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Biomedical subjects

W M Hunter

Publications and source records attributed to W M Hunter.

At least 19 recordsLinked to original sources
PubMed1991

Progress in immunoassays for serum prolactin: evidence from the UK External Quality Assessment Scheme (EQAS) 1980-1989.

The quality of serum prolactin assays routinely performed by UK laboratories has been monitored in an external quality assessment scheme (EQAS) over a 10-year period, during which participation in the EQAS increased three-fold, and considerable changes in methods and standardization were introduced. The all-laboratory mean was used as the sample target value, and proved to be stable and accurate. Overall between-laboratory agreement in the clinically important range improved from a geometric coefficient of variation (GCV) of 25% to 14%. This appears to reflect the increased use of kits in place of 'in-house' assays, the more widespread availability of international standards and the absence of any marked differences in bias between the commonly used methods. Published guidelines on the clinical interpretation of prolactin values should, therefore, be widely applicable. The EQAS data indicate that, in general, the quality of performance of prolactin assays is adequate for their clinical application.

Antibodies, Monoclonal↗
PubMed1979

A prospective, controlled trial of six forms of hormone replacement therapy given to postmenopausal women.

This study was undertaken to investigate the effect of various forms of hormone replacement therapy (HRT) upon postmenopausal women while controlling as many variables as possible. It was felt that the age, duration of amenorrhoea and the general health of the patients should be as comparable as possible and that each patient should provide her own pretherapy and post-therapy control data. In addition, it was felt that any placebo effect should be investigated and the patients were therefore randomly allocated to placebo tablets or one of six available forms of HRT. The age/sex registers of two large general practices were scrutinized and all women between 49 and 54 years of age were asked to cooperate; for a variety of reasons only 56 women were suitable and willing to take part in the project, yielding 8 women for each of the seven possible therapy groups. Blood samples were taken at 7-day intervals three times before therapy was given and the mean of the three values was used as the control value. The women returned on day 21 of each subsequent therapy cycle for six consecutive months and finally three months after discontinuing therapy. From the data the following broad conclusions can be drawn: (i) some women have classic symptoms of hot flushes and sweating despite high endogenous oestrogen concentrations; (ii) vaginal cytology is a relatively poor indicator of endogenous oestrogen status; (iii) while follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations are reduced on HRT neither is decreased to anywhere near premenopausal values while prolactin is unaffected; (iv) plasma cholesterol levels are reduced on HRT, the pulse rate is slower and both systolic and diastolic blood pressure are reduced to a small but significant extent; (v) there is no adverse effect upon blood clotting; and (vi) most women experience significant or complete relief of symptoms on all forms of HRT as do some women taking a placebo. The combined preparations containing an oestrogen and progestogen produced vaginal bleeding in only 80 per cent of the women. Thus protection by regular endometrical shedding may not be afforded to all women. As vaginal bleeding is unacceptable to most women if they can achieve the same symptomatic relief without inducing menstruation, it is suggested that women have a low dose oestrogen preparation prescribed cyclically for 6 to 12 months. If therapy is to be maintained for a longer time, uterine curretage should be undertaken at regular intervals to exclude the possibility of endometrial carcinoma developing.

Climacteric↗
PubMed1979

Quality control of radioimmunoassays for proteins: the first two and a half years of a national scheme for serum growth hormone measurements.

The philosophy and achievements of the first two and a half years of a national quality control scheme for serum growth hormone assays are described. Three serum samples were distributed to participating laboratories every two weeks. A computer-produced summary of the quality control results, which contained scattergrams and a statistical analysis, was returned to participants four weeks after despatch. The performance of 11 experienced (SAS) laboratories was found to fulfil the necessary accuracy criteria, and their results provided the 'reference group mean', which served as the target value. Gross positive bias exhibited by several laboratories was due to the use of assays with inadequate sensitivity, and this practice was eliminated during the first six months. During the course of the Scheme the average bias fell from 30 to 14%. With assays of adequate sensitivity, bias was almost invariably due to the misuse of standards. Median within-laboratory, between-batch precision (CV) improved from 23 to 15%. The best performers achieved between-batch CV of 7% which was 1.5 x their within-batch CV: the worst had three- to four-fold differences between within- and between-batch CV. Rudimentary quality control of interpretation was found to result in improvements in interpretation per se and also served to reinforce the desire to improve numerical agreement. A 'recommended procedure' based upon supplied first and second antibody, and a communal 'reference range' from 280 untreated acromegalics, both proved valuable.

Growth Hormone↗
PubMed1979

The effects of low doses of cyproterone acetate on some functions of the reproductive system in normal men.

One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly (0.991 less than P less than 0.05). Sperm penetration assessed by the Kremer test did not show any decrease during treatment. Serum levels of testosterone and FSH decreased, but those of LH remained unchanged during treatment. Two pregnancies occurred after 13/4 and 51/2 months of CA-treatment. The serum-CA concentration in these 2 volonteers did not differ from that of the remainder. Three subjects who began the study were withdrawn because of depressive mood changes (2) and weakness combined with dizziness (1). Data from these subjects were not included. The results indicate that daily doses of 5 mg and 10 mg of cyproterone acetate are not effective as a male contraceptive.

Adult↗
PubMed1979

Reduction of non-specific serum responses in human pituitary gonadotrophin radioimmunoassays.

Serum and plasma from human and domestic animals contain variable amounts of non-specific material(s) which may be mistaken for hormone in assays for human LH and FSH, based upon antisera of high sensitivity and hormonal monospecificity. The non-specific response curves are generally, but not invariably, less steep than those of the hormone standards and endogenous homologous hormones. The levels of non-specific intrusion can be of sufficient magnitude to obscure specific estimations seriously, particularly at low hormone levels, unless the assays are designed to minimize this effect. The non-specific effects could be minimized (but not abolished) by careful optimization of the assays which involved making the response curve as sensitive as possible and incorporating the serum at a final dilution of 1 : 2, since further dilution increased the relative contribution of the non-specific substance(s). The optimized assays require only 48 h of total incubation and show a sevenfold increase in the mean concentration of LH between sera from prepubertal children and adults accompanied by a mean threefold difference in the concentration of FSH.

Adult↗
PubMed1978

Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid.

Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid have been performed with a view to producing optimal assay conditions. Cholic acid-BSA was found to be the best immunogen to produce antibodies to conjugated cholic acid and the response was of an IgG type. Incorporating a spacer (hexanoic acid) between hapten and carrier protein resulted in a decrease in antiserum titre. Optimal conditions for the assay were found using [125I]histamine-glycocholic acid as ligand with a dilution of antiserum to produce 60% binding of ligand and a pH of 7.4. Using these assay conditions no serum effects were found; extraction of serum prior to assay was therefore unnecessary. The assay was sensitive enough to detect post-prandial increased in serum bile acid concentrations following a liquid test meal; no increase was observed throughout the same time period in a fasting control.

Antibody Specificity↗
PubMed1978

beta-thromboglobulin and deep vein thrombosis.

The measurement of plasma beta-thromboglobulin as a potential diagnostic test for venous thrombosis has been investigated in 16 normal volunteers, 24 patients presenting with deep vein thrombosis (DVT) or pulmonary embolism and 46 patients screened by 125I fibrinogen test (IFT) for post-operative DVT. The normal mean was 33 ng/ml (range 15-117 ng/ml). Of the 24 patients with clinical thrombotic disease 22 presented with DVT confirmed by phlebogram or IFT and 2 presented with embolism confirmed by lung scan. At the time of first presentation 12 out of 24 had betaTG values greater than 70 ng/ml. All except 3 of this group of 24 patients had values of greater than 70 ng/ml at some stage during a subsequent week of daily sampling. DVT was detected in 13 out of 46 screened post-operative patients. There was a rise om betaTG observed within 24 hr of the IFT becoming positive but the mean rise did not reach significance at the 5% level. An association between DVT and high betaTG values has been confirmed. However, its clinical value cannot yet be fully elucidated until factors, probably related to blood sampling and clearance, are further investigated.

Beta-Globulins↗
PubMed1978

Rapid detection of hepatitis B surface antigen by double antibody radioimmunoassay.

HBsAg and anti-HBs can be detected by double-antibody radioimmunoassay in a reliable routine overnight assay of sensitivity approaching that of solid-phase immunoradiometric assay. The test requires careful standardisation and regular preparation of I125-HBsAg of appropriate quality, but otherwise uses only small quantities of commercially available reagents. In this paper, the reaction kinetics of the first incubation (test sample + limiting amount of rabbit anti-HBs), second incubation (reaction mixture + I125 -HBsAg) and precipitation reaction (reaction mixture + antirabbit globulin) were examined, to determine the minimum time required for the assay compatible with adequate sensitivity and user convenience; in addition, in order to reduce the time of radioactive counting, the maximum amount of I125-HBsAg per test compatible with a satisfactory assay was examined. It was concluded that, by terminating each reaction before equilibrium was reached, results could be obtained in 2--3 hours with a detection limit similar to the standard overnight procedure. To allow routine examination of large numbers of samples, the possibilities of complete automation of this liquid-phase type of assay were discussed.

Hepatitis B Antibodies↗
PubMed1978

Serum prolactin, gonadotrophin and oestrogen levels in women receiving hormone replacement therapy.

Prolactin, oestrone, oestradiol, FSH and LH concentrations have been determined in postmenopausal women receiving different forms of hormone replacement therapy. While the serum oestrogen levels achieved were sufficient to cause a significant decrease in circulating FSH and LH levels, no significant change in prolactin concentrations was found. Two other findings are of interest: despite the absolute concentrations achieved, the ratio of FSH to LH and the ratio of oestradiol to oestrone did not change significantly on any of the hormone formulations used; and while FSH and LH were both suppressed to a significant degree on therapy neither was suppressed to premenopausal values suggesting the possibility of a 'female inhibin' in the normal regulation of gonadotrophin secretion.

Estrogens↗
PubMed1978

Impaired estrogen-induced luteinizing hormone release in young women with anovulatory dysfunctional uterine bleeding.

Spontaneous ovarian activity, as reflected by the urinary excretion of total estrogen and pregnanediol measured serially (thrice weekly) over a period of 3-4 months, was studied in nine young women (15-27 yr old) with a history of dysfunctional uterine bleeding of at least 2-yr duration. Results were compared to those obtained in sex regularly menstruating women, aged 23-45 yr. All control women had ovulatory cycles, but seven of the nine patients with DUB failed to ovulate during at least three consecutive cycles. The profiles of urinary total estrogen excretion in these seven subjects were consistent with regular follicular development, but the follicular phase was prolonged and the amount of estrogen excretion increased, as compared to controls. In four of these seven patients, the endometrium had previously shown cystic glandular hyperplasia. Although the release of LH and FSH after injection of 50 micrograms synthetic LRH was normal, the surge of LH induced in response to exogenous estrogen (200 micrograms ethinylestradiol/day for 3 days) was significantly (P less than 0.005) lower in the patients (16.2 +/- 3.7 mU/ml) than that of control women )35.0 +/- 5.5 mU/ml). It is concluded that the failure to ovulate in young women with anovulatory dysfunctional uterine bleeding is due to inadequate release of LH in response to estrogen. The results support the hypothesis that the basic defect in these women may be a decrease of hypothalamic sensitivity to positive feedback.

Adolescent↗
PubMed1978

The stability of standards for radioimmunoassay of human TSH: research standard A and the international reference preparation initially 68/38.

The stability of the International Reference Preparation of human TSH for immunoassay (previously distributed in ampoules coded 68/38) and of Research Standard A for HTSH has been examined by radioimmunoassay of accelerated degradation samples (stored as the dry ampouled preparations). Potency estimates on degradation samples suggest a high order of stability of immunopotency recognisable by two antisera (MRC 72/356 and Hunter 3A). For the International Reference Preparation the loss of immunopotency during storage at -20 degrees C is predicted to have been 0.56% per year.

Drug Stability↗
PubMed1977

Pituitary-ovarian relationships in polycystic ovary syndrome.

The spontaneous pattern of pituitary gonadotropins and ovarian steroids and their response to dynamic tests were measured in 12 women with polycystic ovarian syndrome (PCO) and the results compared to those from 6 normal women during the early follicllar phase of the cycle (controls). As judged by serial measurements of urinary total estrogen and pregnanediol over a 12-week period, in PCO patients 75% of cycles were anovulatory (anovulatory PCO) as compared to 100% ovulatory in controls. The basal concentrations of LH, androstenedione and estrone were significantly higher and the concentration os FSH significantly lower in anovulatory PCO than in the controls (P less than .05). In PCO patients the concentration of LH was lower following an ovulatory cycle than that following a period of anovulation. Negative and positive feedback responses to an estrogen provocation test (200 microgram ethinyl estradiol per day for 3 days) were normal in anovulatory PCO although the LH peak occurred 24 h earlier than in the controls. The amplitude of the pulses of LH was significantly greater in anovulatory PCO than in the controls and was suppressed in both groups after ethinyl estradiol. The peak release of LH in response to 56 microgram LRF in ovulatory PCO was similar in controls but LH responses in anovulatory PCO were significantly greater. It is suggested that the abnormalities in gonadotropin secretion in PCO are secondary to excessive and prolonged extraglandular production of estrogen from androstenedione.

Adult↗
PubMed1976

Nitrazepam: lastingly effective but trouble on withdrawal.

The sleep of 10 volunteers with an average age of 57 years was recorded electrophysiologically before, during, and after nitrazepam 5 mg nightly for 10 weeks. Sleep was longer and less broken on the drug and no tolerance was obvious after two months' use. Withdrawal of the drug, however, caused sleep to be temporarily worse than before the drug had been taken. Slow-wave sleep was reduced by nitrazepam, but the accompanying secretion of growth hormone was not impaired.

Adult↗
PubMed1976

A comparison of plasma TSH levels in patients with diffuse and nodular non-toxic goiter.

Plasma TSH levels were measured in 115 euthyroid patients with simple goiter, of whom 52 had diffuse and 63 nodular enlargement of the thyroid gland, and in 191 euthyroid patients without goiter. There was no significant difference between the plasma TSH levels in the patients with diffuse goiter and the non-goitrous controls, implying that the maintenance of diffuse hyperplasia is not dependent upon a raised level of plasma TSH. On the other hand, plasma TSH levels in the patients with nodular goiter were significantly lower than those recorded in either the patients with diffuse goiter (P less than 0.01) or in the patients without goiter (P less than 0.0001), supporting the view that thyroid function may be autonomous in nodular goiters.

Adenoma↗