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Biomedical subjects

L J Valenta

Publications and source records attributed to L J Valenta.

At least 37 records · Page 2Linked to original sources

Use of the artificial beta cell (ABC) in the assessment of peripheral insulin sensitivity: effect of chromium supplementation in diabetic patients.

The artificial beta cell (ABC), a closed-loop insulin delivery system, was used to determine insulin sensitivity. Progressively increasing glucose loads were administered after initial stabilization of the blood glucose at euglycemic levels such that the serum C-peptide was suppressed. The amount of insulin required to maintain euglycemia was considered a measure of sensitivity to insulin. Six stable maturity onset diabetics were studied before and after supplementation with chromium-rich brewer's yeast. All patients demonstrated an increase in sensitivity to insulin as indicated by a decrease in the fasting blood glucose concentration and a decrease in insulin requirement during the glucose challenge (P less than 0.02). The data obtained support the hypothesis that chromium or some other factor(s) present in brewer's yeast potentiates the peripheral effects of insulin. It remains to be established whether this effect occurs at the receptor or post-receptor level.

Adult↗

Atypical biochemical findings in Turner's syndrome: identification of a possible subset.

Two patients with Turner's syndrome, Hashimoto's thyroiditis, and partial intrasellar arachnoidocele (empty sella) are described. Both patients had low basal and LH-RH-stimulated gonadotropin release and moderately exaggerated TSH and PRL response to insulin-induced hypoglycemia and TRH. Such findings are typical of a disturbance of the hypothalamic-pituitary axis. In our patients, these findings could be due to the presence of the intrasellar arachnoidocele or might represent a loss of the central dopaminergic tone possibly as the consequence of an autoimmune process. It remains to be established whether the frequency of intrasellar arachnoidocele and Hashimoto's thyroiditis in patients with Turner's syndrome justifies classification of the condition of these patients as a distinct subtype.

Adult↗

Gaba-ergic and dopaminergic regulation of thyroid stimulating hormone. Effects of baclofen and metoclopramide.

The effects of the GABA analogue, baclofen, and the dopamine antagonist, metoclopramide, on basal and TRH-stimulated TSH release were studied in 6 normal male volunteers. Basal TSH secretion was not influenced by baclofen (10 mg orally three times daily for 3 days) or metoclopramide (10 mg i.v.), given alone or together. Baclofen produced a blunting of the TRH-stimulated TSH release (p less than 0.05), which persisted after metoclopramide administration. It is speculated that GABA and its analogues exert an inhibitory effect on TSH secretion, presumably at the level of the pituitary, and this effect is not mediated by dopamine.

Adult↗

Regression of a pituitary adenoma following levothyroxine therapy of primary hypothyroidism.

Two patients are described who were suffering from primary hypothyroidism and who developed a pituitary microadenoma and macroadenoma with suprasellar extension, respectively, diagnosed by CT scan of the pituitary. Both patients originally presented with amenorrhea and galactorrhea. In addition to low serum T4 and T3 levels and an elevated TSH level, they also had hyperprolactinemia. The TRH test performed in one of the patients showed an exaggerated response of both TSH and PRL to TRH. Correction of hypothyroidism by prolonged (months) treatment with levothyroxine resulted in normalization of thyroid function tests as well as hyperprolactinemia and in regression of the pituitary tumor. It was concluded that primary hypothyroidism was the cause of the pituitary adenoma and the amenorrhea/galactorrhea syndrome. It is recommended that routine thyroid function tests be obtained for patients with hyperprolactinemia. Demonstrable primary hypothyroidism should be corrected for prolonged periods of time by levothyroxine therapy, and CT scanning of the pituitary should be repeated before any other treatment such as bromocriptine or surgery is attempted.

Adenoma↗

How to detect hypothyroidism when screening tests are normal. Use of the TRH stimulation test.

In this study, 65 women and two men were examined because of symptoms suggesting hypothyroidism (eg, tiredness, lack of energy, weight gain, dry skin, cold intolerance, constipation, galactorrhea, menstrual disturbances). Some also demonstrated biochemical abnormalities (eg, hyperlipoproteinemia, elevation of creatine phosphokinase). Serum thyroxine (T4) and triiodothyronine (T3) and T3 uptake were normal in all patients. The thyrotropin-releasing hormone (TRH) test differentiated the patients into two groups: Group 1 (47 patients) had an exaggerated response of thyroid-stimulating hormone (TSH) to TRH; group 2 (20 patients) had a normal TSH response. Compared with group 2, the group 1 patients had a higher incidence of typical hypothyroid symptoms and goiter and responded more readily to levothyroxine therapy. We concluded that these patients had borderline hypothyroidism. Results of basal thyroid function tests may be within normal limits in such a condition. The TRH test, then, appears to increase diagnostic accuracy and should be routinely performed in patients who have symptoms suggesting hypothyroidism but normal results of basal thyroid function tests.

Adult↗

Response of thyroid hormones in peripheral and thyroid venous blood to TRH administration in man.

Thyroid vein and cubital vein samples were collected simultaneously in 6 moderately hypercalcemic patients and 1 eucalcemic hypothyroid patient, and thyroid hormones were measured in the serum in the basal state, as well as 30 and 60 min after intravenous administration of TRH. No gradient was detectable between peripheral and thyroid blood in the case of T4, and no significant changes were observed following TRH. The levels of T3 were higher in the thyroid venous effluent than in the periphery and a marked increase occurred following TRH. Serum thyroglobulin also increased following TRH, but there was no peripheral vs. thyroid gradient. Calcitonin demonstrated a marked positive gradient in the thyroid vein compared to the periphery, but no change was observed following TRH. It is concluded that the patterns of response of individual thyroid hormones reflect differences in their secretion and, specifically, that intrathyroid conversion of T4 to T3 occurs during the thyroid hormone secretion.

Female↗

GABA-ergic and dopaminergic mechanisms in gonadotrophin secretion in males--effects of baclofen and metoclopramide.

The GABA analogue, baclofen, and the dopamine antagonist, metoclopramide, were studied with respect to their effects on basal and LRH-induced LH and FSH release in 6 normal male volunteers. Basal gonadotrophin secretion was unchanged following the administration of baclofen or metoclopramide given alone or in combination. LRH-stimulated LH release was significantly blunted after metoclopramide administration in the baclofen pre-treated volunteers. Serum LH concentration (mean +/- SD) in the control phase was 30.1 +/- 17.2 mIU/ml and was 19.4 +/- 9.6 mIU/ml after baclofen plus metoclopramide (P less than 0.02). LRH-stimulated values, however, were unaffected by baclofen or metoclopramide when the drugs were given alone. LRH-stimulated FSH release was not significantly influenced by baclofen or metoclopramide given alone or in combination. Basal Prl secretion increased significantly when baclofen and metoclopramide were given separately and in combination. Basal Prl concentration (mean +/- SD) increased from 14 +/- 2 ng/ml to 18.7 +/- 4.8 ng/ml after baclofen and to 111.5 +/- 31.9 ng/ml after metoclopramide (P less than 0.01). The rise in serum Prl concentration, however, was not significantly different when measured after metoclopramide alone (111 +/- 31.9 ng/ml) or after metoclopramide and baclofen (112 +/- 33.3 ng/ml). It is proposed that GABA and dopamine exert opposing effects on LH secretion in normal men.

Adult↗

A presumptive role for gamma-aminobutyric acid in the regulation of gonadotropin secretion in man.

The effect of di-n-propylacetic acid (valproic acid), a gamma-aminobutyric acid transaminase inhibitor, on the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (LHRH) was studied in five normal women during the proliferative and luteal phases of the menstrual cycle. Valproic acid produced no significant change in the basal serum concentrations of LH, FSH, estradiol, and progesterone in either the proliferative or the luteal phase of the study. In the proliferative phase the delta LH (maximum increment above baseline) following LHRH stimulation rose from 32.8 +/- 21.2 (mean +/- SD) to 52.2 +/- 28.7 mlU/ml (not significant) after valproic acid, while the delta FSH rose from 2.2 +/- 1.1 to 5.0 +/- 3.6 mlU/ml (not significant). Four of the five volunteers showed an augmentation of the delta LH response to LHRH after valproic acid while the fifth subject showed no change. In three subjects the augmented delta LH response after valproic acid was highly significant. By contrast, the delta LH in the luteal phase following LHRH stimulation fell from 65.3 +/- 20.1 to 43.1 +/- 12.9 mlU/ml after valproic acid (p less than 0.03). Corresponding delta FSH values were 2.5 +/- 1.1 and 2.1 +/- 0.8 mlU/ml (not significant). It is speculated that gamma-aminobutyric acid may exert a modulatory role on gonadotropin secretion following LHRH stimulation and that this effect is influenced by the phase of the menstrual cycle.

Adult↗

A new test of peripheral insulin sensitivity in vivo using artificial beta cell.

A new in vivo test of insulin sensitivity is described. It utilizes closed-loop insulin delivery device (GCIIS, Biostator) capable of infusing glucose and insulin according to preselected algorithms. In euglycemic patients, insulin was infused by GCIIS to maintain euglycemia in the face of challenges with gradually increasing doses on intravenously administered glucose. Under the described experimental conditions, the endogenous insulin release was minimized as evidenced by serum C-peptide levels of less than 2 ng/ml, and thus the peripheral disposal of glucose should have depended entirely on the exogenous insulin. The amount of the insulin infused was considered to be a measure of peripheral insulin sensitivity. The test was applied to normal and non diabetic obese individuals, and to diabetics, both insulin dependent and independent. Significant insulin resistance was demonstrated in the obese and diabetic patients. In two obese females, the test was repeated after a prolonged period of starvation, and showed marked increase in insulin sensitivity. In two poorly controlled insulin dependent diabetics, marked increase in insulin sensitivity was also observed, here following a prolonged period of euglycemia (48 hours). It is concluded that the GCIIS controlled insulin sensitivity test is a simple, reliable test of peripheral insulin sensitivity, most convenient for clinical and experimental studies in vivo.

Adult↗

Idiopathic thrombocytopenic purpura and Graves disease.

A 31-year-old black woman was studied who, at the age of 12 years, underwent splenectomy for a bleeding disorder due to idiopathic thrombocytopenic purpura (ITP). More than 20 years after the first signs of her bleeding disorder, the patient developed signs of Graves disease. This condition was treated with 131I with resulting hypothyroidism. The rare combination of ITP and Graves disease was considered to be a manifestation of two separate autoimmune disease. For the second time in the literature, HLA typing was performed in a patient with such a disease combination, and it was found to be of the group A23, A28, and B17. This is different from B8, which is most frequently found in both isolated ITP and Graves disease. Possible racial factors may be involved. It is concluded that more cases of such combined disease need to be studied before possible genetic patterns can be established.

Adult↗

Diagnosis of pituitary tumors by hormone assays and computerized tomography.

One hundred and seventy patients with endocrine abnormalities, 29 males and 141 females, were studied by computerized tomography (CT) scanning of the pituitary and by pituitary hormone assays including basal and stimulated hormone concentrations in the blood. Pituitary macroadenoma was observed in 40 of the 170 patients, microadenoma in 49, primary empty sella in 46, secondary empty sella in 25, including 20 of the 40 patients with macroadenoma after surgical removal or radiation therapy of the tumor. Suprasellar tumor was present in four patients. In 23 women with menstrual abnormalities and 3 men with impotence and hyperprolactinemia, the results of CT scanning were normal. Of the 40 patients with macroadenoma, 24 presented with a hyperfunctioning syndrome (acromegaly or hyperprolactinemia). Among the 49 patients with microadenomas, 46 had the amenorrhea-galactorrhea syndrome, one male presented with acromegaly and one with Cushing's disease, and one female also had Cushing's disease. Primary empty sella was associated with the amenorrhea-galactorrhea syndrome in females and impotence in males. Only four female patients demonstrating an empty sella were asymptomatic. Distinctive biochemical findings were identified in certain groups of patients with different pituitary pathologic features. CT scanning was found very useful in the assessment of the size of the tumor, its suprasellar or parasellar extension and response to therapy, and in differential diagnosis of tumor and empty sella. Disappointing results were obtained in patients with endocrine abnormalities and normal results of CT scanning, and in patients following surgical treatment for a pituitary tumor, when the identification of recurrent tumor was impossible from a single examination. It is concluded that CT scanning is the most advanced technique in the diagnosis of anatomic pituitary abnormalities and it should replace the traditional invasive diagnostic procedures.

Adenoma↗

Hyperparathyroidism due to a cystic parathyroid adenoma after irradiation of the neck.

A 48-year-old female with hypercalcaemia diagnosed 3 years prior to admission is described. The patient underwent x-ray therapy of the neck for keloid scars 35 years prior to the diagnosis of hypercalcaemia. The hypercalcaemia was found to be the result of primary hyperparathyroidism. A cystic parathyroid adenoma was identified during surgery and was, on microscopic examination, composed of oxyphil cells rich in mitochondria. The cystic fluid contained 360 times higher C-terminal PTH than peripheral serum and almost 4000 times higher PTH as intact 1-84 amino acid residue species. We concluded that previous X-ray irradiation was related to the pathogenesis of the patient's parathyroid adenoma. The mild nature of the patient's hyperparathyroidism was possibly related to the composition of the tumour of oxyphil cells, known to be a poorly functioning variant of the parathyroid cell. Since parathyroid 'cysts' are obviously necrotic parathyroid adenomas, aspiration of the cysts alone cannot be expected to be curative and, therefore, it is recommended to treat cystic parathyroid adenomas by surgical extirpation.

Adenoma↗

Attenuation of hypertension by conjugation estrogens.

An unusual case of hypertension in a female that was normalized by the administration of conjugated estrogens is reported. During the period when no estrogens were administered, marked sodium retention was noted with an associated increase in sensitivity to the vasopressive effect of infused catecholamines and an increase in the electronegativity of the colonic mucosal potential difference. These findings suggested the presence of a mineralocorticoid influence that was reversed by estrogen therapy. The increase in arteriolar sensitivity occurred despite normal serum concentrations of aldosterone, deoxycorticosterone and 18-hydroxy 11-deoxycorticosterone and paralleled the sodium-retaining state. All the abnormalities were corrected with estrogen administration.

Estrogens, Conjugated (USP)↗

Acute effects of iodine on the stimulated rat thyroid.

Rats fed a low iodine diet (LID) for 5 weeks were given 125I as NaI to prelabel their thyroids; 24 h later, they were injected ip with 1 mg KI. They were then killed at different time intervals of up to 4 h. Thyroids of control animals not injected with KI were hyperplastic, the tissue showed microfollicles devoid of colloid, thyroglobulin was poorly iodinated, and thyroid peroxidase activity was increased. Within 4 h after KI injections, there was 1) a decrease in thyroid weight, 2) expansion of the follicular lumens of the hyperplastic in thyroid tissue and accumulation of colloid, 3) an increase in the thyroglobulin iodine concentration, and 4) a decrease in the thyroid peroxidase activity. Some of these changes started to occur as early as 60 min after KI administration. By that time, using the microprobe, most of the organically bound iodine was detectable inside the follicular cells. Radioiodine (125I) used to prelabel the thyroids was accumulated inside the follicles during the entire observation period. The serum TSH level was elevated and did not decrease after KI administration. It is concluded that excess iodine in LID rats may produce acute morphological and biochemical changes which seem to be a direct effect of iodine not mediated by modifications of TSH. The distribution of organically bound iodine, as determined by the microprobe, and the biochemical studies were interpreted as suggesting intracellular thyroglobulin iodination in these stimulated rat thyroids.

Animals↗