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Biomedical subjects

P M Horrocks

Publications and source records attributed to P M Horrocks.

At least 19 recordsLinked to original sources

Metabolic effects of pharmacological adrenergic blockade in phaeochromocytoma.

Twelve-hour hormonal and metabolic profiles were performed in a 68-year-old woman with a benign adrenal phaeochromocytoma (a) prior to adrenergic blockade, (b) after the establishment of pharmacological alpha-blockade with phenoxybenzamine, (c) after combined alpha and beta-blockade with phenoxybenzamine and propranolol, and (d) after successful surgery and withdrawal of medication. Pretreatment, (a) vs (d), significant elevations (12-h mean +/- SD) were observed in the concentrations of noradrenaline (44.9 +/- 14.4 vs 2.3 +/- 0.7 nmol/l, P less than 0.01), glucose (6.9 +/- 1.9 vs 5.0 +/- 1.0 mmol/l, P less than 0.05), glycerol (0.22 +/- 0.02 vs 0.07 +/- 0.01 mmol/l, P less than 0.01), non-esterified fatty acids (0.71 +/- 0.28 vs 0.34 +/- 0.08 mmol/l, P less than 0.01), and total ketone bodies (0.08 +/- 0.03 vs 0.03 +/- 0.02 mmol/l, P less than 0.01). Alpha-blockade, (b) vs (a), was associated with an increase in noradrenaline levels (P less than 0.01) but not with any significant alterations in intermediary metabolite concentrations. Following the establishment of combined alpha and beta-blockade, (c) vs (b), plasma noradrenaline returned to its pretreatment level while the concentrations of glycerol, fatty acids and ketone bodies were normalized. A completely physiological 12-h blood glucose profile, however, was observed only post-operatively. No significant differences were observed in mean plasma insulin levels between the four studies. These results indicate impaired regulation of multiple aspects of carbohydrate, lipid and ketone body metabolism in our patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

Qualitative and quantitative abnormalities of von Willebrand antigen in patients with diabetes mellitus.

Previous reported studies of vVWf antigen (vWf:Ag) in patients with diabetes mellitus have not shown qualitative abnormalities despite frequent documentation of raised vWf:Ag. Twenty two patients with established diabetes mellitus have been studied and qualitative abnormalities of vWf:Ag multimers were found in 10 patients who had poorer glycaemic control (as judged by plasma fructosamine) than the other 12 patients. Seven of the 22 patients were restudied after a 3 month period of improved glycaemic control and the vWf:Ag multimer abnormalities disappeared in 6 of these. Some of the structural abnormalities were accompanied by loss of vWf functional activity. As vWf:Ag is synthesised in the endothelial cell, vWf:Ag abnormalities during periods of poor glycaemic control may reflect endothelial cell damage with vWf:Ag release and possibly subsequent proteolysis.

Antigens↗

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↗

Xiaoke tea, a Chinese herbal treatment for diabetes mellitus.

Xiaoke tea, a traditional Chinese treatment for diabetes mellitus, lowered blood glucose concentrations in streptozotocin diabetic mice. To investigate Xiaoke clinically, a double-blind crossover study was undertaken in 12 non-insulin-treated diabetic patients. Xiaoke tea and ordinary tea (infusion of 2.72 g, 4 times daily) were consumed in random order for 4 weeks. A standard breakfast meal was taken before and after each treatment period. Xiaoke did not significantly affect glycosylated haemoglobin, basal or post-breakfast serum glucose and insulin concentrations, intermediary metabolite concentrations, triglyceride and cholesterol. No adverse side-effects of Xiaoke were evident.

Blood Glucose↗

Effects of long term dexamethasone treatment in adult patients with congenital adrenal hyperplasia.

We have followed nine adult patients with congenital adrenal hyperplasia (CAH) for between 7-77 months on dexamethasone (DXM) 0.5 mg mane and 0.25 mg nocte, reducing to 0.5 mg mane. Twenty-four hour profiles of ACTH, 17-hydroxyprogesterone (17OHP), and androstenedione were performed; the areas under the curves (AUC) and the heights of the morning peaks were used to assess biochemical control. Comparisons were made between treatment before DXM (pre-DXM), 0.75 mg for 2 weeks (DXM-ST), 0.75 mg for at least 3 months (DXM-LT), and 0.5 mg for at least 3 months (DXM-0.5). None of the three males suffered any significant side-effects. All women had menstrual disturbance but in three ovulation was induced. One female developed Cushing's syndrome and two developed hirsutism which resolved on stopping DXM. Overall there was no significant difference between DXM-ST and DXM-LT (mean AUCs for ACTH: DXM-ST 660, DXM-LT 383, for 17OHP: DXM-ST 1177, DXM-LT 587, for androstenedione DXM-ST 232, DXM-LT 121). Reduction of the dose from 0.75 mg to 0.5 mg led to significant deterioration in control (Mean AUC's for ACTH DXM-0.5, 1123 (P less than 0.02), for 17OHP DXM-0.5, 2068 (P less than 0.002), for androstenedione DXM-0.5, 213 (P less than 0.5). We conclude that DXM is a satisfactory regime but the dose must be adjusted for each patient.

17-alpha-Hydroxyprogesterone↗

Metabolic and hormonal responses during squash.

The metabolic and hormonal response during squash was observed in eight normal men. Significant increases from resting were found for blood glucose, lactate, pyruvate, alanine and glycerol while total ketone bodies and plasma nonesterified fatty acids rose after play stopped. Insulin and C-peptide decreased significantly and catecholamines, ACTH, prolactin and growth hormone increased.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

Sleep apnoea in acromegaly.

Day time somnolence or excessive snoring, or both, occurred in five out of 11 patients with acromegaly. All five had episodes of sleep apnoea, and three had the sleep apnoea syndrome. Growth hormone concentrations were higher (p less than 0.025) in these patients than in the six patients without these symptoms. One patient with daytime somnolence and one asymptomatic patient had flow loop evidence of upper airways obstruction. Two of the patients with the sleep apnoea syndrome had cardiomegaly. Sleep apnoea appears to be common and clinically important in acromegaly, and it may be central, obstructive, or mixed. Polygraphic nocturnal monitoring is indicated to assess these patients properly.

Acromegaly↗

Urinary pregnanetriol excretion in hirsutism.

Eighteen consecutive hirsute women attending an endocrine clinic have been studied by measurement of the urinary pregnanetriol excretion before and following the concurrent administration of corticotrophin and metyrapone. An abnormal increment in pregnanetriol excretion was observed in 11 of these 18 patients. It is suggested that this is evidence that an adrenal abnormality, probably operative at the 21-hydroxylase level, might be a factor responsible for the hirsutism in these 11 patients. Five adrenalectomized women who were also studied showed no significant increase in urinary pregnanetriol excretion in response to concurrent corticotrophin and metyrapone administration.

Adrenalectomy↗

Anticholinergic withdrawal and benzhexol treatment in Parkinson's disease.

The effects of slow withdrawal of anticholinergic medication and addition of benzhexol (8 mg/day) have been studied in patients with Parkinson's disease on stable levodopa therapy. Withdrawal of anticholinergic drugs led to measurable and often severe deterioration in about two-thirds of patients. Addition of benzhexol produced a slight but definite additional improvement in those patients in whom anticholinergics were withdrawn before the trial. Anticholinergic drugs thus still have a part to play in the treatment of Parkinson's disease, for they produce benefit in addition to that provided by levodopa.

Adult↗