves. The vector slopes correlated highly with %Beta, a mathematical model-derived measure of Beta-cell function using constant infusion of glucose model assessment, Spearman r = 0.95 and 0.93 for insulin and C-peptide, respectively. G-I vector slopes in 21 diet-treated Type 2 diabetic subjects with fasting glucose (mean + 1 SD) 7.5 +/- 2.3 mmol/l, were lower than in 28 non-diabetic subjects, (geometric mean, 1 SD range, 8.4 pmol/mmol (3.3-21.0) and 25.1 pmol/mmol (14.3-44.1), p less than 0.001, respectively), indicating an impaired Beta-cell response. The G-I vector slopes correlated with obesity in both groups (r = 0.54 p less than 0.02 and 0.72, p less than 0.001 respectively), and, in 15 non-diabetic subjects, correlated inversely with insulin sensitivity as measured by a euglycaemic clamp (r = -0.66, p less than 0.01). Thus, Beta-cell function needs to be interpreted in relation to obesity/insulin resistance and, taking obesity into account, only 4 of 21 diabetic patients had Beta-cell function (G-I vector slope) in the non-diabetic range. The fasting plasma glucose in the diabetic subjects correlated inversely with the obesity-corrected G-I and G-C vector slopes (partial r = -0.57, p less than 0.01 and -0.86, p less than 0.001, respectively). The insulin or C-peptide response to the glucose infusion provides a direct empirical measure of the Beta-cell function, which can be interpreted in relation to obesity or to insulin resistance to assess underlying pancreatic responsiveness.

Blood Glucose↗
PubMed1991

Understanding "insulin resistance": both glucose resistance and insulin resistance are required to model human diabetes.

A mathematical model of normal glucose/insulin homoeostasis has been based on the known, experimentally determined responses of the liver and periphery to different glucose/insulin concentrations. Different defects of glucose resistance and insulin resistance have been applied to the model to investigate the degree to which these abnormalities could successfully predict the range of fasting glucose and insulin values found in normal, obese, and diabetic subjects. Modeling glucose resistance or insulin resistance at the liver or the periphery alone did not increase the plasma glucose to levels observed in diabetes, even when associated with marked deficiency of beta-cell function. A defect of either glucose resistance or insulin resistance affecting both periphery and liver allowed a wider range of basal glucose and insulin concentration values, but resulted in unphysiologically low hepatic glucose output: with modeling insulin resistance, hyperglycemia suppressed glucose output, whereas with glucose resistance, raised insulin levels suppressed hepatic glucose output. A wide range of glucose and insulin values, with appropriate basal hepatic glucose output, could only be modeled by insulin resistance at both the liver and periphery with additional glucose resistance at the liver. The modeling results are in accord with investigative studies that suggest secondary hepatic and peripheral glucose resistance in response to hyperglycemia. Modeling provides a systematic means of examining the likely effect of different putative defects in a complex physiological system.

Diabetes Mellitus↗
PubMed1991

The physiological action of gliclazide: beta-cell function and insulin resistance.

There is continuing debate about the physiological mechanisms of the action of sulphonylureas in man. In those patients taking sulphonylureas insulin secretion can be demonstrated to be higher, but there are also data which have been interpreted as evidence that these drugs may cause an alteration in peripheral insulin sensitivity. The physiological effects of the sulphonylurea gliclazide in diabetic subjects has been examined using a variety of experimental protocols to address this question: an intravenous gliclazide infusion, experiments using glucose clamping, mathematical modelling of the insulin and glucose data from subjects on and off gliclazide therapy, and the infusion of amino acids and glucose separately or in combination. The data from all these analyses suggest that the primary effect of gliclazide is on the beta-cell and that any effects on the peripheral insulin sensitivity are either slight or secondary to the improvement of the secretory capacity of the pancreatic islets.

Amino Acids↗
PubMed1991

Impact of increased growth hormone secretion on carbohydrate metabolism in adolescents with diabetes.

Growth hormone (GH) and fasting insulin concentrations rise during puberty in normal subjects. Any increase in GH secretion in adolescents with insulin-dependent diabetes mellitus (IDDM) might be expected to lead to further insulin resistance and metabolic disturbance. Despite the high incidence of delayed growth in IDDM, the relationship between GH, insulin-like growth factor I (IGF-I) and IGF binding protein 1 (IGFBP-1) has not been clearly established. Twenty-six adolescents with IDDM and 34 healthy siblings underwent measurement of their overnight GH secretory profiles (20.00-08.00 hours, 15-minute sampling). The diabetic subjects were studied either on their normal insulin regimen (n = 15) or during a euglycaemic clamp (n = 26). A second clamp study was undertaken (n = 7) with addition of pirenzepine to suppress GH secretion. GH profiles in the diabetic subjects were characterized by increases in both pulse amplitude and baseline GH concentrations. Deconvolution analysis also revealed an increase in the frequency of GH secretory episodes. In the subjects with diabetes, a direct link between the dawn rise in insulin requirements, increased concentrations of beta-hydroxybutyrate and the elevated concentrations of GH was established. These abnormalities were reversed by the suppression of GH pulse amplitude following pirenzepine. Serum IGF-I concentrations and IGF-I bioactivity in the diabetic subjects were low and were positively correlated with mean GH concentrations. In conclusion, well controlled adolescents with IDDM show persisting abnormalities of GH, beta-hydroxybutyrate and IGF-I despite normoglycaemia. The role of inappropriate insulin delivery in the development of these abnormalities is discussed.

3-Hydroxybutyric Acid↗
PubMed1991

Reproducibility of 24-hour serum growth hormone profiles in man.

OBJECTIVE: To study the reproducibility of 24-h serum growth hormone (GH) concentration profiles in adults. DESIGN: 24-h serum GH concentrations were constructed by drawing blood samples at 20-min intervals. Four study occasions over a period of 1 year were chosen to assess the reproducibility. SUBJECTS: Six healthy adult male volunteers of normal height and weight and aged between 20 and 22 years. MEASURES: The resulting GH data arrays were analysed by Fourier transformation. Between and within individual variations were calculated and expressed in terms of coefficients of variation and data plotted to show variations between groups and individuals. RESULTS: The frequency component of GH secretion occurred with a dominant periodicity of between 160 and 240 min. Precise estimates of spectral power (strength of oscillatory activity) and period were obtained for group data, but such estimates cannot be inferred from a single profile. There was no significant difference in 24-h mean serum GH concentration over the year of study: occasion 1 (February) mean 2.0 mU/l (SD 0.5); occasion 2 (March) mean 3.7 mU/l (SD 2.8); occasion 3 (July) mean 2.7 mU/l (SD 1.4); occasion 4 (February) 2.5 mU/l (SD 1.5) (mean within individual coefficient of variation 35%, range 9-58). The concentrations of factors known to influence GH synthesis and secretion, insulin-like growth factor I, thyroxine, testosterone and oestradiol, varied little over the year of study. CONCLUSIONS: These data demonstrate that group data are reproducible in terms of oscillatory activity and the amount of GH secreted and that 24-h GH profiles should be used predominantly for analysing group data. The variability between individual profiles limits their value in the investigation of children with growth failure and suspected GH insufficiency.

Adult↗
PubMed1991

The pituitary gland is capable of responding to two successive doses of growth hormone releasing hormone (GHRH)

We have studied the serum growth hormone (GH) response to two consecutive doses of growth hormone releasing hormone (GHRH) (50, 100, 200 micrograms) given 1, 2 or 3 h apart in seven adult males. The serum GH profile was analysed by deconvulution incorporating a variable half-life for GH. All three doses of GHRH stimulated maximal GH secretion: 50 micrograms, 146.0 mU/min (SEM 24.0); 100 micrograms, 128.1 mU/min (SEM 14.3); 200 micrograms, 134.1 mU/min (SEM 20.5) (one-way ANOVA, P = NS). The magnitude of the second secretory burst after the second dose of GHRH was less than that induced by the first injection of GHRH, particularly when doses of 200 micrograms were used. Factors influencing the response to the second dose were the GH secretory status at the point that the stimulus was applied and the time interval between administration of the first and second doses. These studies demonstrate that the pituitary gland is capable of responding to two consecutive doses of GHRH although the second response is always less than the first. The data demonstrate the importance of using methods of assessing GH secretion and not relying simply on measured serum GH concentration values.

Adult↗
PubMed1991

A distribution method for analysing the baseline of pulsatile endocrine signals as exemplified by 24-hour growth hormone profiles.

OBJECTIVE: To develop a method for quantifying the distribution of concentrations present in hormone profiles, which would allow an observer-unbiased estimate of the time concentration attribute and to make an assessment of the baseline. DESIGN: The log-transformed concentrations (regardless of their temporal attribute) are sorted and allocated to class intervals. The number of observations in each interval are then determined and expressed as a percentage of the total number of samples drawn in the study period. The data may be displayed as a frequency distribution or as a cumulative distribution. Cumulative distributions may be plotted as sigmoidal ogives or can be transformed into discrete probabilities (linear probits), which are then linear, and amenable to regression analysis. Probability analysis gives estimates of the mean (the value below which 50% of the observed concentrations lie, which we term 'OC50'). 'Baseline' can be defined in terms of percentage occupancy--the 'Observed Concentration for 5%' (which we term 'OC5') which is the threshold at or below which the hormone concentrations are measured 5% of the time. PATIENTS: We report the use of applying this method to 24-hour growth hormone (GH) profiles from 63 children, 26 adults and one giant. RESULTS: We demonstrate that GH effects (growth or gigantism) in these groups are more related to the baseline OC5 concentration than peak concentration (OC5 +/- 95% confidence limits: adults 0.05 +/- 0.04, peak-height-velocity pubertal 0.39 +/- 0.22, giant 8.9 mU/l). CONCLUSIONS: Pulsatile hormone profiles can be analysed using this method in order to assess baseline and other concentration domains.

Circadian Rhythm↗
PubMed1991

Pattern of secretion of bioactive and immunoreactive gonadotrophins in normal pubertal children.

OBJECTIVE: The aim was to investigate the relationship between the nocturnal pulsatile secretory patterns of immunoreactive and bioactive luteinizing hormone in normal children at various stages of puberty. DESIGN: Blood samples were taken at 15-minute intervals from 2000 hours to 0800 hours. Pubertal stage was assessed by the method of Tanner (1962). PATIENTS: Thirty-four healthy siblings (17 males, 17 females) of diabetic children were recruited (median age 13.1, range 9.1-20.9 years). They were of normal height, non-obese, and covered the range of puberty. MEASUREMENTS: Follicle stimulating and luteinizing hormone levels were measured by radioimmunoassay in all 34 subjects; bioactive LH (B-LH) was assayed in a subgroup of 13 subjects selected to encompass the range of normal puberty. Oestradiol (girls) and testosterone (boys) were also measured at hourly intervals. RESULTS: Immunoreactive luteinizing and follicle stimulating hormone concentrations showed a progressive rise during puberty in both sexes. FSH concentrations were significantly higher in females than in males at all stages of puberty. Overnight mean bioactive luteinizing hormone concentrations were higher than immunoreactive luteinizing hormone levels in all the girls studied (n = 7). Although the number of bioactive luteinizing hormone pulses (31) was greater than immunoreactive pulses (27), the profiles were generally very similar. In the early pubertal girls an increase in the bioactive: immunoreactive ratio was observed during the middle of the night with the onset of pulsatility. Oestrogen was detected in the girls in breast stage 4-5 but not in two of the early pubertal girls, despite pulses of immunoreactive and bioactive luteinizing hormone. The boys had higher mean bioactive than immunoreactive luteinizing hormone levels and overall bioactive and immunoreactive luteinizing hormone and testosterone concentrations increased with puberty stage. Concordance between bioactive and immunoreactive hormone pulses was good although more immunoreactive pulses (16) were seen than bioactive pulses (14). As in the girls, an increase in the bioactive: immunoreactive ratio was observed in the middle of the night with the onset of pulsatility at genital stage 2 but, in contrast to the oestrogen data in the girls, testosterone secretion always followed luteinizing hormone pulsatility overnight. CONCLUSION: We conclude that mean overnight immunoreactive luteinizing and follicle stimulating hormone concentrations increase during puberty in both sexes. Bioactive luteinizing hormone levels are two to three times higher than immunoreactive luteinizing hormone in both sexes, but there is very little discordance between immunoreactive and bioactive luteinizing hormone pulsatility. The bioactive: immunoreactive ratio increases with the occurrence of pulsatility overnight in early pubertal children. The relationship between these changes in bioactive and immunoreactive luteinizing hormone and sex steroids is clearest in boys where the nocturnal testosterone rise always follows pulsatile LH secretion.

Adolescent↗
PubMed1991

The interaction of growth hormone releasing hormone and somatostatin in the generation of a GH pulse in man.

OBJECTIVE: To study the regulation of the growth hormone (GH) response to growth hormone releasing hormone (GHRH) in the presence or absence of somatostatin pretreatment. DESIGN: Seven healthy adult male volunteers of normal height and weight and aged between 19 and 29 years underwent four separate studies (each containing three cycles in one day) in random order. The studies were separated from each other by at least a week. On day 1, three consecutive cycles (between 0800 and 2000 hours) consisted each of a saline infusion for 3 hours which was stopped prior to a bolus injection of saline and followed by 60 minutes of more intensive blood sampling. On day 2, the bolus injections were of GHRH given after saline infusion. On days 3 and 4 somatostatin infusions were administered instead of saline over the 3-hour periods followed by bolus injections of saline or GHRH respectively. In all studies, samples were collected for the measurement of serum GH concentration at 15-minute intervals from time 0 to 180 minutes and then at 5-minute intervals for a further 60 minutes, this cycle being repeated three times. MEASUREMENTS: Serum GH concentrations were analysed by serial array averaging. RESULTS: Prompt release of GH was observed in response to GHRH given against a saline background (day 2, cycle 1) (mean at 60 minutes 49.2 +/- 14.7 mU/l) but the responses observed during the second and third cycles were attenuated (mean at 60 minutes 17.2 +/- 4.0 mU/l; P = 0.025). GH release between somatostatin infusions (somatostatin withdrawal; day 3) occurred twice as often as that observed during saline infusions (62% day 3: 29% day 1). The response, although qualitatively similar to that induced by GHRH, was reduced in amplitude and the time of onset variable (5-45 minutes). On day 4, the administration of GHRH as a bolus injection combined with somatostatin withdrawal led to consistent and repeatable GH responses (mean at 60 minutes, cycle 1, 39.7 +/- 10.8 mU/l; cycles 2 and 3, 37.4 +/- 9.4 mU/l) which were similar to those observed with GHRH alone (day 2, cycle 1) (mean 39.7 +/- 10.8 mU/l) (P = NS). CONCLUSIONS: These data suggest that endogenous somatostatin secretion is important in determining the ability of the somatotroph to respond to repeated growth hormone releasing hormone stimulation and that for regular GH pulse generation a close interplay between growth hormone releasing hormone and somatostatin is required.

Adult↗
PubMed1991

Capillary and venous blood glucose measurements using a direct glucose-sensing meter.

The aim of the study was to evaluate the precision and accuracy of the ExacTech home blood glucose meter when used with either capillary or venous blood and to compare this with a reference whole blood glucose assay. Non-fasting glucose measurements were used since a validation study showed no capillary-venous differences between fasting and post-prandial states. In a cross-sectional study, blood was taken from 182 patients and measured in duplicate on three batches of strips. Altogether we analysed 1089 readings. The regression of the data from capillary blood samples (meter vs reference method) had a correlation coefficient, of 0.93, and a mean bias of 0.2 mmol l-1. The corrected 90% confidence interval was +/- 1.5 mmol l-1 overall, and +/- 0.9 mmol l-1 for readings under 7.0 mmol l-1. Regression of the data from venous blood samples (meter vs reference method) had a correlation coefficient of 0.93 and a slope of x 1.1. The corrected 90% confidence interval was +/- 1.7 mmol l-1. Thus venous blood may be used even though the meter is calibrated for capillary samples but the value must be corrected by dividing by 1.1. Error-grid analysis showed that day-to-day clinical decisions could be made on the basis of ExacTech readings, although a diagnosis of borderline diabetes may not be possible.

Blood Glucose↗
PubMed1991

Evidence for temporal coupling of growth hormone, prolactin, LH and FSH pulsatility overnight during normal puberty.

The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00-08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9.1-20.9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization. The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150-180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30-75 min (r = 0.32; P less than 0.001) and 30 min (r = 0.47; P less than 0.0001) respectively. Generally, LH and prolactin pulses were in phase (r = 0.42; P less than 0.0001) and there was a highly significant correlation (r = 0.64; P less than 0.0001) between FSH and LH pulsatility. Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150-180 min was established and there was remarkable temporal coupling of pulsatility.

Adolescent↗