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Biomedical subjects

W J Irvine

Publications and source records attributed to W J Irvine.

At least 37 records · Page 2Linked to original sources

The correlation between the results of tests for thyroid autoantibodies to cell surface and microsomal antigens and to thyroglobulin.

Autoantibodies reactive with human thyroid cell surface membrane and human thyroid microsomes were studied in sera of patients with autoimmune thyroid diseases and of controls. A strong correlation was found between the presence of antibodies reactive with the surface of human thyroid cells in tissue culture (detected by anti-IgG-immunofluorescence) and the presence of antibodies reactive with thyroid microsomes in cryostat sections of human thyroid tissue (detected by anti-IgG-FITC or by anti-C3c-FITC) or coated on the surface of turkey red cells (as detected by haemagglutination). This contrasts with the findings previously observed for islet cell antibodies in patients with Type 1 (insulin-dependent) diabetes. It suggests that in the case of thyroid cells, as opposed to islet cells, microsomal antigens are either also present in the thyroid cell surface membrane; or that microsomal and cell surface antigens (although separate and distinct) are very frequently associated with each other, with a strong tendency for autoantibodies to be formed against both antigens if they are formed at all.

Antibody Specificity↗

Plasma exchange in conjunction with immunosuppressive drug therapy in the treatment of endocrine exophthalmos.

We describe three patients who developed severe endocrine ophthalmopathy at 3, 12 and 18 months after treatment with iodine-131. In two cases with congestive ophthalmopathy steroids alone and plasma exchange alone failed to produce a satisfactory response, but the combination of plasma exchange with steroids or steroids plus cyclophosphamide was followed by resolution of papilloedema and return of visual acuity to normal as well as definite improvement in the other signs of ophthalmopathy. In the remaining case, which did not have papilloedema the signs of ophthalmopathy were progressive despite treatment with steroids. Combined treatment with plasma exchange, steroids and cyclophosphamide resulted in improvement in visual acuity and resolution of periorbital oedema and diplopia. Plasma exchange may be a useful adjunct to immunosuppressive therapy in the treatment of acute progressive endocrine exophthalmos.

Aged↗

The detection of circulating immune complexes in normal subjects using four different methods.

336 estimations of circulating immune complexes have been performed on the sera of blood donors by four different methods: the solid phase C1q binding test, the fluid phase C1q binding assay, the conglutinin binding test and the Raji cell radio-immune assay. Between 68 and 105 subjects were used in the analysis of each method. With the first three methods, immune complex levels showed a peaked asymmetric distribution with a positive tail including about 10% of subjects, whereas using the fourth method immune complex values were widely spread. No difference in immune complex values between males and females was found. There was a significant trend for the prevalence of immune complexes to increase with age when methods were used which detect complexes through C3 binding. In a further 13 subjects tested at regular intervals during a period of 24 hours, using the fluid phase C1q binding test, significant variations in immune complex levels were found but no consistent pattern of variation at different hours of the day or after meals could be seen. In studies of immune complexes on small groups of patients it is advisable to test multiple samples from te same subjects taken at different times, whereas when large series of patients are being studied results should be compared to those obtained with age matched controls.

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↗

Paracetamol pharmacokinetics in thyroid disease.

The absorption, distribution and elimination of oral paracetamol have been studied in patients before and after treatment of thyrotoxicosis (n = 7) and hypothyroidism (n = 4). Absorption was faster in patients with untreated thyrotoxicosis than when subsequently euthyroid. The peak paracetamol concentration, however, was lower in thyrotoxic patients due to an apparent increase in the total body clearance and a shorter plasma half-life. Both absorption and elimination rates were reduced in hypothyroid patients, but were not significantly different from the euthyroid results. When estimated using a two compartment model the total volume of distribution and the hybrid distribution rate constants were unrelated to thyroid status, but the apparent volume of the central compartment was significantly greater in the thyrotoxic group. These changes in drug disposition may contribute to differences in drug response seen in thyroid disease.

Acetaminophen↗

Measurement of circulating immune complexes by radioimmunoassay of immunoglobulin in high molecular weight fractions.

A method for detecting circulating immune complexes is described based on radioimmunoassay of IgG following the rapid separation of immune complexes from monomeric IgG on short columns of Sephacryl S-300. Values obtained using sera from patients with immune complex associated diseases were distinctly higher than those obtained with sera from healthy control subjects. The same serum samples were assayed by 3 other methods for detecting immune complexes; significant correlation was obtained.

Animals↗

Transient hypothyroidism after iodine-131 treatment of thyrotoxicosis.

Thirty consecutive patients with thyrotoxicosis were followed up at monthly intervals for 6 months after treatment with iodine-131. Serum total T4, serum total T3, and serum TSH response to TRH were measured at each review. Biochemical evidence of hypothyroidism (low T4 raised basal TSH) developed in 18 patients 1-4 months after treatment. In 5 of these patients, symptoms and signs of hypothyroidism remained absent or minimal and spontaneous recovery of thyroid function occurred during the ensuing 2 months. If biochemical hypothyroidism occurs during the first 6 months after radioiodine therapy, it is recommended that T4 replacement be withheld for 2 months unless the severity of symptoms demands treatment.

Adult↗

Influence of thyroid status on dopaminergic inhibition of thyrotropin and prolactin secretion: evidence for an additional feedback mechanism in the control of thyroid hormone secretion.

Serum TSH and PRL concentrations were measured after the randomized oral administration of either metoclopramide, L-dopa, or placebo on 3 consecutive days to five patients with overt primary hypothyroidism (low serum total T4 and raised serum TSH) and to five patients with subclinical hypothyroidism (normal serum total T4 and raised serum TSH). In both groups there was a rise in serum TSH and PRL concentrations after metoclopramide and a fall after L-dopa when compared with the effect of the placebo. However, the rise in serum TSH and PRL concentrations was significantly greater in patients with subclinical hypothyroidism compared to that in patients with overt hypothyroidism. It was not possible to show any significant difference in the degree of fall of these pituitary hormones after L-dopa administration in the two groups. These results suggest that in addition to the established negative feedback of thyroid hormones at the level of anterior pituitary thyrotropes, there is a previously unrecognized effect of thyroid hormones at the hypothalamus, resulting in increased dopaminergic inhibition of TSH release. Stimulation of hypothalamic dopamine by thyroid hormones also inhibits PRL secretion.

Feedback↗

Glucose and insulin responses to oral glucose in overt non-insulin-dependent diabetics with and without the islet cell antibody.

Plasma insulin, glucose, and insulin/glucose responses to a 50-g oral glucose tolerance test (OGTT) were compared in 14 islet cell antibody (ICAb) positive non-insulin-dependent diabetics (NIDDM), 14 matched ICAb negative NIDDM, and 14 ICAb negative nondiabetic controls. Both groups of NIDDM exhibited marked carbohydrate intolerance with insulinopenia. Despite having significantly higher plasma glucose concentrations during the study, the ICAb positive NIDDM had significantly lower insulin levels, and thus lower insulin/glucose ratios, than the ICAb negative NIDDM both in the fasting state and in response to the OGTT. Similarily, ICAb positive NIDDM had higher integrated glucose responses (delta G), lower integrated insulin responses (delta I), and lower delta I/delta G values than ICAb negative NIDDM. Three ICAb negative and seven ICAb positive NIDDM subsequently required insulin treatment. These findings show that ICAb positive NIDDM suffer from a greater disturbance of B-cell function than do matched ICAb negative NIDDM.

Adult↗

The significance of pancreatic islet cell antibody and abnormal glucose tolerance during pregnancy.

Five out of 50 pregnant subjects with impaired glucose tolerance (a 2 hr venous plasma glucose concentration over 6.6 mmol/1) had cytoplasmic islet cell antibody (ICAb cyto) in their sera. Three of these 5 developed unequivocal insulin-dependent diabetes in the first year following pregnancy, while none of the others did so. When taken in conjunction with the presence of islet cell antibody, the severity of impairment of glucose tolerance during pregnancy (but not obesity) was an additional indicator of the likelihood of developing insulin-dependent diabetes during the first postpartum year.

Antibodies↗

Immune complexes in type I diabetics with persistent islet cell antibodies.

The sera of 33 type I diabetics found to have pancreatic IgG antibodies to the cytoplasm of pancreatic islet cells (ICAb) at three or more years after diagnosis were tested for immune complexes (AgAb), insulin antibodies and thyroid and gastric cytoplasmic antibodies, and the subjects were HLA typed. Sera from 69 insulin treated diabetics of comparable duration of disease and without ICAb at the time of study were also included in the investigation. The prevalence of AgAb in patients with persistent ICAb was found to be 52% in comparison with 19% of ICAb negative diabetics (p < 0.001) and 10% of normal blood donors (p < 0.0005). AgAb positivity was increased, but not significantly, in HLA-B8 positive compared to B8 negative ICAb persisters. There was a significant negative correlation between AgAb levels and insulin antibody titres. Circulating AgAb were not significantly correlated with the presence of either thyroid or gastric cytoplasmic antibodies.

Antibodies↗

Failure of the TRH test to predict the clinical course of patients in remission after antithyroid drug therapy for Graves' disease.

In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean +/- SE intervals since the withdrawal of drug therapy were 23.2 +/- 1.6 and 20.4 +/- 0.7 months, respectively, at the outset of the study. Five patients (45%) from group I and 7 patients (30%) from group II relapsed during the period of observation. In addition, a change from a subnormal TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.

Adult↗

Studies of the TSH radioreceptor assay.

We have examined several variables in the reagents and procedures used in the TSH radioreceptor assay, the binding of iodinated TSH to its thyroidal receptor. We found that iodinated bovine TSH (S.A. 30 U/mg) was more effectively bound to receptor than iodinated human TSH (S.A. 7.3 U/mg). Iodination of TSH was the Bolton-Hunter acylation method apparently prevented binding to TSH receptor. Surgically removed human thyroid tissue specifically bound 10.3 +/- 1.0 (mean +/- SEM) of added [125I]TSH, but post-mortem human thyroid bound only 3.9 +/- 0.4% of [125I]TSH (p less than 0.001). Maximal binding of [125I]TSH was found at pH 5.8. Many tissue preparations contained activity, possibly due to proteases, which inactivated TSH, and inclusion of a protease inhibitor, aprotinin, significantly increased specific binding.

Animals↗

Primary hypothyroidism preceding thyrotoxicosis: a report of 2 cases and a review of the literature.

Two cases are reported in whom primary hypothyroidism preceded thyrotoxic Graves' disease. The hypothesis is advanced that this sequence of events was mediated by spontaneous changes in the patient's autoimmune reactions to thyroid. In particular, it may reflect a spontaneous alteration in the balance between blocking antibodies reactive at or near the TSH receptor or cytotoxic thyroid autoimmune mechanisms on the one hand, and thyroid stimulating autoantibodies on the other.

Antibodies↗