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Biomedical subjects

G F Read

Publications and source records attributed to G F Read.

At least 37 records · Page 2Linked to original sources

Potential value of salivary steroids in chronoepidemiological and endocrine-related studies.

Experience from Institute studies has clearly demonstrated the advantages of salivary steroids in clinical endocrinological research and their potential value in chronoepidemiological studies of many kinds that may involve hormones. Of course, the examples and suggestions for areas of research involve many more covariates than those mentioned; but sufficient evidence has been presented to indicate the chronobiological potential of salivary steroid assays in studies of mental health, aggression and behaviour, stress, the endocrine changes occurring from birth to old age and those relating to endocrine cancer. The pioneering studies of Halberg et al (1981) and Haus et al. (1987) have demonstrated the feasibility of carrying out international epidemiological studies as they relate to breast cancer risk and studies of the general population. The potential value of salivary steroid assays in clinical, physiological and epidemiological studies is judged to be considerable.

Chronobiology Phenomena↗

The pharmacokinetics of low-dose dexamethasone in congenital adrenal hyperplasia.

The pharmacokinetics of dexamethasone, given at low dose, were studied in 13 patients with congenital adrenal hyperplasia (CAH) to ascertain whether kinetics differed in this inherited disorder of cortisol metabolism from those seen in healthy individuals. Changes in plasma dexamethasone concentration after intravenous bolus, measured using a simple novel radioimmunoassay, were well described by a two-compartment open model with first-order kinetics. Values for lambda 2: 0.206 h-1, t1/2: 3.53 h, Vc: 24.41 and f: 0.64 were similar to those previously reported for normal subjects. There were considerable interindividual differences in parameter values and Cmaxp.o. (range 22-67 nmol/l). As suppression of the hypothalamo-pituitary-adrenal axis correlates with plasma dexamethasone levels, this variability may partly explain the differing dose and dose schedule requirements necessary to achieve adequate therapeutic control in the clinical management of CAH.

Administration, Oral↗

Salivary steroids and psychometric parameters in male marathon runners.

Testosterone and cortisol in male marathon runners (n = 11) were determined in saliva samples (n = 28) collected during the three rest days preceding a competitive marathon and in the samples collected at 08.00h on the race day. An Eysenck Personality Inventory was completed on the first rest day and psychological state was assessed on rest days and on the morning of the marathon by completion of visual analogue scales for anxiety, depression, hostility and libido at four times each day. Anxiety, depression and hostility were positively inter-correlated. Extraversion and depression were negatively correlated. At 08.00h on the day of the marathon, anxiety and hostility scores were significantly higher than those on rest days, but depression and libido scores were unchanged. No relationship was found between depression or libido and any hormonal parameter. Race day cortisol correlated negatively with hostility, and changes in cortisol (09.00h) between the race day and the mean rest-day levels correlated with the corresponding changes in anxiety.

Adult↗

Review of the endocrine actions of luteinising hormone-releasing hormone analogues in premenopausal women with breast cancer.

The endocrinological actions of the luteinising hormone-releasing hormone (LHRH) analogue, Zoladex (goserelin) in premenopausal women with advanced breast cancer are reviewed. LHRH analogues are an interesting addition to the currently available treatments for hormone-sensitive breast cancer in premenopausal women. Their modest side effects and ease of administration are in contrast to the risks and morbidity of surgical endocrine therapy.

Adult↗

Progesterone concentrations in samples of saliva from adolescent girls living in Britain and Thailand, two countries where women are at widely differing risk of breast cancer.

Menstrual-cycle patterns of salivary progesterone concentration were obtained for 131 and 245 adolescent girls up to 4 years postmenarche living in Britain and Thailand respectively. These patterns were graded on a scale of 1 (little or no activity) to 5 (activity similar to that exhibited by the mature premenopausal woman) and the frequency of these grades within groups of girls from each centre was analysed. The major finding was that British girls exhibited a predominance of higher grades of progesterone activity when compared with their Thai counterparts (n = 2 x 58) when matched for chronological and gynaecological ages (P approximately 0.002). This was particularly so for the girls from these two matched groups in the gynaecological age range 2-4 years (P approximately 0.03). The major contribution to this significant difference between the two groups is attributed to the greater effect of chronological age on progesterone secretion in the British girls (P approximately 0.03) compared with the Thai girls (P approximately 0.29). These findings may have implications for facilitating our understanding of the reason for the differing risk of breast cancer in women in both countries.

Adolescent↗

Non-insulin-dependent diabetic patients (NIDDMs) do not demonstrate the dawn phenomenon at presentation.

A dawn rise of plasma glucose (PG) and/or insulin, the 'dawn phenomenon', has been commonly reported in treated diabetic patients and normal subjects. To evaluate the effect of treatment on this phenomenon in non-insulin-dependent diabetics (NIDDMs), PG, C peptide, immunoreactive insulin (IRI), growth hormone (GH), cortisol, epinephrine, and norepinephrine were measured hourly between 24.00 and 09.00 h in 17 newly diagnosed untreated NIDDMs (group 1). The study was repeated in 11 patients after a year of treatment (group 2). The PG levels did not change significantly at any time from 03.00 to 08.00 h in group 1 but increased continuously from 6.7 +/- 0.5 mmol/l at 04.00 h to 7.8 +/- 0.5 mmol/l at 08.00 h (P less than 0.01) in group 2. IRI and C peptide decreased significantly after 07.00 h in both groups. GH and catecholamine changes were similar in group 1 and group 2. Cortisol levels showed a nadir at 02.00 h and a peak after 07.00 h in both groups. Our results demonstrate no dawn rise of mean PG, IRI and C peptide in newly diagnosed untreated NIDDMs but a significant rise of PG in the early morning period in NIDDMs after a year of treatment with diet alone and diet plus sulphonylureas. Therefore other factors such as treatment and/or duration of the diabetes may play an important role in the pathogenesis of the dawn phenomenon.

Blood Glucose↗

Anxiety and the dexamethasone suppression test monitored with saliva.

To assess the effect of anxiety on response to the Dexamethasone Suppression Test (DST), cortisol concentrations were determined in patients who had various diagnoses, with anxiety as a secondary characteristic. Saliva was collected before and after venepuncture at 4:05 PM following completion of the Leeds Questionnaire at 3:00 PM. Matrix effects, which caused an initial artefactual decrease in cortisol levels in some saliva samples in patients with high anxiety, could be eliminated by repeated freezing/thawing. There was no significant difference between salivary cortisol concentrations before and after venepuncture, indicating that variability in response to the DST is not a correlate of anxiety and stressful venepuncture. There was no association between anxiety scores and plasma or salivary cortisol values: thus, anxiety is unlikely to be a major contributory cause of nonsuppression of hypercortisolemia in the DST.

Adult↗

Endocrine basis for the clinical presentation of hidradenitis suppurativa.

Clinical assessment of 134 patients with hidradenitis suppurativa revealed clinical evidence supporting an androgen-based endocrine disorder underlying the condition. Such features included postpubertal onset maximal during the third decade; female preponderance (13:5); premenstrual flare in 57 per cent of women; absence of this flare associated with irregular or anovulatory menstrual cycles; and an increased incidence of obesity and acne. Detailed hormone profiles in 36 female patients and 14 controls showed evidence of relative androgen excess and decreased progesterone levels in those patients without a premenstrual flare. Obesity and enhanced peripheral androgen conversion by apocrine tissue are possible explanations for normal serum androgen profiles in patients with a flare. Precise elucidation of the hormonal abnormality is a prerequisite for effective medical treatment of early disease.

Age Factors↗

170H-progesterone rhythms in congenital adrenal hyperplasia.

Serial blood spot and saliva samples were collected at home by 18 patients being treated for congenital adrenal hyperplasia to determine the circadian rhythm of 170H-progesterone as an index of therapeutic control. There was a strong correlation between the magnitude of the circadian fall and a single morning measurement of the plasma testosterone concentration taken near the time of the 170H-progesterone rhythm samples. Poor control in pubertal girls produced an exaggerated circadian fall in 170H-progesterone concentrations that were raised at all sampling times. Optimal control (plasma testosterone 1.5-2.5 nmol/l) was associated with blood spot and salivary 170H-progesterone concentrations at 0800 hours of between 30-70 nmol/l and 260-1000 pmol/l, respectively, falling thereafter to less than 10 nmol/l and less than 150 pmol/l, respectively. Similar results were obtained in prepubertal patients. Nomograms have been constructed to interpret the daily profiles of blood spot or salivary measurements of 170H-progesterone, or both. The analysis of 170H-progesterone circadian rhythms is useful in monitoring treatment in patients with congenital adrenal hyperplasia, particularly those who may be overtreated.

17-alpha-Hydroxyprogesterone↗

Salivary cortisol for monitoring adrenal activity during marathon runs.

In non-elite male runners (n = 8), changes in adrenal activity were monitored by measurement of salivary cortisol in samples collected at 4-mile intervals during marathon runs. These changes were compared with those in similarly timed samples collected on rest days. Immediately prior to the Cardiff marathon, at 09.00 h, mean salivary cortisol concentrations (21.5 nmol/l) were higher than those in similarly timed rest day samples (14.9 nmol/l). Cortisol concentrations increased during the marathon, and although values at 25 miles were high (79.4 nmol/l), maximum values (87.9 nmol/l) were observed in samples collected 30 min after completion of the run. Some Cardiff marathon runners also participated in the Bristol marathon (n = 4) and a non-competitive event (n = 3). The changing pattern in secretory activity was similar in all events. The easy collection of saliva without cessation of exercise is ideal for monitoring the hormonal response to exercise.

Adrenal Cortex↗

Determination of ovarian steroid hormone levels in saliva. An overview.

Assessment of ovarian activity based on saliva samples has proven particularly useful in studies of women in well-developed countries and is potentially of even greater value in women of lower socioeconomic status in Third World countries. Assay techniques suitable for measuring low concentrations of steroids in saliva have become available only recently, so data derived from salivary sampling regimens are far less extensive than those based on plasma or urinary sampling procedures. Collecting saliva is an attractive alternative to the more conventional procedures because of the ease of frequent collection and freedom from religious and social constraints. Simple, direct assays for salivary progesterone have been established, but those for estradiol require considerably more research before becoming useful in routine practice. Predicting ovulation with data derived from saliva sampling awaits the development of more suitable assays for salivary estradiol.

Estradiol↗

Daily salivary progesterone levels in cyclical mastalgia patients and their controls.

Progesterone levels were measured in samples of saliva collected daily throughout the menstrual cycle in patients with pronounced cyclical mastalgia and breast nodularity. A control group matched for age, length of menstrual cycle and parity was also studied. No significant differences in progesterone levels were detected between the two groups for the luteal phase of the cycle. These data indicate that cyclical mastalgia is not associated with significant luteal phase progesterone insufficiency, as demonstrated by salivary levels and, by implication, serum levels of progesterone.

Adult↗

Changes in adrenal and testicular activity monitored by salivary sampling in males throughout marathon runs.

Measurement of cortisol and testosterone in saliva samples provided by marathon runners at 6.4 km (4-mile) intervals has been used for monitoring acute changes in adrenal and testicular activity, and the changes compared with mean values in timed samples on five rest days. The collection of mixed whole saliva was well accepted; the missed sample rate in the 8 runners in the Cardiff marathon was less than 10%. On rest days, salivary cortisol and testosterone were within the normal male range and showed a circadian rhythm; mean values at 08.00 h (23.5 nmol L-1; 258 pmol L-1, p less than 0.001, p less than 0.001 respectively) were higher than at 22.00 h (2.8 nmol L-1; 130 pmol L-1). In samples collected at 09.00 h, immediately prior to the Cardiff marathon, cortisol (25.1 nmol L-1) and testosterone (304 pmol L-1) were higher than the mean values (14.9 nmol L-1; 209 pmol L-1) on non-run days. Concentrations of both steroids increased during the marathon; testosterone peaked (442 pmol L-1) at 21 miles, whereas cortisol continued to increase, being maximal (87.9 nmol L-1) at 30 min after completion of the run. Four of the runners in the Cardiff marathon also participated in the Bristol marathon and the changing patterns in salivary hormones were strictly comparable. Salivary sampling would appear to be of value in monitoring acute and rhythmic changes in endocrine function in marathon runners. The temporal relationship between changes in salivary cortisol and testosterone are consistent with direct inhibition of testicular secretion by high cortisol concentrations.

Adrenal Glands↗

Transient increases in progesterone in daily and 2-hourly saliva specimens from adolescent girls.

Daily progesterone profiles obtained from saliva specimens from 101 peri- and postmenarcheal girls showed episodic 'spikes' which reached up to 600 pmol/l from baselines of approximately 40 pmol/l. The authenticity of progesterone in the 'spike' specimens was established using gas chromatography-mass spectrometry. 'Spikes' of progesterone occurred in 5.3% of premenarcheal saliva specimens but in only 1-2% of specimens from girls who were 4-6 years postmenarche. Two-hourly specimens from 53 pre- and postmenarcheal girls had 'spike' frequencies similar to those measured in daily specimens.

Adolescent↗

Sub-hourly variations in salivary estriol concentrations in the last trimester of pregnancy.

Sub-hourly variations in salivary estriol were measured in women in the last trimester of pregnancy. The mean and variation of salivary estriol concentrations in specimens collected at 5-min intervals for 30 min were greater on awakening in the morning (when subjects were recumbent and fasting) than in the afternoon. The differences in variation between morning and afternoon serial specimens were eliminated by the omission of the first two specimens collected in the morning. Significant differences between the mean concentrations obtained for morning and afternoon specimens were minimized by use of a recumbent posture for the afternoon specimen collection. The mean estriol concentration of four saliva samples collected at 5-min intervals for 15 min did not differ significantly from the concentration of saliva collected continuously over the subsequent 15 min. For routine estriol monitoring, therefore, samples should be collected over a 15-min period. This ought to be carried out at the same time of day, in the same posture on each occasion, but preferably not in the early morning.

Circadian Rhythm↗