Chronic treatment of intact rats with various doses of TSH increased the thyroidal 35S accumulation after single doses of [35S]methimazole (MMI) and [35S]propylthiouracil (PTU). However, no effect on the intrathyroidal breakdown of the drugs was observed. Thus absolute thyroidal levels of unmetabolized MMI and PTU were increased by factors of up to 2 and 3, respectively, compared to the control groups. Simultaneous decreases in the levels of thyroidal total iodine were observed. Hypophysectomized rats showed a marked inhibition of both thyroidal accumulation and oxidation of [35S]-MMI but TSH treatment of hypophysectomized rats restored the accumulation and oxidation to sham-operated and control group levels. The results show that in rats TSH has an important role in the control of thyroidal levels of antithyroid drugs currently used in the treatment of hyperthyroidism.

Animals↗

PubMed1977

Biguanides and lacticacidosis.

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Diabetes Mellitus↗

PubMed1977

Early diastolic murmurs in end-stage renal failure.

An early diastolic murmur thought to indicate functional aortic regurgitation was heard in 7 of 74 consecutive patients with end-stage renal failure assessed for chronic intermittent haemodialysis and transplantation. In all 7 cases the murmur was transient and related to episodes of hypertension and fluid overload and disappeared on correction of these factors. In a further 2 patients aortic regurgitation resulted from a structural abnormality of the aortic valve. Thus, an early diastolic murmur is not uncommon in this situation and does not necessarily indicate organic aortic valve disease which might preclude selection for haemodialysis and transplantation.

Adolescent↗

PubMed1977

The urinary sodium: potassium ratio and response to diuretics in resistant oedema.

Nineteen patients with severe oedema due to either cirrhosis of the liver or to congestive cardiac failure, who had failed to respond to previous diuretic therapy, were treated with either increasing doses of frusemide (Group A), or with frusemide in a fixed dose of 80 mg daily and increasing doses of spironolactone (Group B). In Group A there was an inverse correlation between the baseline 24-hr urinary sodium: potassium (Na : K) ratio and the 24-hr urinary potassium excretion during diuresis, and a direct correlation between the urinary Na : K ratio before and after diuresis. Thus, in patients of this group during diuresis, there was a significantly higher urinary potassium excretion in those with a baseline urinary Na : K ratio of less than 1, as compared with those with a ratio of greater than 1. In Group B a satisfactory diuresis was achieved without marked urinary potassium loss in those patients with a baseline urinary Na : K ratio of less than 1, whereas no diuresis was obtained in the two patients with a baseline urinary Na : K ratio of greater than 1. These results suggest that the measurement of the baseline urinary Na : K ratio is of help in determining the potential value of spironolactone in patients with resistant oedema.

Adult↗

PubMed1977

Role of TSH in the changes in thyroidal metabolism of [35S]methimazole in phenobarbital and thyroxine-treated rats.

The effect of phenobarbital (PB) and/or thyroxine on the thyroidal accumulation and oxidation of [35S]methimazole (MMI) and serum TSH levels was studied in rats. PB treatment increased the accumulation of MMI and the serum TSH levels, but concurrent administration of T4 reversed these effects. It was concluded that increased TSH secretion in PB-treated animals was likely to be the major mechanism involved in the increased MMI accumulation. PB also increased the intrathyroidal oxidation of MMI to sulphate. However, in contrast to the PB effect on accumulation, concurrent T4 administration only partially reversed the effect on oxidation. The results suggested that the increased oxidation of MMI in PB-treated animals was due to a direct effect of PB or possibly a combination of this direct effect and the indirect TSH effect. Possible mechanisms postulated for a direct effect were thyroidal microsomal enzyme induction and/or changes in thyroidal protein binding of MMI.

Animals↗

PubMed1977

The placental transfer of propylthiouracil, methimazole and carbimazole.

The placental transfer of 35S-labelled methimazole (MMI), carbimazole and propylthiouracil (PTU) has been examined in the rat in late pregnancy and in patients undergoing therapeutic abortion. Although rapid equilibrium of fetal and maternal serum radioactivity (FS:MS ratio 1:1) occurred after iv administration of 35S-carbimazole or 35S-MMI in rats, a persistent fetal to maternal ratio of less than one was observed after 35S-PTU administration. Results from human studies after a single oral dose indicate that, as in the rat, the placenta appeared to be more permeable to 35S-MMI than to 35S-PTU as shown by the marked difference in fetal serum:maternal serum ratios and amounts accumulated in the fetus. Localization of radioactivity in the human fetal thyroid was also observed after administration of 35S-labelled MMI, carbimazole or PTU.

Abortion, Induced↗

PubMed1977

The effect of insulin on vascular reactivity to norepinephrine.

The effect of insulin on the vasoconstrictor response to norepinephrine of the resistance bed of the isolated perfused rat tail has been studied. Insulin produced a significant attenuation of this response in concentrations of both 120 mU./ml. and 150 micronU./ml. It is suggested that this effect may be relevant to the hypotensive action of insulin observed in diabetics.

Animals↗

PubMed1977

Sporadic non-toxic goitre. A long-term follow-up of 36 patients.

Thirty-six patients with non-toxic goitre were reviewed after a mean period of 13 years. Initially 19 patients were iodine deficient (Group I) and 17 had normal plasma inorganic iodine (Group II). In general the iodine deficient patients had larger goitres, developed more complications (26% became hyperthyroid, hypothyroid or required partial thyroidectomy), and required more treatment. There were marked changes in thyroid function tests. In both groups thyroid uptake fell and PII rose though the final PII remained significantly lower in Group I patients. Thyroid and renal iodide clearance fell significantly in Group I patients only. In both groups the final mean total serum T3 levels were abnormally elevated whereas the mean PBI levels did not change significantly during the period of study and the final mean total T4 concentrations were noraml. All goitres became smaller and there were no complications in patients whose goitre became impalpable. No cases of malignancy and no postoperative recurrences of goitre were observed. It is suggested that the incidence of complications in those patients who persist with palpable goitres is sufficent to merit follow-up of this group.

Aged↗

PubMed1976

Letter: Guanethidine in hypertension.

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Drug Therapy, Combination↗

PubMed1976

Total thyroidal content of iodine in thyrotoxic patients measured by in vivo neutron activation analysis.

This paper describes an in vivo method for measuring total thyroidal iodine stores by activation analysis, its evaluation and measurements in thyrotoxic patients. There was good correlation between measurements of solutions of iodine and post-mortem thyroids by activation analysis and chemical analysis. Measurements in thyrotoxic patients showed low levels in untreated and treated (antithyroid drugs) patients and a marked increase in patients studied whilst in clinical remission. The practical importance of this method of measurement of thyroidal iodine stores is that it is a reliable in vivo measurement obtained at a single visit and should enable the definition of the relationship of thyroidal iodine stores to pathophysiology and prognosis.

Activation Analysis↗

PubMed1976

Chlorpropamide and fibrinolytic activity in maturity onset diabetes mellitus.

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Aged↗

PubMed1975

Geriatric patients in an acute medical ward.

During a nine-month study 160 out of 482 bed-weeks in an acute medical ward were accounted for by 11 patients who no longer needed to be there. This was unsatisfactory both for the 11 patients concerned and for those patients requiring admission for whom the beds were blocked.

Aged↗