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Biomedical subjects

H Perrild

Publications and source records attributed to H Perrild.

At least 37 records · Page 2Linked to original sources

Characterization of the natural killer cell activity in Hashimoto's and Graves' diseases.

Natural killer (NK) cell activity and blood mononuclear cell subpopulations were characterized in patients with Hashimoto's thyroiditis (n = 11), Graves' disease (n = 20), non-toxic goitre (n = 10) and in normal controls (n = 22). NK cell activity against K 562 target cells and the capability of IFN-alpha, Il-2, and indomethacin to enhance NK cell activity in vitro did not differ significantly between the groups. The percentages of large granular lymphocytes, CD5+, CD4+, CD8+ and CD16+ cells were normal in patients with non-toxic goitre, Hashimoto's and Graves' diseases. There was no correlation between NK cell activities and TgAb, MAb and TSAb. Although NK cell activity is suppressed in several autoimmune diseases, NK cell function is normal in patients with autoimmune thyroid disorders.

Adult

Parkinson's disease and autoimmunity.

Sera from 22 patients with Parkinson's disease were tested for autoantibodies in 11 different assays, including a test for autoantibodies directed against determinants in the pituitary gland. All patients were tested twice with a 12-month interval between tests. No pituitary autoantibodies were detected. The other autoantibodies investigated were found in low frequencies and in low titers. Our data supports the view that the pathogenesis of Parkinson's disease is not autoimmune.

Adult

Suppressed natural killer cell activity in patients with euthyroid Graves' ophthalmopathy.

The purpose of the present study was to determine whether patients with euthyroid Graves' exophthalmopathy have an impaired NK cell function compared to patients with Graves' hyperthyroidism and healthy controls. The NK cell activity measured against K562 target cells was significantly suppressed (p less than 0.01) in patients with euthyroid Graves' ophthalmopathy, whereas the NK cell activity of patients with Graves' hyperthyroidism was not. Although interferon-alpha, interleukin-2 and indomethacin significantly enhanced (p less than 0.01) the NK cell activity in all three groups, none of these agents fully restored the defective NK cell activity in euthyroid Graves' ophthalmopathy. The concentrations in the blood of large granular lymphocytes and CD16 positive cells did not differ between the three groups, furthermore an immunosuppressive serum factor was not detected. The number of effector/target cell conjugates did not differ between patients and controls, whereas the interferon-alpha induced production of a soluble natural killer cytotoxic factor (NKCF) with specificity for NK sensitive target cells was suppressed in patients with Graves' euthyroid ophthalmopathy. We conclude that one of the mechanisms underlying the defective NK cell activity in patients with euthyroid ophthalmopathy may be an impairment of the release of NKCF from the NK cells.

Adolescent

Relationship between serum thyroglobulin, thyroid volume and serum TSH in healthy non-goitrous subjects and the relationship to seasonal variations in iodine intake.

In order to investigate the interrelationship between serum thyroglobulin (Tg), thyroid volume and serum TSH by a sensitive method, 176 healthy euthyroid non-goitrous subjects were studied. Furthermore the seasonal influence, assuming seasonal differences in iodine intake in Denmark, was studied in 13 healthy male volunteers. A weak correlation between serum Tg and thyroid volume was found only in female non-goitrous subjects. No correlations between serum Tg, thyroid volume, free T4 and free T3 indices, T3/T4 ratio, serum TSH by sensitive method or age were seen. Thyroid volume was increased (P less than 0.01) during the winter without any change in thyroid function or TSH level, whereas serum Tg level in these subjects was significantly lower (P less than 0.02) during the winter compared with the summer. In conclusion, serum Tg showed no correlation with either thyroid volume, super-sensitive TSH or thyroid function in a population of non-goitrous subjects in Denmark. The lack of correlation between increased thyroid volume and decreased serum Tg during the winter compared with the summer is unexplained. It might be hypothesised that short-term changes in iodine intake induce only colloid accumulation (i.e. increased thyroid volume) without changes in the glandular secretion of Tg or thyroid hormones.

Adolescent

Three-week beta-adrenergic blockade does not impair or improve general intellectual function in young healthy males.

The widespread use of beta blockers in treatment of both cardiovascular and nonvascular conditions has generated interest in changes in functions of the central nervous system during treatment. We studied the effect of 3 weeks of beta blockade on learning and memory ability, concentration, and verbal abstraction in 32 young normotensive healthy men. We chose healthy males to exclude the possible influence of changes related to a hypertensive state. Subjects were randomized into a 3-week treatment protocol with either atenolol 50 mg X 2 (cardioselective, hydrophilic), metoprolol 100 mg X 2 (cardioselective, lipophilic), propranolol 80 mg X 2 (noncardioselective, lipophilic), or placebo X 2. Each subject underwent two neuropsychological testing sessions. We found no significant enhancement or impairment of intellectual or psychomotor performances after the 3-week treatment with beta-adrenergic-blocking agents compared to a placebo-treated control group. Differences in pharmacokinetic profiles of the drugs (e.g., central nervous system penetrability, lipophilicity, or membrane-stabilizing effect) did not influence the test outcome. Antihypertensive treatment with beta blockers over a prolonged period does not affect young peoples' learning and memory abilities or reasoning powers, nor their ability to concentrate and perform psychometric tasks.

Adrenergic beta-Antagonists

Serum magnesium, calcium, phosphate and PTH following long-term beta-blockade in ischaemic heart disease.

In 40 patients with ischaemic heart disease the serum levels of magnesium, parathyroid hormone (PTH), phosphate, calcium, and ionized calcium remained unchanged and within normal limits following treatment for 12 months with alprenolol (n = 20) or placebo (n = 20). No changes occurred during a 2 week withdrawal period. The clinical implication is that the non-cardioselective betablocker alprenolol can be given to patients with ischaemic heart disease without the risk of inducing potentially cardiotoxic disturbances in serum magnesium and serum calcium levels. Whether this applies to cardioselective beta-blockers remains to be established.

Adrenergic beta-Antagonists

Acute stimulation of thyroidal NAD+ kinase, NADPH reoxidation, and peroxidase activities by physiological concentrations of thyroid stimulating hormone acting in vitro: a quantitative cytochemical study.

Quantitative cytochemical techniques have been employed in a study of some of the acute effects of low doses (0.01----1 mU/liter) of TSH on the metabolism of guinea pig thyroid segments maintained in nonproliferative organ culture. The enzymes involved in the synthesis of NADP+ (NAD+ kinase), its reduction by the pentose-shunt (glucose 6-phosphate dehydrogenase), and its reoxidation both by the microsomal electron chain (diaphorase activity) and by participation in other cellular processes, have been examined. The effect of TSH on peroxidase activity has also been studied. After 10 min stimulation with TSH (1 mU/liter) there was a 60% increase in NAD+ kinase activity which preceded changes in the microsomal reoxidation of NADPH (up 33% by 30 min). There were no changes in the activity of glucose 6-phosphate dehydrogenase. There was a sustained rise in peroxidase activity which reached 129% over control after 30 min. This is the first in vitro demonstration of an acute stimulation of peroxidase and kinase activities by physiological concentrations of TSH. NADPH reoxidation after stimulation with TSH was such that the ratio of NADPH reoxidized via the microsomal respiratory pathway (diaphorase, hydrogen pathway 1) relative to that available for cytosolic utilization (hydrogen pathway 2) increased compared to the unstimulated controls. We suggest that increased NADP+ production (via NAD+ kinase activity) and the preferential shuttling of the NADPH for reoxidation via the microsomal respiratory pathway, coupled with greatly stimulated peroxidase activity, may be important regulators of the control of thyroglobulin iodination and hence thyroid hormone production.

Animals

Thyroid function in patients with breast cancer.

Thyroid function was evaluated in 58 patients with breast cancer and compared with data obtained from an age-matched control group of healthy women. Thyroid antibodies at low levels were present in 29 patients (50%): 21 patients (36%) had thyroid stimulating antibodies at low activity. Ten patients (17%) had thyroglobulin antibodies compared with 3 in the control group (P less than 0.05). Nine of 10 patients with thyroglobulin antibodies had microsomal antibodies as well. Two patients had only microsomal antibodies. Additionally 10 autoimmune antibodies were determined. These were, however, either absent or present in low concentrations in serum. Independent of the stage of disease, no differences were demonstrated between patients and controls in serum levels of triiodothyronine, thyroxine, free T3 index, free T4 index, thyroid stimulating hormone, and thyroglobulin. In conclusion, we found an increased frequency of thyroid autoantibodies in euthyroid patients with breast cancer compared with healthy controls suggesting a possible relation between this disease and autoimmune thyroid disease.

Adult

Serum phosphate increase during short-term beta-adrenoceptor blockade in thyrotoxicosis.

We studied the changes in blood plasma electrolytes during acute and short-term treatment with four different beta-adrenergic-blocking agents in 31 patients with hyperthyroidism. Serum phosphate increased during the first four hours and remained elevated after one week both after cardioselective (acebutolol) and non-cardioselective (oxprenolol, pindolol and timolol) beta-blockade (p less than 0.05). Albumin decreased after four hours but no change was found after one week. Serum creatinine increased after one week in the acebutolol-treated group, while sodium, potassium and albumin-corrected calcium in serum did not change. The hyperphosphatemic effect may be due to blockade of beta 1-adrenoceptors, since the effect of the cardioselective acebutolol was no less than that of the non-cardioselective beta-adrenoceptor blockers.

Acebutolol

Short-term beta-adrenergic blockade decreases serum thyroglobulin in hyper- and euthyroid patients.

Cardioselective [Acebutolol (N = 10)] or noncardioselective [Oxprenolol (N = 9)] or [Pindolol (N = 9)] beta-adrenergic blockers were given to patients with suspected hyperthyroidism. Four h after start of the beta blockade median serum thyroglobulin (Tg) had decreased to 33 (range: 13-325) micrograms/l from 41 (range: 12-333) micrograms/l before start in the acebutolol treated group (p less than 0.05). A significant decrease in serum Tg was also found in the oxprenolol-treated group [before start: 45 (24-423) micrograms/l and after 4h: 43 (18-363) micrograms/l (p less than 0.01)] and in the pindolol-treated group [before start: 154 (33-210) micrograms/l and after 4 h: 63 (19-157) micrograms/l (p less than 0.05) treated groups. After 7 days treatment the decrease in serum Tg was significant [to 85 (34-182) micrograms/l (p less than 0.02)] only in the Pindolol-treated group. It is suggested that both hemodynamic changes as well as interference with the intrathyroidal 12 S Tg to 19 S Tg dimerization might explain the changes in serum Tg during beta blockade. Knowledge of drug influence on serum thyroglobulin is important for the interpretation of variations found in patients where thyroglobulin is being used for diagnostic purposes.

Acebutolol

Intellectual impairment after hyperthyroidism.

Electroencephalography (EEG) and neuropsychological tests empirically shown to be sensitive to diffuse cerebral damage were performed in 26 patients 10 years after successful treatment of hyperthyroidism and in a control group with non-toxic goitre. In the hyperthyroid state 81% had abnormal EEG before treatment, and 10 years after treatment 68% still had abnormal EEG compared with 41% in the control group (P less than 0.05). In 7 out of 11 neuropsychological tests the previously hyperthyroid patients showed significant impairment compared with the control group. Twenty-three per cent of the patients displayed marked to severe intellectual impairment, 31% moderate and 41% slight or no impairment compared with 0%, 31% and 69%, respectively, in the control group (P less than 0.05). Four patients had been granted disability pension on the basis of the intellectual dysfunction. Signs of intellectual impairment indicating irreversible brain dysfunction after thyrotoxicosis thus seem to be a frequent, although hitherto not generally recognized, finding.

Adult

Increased frequency of goitre in epileptic patients on long-term phenytoin or carbamazepine treatment.

Thyroid function, the clinical occurrence of goitre and ultrasonically determined thyroid gland volume were investigated in 23 patients with phenytoin- and 28 patients with carbamazepine-treated convulsive disorders and compared with matched healthy controls. In the phenytoin treated group median thyroid volume was 26 ml (range 14-57 ml) compared to 17 ml (range 8-41 ml) in the controls (P less than 0.01). Ten patients and four controls had a goitre (NS). Median serum T4 and FT4I levels were reduced, serum TSH level increased and serum T3, T3RU, FT3I and thyroglobulin levels unaltered compared with the controls. In the carbamazepine treated group median thyroid volume was 25 ml (range 13-66 ml) compared to 16 ml (range 9-44 ml) in the controls (P less than 0.01). Thirteen patients and three controls had a goitre (P less than 0.02). Median serum T4, FT4I and FT3I levels were reduced, serum thyroglobulin increased and serum T3, T3RU and TSH levels unaltered compared with the controls. The increase in thyroid size is probably a compensatory mechanism due to the low free thyroid hormones in serum caused by an increased hepatic degradation of thyroid hormones by phenytoin and carbamazepine.

Adolescent

Thyroid gland volume and serum concentrations of thyroid hormones in chronic renal failure.

Thyroid gland volume, ultrasonically determined, and thyroid function were investigated in 40 patients with chronic renal failure (33 of these on hemodialysis) and 40 sex-, age- and weight-matched healthy controls. None had thyroid autoantibodies or a clinically detectable goiter. The median thyroid gland volume was significantly elevated in the uremic patients: 24 ml (range 8-43 ml) compared with the healthy controls 17 ml (range 10-22 ml) (p less than 0.005). The serum concentrations of thyroxine (T4), triiodothyronine (T3), free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were significantly decreased in uremic subjects compared with the controls. The serum concentration of thyrotropin did not differ significantly between patients and controls. None of the thyroid function variables correlated with thyroid gland volume. In conclusion, thyroid gland volume was increased in patients with chronic renal failure. The alterations in thyroid hormone concentrations could, however, not explain this finding.

Adolescent

"Low T3-syndrome" in acute myocardial infarction--relationship to beta-adrenergic blockade and clinical course.

Serum levels of T4, T3 rT3 and resin T3 uptake were followed for 5 days in 40 patients with acute myocardial infarction (AMI) allocated to early treatment either with alprenolol or placebo. There was a significant fall in T3 (P less than 0.05) and an increase in rT3 (P less than 0.05) without any significant difference between the alprenolol - (n = 19) and placebo - (n = 21) treated groups. The risk of missing a further 20% change in se-T3 and se-rT3 after alprenolol compared to placebo treatment (beta) was less than 0.10 and less than 0.50, respectively. In patients with a severe clinical course, the fall in T3 and increase in rT3 was significantly greater than in patients without complications. No change in T4 was observed either with respect to the clinical course nor following alprenolol. The data suggest that alprenolol can be given in the acute phase of myocardial infarction without causing any additional disturbance in the serum levels of T3 and T4.

Adrenergic beta-Antagonists

The cytochemical assay of NAD+ kinase activity in the follicular cells of guinea-pig thyroid gland.

A quantitative cytochemical assay for NAD+ kinase-like activity in the guinea-pig thyroid gland is described. The NADP+ produced by the activity of the kinase was used to drive the NADP+-dependent enzyme glucose-6-phosphate dehydrogenase which is endogenous to the tissue. The activity of glucose-6-phosphate dehydrogenase is greatly in excess of that of the kinase and was unaffected by the constituents of the kinase incubation medium (ATP, Mg2+ and NAD+) either alone or in combination. Kinase activity was dependent both on ATP and Mg2+, with maximal activity seen when the Mg-ATP ratio was between 1:1 and 4:1. Free ATP inhibited the activity of the enzyme. Enzyme activity was exhibited over a broad pH range (7-9) with a peak at pH 8.2. The sulphydryl-blocking agents, p-chloromercuribenzoate, iodoacetate and iodoacetamide (at 1 mM), completely abolished kinase activity but were without effect on glucose-6-phosphate dehydrogenase activity. N-ethylmaleimide and citrate (both at 1 mM) had no effect on either kinase or glucose-6-phosphate dehydrogenase activities.

Adenosine Triphosphate