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Biomedical subjects

K Mashiter

Publications and source records attributed to K Mashiter.

At least 73 records · Page 4Linked to original sources

Interstitial pituitary irradiation with 90Y for the treatment of acromegaly. A reappraisal.

The management of 54 acromegalics referred to us between 1974 and 1978 has been analysed. Twenty-two patients were treated with pituitary implants of yttrium-90 (90Y). Eleven are in complete remission (mean growth hormone (GH) less than 11 mIU/l), 8 had improved (mean GH 11-20 mIU/l or 50% less than preoperatively) and 3 were poor responders. Two patients had temporary 6th nerve paresis. Seven patients are on replacement therapy. Thirty-one patients were not implanted for the following reasons with a number of patients having more than one: extension of the tumour into the sphenoid sinus 10, or above the sella 3, partially empty sella 9, internal carotids too close to midline 2, invisible landmarks 1, mild acromegaly 6, poor general health 3, declined investigations or operation 6. It is concluded that pituitary implant of yttrium is an effective and safe form of treatment in carefully selected patients.

Acromegaly↗

Growth hormone and prolactin secretion by dispersed cell cultures of a normal human pituitary: effects of thyrotrophin releasing hormone, theophylline, somatostatin, and 2-bromo-alpha-ergocryptine.

Growth hormone (GH) and prolactin (Prl) secretion by a normal human pituitary in dispersed cell culture has been investigated. Prl secretion was significantly stimulated after 0.5, 1, 2 and 4 h exposure to 1, 10, 100 and 1000 ng/ml thyrotrophin releasing hormone (TRH). Maximal effects were obtained with 10 ng/ml TRH at 2 h, higher doses being less effective. GH secretion was unchanged with the exception that 1 ng/ml TRH produced a small decrease at 4 h. GH and Prl secretion was significantly inhibited by incubation with 0.01, 0.1, 1 or 10 micrograms/ml 2-bromo-alpha-ergocryptine (bromocriptine). The inhibition persisted for a further 24 h after removal of bromocriptine. Theophylline (10(-2) M) significantly increased GH and Prl secretion during a 4 h incubation and this effect was blocked by co-incubation with 10 ng/ml somatostatin (SRIF). SRIF also inhibited basal GH and Prl secretion during 4 h and removal of SRIF and incubation for at further 4 h led to a rebound in GH and Prl secretion to levels greater than control. It is concluded that cell culture techniques previously applied to the study of hormone secretion by pituitary adenomas can be equally applied to the normal human pituitary.

Bromocriptine↗

Deoxycorticosterone and aldosterone excretion in Cushing's syndrome.

We have used specific radioimmunoassays to measure urinary free deoxycorticosterone (DOC) and total aldosterone excretion in 15 patients with Cushing's syndrome. Free DOC excretion was increased in 6 of 8 patients with pituitary-dependent adrenal hyperplasia, in 2 of 3 patients with adrenal adenoma, and in all 4 cases with adrenal carcinoma. The most marked increase was noted in the adrenal carcinoma cases. Aldosterone excretion was high, normal, or low in each of the three types of Cushing's syndrome. The free DOC response to metyrapone in Cushing's syndrome due to adrenal adenoma was markedly different from that in patients with adrenal hyperplasia (pituitary-dependent) and may serve as a test to ascertain the etiology of the disorder. Correlations of free DOC and aldosterone excretion with free cortisol excretion, and their responses to the administration of metyrapone and dexamethasone were compatible with ACTH dependency in adrenal hyperplasia, autonomous production of steroids in adrenal adenomas and a chaotic steroidogenesis in adrenal carcinoma.

Adenoma↗

Beta-adrenergic blockade and the metabolic response to surgery.

The effect of the administration of propranolol 0.15 mg per kg body weight i.v. on the metabolic response to pelvic surgery was compared with results in similar patients who had not received propranolol. The only significant difference between the two groups was a lower plasma insulin concentration in the beta-blockade patients after 60 and 90 min of surgery. The glycaemic response to surgery was unimpaired in the propranolol-treated patients and there were no adverse haemodynamic effects. We conclude that beta-adrenergic blockage is unlikely to have deleterious metabolic effects on healthy patients.

Adult↗

Adrenocorticotropin and lipotropin secretion by dispersed cell cultures of a human corticotropic adenoma: effect of hypothalamic extract, arginine vasopressin, hydrocortisone, and serotonin.

Basal and modulated secretion of ACTH and lipotropin (LPH) by cultures of trypsin-dispersed cells of a biopsy of a human corticotropic adenoma have been examined. ACTH secretion was detectable throughout the period of culture (13 days) but declined steadily from an initial production rate of 238 +/- 124 ng/3 X 10(5) cells/12 h. The time course of secretion showed a slower phase over the first 4 h, with increases up to 12 h. An extract of rat stalk median eminence caused a significant (P less than 0.005) dose-dependent increase in both ACTH and LPH secretion during 30 min. The patterns of response for ACTH and LPH were very similar; both exhibited a decline in the basal release of peptide subsequent to the period of stimulation. The addition of hydrocortisone (0.2 micrograms/ml) did not suppress basal ACTH secretion during 30 min but significantly (P less than 0.05) inhibited stimulation produced by rat stalk median eminence extract. Arginine vasopressin (dose range, 1-9 ng/ml) significantly (P less than 0.025) stimulated both ACTH and LPH secretion during 30 min. The patterns of response were again very similar. Serotonin (dose range, 0.01-10 micrograms/ml) did not affect ACTH secretion during incubations of 30 min to 4 h. The results obtained with the cell cultures of a human corticotropic cell adenoma concur with in vivo findings of incomplete autonomy of secretion, parallel secretion of ACTH and LPH in response to provocative stimuli, and suppression by corticosteroids. The technique has potential for exploring the cellular mechanisms controlling secretion by human corticotropic adenomas as well as the nature of the hormones produced.

Adrenocorticotropic Hormone↗

Treatment of Cushing's disease in juveniles with interstitial pituitary irradiation.

Nine juvenile patients (five boys and four girls aged 10--18 with Cushing's disease were treated with pituitary implantation of 198Au and/or 90Y. No patient had any surgical complication from the procedure. At the latest assessment, 3 months to 17 years after operation, Cushing's disease was in remission in all the patients; the response time following operation was a few days to 3 months. Radiology of the pituitary fossa at time of pituitary implantation was normal in all patients and remains so. The final height in six patients is 149--172 cm (59--67.5 inches) and three patients who continue to grow have increased by 13, 6 and 3 cm since implantation. Only one patient required full pituitary hormone replacement therapy, and he had been previously treated by external irradiation, and one other patient failed to complete puberty. In all the other seven sexual maturation is normal and one has fathered two children. We conclude that pituitary implantation with interstitial irradiation is a satisfactory form of treatment for Cushing's disease in juveniles.

Adolescent↗

Pregnancies in women with hyperprolactinaemia: clinical course and obstetric complications of 41 pregnancies in 27 women.

Observations are reported on 41 pregnancies in 27 patients who initially had infertility and raised serum prolactin concentrations. Associated symptoms were secondary amenorrhoea (81 per cent) and galactorrhoea (81 per cent). All patients were at risk of pituitary expansion during pregnancy, especially these 19 (70 per cent) with radiological evidence of pituitary tumours. Fifteen patients had 21 pregnancies after pituitary implantation with 90yttrium; 14 patients had 20 pregnancies without prior pituitary implantation or any other attempt to prevent tumour expansion. During pregnancies, tumour enlargement as shown by diminished visual acuity, visual field defects, severe headaches, diabetes insipidus and radiological changes occurred only in 3 of the 14 patients who had not had implants. Two patients who became pregnant both before and after pituitary implantation suffered tumour expansion in their pregnancies before implantation, but not when pregnant after the operation. The induction and Cesarean section rates were about 30 per cent in 32 term pregnancies in 25 patients. Details of how pregnancy was achieved and the associated obstetric problems are given.

Adult↗

Riedel's thyroiditis leading to severe but reversible pituitary failure.

This patient with histologically proved Riedel's thyroiditis had hypothyroidism of sufficient severity to cause panhypopituitarism, and it was this which first brought him to medical attention. The beneficial effects are described of surgery in relieving severe dysphagia and stridor, and of prednisone in softening and shrinking the hard neck mass. The extent of pituitary failure, and the degree of recovery on treatment with thyroxine are reported, together with details of 4 other cases of Riedel's thyroiditis seen by one of the authors (S.T.).

Adult↗

Cushing's syndrome due to adrenocortical carcinoma - a comphrensive clinical and biochemical study of patients treated by surgery and chemotherapy.

Four post-menopausal women had Cushing's syndrome due to adrenal cortical carcinomas. Comprehensive analyses of blood and urinary steroids showed that although the steroid profiles differed between patients, the pattern in each patient remained almost constant as the disease progressed, or remitted due to therapy. Elevations of serum testosterone and oestradiol were commensurate with the extent of virilisation, and the urinary output of aldosterone was associated with the severity of hypertension. A new finding was that all had substantially increased urinary free deoxycorticosterone. Complete surgical removal of the primary tumours was impossible but when most of the tumour tissue was removed, full clinical and biochemical remissions were obtained for a short time in 2 patients. One patient obtained a clinical and biochemical remission from op'DDD. In another patient the drug caused reduction both in blood pressure and in urinary aldosterone excretion, but there were unpleasant side effects. A third patient could not tolerate op'DDD. Metyrapone therapy produced neither clinical nor biochemical improvement in 3 patients. The mean duration of survival was 17 months after the first symptoms and 10 months from the date of operation. Despite advances in drug therapy, adrenal cortical carcinoma remains a lethal disease. Biochemical screening of multiple steroids offers a means of early diagnosis and disease monitoring. Extensive surgical removal of the tumour offers the best chance of a clinical and biochemical remission.

17-Ketosteroids↗

Pharmacokinetic and concentration-effect studies with intravenous metoclopramide.

1 Pharmacokinetic and concentration-effect studies have been carried out following intravenous injection of 10 mg metoclopramide hydrochloride to seven normal male volunteers. 2 It is proposed that a two-compartment model adequately describes the disposition of the drug which is rapidly distributed (T1/2alpha = 4.9 +/- 1.1 min) and eliminated (T1/2beta = 165.7 +/- 20.2 min). Total body plasma clearance of the drug is high (10.9 +/- 1.5 ml min-1 kg-1) and approximates to liver plasma flow. 3 Metoclopramide i.v. increases gastric emptying as measured by an ethanol absorption test (P less than 0.005). The duration of this effect is at least 3 h. 4 Ethanol given after i.v. metoclopramide administration produces significant sedation during the first hour and at 3 h (P less than 0.001). 5 The effect of metoclopramide on gastric emptying, and the degree of sedation induced by ethanol would appear to be related to plasma metoclopramide concentration. 6 Metoclopramide increases serum prolactin to 59 +/- 5.8 microgram/1 at 30 min after injection. There is a linear relationship (r = 0.809) between serum prolactin increase and plasma metoclopramide concentration.

Adult↗

Treatment of prolactin-secreting pituitary tumours in young women by needle implantation of radioactive yttrium.

Twenty-one young female patients are described who presented with amenorrhoea, galactorrhoea or infertility, and were treated by 90Y pituitary implantation of 20,000 rads. There was no morbidity. In all patients serum prolactin values were elevated and radiographs of the pituitary fossa were abnormal. Observations are available for 1--76 months (mean 27) after implantation. The median fall in prolactin values was 60 per cent while there was no deterioration in pituitary function if normal pre-operatively. Luteinizing hormone values, both basally and following gonadotrophin-releasing hormone, rose to normal after operation; several instances of sellar remodelling were observed radiologically, and no instance of relapse was found radiologically, biochemically or clinically. Thirteen patients desiring fertility have been observed since implantation; so far nine have become pregnant, in three instances without any additional therapy; since four patients became pregnant twice, a total of 13 pregnancies have occurred. No case of tumour expansion was observed during pregnancy. 90Y implantation can be considered as a therapeutic procedure in young female patients requiring fertility which is competitive with surgical methods, and together with a short course of bromocriptine if needed, could prove to be the treatment of choice.

Adult↗