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Biomedical subjects

W M Hunter

Publications and source records attributed to W M Hunter.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Thyroid function in the long-term follow-up of patients treated with iodine-131 for thyrotoxicosis.

In February, 1972, 58% of patients euthyroid after iodine-131 therapy for thyrotoxicosis between 1954 and 1966 had a raised plasma thyroid-stimulating-hormone (T.S.H.) (greater than 7-4 mU/l) and 42% a normal T.S.H. level. A group of 69 of the euthyroid patients with a raised plasma T.S.H. (25-0 +/- 2-0 mU/l) in 1972 was re-examined annually for three years. There was no apparent change in the mean plasma T.S.H. level between 1972 and 1975 in the patients remaining euthyroid, but overt hypothyroidism developed in 3 patients in 1973, in a further 3 patients in 1974, and in 1 patient in 1975. In contrast, none of a group of 61 patients, euthyroid with a normal plasma T.S.H. (4-0 +/- 0-2 mU/l) in 1972, developed overt hypothyroidism over the next three years, although slightly raised T.S.H. levels were recorded in 3 patients in 1974 and in a further 6 patients in 1975. Both the mean serum T-4 and T-3 in the euthyroid patients with a raised plasma T.S.H. were significantly lower, but still in the respective normal ranges, than those in the euthyroid patients with a normal plasma T.S.H. No significant difference in the fasting serum-cholesterol or triglyceride levels could be demonstrated between the two groups. Since no patient with a normal plasma T.S.H. after iodine-131 treatment for thyrotoxicosis six to eighteen years earlier developed overt hypothyroidism over a three-year period, the follow-up of such patients need not be so frequent as that of similarly treated euthyroid patients with a raised plasma T.S.H. in whom overt hypothyroidism develops at the rate of 2-5% per year.

Cholesterol↗

Cyproterone acetate: a study involving two volunteers with idiopathic hirsutism.

Two female volunteers, of menstrual age, with severe idiopathic hirsutism were treated for eight cycles and fifteen cycles respectively with cyproterone acetate 50 mg twice daily on days 5-14 of the cycle. In all but one cycle, ethinyl oestradiol in a dose of 50 mug daily from day 5 to 21 was given in addition. Cyproterone acetate when given alone abolished the mid-cycle LH surge. Combined therapy with cyproterone acetate and ethinyl oestradiol produced a significant improvement in both patients' hirsutism and was accompanied by a marked reduction in the urinary excretion of LH, FSH and androgens and by a fall in plasma testosterone. However, the clinical benefit derived from this drug was due principally to its action as a peripheral antiandrogen.

Adult↗

Plasma growth hormone and slow wave sleep increase after interruption of sleep.

A comparison was made of plasma hGH and of sleep stages during one night of undistrubed sleep and one night in which sleep was interupted by an hour of enforced wakefulness folowing the end of the second NREM-REM sleep cycle in 8 normal subjects. Plasma was sampled at 15-min intervals. HGH and slow wave sleep were both significantly increased in the two cycles immediately following the period awake compared with the same two cycles during nights of uninterruped sleep. The difference arose predominantly in the fourth cycle of the night, i.e., in the second cycle after the sleep interuption. The findings are consistent with the belief that extra wakefulness brings additional sleep of high RESTORATIVE properties.

Adult↗

Changes in the concentration of pituitary and steroid hormones in the follicular fluid of human graafian follicles throughout the menstrual cycle.

The concentrations of FSH, LH, prolactin, oestradiol and progesterone were measured in peripheral plasma and follicular fluid of women throughout the menstrual cycle. With the exception of prolactin, concentrations of pituitary and steroid hormones in follicular fluid correlated with those in peripheral plasma. Follicle-stimulating hormone was present in a greater number of small follicles (smaller than 8mm) during or just after the peaks of FSH in peripheral plasma. During the mid-follicular phase the concentration of both FSH and oestradiol in fluid from large follicles (larger than or equal to 8 mm) was high. During the late follicular phase the large follicles (larger than or equal to 8 mm) contained high amounts of progesterone in addition to oestradiol, low physiological levels of prolactin, and concentrations of LH and FSH about 30 and 60% respectively of those found in plasma. By contrast no large 'active' follicles (larger than or equal to 8 mm) were found during the luteal phase although many contained both LH and FSH. Luteinizing hormone was present in a proportion of small follicles (smaller than 8 mm) during the late follicular and early luteal but not at other stages of the menstrual cycle. It is suggested that a precise sequence of hormonal changes occur within the microenvironment of the developing Graafian follicle; the order in which they occur may be of considerable importance for the growth of that follicle and secretory activity of the granulosa cells both before and after ovulation.

Adult↗

Plasma TSH and serum T-4 levels in long-term follow-up of patients treated with 131-I for thyrotoxicosis.

In February 1972 58% of patients euthyroid after iodine-131 therapy given for thyrotoxicosis between 1954 and 1966 had a high plasma TSH (>7.4 muU/ml) and 42% a normal plasma TSH level. A group of 69 of the euthyroid patients with high plasma TSH levels (25.0+/-2.0 muU/ml) in 1972 were re-examined 15 and 24 months later. The mean plasma TSH in the 66 patients remaining euthyroid at 15 months was 22.6+/-1.8 muU/ml, while three patients had become hypothyroid. At 24 months 64 of the patients were still available for study, of whom 61 remained euthyroid with a mean plasma TSH of 21.6+/-2.0 muU/ml, and a further three had become hypothyroid.All of a group of 61 of the euthyroid patients with normal plasma TSH levels (4.0+/-0.2 muU/ml) in 1972 remained euthyroid at 24 months with a mean plasma TSH of 4.1+/-0.3 muU/ml, though the plasma TSH level had become slightly raised in three.The mean serum T-4 level in the euthyroid patients with a high plasma TSH was significantly lower, though still in the normal range, than that in the euthyroid patients with a normal plasma TSH both in 1972 and in 1974.Since no patient with a normal plasma TSH level after iodine-131 treatment six to 18 years earlier for thyrotoxicosis developed hypothyroidism over a two-year period, the follow-up of such patients need not be so rigorous as that of similarly treated euthyroid patients with raised plasma TSH levels in whom hypothyroidism developed at the rate of 5% per year.

Follow-Up Studies↗