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Biomedical subjects

D R London

Publications and source records attributed to D R London.

At least 37 records · Page 2Linked to original sources
PubMed1983

Effectiveness of pergolide mesylate in long term treatment of hyperprolactinaemia.

Twenty five patients with hyperprolactinaemia were treated with pergolide mesylate, a new dopamine receptor agonist. Twenty three received treatment for six to 20 months, and in all serum prolactin concentrations were considerably reduced. In most patients prolactin concentrations were maintained in the normal range by a low, once daily dose of pergolide and reversal of associated reproductive disorders was observed. Tumour volume as assessed by computed tomography decreased considerably during treatment in three out of four patients with a pituitary tumour. The drug was well tolerated. Side effects were similar to those of bromocriptine, but four out of eight patients who had been forced to stop taking bromocriptine because of untoward effects were subsequently able to tolerate treatment with pergolide. Pergolide mesylate promises to be a useful addition to the currently available long acting dopamine agonists in the management of hyperprolactinaemia.

Adult↗
PubMed1983

Pharmacokinetics of diltiazem after intravenous and oral administration.

The kinetic profile of diltiazem, a novel calcium antagonist, was studied in 12 volunteers following oral (60 mg) and intravenous (15 mg) administration. After i.v. administration biphasic elimination was observed, with a distribution half-life of 0.3 +/- 0.2 h and an elimination half-life of 3.1 +/- 1.0 h; the apparent volume of distribution was 5.3 +/- 1.71/kg and the total clearance was 1.28 +/- 0.48 l/kg/h. After the oral dose the elimination had a half-life of 3.2 +/- 1.3 h. The absolute bioavailability of diltiazem ranged from 24 to 74% (mean 42 +/- 18%). The interindividual variation may be explained by a variable first pass effect.

Administration, Oral↗
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↗
PubMed1982

Diagnostic value of 9 am plasma adrenocorticotrophic hormone concentrations in Cushing's disease.

Morning plasma adrenocorticotrophic hormone (ACTH) concentrations were measured in 58 normal subjects and seven patients with pituitary-dependent Cushing's syndrome (Cushing's disease). Particular note was taken of the time of venepuncture. The range of values for the normal subjects irrespective of timing was 9-77 ng/l. The range between 9 0 am and 9 30 am was 9-24 ng/l. In the patients with Cushing's disease the ACTH concentrations were in the range 39-109 ng/l. To distinguish patients with Cushing's disease from normal subjects it is therefore important to define accurately the 9 am normal range, since these results show no overlap.

Adrenocorticotropic Hormone↗
PubMed1982

An acth-secreting pituitary tumour arising in a patient with congenital adrenal hyperplasia.

The case reported is of a 46-year-old woman who had congenital adrenal hyperplasia due to a 21-hydroxylase deficiency, and in whom there was the development of an ACTH secreting pituitary tumour. The patient was untreated with glucocorticoids until the age of 32 years when she presented with infertility. She next presented with amenorrhoea at the age of 44 years when she was found to have an enlarged pituitary fossa. Despite treatment with bromocriptine and adequate doses of dexamethasone, the tumour enlarged and required operative treatment 1 year later. Before and after operation, plasma ACTH levels were between 300 and 400 ng/l, immunocytochemistry showed staining for ACTH and other structurally related pro-opiocortin peptides but for no other hormones, and the tumour secreted large amounts of ACTH in vitro. The report of this case is to our knowledge the first account of a feedback tumour in congenital adrenal hyperplasia and provides yet another reason why patients with this condition should be treated, and good control achieved.

Adenoma, Basophil↗
PubMed1982

A comparison of three glucocorticoid suppressive regimes in adults with congenital adrenal hyperplasia.

We have compared three glucocorticoids, hydrocortisone (HC) (20 mg mane & 10 mg nocte), cortisone acetate (CA) (25 mg mane & 12.5 mg nocte), dexamethasone (DXM) (0.5 mg mane & 0.25 mg nocte), for their effect on the biochemical control of adult patients with congenital adrenal hyperplasia (CAH). Twenty-four-hour profiles of plasma concentrations of ACTH, 17-hydroxyprogesterone (170HP) and androstenedione (delta 4A), and 09.00 h dehydroepiandrosterone sulphate (DHAS) plasma concentrations were used to assess control. The patients were studied after 2 weeks on each glucocorticoid. The areas under the curves, the heights of the morning peaks of each hormone, the midnight concentrations, and the concentrations of hormones just before the evening dose were analysed. The results show that all the indices, except the midnight concentrations which were uniformly low, were significantly lower on DXM than on either HC or CA. There were no significant differences between HC and CA for any of the indices. The DHAS concentrations were low on all three glucocorticoids but again significantly lower on DXM. DXM (0.5 mg mane & 0.25 mg nocte) is therefore, in the short term, a better suppressor of the pituitary-adrenal axis in adults with CAH than either HC or CA, and in the dose used did not suppress ACTH to undetectable levels, nor the steroids to below levels found in normal subjects.

17-alpha-Hydroxyprogesterone↗
PubMed1981

Treatment of hyperprolactinaemia with pergolide mesylate: acute effects and preliminary evaluation of long-term treatment.

The acute and long-term effects of oral pergolide mesylate, a new potent, long-acting dopamine agonist, were investigated in 10 hyperprolactinaemic patients. After a single 50 micrograms dose of pergolide mesylate, serum prolactin concentrations fell steadily to reach a mean minimum value at 6 h of 20% of baseline values; this degree of suppression was maintained throughout the 24 h study period. In one patient serum prolactin was measured for 2 days after a single dose and remained suppressed for 45 h. There were no acute changes in the serum concentration of luteinising hormone, follicle-stimulating hormone and growth hormone. Preliminary evaluation of longer term treatment with pergolide indicates that this drug at a once-daily dose of 50-150 micrograms is a safe, well tolerated, and effective new treatment for hyperprolactinaemia.

Administration, Oral↗
PubMed1980

Cardiovascular effects of single oral doses of the new beta-adrenoceptor blocking agents betaxolol (SL 75212) in healthy volunteers.

1 The effects of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, on the cardiovascular response to exercise have been studied in six normal subjects after placebo and single oral doses of 5, 10, 20 and 40 mg given double-blind in a randomized sequence. 2 All doses reduced exercise heart rate, with a significant reduction persisting to 23 h after doses of 20 mg and 40 mg. Systolic blood pressure on exercise was reduced after all doses, with a reduction continuing to 23 h after doses of 10 mg and above. 3 The mean elimination half-life of SL 75212 was 17.5 +/- 3.9 h. The plasma clearance ranged from 0.15--0.48 1 kg-1 h-1 and the volume of distribution from 5.8--13 1 kg-1. 4 There was a significant correlation between the peak blood levels and change in exercise heart rate (r = 0.53, P less than 0.05) and between the area under the blood concentration curve and the effect of the exercise heart rate (r = 0.55, P less than 0.01).

Adrenergic beta-Antagonists↗
PubMed1980

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↗
PubMed1980

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↗
PubMed1979

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↗
PubMed1979

Oestrogen-gonadotrophin feedback abnormalities in hyperprolactinaemic amenorrhoea demonstrated by the response to clomiphene administration.

Clomiphene was administered to 16 patients with elevated serum prolactin levels in doses of 100, 200 and 300 mg/day for five days in succeeding months and total urinary oestrogens estimated on days 0, 5, 8, 12 and 15 following commencement of treatment. The responses were compared with six patients who were amenorrhoeic but had normal serum prolactin levels and absent positive feedback to oestrogen. The increased outputs of oestrogens were similar in the two groups. In the hyperprolactinaemic group 5 out of 16 subjects showed evidence of ovulation whilst the remainder showed a secondary failure of response. Six subjects who failed to ovulate were treated with clomiphene and human chorionic gonadotrophin (HCG) and ovulations were induced in 31 out of 34 treatment cycles but no pregnancies were achieved. The responses to clomiphene therapy in the hyperprolactinaemic subjects were compared to the assessment of positive feedback mechanisms by means of oestrogen provocation and oestrogen amplification tests and good correlation was obtained. Only those with evidence of positive feedback to these tests were likely to ovulate on clomiphene.

Amenorrhea↗
PubMed1978

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↗
PubMed1978

Response of acromegaly to long term bromocriptine therapy: a biochemical and clinical assessment.

The long term effects of bromocriptine in 12 acromegalics treated for a mean duration of 10.2 months are reported. Seven showed a significant (P less than 0.05) and sustained fall in serum immunoreactive growth hormone (GH) levels throughout 24 h, 6 of whom had a 50% or greater reduction in mean circulating GH during glucose tolerance testing. Only one patient had mean serum GH levels throughout the day suppressed to normal (less than 5 mIU/l) but 3 had suppression of mean serum GH during GTT to normal or very near normal (less than 10 mIU/l). The effective dose was 20 mg daily. Only 4 patients reported any improvement in soft tissue swelling and acral features, which was unrelated to the GH response. Possible reasons for the discrepancy between clinical and biochemical responses are discussed. In 9 of the 12 patients bromocriptine was discontinued and pituitary ablative therapy offered. Three out of 4 patients who underwent trans-sphenoidal hypophysectomy had mean GH levels during GTT reduced to less than 7 mIU/l. In the three who continued bromocriptine treatment GH suppression was maintained at less than 10 mIU/l for up to 3 years but with little change in acral features. Although bromocriptine is safe and was well tolerated it is not as effective as existing forms of pituitary ablative therapy and should be reserved for those cases where ablation is contraindicated or unsuccessful.

Acromegaly↗