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Biomedical subjects

G Holder

Publications and source records attributed to G Holder.

At least 19 recordsLinked to original sources
PubMed2000

Recovery of visual field constriction following discontinuation of vigabatrin.

Epilepsy patients treated with vigabatrin may develop symptomatic or asymptomatic concentric visual field constriction due to GABA-associated retinal dysfunction. The prevalence and course of this side effect are not established yet; in previously reported adult patients the visual disturbances seem to be irreversible. We present two patients with a significant improvement of visual field constriction and retinal function after the discontinuation of vigabatrin. These findings suggest that vigabatrin-associated retinal changes are at least partly reversible in some patients, and that these patients may benefit significantly from a withdrawal of vigabatrin. Larger scale clinical studies are needed to identify predictive factors both for the occurrence and reversibility of vigabatrin-associated visual field defects.

4-Aminobutyrate Transaminase↗
PubMed1999

[Tablets in stool? A common problem!].

Patients and their physicians are often thrown into doubt by the excretion of apparently intact tablets in stools after oral drug administration. This occurs whenever patients receive certain pharmaceutical forms designed to prolong the rate of drug release. The active compound is continuously released during intestinal passage of these pharmaceutical forms and their insoluble coats are visibly excreted into stools wholly or in part. The assumption that the drug was not released from the tablet in these cases is therefore erroneous and no further action is required.

Capsules↗
PubMed1995

External quality assessment of urinary-free cortisol measurement in the UK against a gas chromatography mass spectroscopy reference method.

The performance of methods used for the measurement of urinary-free cortisol (UFC) has been monitored in the UK by an external quality assessment scheme (EQAS). Bias and variation of the bias (VAR) from the all laboratories trimmed mean (ALTM) show that mean bias ranged from -15.5% to +83.1% and mean VAR from 9.3% to 53.2%. The dominant kit methods had a bias range of -4.2% and +56.9% and VAR between 11.4% and 18.4%. Recovery of added cortisol ranged from 74.9% to 207.2%. The precision of the estimate of urinary-free cortisol was different for different methods and changed with concentration. When methods were compared with a gas chromatography mass spectroscopy (GCMS) target there was a linear correlation between per cent bias from the ALTM and from the GCMS result with the ALTM averaging 63.1% greater than the GCMS value.

Evaluation Studies as Topic↗
PubMed1995

11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome.

A characteristic feature of the ectopic ACTH syndrome is a state of mineralocorticoid excess, although the etiology remains obscure. Some forms of endocrine hypertension, such as licorice ingestion, have been explained by cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible for the conversion of cortisol (F) to hormonally inactive cortisone, and its activity in vivo can be inferred from the ratio of the urinary excretion of tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone. Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic, and 2 adrenal adenomas) and 13 controls were studied. Compared to controls. Cushing's patients had a significant increase (P < 0.001) in the excretion of all principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1 (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81 (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD activity. Furthermore, compared to patients with pituitary-dependent Cushing's, this ratio was significantly higher in patients with the ectopic ACTH syndrome (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid excess state of the ectopic ACTH syndrome appears to be that cortisol gains inappropriate access to the mineralocorticoid receptor through failure of its normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD activity is unclear, but it may be secondary to substrate saturation, inhibition by other adrenal steroids, or product inhibition.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Evidence for downregulation of hypothalamic 5-hydroxytryptamine receptor function in endurance-trained athletes.

Serum prolactin (PRL) was used as a hormone marker of serotoninergic function following oral administration of an acute dose of a serotoninergic agonist. Five male endurance-trained athletes (ET) and five healthy non-endurance-trained controls (NT) were studied. The peak PRL concentration was lower (P = 0.031) for the ET athletes (486 +/- 208 mU l-1; mean +/- S.D.) than for the NT controls (1000 +/- 385 mU l-1); the total release of PRL was also lower (P = 0.042) for the ET subjects. The lower neuroendocrine response to a serotoninergic agonist in the endurance-trained athletes suggests a downregulation of central serotoninergic receptor function in response to endurance training in man.

Adult↗
PubMed1990

Hormonal studies on women with polycystic ovaries diagnosed by ultrasound.

Eighty-six patients were diagnosed by ultrasound to have polycystic ovaries. Twelve have fairly regular but anovular cycles (P1), 56 had oligomenorrhoea (P2) and eight had primary or secondary amenorrhoea (P3). The remaining 10 patients had raised progesterone concentrations and were excluded from the hormonal studies. Gonadotrophins, steroid hormones and sex hormone binding globulin (SHBG) were measured in all patients and the results were compared with those of 29 normal women who acted as controls. A high LH:FSH ratio was the most frequently found abnormality (raised in 68.4% of patients) followed by LH (65.8%), free testosterone (FT, calculated from total testosterone (T) and SHBG) (59.2%) and 17-OHP (48.7%). Each of these four estimations was above the normal ranges in 25% of patients: proportionally most of the results outside the normal range occurred in group P3 followed by P2 and P1 respectively. To obtain a quantitative measure of the abnormalities, results were expressed as percentages of the mean control value for each hormone and these percentages were then summated. The four measurements, LH:FSH ratio, LH, FT and 17-OHP gave abnormality scores ranging from a mean of 667 in P1 to 1189 in P3 compared with 405 in controls. Twenty-one of the 76 patients were hirsute with significantly higher androgens than the nonhirsute patients. Their mean abnormality score was 1141 compared with 855 in the non-hirsute group and they all had at least one hormonal abnormality. The study demonstrates that there is a relationship between the degree of hormonal abnormality and the menstrual irregularities and hirsutism in women with PCOS suggesting that there may be a progressive nature to the syndrome.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Patterns of ACTH and cortisol pulsatility over twenty-four hours in normal males and females.

Patterns of plasma ACTH and cortisol concentrations were studied in 10 healthy subjects (five male, five female in the early follicular phase, overall age range 21-32 years) by sampling through an indwelling cannula every 15 min for 24 h. The subjects were in hospital, ambulant, and taking normal meals. Plasma ACTH was measured by a two-site immunoradiometric assay with a detection limit of 3.9 ng/l (0.9 pmol/l). Pulses were identified by the method of Clayton et al. (1987) using stringent criteria to minimize false positive peaks. All subjects showed a circadian rhythm of ACTH, the acrophase occurring between 0615 and 0920 h in all but one subject and the mesor value was between 9.2 and 18.6 ng/l (2.0 and 4.1 pmol/l). There were significantly fewer pulses between 1800 and 2400 h compared with the other three 6-h periods. The pattern of ACTH differed between males and females in several respects: more pulses (18 vs 10), greater mean peak amplitude (16.8 vs 10.3 ng/l), greater area under the 24-h profile (350.9 vs 206.6 ng/l h) and higher mean level (14.7 vs 8.6 ng/l) in the males. In contrast, the cortisol pattern did not show statistically different sex differences. The sex differences suggest greater sensitivity to, or availability of, ACTH to the female adrenal cortex, or different set points in cortisol feedback.

Adrenocorticotropic Hormone↗
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↗