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Biomedical subjects

R Hall

Publications and source records attributed to R Hall.

At least 397 records · Page 22Linked to original sources

Thyroid antibodies are produced by thyroid-derived lymphocytes.

The significance of the characteristic lymphocytic infiltrate in the target organ in organ-specific autoimmune disease is unknown. We have demonstrated the production of thyroglobulin antibodies and immunoglobulins (IgG, IgM and IgA) by thyroid-derived lymphocytes in Graves' disease and Hashimoto's thyroiditis two plaque forming cell (PFC) assays. The thyroid appears to be an important site of thyroglobulin antibody production but the thyroid lymphocytes also contain many IgG PFCs of non-thyroglobulin specificity. Short-term culture and direct thyroglobulin antibody assay on micro-ELISA plates confirmed the results of the PFC assay. Therapies such as carbimazole may therefore be acting on a localized source of autoantibody production.

Adult↗

Sites of autoantibody production in rats with thyroiditis.

We have developed a thyroglobulin-specific haemolytic plaque assay and investigated potential sites of autoantibody synthesis in good and poor responder strains of rats immunized with thyroglobulin and in rats subjected to thymectomy and sub-lethal irradiation which subsequently develop thyroiditis spontaneously. The bone marrow appears to be the most important site of thyroglobulin antibody synthesis in all groups, but spleen and cervical lymph nodes are also involved. No thyroglobulin plaque-forming cells could be found in the thyroid. These results imply widespread involvement of the humoral immune system in organ-specific autoimmune processes.

Animals↗

[Prolactin-secreting pituitary adenomas: explorations and treatment (author's transl)].

Prolactin-secreting pituitary adenomas have only recently been recognised as distinct entities, but probably represent the most frequent type of secreting pituitary adenomas. As they occur mainly in young women during the period of genital activity, and as therapeutic success depends on their being detected while they are still small, accent is currently being placed on early diagnosis and specific therapy. Early diagnosis depends mainly on the results of exploration of the neuro-endocrine factors of the hypothalamus-pituitary axis. Treatment, while dependent upon the attitudes of the different teams, has been transformed by the re-introduction of the trans-sphenoidal surgical approach, and the availability of bromocriptine, an orally active dopamine agonist. Their combined use has produced selective successful results in the treatment of microadenomas. Bromocriptine can reduce the size of large prolactin-secreting adenomas, and is probably a better choice than surgery because of the high failure rate of trans-sphenoid operations in the case of macroadenomas, Long-term results of these two therapeutic procedures have still to be evaluated.

Adenoma↗

Effects of prosomatostatin on growth hormone and prolactin response to arginine in man. Comparison with somatostatin.

The effects of the hypothalamic 28 aminoacid peptide prosomatostatin (Pro-SS) on arginine-induced growth hormone (GH) and prolactin (PRL) release and blood glucose levels in man are compared with those obtained after an equimolar dose of somatostatin (SS). In comparison with SS, Pro-SS caused greater and more prolonged inhibition of GH release, a more marked reduction of the PRL response to arginine, and greater enhancement of the hyperglycaemic action of arginine. The greater potency and prolonged action of Pro-SS make it an interesting tool to study hormonal control mechanisms in a variety of physiological and pathological conditions.

Adult↗

Natural history of autoimmune thyroiditis.

One hundred and sixty-three asymptomatic people with thyroid antibodies or raised serum thyrotrophin (TSH) concentrations, or both, and 209 age-matched and sex-matched controls without either marker of thyroid disorder were followed up for four years to determine the natural history of autoimmune thyroiditis. Mildly raised TSH concentrations alone and the presence of thyroid antibodies alone did not significantly increase the risk of developing overt hypothyroidism during the four years compared with the controls. Overt hypothyroidism developed at the rate of 5% a year in women who initially had both raised TSH concentrations and thyroid antibodies. Prophylactic treatment with thyroxine may be justified in women found to have both markers of impending thyroid failure. The cost effectiveness of screening the adult population remains to be evaluated.

Adult↗

Chemotherapy following palliative resection of gastric cancer.

Twenty-five patients with residual tumour after resection of a primary gastric cancer were randomized to receive either 5-Fluorouracil or BCNU postoperatively or kept under close observation. Some patients receiving chemotherapy may have benefited by a delay in progression of their disease but this was short lived and subsequently all but one patient has died within a 4-year period of follow-up. There does not seem to be any advantage in treating patients who have residual gastric cancer with 5-FU and BCNU therapy.

Aged↗

Bromocriptine therapy for "nonfunctioning" pituitary tumors.

Bromocriptine therapy may cause regression of prolactinomas, but its effect on nonsecretory pituitary tumors is uncertain. Conventional treatment for such "functionless" tumors is surgery and/or radiotherapy, but recurrences pose a therapeutic dilemma. We describe a patient with such a tumor treated by surgery and radiotherapy who presented with recurrent disease 14 days later. On treatment with bromocriptine, 20 mg daily for 25 months, the intrasellar tumor recurrence had diminished in size and a suprasellar extension had almost disappeared. Bromocriptine therapy may therefore benefit some patients with nonsecretory pituitary tumors considered unsuitable for surgery or radiotherapy.

Adenoma, Chromophobe↗

Sex hormones enhance immunoglobulin synthesis by human peripheral blood lymphocytes.

Using a protein A haemolytic plaque assay to detect immunoglobulin synthesis by human peripheral blood lymphocytes cultured with pokeweed mitogen, we have shown a significant increase in IgG plaque-forming cells in the presence of physiological concentrations of testosterone and oestradiol. Higher concentrations of these steroids inhibit plaque-forming cells. There was no difference in the response to testosterone and oestradiol of lymphocytes derived from male subjects or menstruating or post-menopausal females.

Adult↗

Characterization of ventricular tachyarrhythmias on ambulatory ECG recordings in post-myocardial infarction patients: arrhythmia detection and duration of recording, relationship between arrhythmia frequency and complexity, and day-to-day reproducibility.

We performed three consecutive 24-hour ECG recordings in 57 ambulatory patients approximately 8 to 11 days of post-myocardial infarction. There was considerable additional detection of each type of complex ventricular ectopic beat (VEB) with recordings beyond 24 hours. Multiform, R-on-T, pairs, and bigeminy were often first detected from 24 to 48 hours and 5 of 12 patients with ventricular tachycardia had this rhythm detected only after 48 hours of monitoring. Complex forms were deleted with short recording durations primarily in patients who had complex forms present during a large number of hours during the 72-hour recording session. The occurrence of each type of complex ectopic beat was strongly related to PVC frequency and some type of complex form was seen in virtually all 24-hour recordings with greater than a total of 100 VEBs. Sixty-five percent of 24-hour recordings with infrequent VEBs (2 to 10 per 24 hours) also had complex forms present. The day-to-day reproducibility of VEB frequency and complexity was reasonable, but was largely accounted for by the fact that most recordings were free of frequent ectopic beats and a given type of complex PVC. These data suggest that for longer ECG recording period, the frequency of occurrence of complex forms rather than simply their presence or absence may be important for identifying high risk subgroups.

Adult↗

Simple method of assessing splenic function in coeliac disease.

1. Erythrocytes with membrane abnormalities seen on interference contrast microscopy ('pitted erythrocytes') were counted in venous blood samples from patients with treated coeliac disease and dermatitis herpetiformis, and from control subjects and patients who had had an elective splenectomy. 2. The percentage of 'pitted erythrocytes' was compared with the 99mTc-labelled heat-damaged erythrocyte clearance, and with the splenic size computed from scintiscans. 3. There was a significant correlation between percentage 'pitted erythrocytes' and the above methods of measuring splenic function and size. Increase in the percentage of 'pitted erythrocytes' above the control range indicated splenic hypofunction. 4. The number of coeliac patients with percentage 'pitted erythrocytes' above the control range increased with increasing age at which they started a gluten-free diet. 5. Counting of 'pitted erythrocytes' is a simple and sensitive method of assessing splenic hypofunction in treated coeliac disease. It avoids radiation exposure, and is applicable to all ages and repeatable without risk. 6. The incidence of splenic hypofunction in coeliac patients may be related to the duration of untreated disease.

Adolescent↗

Altered dopaminergic regulation of thyrotrophin release in patients with prolactinomas: comparison with other tests of hypothalamic-pituitary function.

This study was carried out to test the hypothesis that sustained hyperprolactinaemia in patients with prolactinomas stimulates hypothalamic dopaminergic activity via a short loop positive feedback effect of prolactin (PRL). The intensity of dopamine (DA) effects on the pituitary around the adenoma was evaluated by measuring thyroid stimulating hormone (TSH) responses to intravenous injection of domperidone (10 mg) a new DA receptor blocking drug that does not penetrate the blood-brain barrier. TSH responses have been compared with those of PRL to the same agent. Eight females with prolactinomas showed greater TSH release after domperidone than nine normal females (sum of TSH increments over 20 min 17.5 +/- 1.7 v. 8.9 +/- 1.5 mu/l, P less than 0.001) whilst PRL release was reduced (sum of PRL increments over 120 min 5.9 +/- 2.4 v. 21.8 +/- 3.8 mu/l x 10(-3), P less than 0.01). Amongst nineteen hyperprolactinaemic females with apparently normal pituitary fossae (plain skull X-ray), ten showed an exaggerated TSH response (delta TSH, 4.2 +/- 0.6 mu/l, range 2.5-9.0 mu/1) and reduced PRL response to domperidone, comparable with established tumor cases. In the remaining nine normal fossa hyperprolactinaemic females, the TSH and PRL responses to dopaminergic were similar to normal females. These results support the initial hypothesis and indicate the coexistence of a defect in the dopaminergic inhibition of PRL release and increased dopaminergic inhibition of TSH release in patients with prolactinomas. The presence of an exaggerated TSH response to DA antagonism in a euthyroid, radiologically normal (plain skull X-ray), hyperprolactinaemic patient is compatible with the presence of an autonomously-functioning, PRL secreting, pituitary microadenoma and the TSH changes seen in these patients after DA antagonist administration can be readily detected by sensitive TSH radioimmunoassay.

Adenoma↗

Use of plaque assays to study thyroglobulin autoantibody synthesis by human peripheral blood lymphocytes.

Plaque assays have been used to study thyroglobulin autoantibody synthesis and total immunoglobulin production by cultures of peripheral blood lymphocytes from patients with Hashimoto's thyroiditis. Freshly isolated Hashimoto or normal lymphocytes contained small numbers (7-1300) of total IgG plaque-forming cells (PFC) and total IgM PFC, but specific thyroglobulin antibody PFC was undetectable. After 5-8 days' culture with pokeweek mitogen (PWM), total IgG and IgM PFC were markedly increased to a geometric mean of 10,140 (8414-12,220) IgG PFC and 3450 (163-7534) IgM PFC per 10(6) cultured lymphocytes (95% confidence limits in parentheses). Furthermore, a mean of 63 (22-287) specific IgG thyroglobulin antibody PFC per 10(6) lymphocytes were detectable in cultures of Hashimoto lymphocytes. The IgG thyroglobulin antibody PFC were stimulated by Epstein-Barr virus (EBV) infection, suggesting that EBV infection may be useful in obtaining monoclonal thyroid autoantibodies.

Adult↗