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Biomedical subjects

J Date

Publications and source records attributed to J Date.

At least 37 records · Page 2Linked to original sources

Serum thyroglobulin and its autoantibody following subtotal thyroid resection of Graves' disease.

Thyroid surgery leads to marked changes of the levels of serum thyroglobulin and its autoantibodies in the subsequent 3 postoperative weeks. Furthermore in Graves' disease progression of exophthalmos has sometimes been seen following thyroidectomy. Nineteen medically pretreated patients with Graves' disease and no signs of exophthalmos were studied systematically up to 6 months postoperatively. Nine patients had thyroglobulin antibodies. Mean values rose to 3.5 times pretreatment values within 2 months (P less than 0.001) followed by a gradual fall below pretreatment level after 6 months. None of the antibody negative patients reverted to positive or vice versa. Serum thyroglobulin (n = 10) was elevated preoperatively (mean 309 micrograms/l, SD 251), their values being normalized within 1-2 months (mean 19.4 micrograms/l, SD 7.3). The preoperative serum thyroglobulin correlated to the weight of the removed thyroid tissue (r = 0.87, P less than 0.01). Three patients showed elevated thyroid stimulating hormone after 1 month. Of these, two developed myxoedema, the third remained euthyroid with persistently elevated serum thyroglobulin. None showed recurrence or developed exophthalmos within the period of observation. In spite of rising levels of thyroglobulin antibodies in all patients with antibodies none developed exophthalmos and only one patient with thyroglobulin antibodies had clinical myxoedema.

Adolescent↗

Thyroid stimulating antibodies, thyroglobulin antibodies and serum proteins during treatment of Graves' disease with radioiodine or propylthiouracil.

The relation between serum concentrations of thyroglobulin antibodies (TgAb), thyroid-stimulating antibodies (TSAb) and serum immunoglobulins during treatment of Graves' disease was studied in 36 consecutive patients treated randomly with 131-iodine (n = 16) or propylthiouracil (n = 20). The patients were investigated before treatment was started and on seven occasions within the following year. In the entire patient group 78% were positive for TSAb and 47% for TgAb. There was a significant correlation between TSAb and TgAb in 15 patients concomitantly positive. There were no significant changes in serum immunoglobulins during treatment in either group of patients. In the radioiodine-treated group of patients TgAb was reduced after 1 week, whereas TSAb showed insignificant variations. After 5-10 weeks both antibodies increased, for TgAb with a median peak level 3 time above the initial concentration. Of 16 patients treated with radioiodine five developed myxoedema and four of these were positive for TgAb. There was a relation between the development of myxoedema and the ratio between increases of TSAb and TgAb. Increase in TSAb was not related to serum thyroglobulin (Tg) measured in TgAb-negative patients. Propylthiouracil showed minor effects on the studied variables, but with lower mean values of Tg, TgAb and TSAb at the end of the observation period. The results indicate an immunological relation between TSAb and TgAb, although differences between their course exist in some situations.

Adult↗

A prospective study of the differential changes in serum thyroglobulin and its autoantibodies during propylthiouracil or radioiodine therapy of patients with Graves' disease.

Measurement of serum thyroglobulin (Tg) and its autoantibody (TgAb) by radioimmunological methods was performed in 48 patients with Graves' disease during treatment with radioiodine (n = 16) or propylthiouracil (PTU) (n = 32). Twenty-five of the 48 patients were TgAb positive, their sera being inaccessible to measurement of serum Tg. TgAb showed only minor changes during PTU treatment, whereas TgAb fell rapidly after radioiodine, in 5 of 16 patients to unmeasurable levels, followed by a secondary rise to 4.5 times pre-treatment level after 20 weeks. Serum Tg showed a steady increase during the first weeks after radioiodine treatment, but fell to lower levels after one year. PTU caused only minor changes in the serum Tg concentration. There was no shift in molecular sizes of either Tg or TgAb during the course of the treatments. Five of 16 131I-treated patients developed myxoedema, 4 of whom were TgAb positive. Another 3 patients had high increases in TgAb without myxoedema. Six of 18 patients had relapse of thyrotoxicosis after withdrawal of PTU-treatment. There was no significant difference in serum concentrations of TgAb or Tg between those developing relapse and those remaining in remission, and it is concluded that serum Tg is a poor predictor of relapse in medically treated thyrotoxicosis.

Adult↗

Propranolol in the treatment of thyrotoxicosis. A randomized double-blind study.

Twenty-five patients with newly diagnosed thyrotoxicosis participated in a double-blind study of the added effect of propranolol during tiamazol treatment. During the trial, the effect of treatment was ascertained by estimation at regular intervals of the clinical score (Crooks-Wayne index), free thyroxine index, serum triiodothyronine, serum reverse triiodothyronine, serum thyroglobulin and serum thyroglobulin antibodies. Both groups became euthyroid within two weeks. No statistically significant difference in the values for the clinical score or for any of the laboratory parameters measured was found between propranolol- and the placebo-treated patients. It is concluded that propranolol has no beneficial effect on tiamazol-treated hyperthyroid patients.

Adult↗

In vitro characterization of synthesized thyroglobulin immune complexes (IC). A model for studies of IC containing an autoantigen.

Human thyroglobulin (Tg) immune complexes (TgIC) were preformed at different ratios from purified Tg, and Tg antibodies (TgAb) obtained from six patients with autoimmune thyroid diseases. TgIC were characterized by precipitation with polyethylene glycol, and sedimentation in sucrose gradient. TgIC from one patient were further characterized by concanavalin A (con A), and binding to the complement factor Clq and rheumatoid factor (RF). Tg and TgIC had almost identical binding to con A, no binding to Clq, but could be partially separated by ultracentrifugation and polyethylene glycol. The highest degree of separation was obtained by a RF-coated plastic tube radiometric assay, using 125-I-rabbit TgAb as indicator. Tg showed no binding to RF, and a dose-response curve of TgIC in serum could be established. There was a dependence of the Tg-TgAb ratio, TgIC at equilibrium and in antibody excess being detected most efficiently. The method may serve as an aid in the evaluation of the fate of Tg, TgAb and TgIC following thyroid damage (surgery, radioiodine) and may be extended as a model system in the investigation of immune complexes in connection with autoimmune disorders.

Antigen-Antibody Complex↗

Sequential changes in serum thyroglobulin (Tg) and its autoantibodies (TgAb) following subtotal thyroidectomy of patients with preoperatively detectable TgAb.

The changes in serum concentrations of thyroglobulin antibodies (TgAb) were investigated in eight patients with various thyroid disorders before, during and after thyroid surgery. TgAb was measured by a radioassay using 125I-thyroglobulin. In six patients the TgAb decreased rapidly during operation. Of these patients four had low concentrations pre-operatively, and the decrease in TgAb resulted in undetectable concentrations for more than 2 days, Serum thyroglobulin (Tg), measured in the specimens with undetectable TgAb, i.e immediately following surgery, showed concentration vs time curves resembling curves from patients with no antibody present. Furthermore, two of these patients had such a high concentration of TgAb pre-operatively that the initial Tg release was not sufficient to remove the TgAb, resulting in detectable TgAb throughout the investigation period. Serum samples drawn during and after operation were chromatographed according to molecular size, showing measureable Tg corresponding to 19S Tg. TgAb was only measureable in fractions corresponding to 7S IgG. The expected presence of complexed Tg and TgAb could not be demonstrated, but the analytical methods might have been unable to reveal this. The remaining two patients with thyroiditis showed no decrease in TgAb. This was compatible with a low content of Tg in the throid measured in one of them.

Adult↗

An improved co-precipitation assay for determination of thyroglobulin antibodies.

A radioassay for determination of thyroglobulin antibodies in human serum using [125I]thyroglobulin co-precipitated with antihuman IgG is described. Serial dilutions of the antibody containing sera gave nearly rectilinear and parallel logit-log curves in conditions of moderate antigen excess. A secondary standard serum calibrated against the Medical Research Council Research standard A 65/93, which by definition c;ntains 1 Mega unit/1 (MU/1) was used for standardization. The mean imprecision in the concentration range 0.74-241 MU/1 was CV = 3% (within assay) and CV = 8% (total). The detection limit was 0.002 MU/1. The assay was compared to an antigen binding capacity method with an imprecision of 15% (total) and a detection limit of 0.1 MU/1. The coefficient of correlation between the two methods was: R = 0.997 (our method = 0.019 x antigen binding capacity -0.33). Based on this 1 Mega unit was found equivalent to 53 nmol thyroglobulin.

Antibodies↗

Effect of clomifene on thyroid function in normal men.

To study the effect on thyroid function 100 mg of clomifene citrate was given once a day to two groups of healthy male volunteers for 5 and 12 consecutive days, respectively. In both groups serum concentrations of TSH, thyroxine, triiodothyronine, T3 resin uptake test and thyroid hormone binding proteins were measured before, during and after oral administration of clomifene. The effect of clomifene treatment was evaluated in Group 1 by means of serum FSH and LH measurements. Further in Group 2 the serum TSH response to iv TRH (200 microgram) was also investigated. The mean per cent elevations in serum concentrations of FSH and LH were 145 and 200, respectively. In Group 1 a small but statistically significant decrease within reference limits in triiodothyronine (P less than 0.01) and free thyroxine index (P less than 0.02) was found on day 4 of clomifene. On day 5 a slight increase in TSH was observed (P less than 0.05). In Group 2 the response of TSH to TRH showed a non-significant increase after 5 days and a significant increase (P less than 0.01) after 12 days of clomifene. Eight days after discontinuation of the drug the response was restored to normal. No changes in the thyroid hormone binding proteins in serum could be demonstrated. Though the observed changes were slight, they indicate that clomifene exerts an influence directly on the thyroid function.

Adult↗

Sex and age correlated reference values of serum thyroglobulin measured by a modified radioimmunoassay.

The aim of the present investigation was to describe variations in serum thyroglobulin in relation to sex and age in a group of normal persons. The method used was a modified double antibody radioimmunoassay characterized by pre-incubation at 37 degrees C of standard or sample with antiserum, resulting in a reduced total incubation time. Both sensitivity and precision were comparable to other published methods. Of the 152 blood-donors initially investigated, 7 were excluded due to the presence of antithyroglobulin antibodies as evidenced by a radioassay. Both sexes were equally represented with an even distribution of ages from 20-65 years. Increased serum thyroglobulin with increasing age was demonstrated, the correlation being significant in women (Kendall's tau, P less than 0.001). Detectable concentrations of serum thyroglobulin (above 1.7 microgram/1) were found in 94%. Based on the logarithmic transformation, the upper reference limits were determined for men less than or equal to 40 years: 36 microgram/l, greater than 40 years: 44 microgram/l (difference between groups not significant, P greater than 0.05), and for women less than or equal to 40 years: 30 microgram/l, greater than 40 years: 60 microgram/l (significant difference, P less than 0.005).

Adult↗

Serum thyroglobulin in patients with toxic and non-toxic goitres compared to sex- and age-matched control subjects.

To study serum thyroglobulin (Tg) levels in patients with thyroid disorders compared to sex- and age-matched control subjects and to correlate the Tg levels to the thyroid function, 71 patients were investigated before treatment was started. Serum Tg, measured by a double antibody radioimmunoassay, was elevated in all groups with thyroid disorders, as compared to their controls, but the values showed large overlaps between groups. The highest median values were seen in the two groups of patients with toxic goitres (toxic adenoma and Graves' disease). The Tg values in patients with non-toxic goitres (diffuse and nodular) and in controls showed a log normal distribution, whereas the distribution of values from patients with toxic goitres was different. No correlation was found between serum Tg and serum thyroxine, serum triiodothyronine and serum TSH, respectively. It is concluded that determination of serum Tg is of little diagnostic value in thyroid diseases.

Adenoma↗

Folic acid supplement and intrauterine growth.

The effect of a folic acid supplment on birth weight and placental weight in women delivering in the early summer in Denmark was investigated. Thirty-six women with normal pregnancy and expected delivery in the first half of June were selected consecutively. They were paired two and two, and allotted to two groups, one of which was supplied daily with 5 mg folic acid, and the second with tablets without folic acid, from the 23rd week of pregnancy. A significant correlation was found between erythrocyte folic acid and birth weight. The infants in the folic acid group were 12.7 per cent heavier than those in the control group (p less than 0.01). A similar difference was found with regard to placental weight and the number of placental cells.

Birth Weight↗

Anticomplementary activity in diffuse and nodular goiters.

The occurrence of anticomplementary activity and its correlation to serum thyroglobulin was investigated in 71 patients with thyroid diseases and 63 age and sex matched control subjects. The patients which were subgrouped according to thyroid function and characteristics of the goiter, were examined at the time of diagnosis. The anticomplementary activity was measured by a complement consumption (CC) assay. Sera from patients with Graves' disease and nontoxic diffuse goiter, showed stronger activity than sera from patients with nontoxic goiter. Seventeen of the patients and one of the controls were positive in the CC-assay. The percentage hemoglobin release in this assay was normally distributed using control sera but not for the patient group. There was no correlation either between CC-activity and serum concentrations of thyroglobulin or CC-activity and antibodies to the O-antigen of Yersinia enterocolitica serotype 3, thyroid cytoplasma, thyroglobulin, nuclear factors, streptolysin O, streptococ hyaluronidase, and parietal cells, respectively. However, correlation between the levels of thyroid stimulating immunoglobulins and CC-activity, was noted (Rho = 0.511, P less than 0.05), which suggests that these immunoglobulins also are present as immune complexes. Thyroglobulin--antithyroglobulin complexes preformed in vitro at high thyroglobulin concentration, gave negative results in the CC-assay.

Adult↗

Thyroglobulin of varying molecular sizes with different disappearance rates in plasma following subtotal thyroidectomy.

To investigate the possible presence of thyroglobulin (Tg of different molecular sizes in plasma, blood specimens were drawn from patients during and after surgery for thyroid adenoma. Tg was measured in all serum samples by a radioimmunoassay. Selected samples were fractionated on a sepharose CL-6B column, and the fractions were assayed for Tg antigen. In serum drawn at maximum Tg concentration, molecular weights of Tg antigen ranging from 660,000 (19S) to less than 100,000 were found. 6 h later the Tg antigen of mol. wt. less than 100,000 could not be detected, and after 3 days only 19S Tg was present. Correspondingly the plasma Tg concentration vs. time curve showed a biphasic course from which two half-lives could be estimated. For 19S Tg, ta1/2 had a mean value of 4.3 days, whereas the over-all half-life for the mixture of smaller molecules, tb1/2, had a mean value of 3.7 h. The smaller molecules also showed different antigenic reactivity in the assay indicating an altered structure of the molecules. The assumption that this might be due to lack of sialic acid would explain the faster catabolic rate.

Antigens↗

Correlation between human chorionic somatomammotropin and placental weight.

Human chorionic somatomammotropin concentration in serum (S-HCS) during the latter half of pregnancy was measured by radioimmunoassay and correlated to the placental weight, in two groups of normal, healthy, pregnant women. In one group, 228 samples from 47 women were examined, which gives a longitudinal series. In the other group, single samples from each of 346 pregnant women were examined, which gives a cross-sectional series. Both groups were randomized on the basis of a prospective selection. The mean values of S-HCS in each week of gestation were almost identical in the two groups, showing a steady increase until 37-38 weeks and a subsequent decrease. In the longitudinal series there was a positive correlation between the S-HCS and placental weight after 37 weeks' gestation, but not before that time. Before 37 weeks gestation the ratio S-HCS/placental weight was significantly higher with small placentae than with large placentae. This difference between small and large placentae disappeared after 37 weeks. These results point to the existence of some regulatory mechanism tending to keep the S-HCS concentration within certain limits, independent of placental weight. This mechanism appears to be lost after 37 weeks of gestation when the S-HCS concentration starts to correlate with placental weight.

Adolescent↗