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Biomedical subjects

G Holder

Publications and source records attributed to G Holder.

At least 37 records · Page 2Linked to original sources
PubMed1986

Pharmacokinetic and endocrinological parameters of a slow-release depot preparation of the GnRH analogue ICI 118630 (zoladex) compared with a subcutaneous bolus and continuous subcutaneous infusion of the same drug in patients with prostatic cancer.

Seventeen patients with advanced prostatic cancer were treated with the gonadotrophin-releasing hormone analogue DSer (tBU)6 AzaGly 10 GnRH (ICI 118630), either as a constant SC infusion, or in the form of a monthly SC slowrelease depot formulation, in which case patients were randomised to receive one of three doses. Six of these patients also received a 250-microgram SC bolus of ICI 118630, for pharmacokinetic studies, before starting the infusion or the depot. Drug levels were measured using a double-antibody radioimmunoassay. In contrast to the SC infusion, which gave a smooth serum 118630 level profile, drug release from the depot preparation was not constant, levels varying in a predictable manner throughout each 28-day period, reaching a peak proportional to the dose of ICI 118630 received, between days 15 and 18 of each cycle. With all methods of administration there was an initial rise in LH, usually followed by a rise in testosterone, after which the SC infusion and the depot were both effective in reducing serum LH to basal levels and testosterone into the castrate range within 1 month. It is too early to make any assessment of clinical response; however, depot treatment was well tolerated: Four patients experienced an initial flare in bone pain, probably related to the initial rise in testosterone, and twelve patients experienced flushing; one patient with pre-existing hydronephrosis and hydroureter developed renal failure, possibly related to a tumour flare reaction. No patients have experienced cardiovascular side effects or local reaction.

Buserelin↗
PubMed1985

Hormonal studies in women with premenstrual tension.

Serum hormone concentrations were determined at intervals during the last 17 days of the menstrual cycle in 35 patients with premenstrual tension (PMT) and 11 control subjects without symptoms. The maximum mean concentration of oestradiol occurred 17 days before menstruation in the patients and 14 days before in the controls. The maximum concentrations of progesterone were similar in the two groups but the mean concentrations rose earlier in the cycle in the patients with PMT. These results suggested that the patients tended to ovulate earlier in the cycle than the controls and on the basis of the ovulatory surge in gonadotrophins two groups could be identified, group A who showed signs of ovulation 14 days or less before menstruation (17 patients, 9 controls) and group B who ovulated more than 14 days before menstruation (18 patients, 2 controls). There were no significant differences between the groups in prolactin, thyroid stimulating hormone or testosterone levels, but cortisol concentrations were uniformly higher in both groups of patients compared with those in the controls. Follicular growth was assessed with ultrasound in 18 patients and 16 control subjects. Mean follicular diameters were significantly lower in the patients than in the control group at the time of ovulation. Oestradiol determinations done at the same time correlated with the diameters and were also significantly lower in the patient group. The results suggest that ovulation tends to occur prematurely in women with PMT.

Adult↗
PubMed1984

An enhanced chemiluminescence enzyme immunoassay for serum progesterone.

A competitive enhanced luminescent enzyme immunoassay for serum progesterone is described, which is based on a 11 alpha-hydroxyprogesterone 11-hemisuccinyl-horseradish peroxidase conjugate and a black polystyrene microtitre plate sensitised with anti-progesterone IgG. Bound label was determined using a mixture of 4-iodophenol, luminol and peroxide, and the light emitted from the wells of the plate quantitated using a luminescent plate reader. The assay was sensitive (detection limit 0.5 pg), precise (CV 2.7 - 9.0% in the concentration range 4.3-67.7 nM) and showed good correlation (r = 0.99) with a conventional radioimmunoassay.

Horseradish Peroxidase↗
PubMed1984

Plasma renin activity in the management of congenital adrenal hyperplasia.

Fourteen children with salt losing and five children with non-salt losing congenital adrenal hyperplasia were studied. Venous samples were collected for measurement of plasma renin activity, serum 17 alpha-hydroxyprogesterone, testosterone, sodium, and creatinine. Overnight urinary sodium and creatinine excretions were measured after collection on an outpatient basis. Eight 'salt losers' had a raised plasma renin activity despite mineralocorticoid treatment, as did one 'non-salt loser'. Six of the children in whom clinical and biochemical control was inadequate, including the 'non-salt loser', had an increase in the dose of fludrocortisone. When the investigations were repeated one month later, a fall in plasma renin activity accompanied by a fall in 17 alpha-hydroxyprogesterone in all but one patient were found. The dose of mineralocorticoid may be as critical as the dose of glucocorticoid in the management of congenital adrenal hyperplasia, and regular determination of plasma renin activity should be made, particularly if clinical control is difficult.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Oedipism reviewed: a case of bilateral ocular self-mutilation.

A 26-year-old Negro male schizophrenic is described with severe bilateral orbital injuries following attempted self-enucleation. Owing to his psychosis there was difficulty in obtaining a visual acuity and in establishing the cause of his fixed, dilated pupils. ACT scan showed bilateral orbital oedema, with surgical emphysema and haemorrhage. The visual evoked potential (VEP) was present in the right eye but absent in the left. High doses of systemic steroids effected rapid resolution of the orbital swelling and recovery of the vision in the right eye. The effects of self-inflicted injury to the orbital content and the value of sophisticated investigation in this unusual case are discussed.

Adult↗
PubMed1983

Acth function in women with the polycystic ovarian syndrome.

Serum androgen levels, including dehydroepiandrosterone sulphate (DHAS) which is thought to be solely of adrenal origin, are elevated in women with the polycystic ovarian syndrome. We have investigated the possibility that this may be due to a mild form of congenital adrenal hyperplasia by measuring basal and stimulated levels of ACTH in women with this condition and have compared them to levels in normal women. We found no difference in the diurnal rhythm of ACTH between patients and normal subjects nor any difference in stimulated levels achieved after a single-dose oral metyrapone test. Thus there is no evidence from this study to support the idea that these patients might have congenital adrenal hyperplasia. There are two alternative hypotheses to explain the elevated DHAS levels. They may be associated with the high oestrogen levels, which interfere with the enzyme 3 beta-hydroxysteroid dehydrogenase, or there may be alteration of the factors controlling adrenal androgen secretion.

Adolescent↗
PubMed1981

Congenital adrenal hyperplasia in a 66-year-old female.

A 66-year-old genotypically female patient was reared as a man. Investigations showed a partial adrenal 21-hydroxylase deficiency, and pituitary gonadotrophin secretion typical of a post-menopausal woman.

Adrenal Hyperplasia, Congenital↗
PubMed1978

Parallel competitive binding and metabolic endpoint assays for hCG based on rabbit granulosa cells.

A competitive binding assay for hCG is described, in which live rabbit granulosa cells adhering to small tubes provide solid-phase binding sites. Parallel assays, in which the synthesis of progestagens and the incorporation of [3H]acetate into lipid serve as endpoints, are also described. The assays are sensitive, reproducible and precise and should be both economical and convenient for studies on the relationship between the molecular structure and the biological activity of hCG and LH.

Acetates↗
PubMed1977

Hormonal effects of tamoxifen in oligospermic men.

The hormonal effects of tamoxifen (10 mg daily for 6 months) have been studied in nine men with oligospermia. Basal concentrations of serum LH (1-7 +/- 0-1 (S.E.M.) i.u./l) increased to a maximum of 4-1 +/- 1-3 i.u./l (P less than 0-001) after 6 months, and FSH rose from 4-9 +/- 1-0 to a maximum of 7-7 +/- 1-3 i.u./l after 4 months of treatment (P less than 0-01). The response to luteinizing hormone releasing hormone (LH-RH) was studied at monthly intervals. Sums of increments of serum LH increased from 35 +/- 4 to 92 +/- 17 i.u./l at 4 months (P less than 0-001) and of FSH from 14 +/- 3-4 to 23 +/- 3-5 i.u./l at 4 months (P less than 0-01). Basal serum androgens rose from 25 +/- 2-7 to 38 +/- 2-4 nmol/l after 4 months of treatment (P less than 0-05), and serum oestradiol-17beta increased from 185 +/- 25 to 631 +/- 90 pmol/l by 6 months (P less than 0-001). No significant changes occurred in sperm counts. Five normal men acted as controls: they were given tamoxifen for 1 week. No significant changes were observed in serum LH, FSH or release of these hormones following administration of LH-RH. Serum androgens and oestrogens however, increased significantly by day 4 of treatment (P less than 0-05).

Androgens↗
PubMed1976

A study of pituitary function in patients with idiopathic hemochromatosis.

Pituitary function was assessed in twelve male patients with idiopathic hemochromatosis. Though clinical features suggestive of hypogonadism were noted in nine cases, impaired pituitary function was demonstrated in only two instances. Our findings suggest that factors other than pituitary or testicular failure contribute significantly to the occurrence of sexual hypofunction and other features suggestive of hypogonadism seen in many of these patients.

Aged↗
PubMed1976

Luteinizing release hormone tests in impotent diabetic males.

Assessment of pituitary-gonadal function was made in impotent diabetic males using luteinizing hormone-release hormone tests. Serum testosterone, sex-hormone-binding globulin capacity, and basal and incremental gonadotrophin concentrations in the impotent diabetics were similar to those in control diabetics, suggesting a primary neurologic rather than an endocrine defect as the cause of the impotence.

Adult↗
PubMed1975

Sex hormone levels and gonadotrophin release in the polycystic ovary syndrome.

The response to synthetic luteinizing hormone-releasing hormone was studied in eighteen patients with the polycystic ovary syndrome. The release of follicle-stimulating hormone was similar to that found in normal women. The mean response of luteinizing hormone was similar to that found in the luteal phase, but significantly greater (P less than 0-02) than that found in the early follicular phase of the normal menstrual cycle. Basal serum levels of FSH and LH, estimated in twenty-five patients, were similar to those found in normal subjects. The sex hormone binding globulin capacity was reduced in twenty-four of them. Basal serum testosterone levels were elevated in twelve of twenty-two patients and the mean level was significantly greater (P less than 0-01) than the mean level of normal women. Basal serum androstenecione levels were elevated in nine of twenty-two patients and the mean level was also significantly greater (P leess than 0-001) between basal testosterone and LH levels. These data suggest the pituitary gland of patients with the polycystic ovary syndrome contains adequate amounts of LH but that the ovulatory surge of LH which occurs in normal women is inhibited by testosterone acting on either the pituitary or, more probably, on the hypothalamus.

Androstenedione↗
PubMed1975

Assay of cortisol in serum by competitive protein binding without solvent extraction.

A method for the determination of serum cortisol by competitive protein binding is proposed in which solvent extraction is replaced by heat inactivation. Results obtained by the new technique correlate well with those obtained by solvent extraction. A saving in manipulative time and glassware is effected when the method is applied in a routine assay.

Animals↗
PubMed1974

Effects of inducers and epoxide hydrase on the metabolism of benzo(a)pyrene by liver microsomes and a reconstituted system: analysis by high pressure liquid chromatography.

The mobilities of 24 potential metabolites of benzo[a]pyrene were examined with high pressure liquid chromatography. Twelve phenols, five quinones, four dihydrodiols, and three oxides were studied. The chromatographic procedure employed allowed the separation and quantitation of benzopyrene metabolites into three major groups consisting of phenols, quinones, and dihydrodiols. Two of the benzopyrene oxides were unstable during chromatography, whereas the third oxide was more stable and chromatographed in the quinone fraction. Treatment of rats with phenobarbital or 3-methylcholanthrene enhanced the metabolism of benzopyrene by liver microsomes and altered the relative amounts of the various metabolites formed. In the absence of epoxide hydrase (EC 4.2.1.63), benzopyrene was metabolized primarily to phenols and quinones but was not appreciably metabolized to dihydrodiols by a solubilized, reconstituted cytochrome P-448 monooxygenase system. Addition of partially purified epoxide hydrase resulted in the formation of benzopyrene dihydrodiols with a concomitant decrease in the formation of phenolic metabolites, indicating that benzopyrene undergoes metabolism via arene oxides that are precursors for dihydrodiols and phenols.

Animals↗