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Biomedical subjects

B T Rudd

Publications and source records attributed to B T Rudd.

At least 37 records · Page 2Linked to original sources

Oestrogen-gonadotrophin feedback mechanisms in the puerperium.

The effect of oestradiol benzoate on serum gonadotrophin concentrations before and after LHRH administration was studied in lactating and non-lactating women at 3 and 6 weeks post-partum. Except in the non-lactating women at 6 weeks, basal serum FSH concentrations were suppressed by oestrogen. There were no significant changes in basal concentrations of LH after oestrogen in the lactating women in either the 3- or 6-week studies. Individual increases in the basal LH concentrations in two out of six non-lactating subjects in the 6-week study occurred but overall there were no significant changes. In the 6-week study amplification of the LH response to LHRH was found in both groups, the effect being significantly greater in the non-lactating women. Overall FSH responses were also significantly different in the two groups, being suppression in those lactating ad amplification in those not lactating. The LH/FSH ratios following LHRH administration in the 6-week non-lactating study were similar to those seen in the early follicular phase in regularly menstruating subjects. The basal ratios in the lactating subjects were, however, significantly less than those seen in the non-lactating subjects both at 3 and 6 weeks. This difference was associated with the relative enhancement of LH release in non-lactating subjects and enhancement of FSH release in those lactating. Taken together the results indicate the presence of an intact negative feedback of oestrogen on gonadotrophin release in both groups being enhanced at 6 weeks post-partum in the lactating subjects; also in the lactating subjects at 6 weeks there was less amplification by oestrogen of the responsiveness of the anterior pituitary to LHRH. At 6 weeks, however, in the non-lactating group these responses were similar to those seen in normal regularly menstruating subjects. These dynamic endocrine studies suggest a possible hypothalamic-pituitary mechanism which may help to explain the delayed return of ovulatory cycles in lactating women.

Estradiol↗

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↗

Adrenal function in subgroups of the PCO syndrome assessed by a long ACTH test.

Fifteen patients with the polycystic ovarian (PCO) syndrome were classified into Group A (n = 6) and Group B (n = 9) based on their LH responses to LHRH before and at 44 and 92h after administration of oestradiol benzoate. Adrenal function in both groups was assessed by comparing the hormone responses to ACTH (0.5mg twice daily for 4 days) with those obtained in nine normally ovulating women during the early follicular phase of their cycles. In Group A patients there was no significant difference from normals in the serum concentration of dehydroepiandrosterone sulphate (DHAS), 17 alpha-hydroxy-progesterone (17-OHP) or androgens (testosterone and dihydrotestosterone). In contrast, the serum concentrations in Group B were significantly higher (P less than 0.01) for each of these steroids before ACTH, and remained higher at 2 and 4 days for DHAS, but not for the other two steroids. The concentration of oestrone was significantly higher (P less than 0.05) in Group B patients before, and 2 days after, ACTH, while in Group A patients higher concentrations (P less than 0.02) were found only after 2 days. The concentrations of oestradiol, on the other hand, were not different from normal in either group before ACTH and became lower than normal in both groups at 2 days and remained lower at 4 days in Group B. The concentration of cortisol was within the normal range throughout in Group A, but was lower than normal after 4 days in Group B patients (P less than 0.05). The ratios between the sums of concentrations of DHAS to cortisol on days 2 and 4 (P less than 0.001) or 17-OHP to cortisol (P less than 0.05) were elevated in Group B compared with normal subjects. LH, FSH and prolactin values were normal throughout in Group A, but in Group B patients the mean value for LH was significantly elevated before ACTH and at 4 days after ACTH (P less than 0.02).

Adrenal Glands↗

Serum dehydroepiandrosterone (DHA) and sulphate (DHAS) after acute growth hormone therapy.

To test the hypothesis that growth hormone (hGH) may increase adrenal androgen production dehydroepiandrosterone (DHA) and its sulphate (DHAS) concentrations were measured by radioimmunoassay in the serum from 7 children with growth hormone deficiency, 2 of whom had delayed puberty. Two injections of hGH (10 mg) were given 48 h apart and the hormone concentrations measured at 3, 6, 24 and 48h after the first injection, 3, 6, and 24h after the second. Basal DHA levels were positively correlated with age and bone age in 6 of the 7 patients (p less than 0.05). Increment of DHA and DHAS above or below basal at each time interval were calculated. The mean increments were higher (p less than 0.01-0.05) at 3 h after the first injection and at 24h (p lesal DHA concentrations were positively correlated with increments in DHA during the first and second 24h of the test (p less than 0.05). DHAS concentrations showed little change throughout the test for all children. It is suggested that some children with growth hormone deficiency and receptive adrenals, increase their serum DHA concentrations after acute hGH therapy.

Adolescent↗

A simple procedure for the radioimmunoassay of 17 alpha-hydroxyprogesterone in serum: comparison with an immunological purification technique.

A simple radioimmunoassay for the measurement of 17 alpha-hydroxyprogesterone in 0.1-0.25 ml serum is described. An antibody prepared against 17 alpha-hydroxyprogesterone 3(O-carboxymethyl)-oxime-BSA as immunogen was used. A correlation of the 17 alpha-hydroxyprogesterone concentration found in the serum of normal subjects and of patients with that obtained by a more complex immunological purification method was good (r=0.924, P less than 0.001). Accuracy, precision, and specificity were acceptable with the simple method. Normal values for infants, children, and adults have been established, and the individual concentrations of 17 alpha-hydroxyprogesterone in the serum of patients withcongenital adrenal hyperplasia were well separated from normal values.

Adrenal Hyperplasia, Congenital↗

Oestrogen modulation of gonadotrophin and prolactin release in women with anovulation and their responses to clomiphene.

An LHRH test was performed before and at both 44 and 92 h after the administration of 2.5 mg oestradiol benzoate in eleven patients with hyperprolactinaemia, eight with idiopathic secondary amenorrhoea and seven with oligomenorrhoea. The basal serum hormone concentrations and the responses to LHRH were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4--6). Mean basal concentrations of oestradiol in each group of patients and oestrone in those with hyperprolactinaemia were significantly lower than in the normal subjects. The mean concentration of prolactin in women with secondary amenorrhoea remained lower than in the normal women throught the tests (P less than 0.05). The LH and FSH responses to LHRH before oestrogen in patients with hyperprolactinaemia and of FSH in those with secondary amenorrhoea, were greater than in the normal subjects (P less than 0.001). After oestrogen treatment the responses were similar in all groups except in those with oligomenorrhoea where LH and FSH responses at 44 h (P less than 0.05 and P less than 0.01 respectively) and LH responses at 92 h (P less than 0.01) were lower than in normal controls. The responses at 92 h in all groups were greater than at 44 h (amplification) but the amplification at 92 h and at 44 h compared to the pre-treatment responses, tended to be lower in each group of patients compared to the normal controls. In the hyperprolactinaemic group of patients there was a negative correlation between the basal prolactin concentration and the gonadotrophin amplifications at 92 h (P less than 0.01), and a positive correlation between the basal oestrone levels and the amplifications at 92 h (P less than 0.01). The results of the oestrogen amplification test in eleven of the non-hyperprolactinaemic anovular patients were compared with the ovulatory response to 100 mg clomiphene given for 5 days. Six showed a normal oestrogen amplification and they all ovulated. Two patients failed to show greater amplification at 92 than at 44 h and required human chorionic gonadotrophin (HCG) as well as clomiphene to ovulate. The other three showed a diminished LH amplification at 92 h; they required 200 mg clomiphene and showed a prolonged follicular phase. The responses of the hyperprolactinaemic patients to clomiphene were poor and there was a negative correlation between prolactin concentration and oestrogen production (P less than 0.01). All ten hyperprolactinaemic patients treated with bromocriptine ovulated and eight conceived. The oestrogen amplification test appears to have some value in predicting the subsequent response to clomiphene in non-hyperprolactinaemic anovular women.

Adult↗

Oestrogen amplification of LH-RH response in the polycystic ovary syndrome and response to clomiphene.

An LH-RH test was performed before and 44 and 92 h after treatment with 2.5 mg oestradiol benzoate in 17 patients with a diagnosis of polycystic ovarian (PCO) disease. The responses were compared with the same tests performed on ten normal subjects during the early follicular phase of their menstrual cycles (days 4--6). Patients were divided into two groups on the basis of their LH responses to LH-RH. In Group A (seven patients) the response at 92 h was greater than at 44 h as in the normal subjects, but in Group B (ten patients) the response at 44 h was greater than at 92 h. Basal serum hormone values were similar in the two groups except for androgens and oestrone, which were significantly (P less than 0.01) higher in Group B patients. There was a negative correlation between the basal androgen and oestrone concentrations and the LH and FSH amplifications at 92 h in all PCO patients. The ratios of the basal concentrations of LH to FSH and the ratios of the highest levels of each achieved during the basal LH-RH test, were significantly higher in the two groups of patients when compared to controls (P less than 0.01). The test is of value in predicting the subsequent responsiveness to clomiphene. All patients in Group A showed evidence of ovulation following treatment with 100 mg clomiphene for 5 days, but only one of Group B responded in this way.

Adult↗

Somatomedin in growth disorders and chronic renal insufficiency in children.

Somatomedin activity was measured using an embryonic chick cartilage assay in 33 normal and short normal children, 23 children with pituitary growth hormone (GH) deficiency, 14 children with sexual precocity, and 13 children with chronic renal insufficiency. In normal children somatomedin activity correlated well with chronological age: low valles in early childhood rose to higher than adult levels at puberty. Children with GH deficiency had significantly lower activities and those with sexual precocity significantly higher activities than normal children. In all three groups somatomedin activity correlated well with bone age. In children with chornic renal insufficiency there was a significant correlation between decreasing somatomedin activity and both a reduced growth velocity and a falling glomerular filtration rate. Somatomedin activity and growth velocity were within normal limits in children with glomerular filtration rates above 30 ml/min/1-73 m2.

Adolescent↗

Recurrent breast cancer treated with the antioestrogen tamoxifen: correlation between hormonal changes and clinical course.

Forty-five post-menopausal women with recurrent breast cancer were treated with the antioestrogen, tamoxifen, 20 mg twice daily. Clinical assessment after 12 weeks indicated that 18 (40%) showed some remission. Gonadotrophins were suppressed within two weeks to relatively constant concentrations within the post-menopausal range, responses to luteinising hormone-releasing hormone (LH-RH) did not change, and androgen concentrations remained within the normal range in all patients. Oestradiol concentrations rose steadily only in women in whom treatment failed. Serum prolactin concentrations were raised in 18 out of the 44 (41%) patients in whom they were measured; 13 of these did not respond to treatment. Treatment did not change the average prolactin concentration when this was within the normal range, but it significantly reduced prolactin concentrations in hyperprolactinaemic patients--within two weeks (P less than 0-01) in those who responded well and by six weeks (P less than 0-05) in those who showed no remission. Among patients with normal prolactin values the release of prolactin after thyrotrophin-releasing hormone was significantly greater in those with no remission than in those who responded to tamoxifen. Responses in those with hyperprolactinaemia were reduced to about half the control values, and again this change occurred faster in those who were successfully treated. Patients therefore seem to have a better chance of responding to anti-oestrogen treatment if prolactin secretion is low.

Androgens↗

Nyctohemeral secretion of growth hormone in normal children of short stature and in children with hypopituitarism and intrauterine growth retardation.

A continuous blood sampling technique has been used to monitor human growth hormone (GH) during sleep in fourteen normal short children (age range 6.5-15.0 years), twelve hypopituitary children (2.8-17.3 years), three children with psychosocial GH deficiency (4.0-13.0 years), and three children with intrauterine growth retardation (9.5-11.3 years). The mean GH level of a 5 h sleep period (22.30-03.30 hours) was used to represent the GH response to sleep. The GH response to insulin induced hypoglycaemia (IST) was also determined. In normal short children there was a significant relationship between 5 h mean GH levels and chronological age. The curve defining this relationship was similar to the third centile linear growth velocity curve. The 5 h mean GH levels of the hypopituitary and psychosocial GH deficiency children were more than 2 SD below the age related mean established for normal short children. The children with intrauterine growth retardation demonstrated values which were more than 2 SD above the age related mean.

Adolescent↗

Increasing growth with raised circulating somatomedin but normal immunoassayable growth hormone.

Two patients are described with elevation of circulating somatomedin A concentration but normal growth hormone levels. One,a young male, appeared clinically acromegalic; the other, a young female, was tall with kyphoscoliosis, and her appearance resembled Marfan's syndrome. In both patients plasma growth hormone concentration was suppressible by hyperglycaemia. It is suggested that their clinical syndromes resulted from excessive somatomedin activity.

Acromegaly↗

A simple method for counting antibody bound labelled steroids.

A simple method is described for the counting of tritiated antibody-bound steroid after acidification and extraction into a toluene based scintillant. The resulting count rate is stable and quenching is minimal. The method give improved count rates when compared with methods employing scintillants containing methanol, dioxane, or Triton and compares favourably with methods involving pre-heating of antibody-bound steroid or extraction of free steroids after the addition of ammonium sulphate. A specific antibody for estradiol has been used to illustrate the application of the technique to antibody titration curves and standard curves.

Animals↗

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↗

A radioimmunoassay for the estimation of serum dehydroepiandrosterone sulphate in normal and pathological sera.

A radioimmunoassay is described for the measurement of dehydroepiandrosterone sulphate in serum. The method requires 0.1 ml of serum that needs no purification other than a single ether extraction. It is both rapid and economical, procedural losses are small and precision and accuracy are acceptable for both normal and pathological sera. Normal values have been established for children and adults which show a relationship to chronological age, values rising steadily as puberty intevenes, peak values occurring between 20 and 27 years, with a decline thereafter. An empirical curve was fitted to the data and approximate normal limits were obtained. The mean value for pregnanat women in the age range 20-40 years, was statistically significantly lower than in non-pregnant, premenopausal women. The levels of dehydroepiandrosterone sulphate in cord and newborn blood, were higher than at any other time during childhood until signs of puberty were demonstrable. Elevated levels are reported in six patients with untreated congenital adrenal hyperplasia and in one patient with a tumour of the adrenal cortex. It is suggested that this assay provides a useful and precise index of adrenal androgen secretion.

Adolescent↗

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↗