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Biomedical subjects

W A Ratcliffe

Publications and source records attributed to W A Ratcliffe.

At least 91 records · Page 5Linked to original sources

Direct 125I-radioligand assays for serum progesterone compared with assays involving extraction of serum.

We compared two direct radioimmunoassays for progesterone in 50 microL of unextracted serum or plasma with assays involving extraction of serum. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11 alpha hemisuccinyl conjugate and the radioligand 125I-labeled progesterone 11 alpha-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r greater than 0.96) with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. We conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum.

Carrier Proteins↗

Generally applicable 125 iodine-based radioimmunoassays for plasma progesterone.

Two methods are described for estimation of plasma progesterone, both employing a heterologous-bridge radioimmunoassay system with anti-sera raised against a progesterone 11 alpha-hemisuccinate conjugate and a radioiodinated progesterone 11 alpha-glucuronide-tyramine conjugate as tracer. Separation techniques based on double antibody methods have been employed to improve assay precision, and the assays described are sensitive, precise, accurate and robust and well suited to the measurement of progesterone levels for routine monitoring of luteal function. Present evidence suggests that the majority of laboratories which already use such antisera could readily adopt this assay system with its advantages of improved performance and gamma-labelled tracer.

Humans↗

Effects of trimethoprim and sulphonamide preparations on the pituitary-thyroid axis of rodents.

The effects on pituitary-thyroid function of the commonly prescribed anti-bacterial preparations co-trimoxazole and co-trifamole, and their component drugs, have been studied in the rat and compared to the changes caused by propylthiouracil. Co-trimoxazole and co-trifamole, in doses 20-fold in excess of a pharmacological dose administered for 10 days, produced marked changes in hormone levels consistent with blocking of hyperplastic goitre formation, were also demonstrated. Propylthiouracil produced less marked changes of thyroid hormone levels but higher levels of thyroid-stimulating hormone. Pharmacological doses of co-trimoxazole and co-trifamole and sulphamoxole, the sulphonamide component of co-trifamole, caused significant changes in thyroid hormone levels consistent with anti-thyroidal activity. In contrast, there was no evidence that trimethoprim, which is common to both preparations, or sulphamethoxazole, the sulphonamide component of co-trimoxazole, had an anti-thyroidal action, indeed, serum thyroxine levels were significantly increased at pharmacological dosage. We have concluded that the new commonly prescribed combination preparations retain the goitrogenic properties of the earlier sulphonamides.

Animals↗

The effect of surgery with carbohydrate infusion on circulating triiodothyronine and reverse triiodothyronine.

The blood levels of thyrotrophin (TSH), thyroxine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured in a group of patients undergoing cholecystectomy and receiving 2000 kcal of glucose daily throughout the study. TSH changes suggested a peroperative peak followed by a fall and subsequent rise. T4 showed no significant changes. T3 fell and rT3 rose postoperatively, with a highly significant fall in the T3/rT3 ratio (p less than 0.001). Surgery and carbohydrate deprivation separately result in similar changes. However, the demonstration of the changes after injury despite adequate carbohydrate intake strongly suggests that they are a primary response to surgery and not a secondary response to the normal consequential fall in caloric and carbohydrate intake. The changes could be an appropriate adaptation to the changed metabolic requirements.

Adult↗

Combination of potassium iodide and propranolol in preparation of patients with Graves' disease for thyroid surgery.

We assessed the efficacy of the combination of propranolol and potassium iodide in the preparation of patients with Graves' disease for thyroid surgery. Potassium iodide was given orally in a dose of 60 mg three times a day for 10 days before operation in 10 patients who were already receiving propranolol. In contrast to previous experience with either drug used singly, the combined regimen caused a significant fall in mean serum total thyroxine and triiodothyronine to levels in the euthyroid range before operation (P less than 0.001). There was also a significant fall (P less than 0.05) before operation and transient rise after operation in serum reverse triiodothyronine. These preliminary results suggest that the combination of potassium iodide and propranolol may prove to be the optimum preoperative preparation for patients with Graves' disease.

Adult↗

The effect of fenclofenac on thyroid function tests in vivo and in vitro.

Clinically euthyroid patients on long term maintenance therapy with the non-steroidal anti-inflammatory drug fenclofenac (Flenac) show an unusual and abnormal pattern of serum thyroid function tests. In all twelve patients studied, total T4 concentrations were grossly subnormal (mean 28.4 +/- 9.9 (SD) nmol/l and total T3 levels low-normal (mean 1.4 +/- 0.3 (SD) nmol/l), whereas rT3 (mean 0.36 +/- 0.06 (SD) nmol/l) and basal TSH levels (mean 1.9 +/- 0.5 (SD) mu/l) were within their respective normal ranges. Free T4 levels were low normal (mean 11.0 +/- 1.0 (SD) pmol/l) while TSH, T4 and T3 responses to intravenous TRH were similar to those found in euthyroid subjects. These effects appear to be due predominantly to in vivo inhibition of binding of thyroid hormones to carrier proteins in serum, rather than in vitro drug interference in the radioimmunoassays employed. Fenclofenac does, however, interfere in those laboratory methods employing serum proteins as binding agents. Thus the Thyopac 4 method for serum total T4 grossly over-estimates T4 levels, while thyroid hormone binding capacity (Thyopac 3) is low. Since fenclofenac is one of the most potent drugs interfering with routine indices of thyroid status, it is suggested that suspected thyroid dysfunction is excluded before commencing therapy with the drug.

Adult↗

TSH response to TRH in substantial obesity.

TSH response to TRH stimulation was studied in 40 non-obese control females and in 40 obese female subjects 40-148 per cent in excess of their ideal weight prior to receiving dietary advice. One patient was found to be hypothyroid and was excluded from further study. There was no significant difference between the basal serum TSH concentration in the subjects and controls. Obese subjects however had significantly greater serum TSH concentrations at 20 and 60 min following TRH stimulation. The implciations of these findings are at present unexplained.

Adult↗

The effects of whole-body irradiation on the serum levels and kinetics of thyroid hormones in rats.

The effects of a single whole-body dose of X-rays on the serum levels and kinetics of thyroid hormones in rats were studied. The influence of radiation-induced anorexia was monitored by using pair fed control groups. A dose of 800 rad caused a reduction in T4 levels and 750 rad had a similar effect on T3; in each case the control group showed a smaller reduction. The kinetic results indicated that, in the control groups, the early reduction in hormone concentrations was caused, by a change in the distribution of the hormone; however, the continuing reduction in hormone levels in the irradiated rats appeared to results from decreased production. The results suggest that the thyroid system may play an active part in the early metabolic changes which follow whole-body irradiation.

Animals↗

Propranolol, triiodothyronine, reverse triiodothyronine and thyroid disease.

Propranolol alone was given to sixteen hyperthyroid, and concomitantly with thyroxine therapy to ten hypothyroid patients. Following treatment of the hyperthyroid group for 1-2 weeks there was a significant decrease in serum triiodothyronine (T3) which correlated with the plasma propranolol steady state concentration. The serum reverse T3 (rT3) rose significantly. Weight loss ceased in this group while weight gain occurred in patients who had a marked fall in serum T3. One patient with T3 toxicosis went into remission. The reduction in serum T3 was maintained in six patients receiving propranolol for more than 1 month. In the hypothyroid group the mean serum T3 level achieved with 0.15 mg thyroxine per day was significantly lower than in a control group who did not receive propranolol. In five patients following propranolol withdrawal there was a significant rise in T3, a fall in rT3 and TSH, and weight loss. Propranol may therefore have a clinically significant and direct action on the peripheral conversion of thyroxine to T3 and rT3.

Adolescent↗

Metoclopramide stimulation: a test of growth hormone reserve in adolescent males.

A comparison was made between the growth hormone (GH) response to metoclopramide ('Maxolon'--Beecham Laboratories) and insulin induced hypoglycaemia in thirty-five short adolescent males. Both tests initially caused adequate release of GH from the pituitary gland in 86% of those subjects who had normal GH reserve. The peak growth hormone responses of the two tests were similar in magnitude and were strongly correlated (r = 0.80, P less than 0.001). Both tests raised serum GH to a similar degree in twenty-nine out of the thirty-five boys (83%), but four boys who responded satisfactorily to hypoglycaemia failed to respond to metoclopramide (MCP) stimulation, and two boys who failed to respond to hypoglycaemia responded satisfactorily to MCP stimulation. MCP stimulation does not require prior preparation of the patient and is relatively free of side effects. Consequently, it is suggested that MCP stimulation may be a useful 1 hour out-patient test for growth hormone deficiency in this relatively common group of patients.

Adolescent↗

Laboratory assessment of prolactin status.

The laboratory assessment of prolactin status was evaluated by detailed study of 921 subjects (587 normal subjects and 334 patients with pathological conditions). The effect on serum prolactin levels of age, sex, circadian rhythm, pulsatility of secretion, stress, drug ingestion, and pregnancy was defined in normal subjects. The normal prolactin responses to stimulation (TRH metoclopramide) and suppression (L-dopa, bromocriptine) were also determined. Basal prolactin levels were measured in patients with defined pathological conditions including prolactinoma, idiopathic hyperprolactinaemia, acromegaly, Cushing's disease, chronic renal failure, primary hypothyroidism, pituitary ablation, Kallman's syndrome, Nelson's syndrome, growth hormone deficiency, gonadotrophin deficiency, craniopharyngioma, panhypopituitarism, and chronic progressive arthropathy. Based on these data, a strategy for the routine laboratory assessment of prolactin status is outlined.

Adolescent↗