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Biomedical subjects

G Phillipou

Publications and source records attributed to G Phillipou.

At least 55 records · Page 3Linked to original sources

Urinary steroid metabolites and the overgrowth of lean and fat tissues in obese girls.

Studies were made of steroid metabolites excreted in the urine of 17 obese girls 11.4 to 16.8 yr and 17 normal girls 11 to 17 yr. Creatinine excretion (muscle mass), total body water (or deuterium space), lean body mass and body fat were determined in the obese girls. Extracellular volume (corrected bromide space) was also measured and by difference with body water, intracellular water or soft tissue cell mass was calculated. In normal girls 24-h creatinine excretion was determined, but body water was predicted from height and weight. It was found, as in previous studies, that the obese girls had excess muscle mass and soft tissue cell mass for height. The excess growth of muscle, lean tissue, and body length in obese girls correlated with increments in oxosteroid (17 ketosteroid) excretion. The overall weight increase correlated with increased excretion of corticosteroid metabolites--a finding of interest since a physiological Cushing's syndrome was postulated for fat girls many years ago. When the normal and obese girls were divided by age at 14 yr and the subgroups compared (normal obese) the younger girls showed differences with respect to height, weight, total body water, fat and percentage fat. Differences in steroid metabolites were not found. In older girls the same findings were made again, but here it was clear that the increments in body size, particularly muscle mass, correlated with augmented oxosteroid excretion. Evidence is cited that these findings are not just related to a larger steroid pool in obese girls.

17-Ketosteroids↗

Aminoglutethimide therapy in advanced breast cancer.

Aminoglutethimide inhibited adrenal steroid synthesis, as assessed by serial estimations of plasma dehydroepiandrosterone sulphate in ten patients with advanced breast cancer. There was a favourable response in seven out of the ten patients, and in four there was an objective remission using UICC criteria. Favourable responses were more common in patients who had shown similar responses to previous endocrine therapy, especially a response to tamoxifen. Side effects were mild: two patients exhibited a drug sensitivity reaction, but neither required cessation of therapy. Adrenal suppression by aminoglutethimide is effective and well tolerated, and is therefore preferable to surgical adrenalectomy in the treatment of advanced breast cancer.

Adult↗

Measurement of plasma progesterone and its O-methyloxime by gas chromatography-nitrogen detection.

A routine method for the quantitation of plasma progesterone, using only 1 ml of sample, has been developed based on gas chromatography-nitrogen detection of the O-methyloxime derivative. Simple solvent extraction of progesterone from plasma using cyclohexane as solvent and medrogestone as internal standard allows measurement at the 3 nmol/l level, while the coefficient of variation at 16, 64, and 127 nmol/l progesterone is 14, 7.5, and 6.5% respectively. Comparison with a radioimmunoassay gave a linear regression equation of Y = 0.84x + 1.4, Syx = 7.8, r = 0.9255 (n = 55).

Chromatography, Gas↗

The role of the pineal gland in seasonality.

The life time reproductive performance of 2 flocks of Merino crossbred ewes pinealectomized at 7-60 days of age, and maintained in South Australia did not differ from that of sham-operated control animals kept in the same flocks. The pineal gland is therefore not a major determinant of reproductive success, but a role for the pineal in adjusting breeding activity to season is not excluded. It was confirmed that pineal denervation of adult ewes by cranial sympathectomy could have disruptive effects and evidence of a seasonal change in pineal function was obtained from studies of plasma levels of melatonin, a putative pineal hormone, and a pineal peptide with gonadotrophin releasing activity. That melatonin stems mainly, but not exclusively, from the pineal gland was confirmed by studies of urinary excretion values. Adult Merino ewes produced 39-90 micrograms melatonin/day, mostly (80%) during the dark period, whereas pinealectomized animals produced less than one-fifth this amount. A link was provided between the pineal gland and diet. Melatonin and other 5-methoxyindoles influenced the activity of alpha-chymotrypsin and may regulate the availability of precursor substances required for the synthesis of neurotransmitters important in reproduction.

Animals↗

Specific quantitation of plasma medroxyprogesterone acetate by gas chromatography/mass spectrometry.

Investigation of various derivatives (O-methyloxime, trifluoroenol acetate and t-butyldimethylsilyl enol ether) coupled with the efficient preparation of a trideuterated analogue of medroxyprogesterone acetate, has allowed the development of a rapid and accurate assay for its quantitation in plasma by isotope dilution gas chromatography/mass spectrometry. High oral doses (2.8 g weekly) of medroxyprogesterone acetate are shown to lead consistently to plasma levels of less than 16 ng.ml-1.

Cholesterol↗

Specific quantitation of urinary 6-hydroxymelatonin sulphate by gas chromatography mass spectrometry.

6-Hydroxymelatonin sulphate, a unique urinary metabolite of melatonin, has been measured in human subjects for the first time using a chromatography mass spectrometry and an isotope labelled internal standard. Urinary levels in both males and females were similar and ranged from 25-125 nmol 24 h-1. A significant nocturnal elevations of 6-hydroxymelatonin sulphate was also established in a male subject.

Deuterium↗

Capillary gas chromatographic measurement of neutral urinary steroids: evaluation and comparison with alternative methodology.

The major neutral urinary steroids have been quantitated by capillary gas chromatography and the reproducibility and accuracy of the method have been fully evaluated. Typical intra- and inter-assay coefficients of variation for individual steroids ranged from 4.9 to 10.1% and from 15.6 to 21.5%, respectively. Comparison of steroid values with alternate and commonly employed procedures for measuring urinary 17-oxosteroids, total 17-oxogenic steroids, and cortisol and plasma dehydroepiandrosterone-sulphate yielded correlation coefficients between 0.71 and 0.79. A definite relationship between serum cortisol and urinary trihydroxy-pregnanedione was also shown. Urinary androstenedione metabolites, however, could not be significantly (P greater than 0.05) correlated with the normalised androgen ratio in plasma.

17-Hydroxycorticosteroids↗

Measurement of urinary production rates of melatonin as an index of human pineal function.

The urinary production rate of melatonin has been estimated for two male subjects at approximately 30 micrograms per 24 h by measurement of the specific incorporation of deuterium label into 6-hydroxy melatonin sulphate following administration of deuterium-labelled melatonin as an isotopic tracer. No pharmacological effect due to the tracer was apparent on endogenous melatonin secretion and the production rates calculated were unaffected by either dosage or time of administration. It is, therefore, concluded that the use of deuterium-labelled melatonin coupled with quantitative gas chromatography-mass spectrometry offers a practical procedure for providing a clinically useful index of melatonin production in man.

Adult↗

Prenatal diagnosis of placental sulphatase deficiency.

A gas chromatographic procedure for the quantitation of neutral steroid sulphates in maternal urine and its application to a suspected case of placental sulphatase deficiency is described. Low levels of oestriol coincident with elevated 16-hydroxylated metabolites of dehydroepiandrosterone in the maternal urine are shown to occur in this particular condition, and thus provide a convenient differentiation from fetal adrenal hypoplasia before birth.

Androstenediols↗

Derivatisation of steroid hormones with t-butyldimethylsilyl imidazole.

An efficient procedure for the derivatisation of hydroxyl and alpha,beta-unsaturated ketonic steroids using t-butyldimethylsilyl imidazole is described. The conditions which employ potassium acetate as a basic catalyst result in quantitative formation of BDMS ethers and greater than 96% yield of BDMS-enol ethers. Various mechanisms involving the catalysed and uncatalysed reactions of t-butyldimethylsilyl imidazole with alcohols and enols are also discussed. The mass spectra of the BDMS-enol ethers, in contrast to the BDMS ethers, are dominated by an intense molecular ion, which facilitates the quantitation of these derivatives in biological samples. An example of the method is shown by the determination of 4-androstene-3,17-dione in urine using a stable-isotope internal standard.

Catalysis↗