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Biomedical subjects

G F Read

Publications and source records attributed to G F Read.

At least 19 recordsLinked to original sources
PubMed1997

Longer term outcome in females with congenital adrenal hyperplasia (CAH): the Cardiff experience.

OBJECTIVE: The outlook for fertility and attaining full adult height is poor in women with congenital adrenal hyperplasia. Such outcomes have followed treatment regimes with variable ages at onset, compliance rates and monitoring. We review final height, vaginal anatomy, ovulation rates and fertility in a group of adult females with the disease. DESIGN AND PATIENTS: Sixteen adult females first diagnosed in infancy or early childhood were reviewed (age range 17-33 years; 11 with salt-wasting disease; five with simple virilizing disease). Case note and clinical review were combined with daily saliva progesterone and weekend 17-hydroxyprogesterone estimation in three consecutive menstrual cycles in a subgroup of eight patients in the ovulation study. MEASUREMENTS AND ANALYSIS: Daily saliva progesterone concentrations were transformed into a cumulative sum curve using a computer program. T95 (defined as the number of days from the start of the luteal phase saliva progesterone rise, in which 95% of total saliva progesterone for the menstrual cycle was obtained) and log C95 (where C95 was defined as 95% of total saliva progesterone for the same cycle) were plotted for each cycle on a boundary diagram obtained from a normal reference population. Weekend saliva 17-hydroxyprogesterone concentrations were compared with published nomograms. RESULTS: The majority of patients attained a final height below the parental target. Mean standard deviation scores (+/-SEM) and ranges were -1.49 (+/-0.34) and -4.2 to 0.8 for the patients and -0.38 (+/-0.24) and -1.89 to 0.97 for their parents. Of the combined group two-thirds had regular menses and one-third hirsutism; 94% had reconstructive genital surgery with 50% requiring second procedures; 77% had an adequate vaginal introitus (of them 84% in the salt-wasting group and 75% in the simple virilizing group were sexually active). Three of five patients with salt-wasting disease and 2/3 with simple virilizing disease who had both an adequate introitus and were sexually active conceived, resulting in eight pregnancies. In the ovulation study, a 40% ovulation rate was observed with good correlation between plasma testosterone concentrations and degree of control as assessed by weekend 17-hydroxyprogesterone concentrations. CONCLUSIONS: Our study highlights the potential for improved fertility in female patients with congenital adrenal hyperplasia, who are treated early, comply with long-term treatment and have adequately reconstructed external genitalia. Attaining full adult height potential remains a problem.

17-alpha-Hydroxyprogesterone↗
PubMed1996

The pharmacokinetics of oral and intramuscular administration of dexamethasone in late pregnancy.

BACKGROUND: To compare the pharmacokinetics of orally administered dexamethasone with intramuscular administration in antenatal patients at risk of preterm delivery. METHOD: Ten antenatal patients at risk for preterm delivery were given two intramuscular and then one oral dose of dexamethasone. Plasma which was collected at set intervals following the first intramuscular dose and the oral dose was assayed for dexamenthasone. The results were analyzed using pharmacokinetic data-fitting software and pharMacokinetic parameters calculated. RESULTS: After oral adminIstration of dexamethasone the mean maximum plasma concentration obtained was 65% that of the intramuscular dose and the bioavailability of the oral route was calculated as 72% of the intramuscular route. The terminal half-lives of dexamethasone were similar for both routes. CONCLUSIONS: These limited data would suggest that if dexamethasone is to be administered orally, which would be both preferable to patients and more economic, then a proportionately increased dose of oral dexamethasone would be required to provide similar maternal plasma pharmacokinetics to the intramuscular dose in current use. Further, larger studies are now required to confirm this.

Administration, Oral↗
PubMed1995

Reliability of salivary testosterone measurements: a multicenter evaluation.

The reliability of salivary testosterone assays was evaluated by nine laboratories in four countries. Each laboratory used its own RIA procedures to assay samples from a set of 100 male and 100 female subjects. Agreement among the laboratories on mean scores was within the range reported by Read (Ann N Y Acad Sci 1993; 694: 161-76). Overall agreement on individual scores, as indicated by the intraclass correlation coefficient computed within subjects across laboratories, was r = 0.87 for men and r = 0.78 for women. Mean agreement between each laboratory and the combined set of all other laboratories (via Fisher's Z-transformation) was r = 0.61 for men and r = 0.58 for women. We take these latter values to be the best estimates of the average reliability of laboratories in their ordering of individual samples.

Female↗
PubMed1995

Oestradiol measurement in women on oral hormone replacement therapy: the validity of commercial test kits.

Four commercially available methods for the measurement of oestradiol were used to assay oestradiol concentrations in samples from women receiving oral hormone replacement therapy. Significant differences in results were found between samples that were measured direct and those subjected to an extraction procedure. There was considerable variability in the extraction: direct ratio between methods, indicating that with some methods an extraction procedure should be performed before analysis on samples from women receiving oral hormone replacement therapy. Factors that account for discrepant results between methods probably include increased concentration of sex hormone binding globulin together with cross-reacting metabolites and conjugates.

Administration, Oral↗
PubMed1994

Maternity blues and major endocrine changes: Cardiff puerperal mood and hormone study II.

OBJECTIVES: To define relation between mood and concentrations of progesterone and cortisol during perinatal period to test hypothesis that rapid physiological withdrawal of steroid hormones after delivery is associated with depression. DESIGN: Prospective study of primiparous women from two weeks before expected date of delivery to 35 days postpartum. SETTING: Antenatal clinic in university hospital, obstetric inpatient unit, patients' homes. SUBJECTS: 120 of 156 primiparous women interviewed. Remainder excluded because of major marital, socioeconomic, or medical problems or because caesarean section required. MAIN OUTCOME MEASURES: Concentrations of progesterone and cortisol in saliva samples; women's moods assessed by various scores for depression. RESULTS: Changes in salivary progesterone and cortisol concentrations were similar to those already characterised for plasma. Peak mean score for maternity blues (5.3 on Stein scale) was on day five postpartum (P < 0.02 compared with mean scores on other postpartum days). High postpartum scores for maternity blues were associated with high antenatal progesterone concentrations on day before delivery (P < 0.05), with high rate of rise of antenatal progesterone concentrations (P < 0.05), with decreasing progesterone concentrations from day of delivery to day of peak blues score (P > or = 0.01), and with low progesterone concentrations on day of peak blues score (P < 0.01). Seventy eight women were designated as having maternity blues (peak score > or = 8 on Stein scale) while 39 had no blues. Women with blues had significantly higher antenatal progesterone concentrations and lower postnatal concentrations than women without blues (geometric mean progesterone concentrations: one day before delivery 3860 pmol/l v 3210 pmol/l respectively, P = 0.03; ten days postpartum 88 pmol/l v 114 pmol/l, P = 0.048). Cortisol concentrations were not significantly associated with mood. CONCLUSION: Maternal mood in the days immediately after delivery is related to withdrawal of naturally occurring progesterone.

Adult↗
PubMed1994

Testosterone levels during systemic and inhaled corticosteroid therapy.

Testosterone has importance both as a sex hormone and as an anabolic steroid promoting bone formation. Osteoporosis is associated with both hypogonadism and corticosteroid therapy. Testosterone levels are reduced by long term prednisolone treatment. Although high dose inhaled corticosteroid therapy may cause a variety of systemic effects including adrenal suppression, dermal thinning and a reduction in total bone calcium, its effect on testosterone levels is not known. Testosterone, luteinizing hormone, follicle stimulating hormone and sex hormone binding globulin were therefore measured in 35 male patients with respiratory disease attending an outpatient clinic (median age 58, range 21-75 years). They were grouped according to steroid therapy and compared with 19 age matched controls. Mean (SD) testosterone levels were 33% lower in 12 men on long term oral prednisolone [14.5 (6.0) nmol 1-1] than in controls [21.7 (6.3) nmol 1-1], but were not significantly reduced in 10 patients on low dose inhaled beclomethasone [200-800 micrograms day-1: 19.7 (3.7)] nor in 13 men taking high dose inhaled beclomethasone [1500-2,250 micrograms day-1: 17.9 (5.6)]. Levels of luteinizing hormone, follicle stimulating hormone and sex hormone binding globulin were similar in all four groups. These cross sectional data confirm that long term systemic corticosteroid therapy reduces testosterone levels. However, testosterone was reduced by only 18% (NS) by long term inhaled corticosteroids. Other mechanisms to explain the disordered bone metabolism should now be explored.

Administration, Inhalation↗
PubMed1993

Cardiff puerperal mood and hormone study. 1. Saliva steroid hormone profiles in late pregnancy and the puerperium: endocrine factors and parturition.

Participants were 120 primiparous women who had vaginal delivery of a non-handicapped child. Saliva was collected twice daily through parturition to day 35 post-partum. In the prepartum, a highly significant circadian rhythm was seen in cortisol, with a lower-amplitude rhythm in progesterone (AM/PM = 1.12). Evening samples showed a rise in cortisol, with a highly significant rise on day -1. The rise was small. The fall in progesterone in the 3 days before parturition was also small (approximately 6%). Neither change provides an obvious trigger for parturition.

Adolescent↗
PubMed1992

A comparison of menstrual cycle profiles of salivary progesterone in British and Thai adolescent girls.

Menstrual-cycle profiles of salivary progesterone concentration, obtained by radioimmunoassay of daily samples collected throughout the cycle, were obtained from Thai (n = 232) and British (n = 130) adolescent girls up to 4 years postmenarche. These profiles were graded from 1 to 5 ranging, respectively from concentrations at the detection limit of the assay to profiles generally observed for the mature premenopausal woman. Contingency table analysis of the grade frequencies for Thai-British pairs of girls matched for chronological age and age at menarche (n = 2 x 90) demonstrated that British girls had more mature cycles (22/90) than Thais (11/90) (P less than 0.05) particularly in the first 2 years postmenarche (P less than 0.01). For these matched pairs of girls there was no evidence to support the view that girls with an early age of menarche develop their profiles more quickly following menarche than those with a late age of menarche, as previously reported and which was thought to be important in the development of breast cancer. The findings of this study also suggest that adolescent girls in Britain develop their menstrual cycle profiles of salivary progesterone more quickly than their Thai counterparts and this may be of value in formulating hypotheses regarding any role that ovarian progesterone secretion may have on subsequent breast cancer risk.

Adolescent↗
PubMed1990

Comparisons of plasma and salivary cortisol determinations for the diagnostic efficacy of the dexamethasone suppression test.

The current status of the saliva dexamethasone suppression test (DST) is discussed and results from the literature reviewed. Evidence is presented that demonstrates that the efficacy of the salivary-based test is equal to that of the plasma DST provided that specifically developed radioimmunoassays are used for determination of salivary cortisol. Such evidence relied on measurement of cortisol in 300 matched samples of plasma and saliva provided by patients admitted to a routine psychiatric ward over a 2-year period. The results according to diagnosis (DSM-III categories) were in line with those generally reported. The influence of anticholinergic medication was examined: this had no significant effects on the performance of the plasma or salivary-based DST.

Depressive Disorder↗
PubMed1990

A robust assay for dexamethasone in plasma using a heterologous 125I radioligand and a magnetizable solid-phase antiserum.

An assay using an antiserum raised against a dexamethasone 21-hemisuccinate conjugate and the heterologous radioligand dexamethasone 21-(carboxymethyl) ether was developed, validated, and used to study the pharmacokinetics of this steroid for 12 h following administration to patients with congenital adrenal hyperplasia. Coupling the antiserum to magnetizable cellulose allowed rapid separation of bound/free steroid. A C-21 rather than a C-3 antiserum was used to minimize interference with a main metabolite, 6 beta-hydroxydexamethasone. Close correspondence of assay (0.35 nmol/L) and curve (0.25 nmol/L) sensitivities suggests that interference by matrix effects is minimal. This was confirmed by good agreement in data from the in-house assay and that of a reference procedure. Good precision was demonstrated by the precision profile and Shewhart chart quality control data. The latter also demonstrated the assay was robust and reliable in routine practice.

Adolescent↗
PubMed1990

Chronobiology in laboratory medicine: principles and clinical applications illustrated from measurements of neutral steroids in saliva.

A number of chronobiological principles, as they pertain to the practice of laboratory medicine, have been discussed. Without doubt, salivary steroid assays are valuable tools for use in clinical studies, not necessarily as a single time-qualified sample but more often as a series of samples that will describe the underlying endocrinological time-structure. It is also important to appreciate that melatonin, certain drugs, and many dietary constituents such as phyto-oestrogens, are among the myriad of substances that can be monitored, and so hold great promise for the chronobiologist interested in the use of saliva as a sampling medium, both in the present and in the future.

Adrenal Glands↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗