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Biomedical subjects

R G Symons

Publications and source records attributed to R G Symons.

14 recordsLinked to original sources

A rat model of the 131I-induced changes in thyroid function.

Thyrotoxic patients treated with Iodine-131 (131I) often present with low thyroxine (T4), normal triiodothyronine (T3) and raised thyrotropin (TSH) concentrations in serum. We have developed a rat model of this low T4, raised TSH state. Rats were injected with 50, 150 or 450 mu Ci 131I. A dose of 50 mu Ci 131I caused no significant effect on thyroid function, as assessed by serum parameters whereas both 150 mu Ci and 450 mu Ci 131I caused a significant fall in serum T4 concentration accompanied by a significant rise in TSH concentration. In all groups serum T3 concentration was not significantly altered when compared to controls. The clearance of 131I from the rats showed a single exponential curve (t 1/2 3.38 +/- 0.61 days) over the range of 131I doses used. Differing body weights had no effect on the serum T4 changes induced by 131I.

Animals

An evaluation of a fluorescence polarization immunoassay of thyroxin and thyroxin-uptake.

We evaluated the fluorescence polarization immunoassay for total thyroxin (T4) and thyroxin-uptake (T-U) in the Abbott "TDx" Analyzer. Between-assay precision was good when we did once-fortnightly calibration and assayed samples in singleton. Measured T4 concentration was decreased in hemolyzed samples with obvious red coloration and undetectable in severely hemolyzed samples. The T-U assay was unaffected by hemolysis. Unlike the triiodothyronine-uptake methods, the T-U assay utilizes labeled T4 and measures a variable related to serum thyroxin-binding capacity rather than the concentration of unoccupied binding sites in serum. The T4 and T-U values of 422 samples correlated highly with a T4 (in-house) radioimmunoassay and a commercial assay for thyroxin-binding globulin, respectively. The free thyroxin ratio (ratio of T4 to T-U, FTI) correlated highly with free T4 concentration as measured by T4-analog-tracer radioimmunoassay (fT4 analog RIA). FTI and fT4 values were discordant in late pregnancy (normal FTI and low fT4) and euthyroid sick patients (above-normal or normal FTI and low fT4), suggesting that the FTI gives fewer misleading results in these patients.

Adult

Acute changes in thyroid function tests following ingestion of thyroxine.

The timing of blood sample collection in relation to ingestion of thyroxine has been thought to be of no consequence in the assessment of patients receiving thyroxine medication. We have investigated changes in serum thyroid hormones after oral ingestion of thyroxine. Therapeutic doses of thyroxine (100-300 micrograms) were given to five normal, euthyroid subjects and eleven patients receiving long-term thyroxine-replacement medication. Blood samples were collected prior to and following ingestion of thyroxine. A significant increase in total thyroxine (T4), free thyroxine index (FTI) and free T4 (FT4) concentration was observed at all doses. No significant change was observed in 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine or thyrotrophin concentrations. Although T4, FTI and FT4 were significantly elevated 1 h after ingestion of all doses of thyroxine and remained elevated for at least 6 h, supranormal values were observed only after ingestion of the highest dose of thyroxine. The levels of T4, FTI and FT4 in patients receiving thyroxine should be interpreted in relation to the time of thyroxine administration. Standardisation of blood collection in patients receiving thyroxine replacement would be desirable.

Humans

Studies on the accuracy of a quantitative kit radioimmunoassay for free thyroxine.

Experiments designed to determine the accuracy of the Corning Immophase Free T4 assay revealed that there was a marked perturbation of thyroxine binding to the serum proteins during the assay; binding of 125I-T4 to the immobilised T4 antibody in the absence of merthiolate increased considerably with buffer dilution of serum; and the free thyroxine concentration declined significantly during pregnancy. These changes in measured fT4 were not observed with an equilibrium dialysis-radioimmunoassay procedure. The assay was precise, easily performed, and as effective as the free thyroxine index (FTI) in diagnosing thyroid disease. We conclude that the assay does not provide an accurate quantitative estimation of serum fT4 concentration in samples with elevated TBG concentration and that the kinetic principles on which the assay is based are altered as serum binding-protein concentration is reduced (serum dilution). Both FTI and fT4 (Corning) data in pregnant patients should be interpreted with caution and with reference to clinical symptomatology and other thyroid function tests.

Humans

Hormones in saliva: mode of entry and consequent implications for clinical interpretation.

Assay of hormones in saliva would be more convenient than assay in blood, but there is no information on the route by which hormones enter saliva, information that would provide insight into the clinical value of such assays. We have examined the mode of entry of various hormones into saliva. The results suggest that unconjugated steroids enter saliva by diffusing through the cells of the salivary glands and that their concentration in saliva does not depend on the rate of saliva production. Conjugated steroids enter saliva via "ultrafiltration" through the tight junctions between the acinar cells, and their concentration in saliva is highly flow-rate dependent. Thyroxin and choriogonadotropin enter saliva via the ultrafiltration route or by contamination of the saliva by plasma or gingival fluid. We conclude that the salivary concentration of unconjugated steroids may usefully reflect the concentration of free (nonprotein-bound) steroids in plasma. Conversely, the concentration of conjugated steroids, thyroxin, and protein hormones such as choriogonadotropin in saliva probably does not reflect their concentration in plasma in any clinically useful way.

Chorionic Gonadotropin

Effectiveness of analysis of free thyroxin concentration in serum for diagnosis of covert thyroid disease.

The indirect indices of free-thyroxin concentration (fT4) are of limited effectiveness in diagnosing covert (mild) thyroid disease. We compared measurements of fT4 and of normalized T4 (NT4, the effective thyroxin ratio) in a group of patients being treated for thyroid disease, most of whom were clinically euthyroid. Although fT4 values correlated well with NT4, many of the patients (34% in one of the comparisons) had fT4 and NT4 values that gave different indications of thyroid status. A review of the patients' treatment and other biochemical indications revealed that measurements of fT4 were more effective in detecting mild disturbances of thyrometabolic status than were assays for NT4, total T4, total triiodothyronine, or thyrotropin. This study suggests that direct fT4 assays are particularly useful in diagnosing covert thyroid disease.

Humans

The effects of iopodate on the serum iodothyronine pattern in normal subjects.

The ingestion by normal subjects of 3 g of sodium iopodate, which is widely used in routine oral cholecystography, resulted in significant decreases of serum total and free T3 to a nadir on day 4 which averaged 43% and 40%, respectively, below initial mean values. Total and free rT3 increased markedly to a peak on day 3, 244% and 189%, respectively, above initial mean values. Total and free T4 and free T4 index rose to a maximum on day 4, but these changes were not statistically significant. A marked TSH increase was also seen, most evident on day 3. All these changes reverted to baseline values by day 14 at a time when serum total iodide was still markedly elevated. It is concluded that the changes observed after iopodate were not due to alterations in serum binding proteins nor to an effect on thyroid gland by the large iodine component of iopodate, but were consistent with an effect on the peripheral metabolism of T4. Difficulty in interpreting routine thyroid function tests may occur for up to 14 days after oral cholecystography with iopodate.

Adult

Linear and quantitative migration of stored sperm through cervical mucus during the periovular period.

The ability of stored spermatozoa to penetrate fresh samples of cervical mucus obtained from 23 patients during 47 menstrual cycles was studied, utilizing an in vitro test. The determination of daily hormonal and gonadotropin values allowed an accurate realationship to be established between the results of sperm-mucus interaction and the environmental milieu. Cervical mucus was found to be effectively penetrable only on day -1 and day 0 when considered with respect to the plasma luteinizing hormone surge. Correlation was apparent between the ability of sperm to penetrate and the favorable clinical parameters of cervical assessment.

Cervix Mucus

Changes in lymphocyte function during pregnancy.

A gradual increase in spontaneous lymphocyte DNA synthesis was demonstrated in each trimester of pregnancy. Autoradiographic studies indicated that lymphocytes were primarily responsible for this activity. PHA-induced lymphocyte transformation in both fetal calf serum and autologous serum was significantly reduced in the second and third trimesters of pregnancy. Spontaneous lymphocyte DNA synthesis was significantly reduced in patients with mild pre-eclampsia. However, no significant differences were seen in patients with severe pre-eclampsia in the third trimester of pregnancy compared with the normal control subjects. No evidence was adduced to implicate inhibitory humoral factors affecting the peripheral blood lymphocytes in pregnany patients in experiments in which washed lymphocytes were cultured in medium containing heterologous serum. In vitro experiments demonstrated that cortisol, progesterone and HPL caused a significant reduction in lymphocyte DNA synthesis, and HGH and HCG had a variable effect. However, only cortisol was regularly inhibitory at physiological concentrations. The progesterone effect was dose-related, producing 90 per cent inhibition of activity at a concentration of 10 mug/ml. No synergism could be shown between HPL and progesterone on lymphocyte transformation. The increase in activity of circulating immunoreactive cells during pregnancy and its depression with the onset of pre-eclampsia is discussed.

Chorionic Gonadotropin