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Biomedical subjects

I A MacFarlane

Publications and source records attributed to I A MacFarlane.

At least 91 records · Page 5Linked to original sources

Increased circulating radioreceptor-active growth hormone in insulin-dependent diabetics.

A radioreceptor assay (RRA) for GH, using pregnant rabbit liver membranes, was used to evaluate the receptor-hormone interaction of circulating (serum) GH in diabetics. Multiple morning blood samples were taken from 18 fasted insulin-dependent diabetics on three occasions and assayed for GH by the RRA and radioimmunoassay (RIA). Samples from 12 normal subjects (GH secretion stimulated by exercise and hypoglycaemia) and 11 acromegalics were also studied. The RRA/RIA ratio was higher in samples from the acromegalics than in normal subjects (0.85 vs 0.65, P less than 0.01) and only a few samples had RRA values greater than RIA. All the samples from 14 of the diabetics had lower RRA values than RIA, but 40% (39 of 96) of samples from the remaining four diabetics had RRA concentrations markedly in excess of the levels measured by RIA. Sephadex chromatography (G100) of serum samples revealed similar proportions of immunoreactive GH forms in the diabetics with high RRA values compared with the diabetics with low RRA values. These findings may indicate intermittent secretion of highly bioactive GH in some insulin-dependent diabetics. Further studies on the biological properties of circulating GH are needed to clarify the role of GH secretion in the development of diabetic microvascular complications.

Acromegaly↗

Circulating growth hormone forms in type 1 diabetic subjects: comparison with normal subjects and acromegalics.

The molecular forms of growth hormone (GH) in serum from 18 Type 1 diabetic patients with poor metabolic control were analysed using sephadex G-100 chromatography. The profiles obtained were compared with those from normal subjects whose GH secretion was stimulated by exercise and hypoglycaemia and eight acromegalic patients. In the three groups three distinct GH forms were found: little (monomeric), big and big-big-GH. Samples from normal subjects contained 45% little-GH which was less than samples from the diabetics and acromegalics (53% and 65%, respectively, P less than 0.01). Further samples from normal subjects after the onset of hypoglycaemia showed an increase in little-GH. In the three groups, the higher the proportion of little-GH, the lower the proportion of big-big-GH, while the proportion of big-GH remained similar. In the acromegalics the proportion of little-GH was strongly correlated with the log concentration of serum GH. As little-GH is cleared from the circulation quicker than the larger forms these data indicate that the main component of the frequent surges of GH secretion in poorly controlled Type 1 diabetic subjects is little-GH (monomeric forms). The sustained release of GH found in acromegaly is composed largely of monomeric forms.

Acromegaly↗

Impaired glucose tolerance in the third trimester of pregnancy.

When the methods and interpretation of glucose tolerance as recommended by the World Health Organisation were applied to 247 patients in the third trimester of pregnancy selected on account of glycosuria, previous large-for-dates offspring, diabetic family history, maternal obesity or a fetus large for gestational age, impaired glucose tolerance (IGT) was found in 20 (8.1%). Patients with IGT were older than those with normal tests: 30.5 +/- 4.8 years (mean +/- S.D.) vs 27.8 +/- 4.8 years (p less than 0.02) and more having IGT had a first degree family history of diabetes (25% vs 10%, p less than 0.05). The majority (15) of the IGT patients then received dietary advice to restrict refined carbohydrate. Post-prandial blood glucose and HbA1 concentrations in these subjects remained within the normal range except for one patient who was treated with insulin. Pregnancy outcome was satisfactory in the patients with impaired tolerance and further studies will be required to assess the clinical significance of IGT in pregnancy.

Adult↗

Discordant serum alpha-subunit and FSH concentrations in a woman with a pituitary tumour.

We have studied a women who presented at the age of 51 with a large FSH and alpha-subunit producing pituitary adenoma. Following insertion of ventriculo-peritoneal shunts and external pituitary irradiation there was no change in the elevated serum concentrations of FSH, and alpha-subunit over a four year period although she developed both ACTH and TSH deficiency. Various drugs, however, did alter the FSH and alpha-subunit concentrations and these changes suggest possible mechanisms controlling FSH secretion. Ethinyloestradiol 0.03 mg daily for three weeks suppressed serum FSH to 77% of the basal level (240 +/- 35 i.u./l to 184 +/- 20 i.u./l) but alpha-subunit rose to 130% of basal level (281 +/- 50 ng/ml to 366 +/- 40 ng/ml). On ethinyloestradiol 0.1 mg daily, FSH suppressed to 17% of basal (40 +/- 11 i.u./l) with no change in alpha-subunit concentration, while on 0.2 mg daily suppression of FSH was similar but alpha-subunit fell to 59% of basal (190 +/- 28 ng/ml). Dexamethasone, 3 mg daily for one week reduced FSH to 53% of the initial concentration and alpha-subunit to 74% while bromocriptine 7.5 mg daily for three months, reduced FSH to 39% and alpha-subunit to 66% of basal. Neither thyroxine, 0.2 mg daily for four weeks, nor an LHRH analogue, (Buserelin, Hoechst) 200 micrograms, three times daily for three months elicited any effect. Chromatography on Sephadex G100 showed that serum FSH and alpha-subunit both had Kav values somewhat lower than those of their standard counterparts (FSH, 0.20 vs 0.25; alpha-subunit 0.35 vs 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Chromophobe↗

Severe postural hypotension following home canoe construction from polyester resins.

On two occasions a 36-year-old man developed severe postural hypotension and neurological signs after working with a polyester resin canoe building kit in an unventilated shed. It is likely that his recurrent illness was caused by styrene intoxication. Postural hypotension secondary to styrene exposure has not previously been reported.

Hobbies↗

The hypothalamic-pituitary-thyroid axis in type 1 diabetes: influence of diabetic metabolic control.

The influence of diabetic metabolic control on indices of thyroid function was studied in 9 euthyroid, insulin-dependent (Type 1) diabetics. During chronic poor metabolic control (mean fasting blood glucose 13 mmol/l and HbA1 concentrations 14.7%) serum T3 concentrations were low (P less than 0.01) while serum T4 and basal TSH concentrations were normal. After 6-8 weeks of improved metabolic control, mean HbA1 concentrations had fallen to 10.7% (P less than 0.01) and serum T3 concentrations had increased into the normal range. Serum T4 and basal TSH concentrations were unchanged. The serum TSH response to iv TRH remained normal throughout the study. In Type 1 diabetics, with chronic poor metabolic control, the serum T4 concentration and the TSH response to TRH are therefore appropriate indicators of thyroid function.

Adult↗

Single daily dose short term carbimazole therapy for hyperthyroid Graves' disease.

Twenty-one patients with hyperthyroid Graves' disease were treated with carbimazole 30 mg daily, given as a single dose. Propranolol was also given for the first 3 weeks. All became clinically euthyroid with normal serum thyroxine (T4) levels, usually within 1-3 months. Patients with large goitres and raised serum alkaline phosphatase concentrations took longer to respond. In 19 patients a positive thyroid stimulating hormone (TSH) response to intravenous thyrotrophin releasing hormone (TRH) developed. Carbimazole was stopped soon after (median time of treatment 18 weeks, range 9-41 weeks) and 18 patients have been followed. Seven of these (39%) have remained in remission from hyperthyroidism for more than one year (median 77 weeks). Carbimazole 30 mg once daily is a convenient and effective treatment for hyperthyroid Graves' disease. Many patients will achieve prolonged remissions if treatment is stopped when serum T3 and T4 levels are in the low-normal range, usually 2-4 months after clinical euthyroidism has been reached.

Adult↗

Cushing's disease treated by total adrenalectomy: long-term observations of 43 patients.

Forty-three patients were treated by total adrenalectomy for pituitary-dependent Cushing's disease. The median period of observation was 10 years (range one to 20 years). Thirty-eight patients (88 per cent) had rapid and lasting remissions. Of the 38 in remission, 21 became pigmented but without pituitary enlargement, 11 became pigmented with evidence of further pituitary expansion (Nelson's syndrome) and six neither became pigmented nor showed pituitary expansion. Pituitary expansion was associated with high plasma ACTH values, and treatment of pituitary tumours by surgery or radiotherapy gave poor results. However, when compared with alternative methods of treatment, total adrenalectomy for Cushing's disease is still satisfactory for many patients, despite advances in pituitary surgery, and has advantages over 'medical adrenalectomy' with drugs.

17-Ketosteroids↗

Vitamin D metabolism in hyperthyroidism.

The serum concentrations of 25-hydroxycholecalciferol (25 OH D3), 24,25-dihydroxycholecalciferol [24,25(OH)-2D3] and 1,25-dihydroxycholecalciferol [1,25(OH)2D3] were measured in twenty-one patients with untreated hyperthyroidism. Compared with control subjects, 25 OH D3 concentrations were not altered, 24,25(OH)2D3 concentrations were increased, although not significantly and 1,25(OH)2D3 concentrations were decreased (P = 0.01). Following oral carbimazole therapy, 24,25(OH)2D3 concentrations fell (P less than 0.01), 1,25(OH)2D3 concentrations increased (P less than 0.01) and 25 OH D3 concentrations were unchanged. The altered 1,25(OH)2D3 and 24,25(OH)2D3 concentrations found in hyperthyroidism are probably due to the effects of thyroid hormone on bone and mineral metabolism. Increased serum calcium and phosphate concentrations with secondary hypoparathyroidism result in stimulation of the renal 24-hydroxylase and suppression of the 1-hydroxylase enzymes. In addition, serum 24,25(OH)2D3 concentrations were significantly correlated with serum triiodothyronine levels (T3) (r = 0.66, P less than 0.002) before treatment. This may indicate a direct stimulatory effect of T3 on 24-hydroxylase activity. No relationship was found between serum 1,25(OH)2D3 concentrations before therapy and serum T3.

24,25-Dihydroxyvitamin D 3↗

Glycoprotein hormone alpha-subunit secretion in patients with pituitary adenomas: influence of TRH, LRH and bromocriptine.

Twelve patients with pituitary adenomas and increased serum concentration of the glycoprotein hormone alpha-subunit were studied. Eight patients were acromegalic and one had a FSH producing tumour. The adenomas in 9 patients had undergone subtotal operative removal and/or external irradiation but no patient was studied within 3 months of these treatments. Many of the acromegalic patients, with moderately elevated alpha-levels, showed marked increases in alpha-concentration after TRH and/or LRH, compared with controls. The non-acromegalic patients, with the highest alpha-levels, showed poor responses to releasing hormones. These results suggest that excessive alpha-subunit secretion in acromegalic patients is often under hypothalamic control whereas in non-acromegalic patients it is often autonomous. Seven patients, 4 with acromegaly, were then given oral bromocriptine, 5 mg over 3 h. There was a significant fall in log mean alpha-level at 4 and 5 h (P less than 0.02). Six patients took bromocriptine for 1--2 months. Log mean alpha-concentration was significantly reduced at the end of treatment (P less than 0.02) and then recovered to basal levels after stopping treatment for one week. alpha-Subunit hypersecretion in some patients with pituitary adenomas is therefore modulated by dopaminergic control mechanisms.

Acromegaly↗

Serum glycoprotein hormone alpha subunit, hormone receptors and disease stage in patients with breast cancer.

The concentration of the common alpha subunit of the glycoprotein hormones was high in the serum of 21/56 (38%) of premenopausal patients and 22/106 (21%) of postmenopausal patients with primary breast cancer, at the time of presentation. 7/59 (12%) of patients with benign disease also had high alpha subunit levels. Tumour cytosol oestrogen and progesterone receptor status was determined in 80% of the patients with cancer, and there was a trend towards higher alpha levels in patients without receptors, but this was not statistically significant. In the premenopausal patients with cancer there was a significant correlation between alpha subunit level and disease stage, R = 0.47, P = 0.0001, but not in the postmenopausal patients. In view of the correlation with disease stage, high levels of alpha subunit in premenopausal patients with breast cancer at presentation with the primary tumour may indicate poor prognosis.

Adult↗

Galactorrhoea following surgical procedures to the chest wall: the role of prolactin.

Normal prolactin levels were found in two cases of galactorrhoea following surgical procedures to the chest wall and one was treated successfully with bromocriptine. Studies were then carried out to test the claim that chest-wall injury is one of the common causes of hyperprolactinaemia. Serum prolactin levels were measured before and after thoracotomy in 7 patients, following traumatic rib fractures in 8 patients and after burns to the chest in one patient. No evidence was found to suggest that sustained hyperprolactinaemia follows chest wall surgery or injury, and the role of prolactin in the condition 'chest wall injury' galactorrhoea is discussed.

Adolescent↗

Acquired von Willebrand's syndrome and Ehlers-Danlos syndrome presenting with gastro-intestinal bleeding.

The clinical and laboratory findings in a patient with severe gastro-intestinal bleeding and the Ehlers-Danlos syndrome are described. Coagulation studies and a lack of history of previous haemorrhage were consistent with a diagnosis of acquired von Willebrand's syndrome. His response to treatment with blood transfusion, Factor VIII, cimetidine, tranexamic acid and cyclophosphamide is described. Family studies revealed other members with Ehlers-Danlos syndrome but normal coagulation.

Aged↗