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Biomedical subjects

F Clark

Publications and source records attributed to F Clark.

At least 55 records · Page 3Linked to original sources

Functional analysis of T and B cells from blood and thyroid tissue in Hashimoto's disease.

B lymphocytes from Hashimoto blood and thyroid tissue have been cultured with autologous T cells from thyroid/blood to assess their ability to synthesise IgG and thyroid autoantibody. Thyroid B cells were able to synthesize microsomal antibody spontaneously in the absence of T cells or pokeweed mitogen (PWM) and this synthesis was increased in the presence of thyroid T cells without PWM or with blood T cells with PWM. In contrast, blood B cells did not secrete thyroid autoantibody spontaneously but could be induced to do so by thyroid T cells spontaneously or by blood T cells with PWM. Despite these differences, lymphocytes from blood and thyroid tissue secreted microsomal or thyroglobulin antibodies in culture which were similar in terms of the IgG subclass distribution. It would appear, therefore, that although the state of activation of B and T cells is different in blood and thyroid tissue, the precursors of thyroid autoantibody secreting cells are the same.

Autoantibodies

The relationship between human adipocyte and monocyte insulin binding.

The assumption that insulin binding to monocytes reflects that of insulin binding to adipocytes has been examined. In normal, diabetic, thyrotoxic and cirrhotic subjects no correlation was observed between monocyte and adipocyte insulin binding. Extrapolation is not justified from monocyte binding data to conclusions about insulin-sensitive tissues.

Adipose Tissue

Polycystic ovarian syndrome in identical twins.

Two 21-year-old female twins are described. They presented simultaneously with hirsutism and oligomenorrhoea. Investigation showed they had polycystic ovaries, they were identical and were not cases of post-pubertal adrenogenital syndrome.

Adult

Dichotic listening performance in normal children and adults.

The purpose of this study was to investigate normative expectations on the dichotic listening test in order to determine the influence of sex and development on dichotic listening performance. Thirty 5-to-6 year olds, thirty 11-to-12 year olds, and 30 adults, 15 males and 15 females in each group, were tested by using consonant-vowel dichotic stimuli. There were no significant differences between males and females except for the 11- to 12-year-old females who were significantly more accurate than the males. Degree of ear asymmetry did not differ among the three age groups; however, the adults and 11-to-12 year olds were significantly more accurate than the 5-to-6 year olds. Guidelines are suggested for the interpretation of dichotic listening test data.

Adult

Defective regulation of the immune response to tetanus toxoid in Hashimoto's disease.

The humoral immune response to tetanus toxoid has been studied in patients with Hashimoto's disease. Although the magnitude of the response was similar to that observed in normal subjects, the Hashimoto patients demonstrated an inability to regulate their levels of tetanus toxoid antibody. This apparent defect in the control of antibody synthesis may be an important factor in both the initiation and perpetuation of autoimmune thyroid disease.

Adolescent

Fenclofenac-secondary effects upon the pituitary thyroid axis.

To elucidate the mechanism of suppression of TSH responsiveness to TRH induced by the initiation of fenclofenac therapy, the early period of drug administration was examined in detail and the effect of the drug during a thyrotrophin releasing hormone infusion was assessed. In addition, the effect of fenclofenac upon the response of ACTH, cortisol, growth hormone and prolactin to insulin-induced hypoglycaemia was examined. The effect of fenclofenac upon an equilibrium dialysis method for estimating free thyroid hormones was evaluated and was found to be insignificant within the therapeutic concentration range of the drug. A sharp, short-lived rise in free thyroxine (21.7 +/- 2.0 to 26.8 +/- 1.9 pmol/l; P less than 0.03) was observed 60 min after the first dose of fenclofenac. Repeated peaks of free thyroxine during chronic fenclofenac treatment, superimposed upon the previously described steady decline of free and total serum thyroxine, are postulated to cause the observed suppression of TSH release which is present only until free and total serum thyroxine levels reach their nadir. The time course of the changes seen during thyrotrophin releasing hormone infusion suggested that the pituitary suppression was secondary to a rise in free thyroxine. The responses to hypoglycaemia of those pituitary hormones examined were not affected by fenclofenac.

Adult

Insulin sensitivity in hyperthyroidism: measurement by the glucose clamp technique.

Sensitivity to porcine insulin has been compared in overnight fasted hyperthyroid and control subjects using a euglycaemic clamp technique. Basal values for blood glucose, lactate, pyruvate, alanine, serum insulin and C-peptide were similar in the two groups, whilst blood glycerol (hyperthyroid 0.11 +/- 0.02 (mean +/- S.E.) vs. control 0.06 +/- 0.01 mmol/l, P less than 0.01) and blood 3-hydroxybutyrate (0.28 [0.03-0.79, range ]vs 0.09 [0.01-0.29 ]mmol/l, P less than 0.05) were increased in hyperthyroidism. During the 2 hour insulin infusion (0.05 U/kg/h), serum insulin plateaued at the same level (44 +/- 4 vs 44 +/- 1 mU/l) and insulin metabolic clearance rates were similar (1.21 +/- 0.10 vs 1.25 +/- 0.03 l/min). Serum C-peptide levels also decreased by similar amounts (40 +/- 8 vs 47 +/- 6%). The amount of glucose infused to maintain euglycaemia was identical during the second hour of insulin infusion (290 +/- 50 vs 330 +/- 30 mg/kg) as were the increments in lactate and pyruvate concentrations. Blood glycerol values decreased in both groups although values in hyperthyroid patients remained significantly higher than in controls. 3-Hydroxybutyrate concentrations fell to similar values in the two groups. These findings suggest that insulin-stimulated glucose metabolism and inhibition of ketogenesis are normal in hyperthyroidism.

3-Hydroxybutyric Acid

Evidence that thyroid hormones regulate gluconeogenesis from glycerol in man.

We have previously reported that glucose production assessed using radioisotopic methods is 50% increased in hyperthyroidism but 30% decreased in hypothyroidism. These studies, however, do not distinguish between glycogenolysis and gluconeogenesis. In fasting man more than 80% of circulating glycerol is cleared by the liver and enters the gluconeogenic pathway. We have therefore measured glycerol clearance following bolus intravenous glycerol administration as an indirect assessment of gluconeogenic capacity. Hyperthyroid and hypothyroid subjects were compared with separate matched controls after an overnight fast. In hyperthyroid subjects blood glucose and blood glycerol were increased but lactate, pyruvate, and alanine concentrations were normal. Glycerol clearance was increased in hyperthyroidism and followed a double exponential decay with a shortened second component half-time. Endogenous glycerol production was increased three-fold. In hypothyroidism fasting circulating levels of glucose, lactate, pyruvate, alanine, and glycerol were normal but glycerol clearance was diminished. Both first and second component half-times were prolonged in hypothyroidism and endogenous glycerol production was decreased by 50%. Thus in hyperthyroidism glycerol clearance is greatly enhanced whilst in hypothyroidism glycerol clearance is diminished. The magnitude of the changes suggests that alterations in gluconeogenesis are probably the major factors concerned in the reported increase and decrease in glucose production in hyperthyroidism and hypothyroidism respectively.

Blood Glucose

The IgG subclass distribution of thyroglobulin antibody synthesized in culture.

Thyroglobulin autoantibodies synthesized by Hashimoto lymphocytes in culture and present in serum have been analysed in terms of their IgG subclass distribution. The autoantibodies produced in vitro were frequently IgG4 or IgG1, whether pokeweed mitogen or Epstein-Barr virus was used to stimulate the cultures, and the subclass distribution of these thyroglobulin antibodies was similar to that observed in the patients' serum. It appears therefore that the antibodies synthesized in vitro in response to polyclonal B-cell activators resemble those produced in vivo, and it seems likely that both pokeweed mitogen and Epstein-Barr virus influence the same B-cell precursors of autoantibody-synthesizing cells, albeit by different mechanisms.

Adolescent

Studies of thyroglobulin autoantibody synthesis using a micro-ELISA assay.

Thyroglobulin autoantibody synthesis by Hashimoto lymphocyte cultures has been studied using an ELISA, a plaque assay and tanned red cell haemagglutination. The ELISA system was found to be the most suitable and using this method IgG-class thyroglobulin antibody synthesis was detectable in cultures of mitogen-stimulated lymphocytes from all 10 Hashimoto patients studied, but not in cultures of lymphocytes from 4 normal donors. The ELISA was also sufficiently sensitive to detect thyroglobulin antibody synthesis in mitogen-free lymphocyte cultures from 4 out of the 10 Hashimoto patients and consequently it should be possible to use this system to study the effect of various pathophysiological factors on autoantibody synthesis which would otherwise be masked by mitogenic stimulation.

Adult

A guide for instrument development and validation.

As occupational therapists become increasingly concerned with accountability, the paucity of adequate instrumentation available for documenting therapeutic effectiveness surfaces as a major problem. Therapists will need to construct new or refine existing instruments to satisfy the requirements of third-party payment. The purpose of this paper is to illustrate how a new instrument is planned, developed, and validated. A sequential step-by-step process is illustrated with a flowchart and applied in the hypothetical construction of an attitude scale to assess school administrators' valuing of the role of occupational therapists in the schools. This example is provided to show how general psychometric principles are applied within an occupational therapy context.

Attitude

Thyrotoxicosis.

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Adrenergic beta-Antagonists

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

Diurnal hormone-metabolite profiles in hypothyroidism.

To investigate the influence of thyroid hormones on intermediary metabolism in man, hormone and metabolite profiles were obtained over a 12-h period of normal meals and activity in eight hypothyroid subjects before and during thyroxine replacement therapy, and in sixteen matched controls. The fasting blood glucose concentration and the mean 12-h blood glucose concentration were normal in hypothyroid subjects but the blood glucose response to breakfast was exaggerated. Fasting blood lactate and pyruvate levels were normal but post-prandial hyperlactataemia and hyperpyruvicaemia were found and mean 12 h values for lactate (hypothyroid 1.80 +/- 0.06 v. control 0.77 +/- 0.03 mmol/l, P less than 0.01) and pyruvate (0.10 +/- 0.01 v. 0.08 +/- 0.003 mmol/l, P less than 0.01) were elevated. Blood alanine concentrations were elevated only in the evening. Although plasma non-esterified fatty acid levels were normal, fasting blood glycerol levels were decreased (0.06 +/- 0.01 v 0.08 +/- 0.01 mmol/l, P less than 0.001) and this decrease persisted throughout the 12-h period. Blood total ketone body concentrations did not differ from controls, but, as for plasma NEFA and blood glycerol, the normal preprandial rise in concentration was absent. Serum insulin, glucagon and growth hormone concentrations did not differ from control values at any time. Six months of thyroxine (T4) treatment produced a rise in blood glycerol concentration (mean 12 h value during T4 therapy, 0.06 +/- 0.01; before T4 therapy, 0.04 +/- 0.005 mmol/l; P less than 0.01) but not to control values (0.08 +/- 0.01 mmol/l). Concentrations of glucose and other gluconeogenic precursors were unaltered by therapy but the insulin response to meals and the mean 12 h serum insulin concentration were increased.

Acetoacetates