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Biomedical subjects

N Barbot

Publications and source records attributed to N Barbot.

11 recordsLinked to original sources

Pentagastrin testing in patients with renal insufficiency: normal responsivity of mature calcitonin.

Calcitonin (CT) is the most sensitive tumor marker for medullary thyroid carcinoma available, but it lacks specificity. Chronic renal failure (CRF) is known to be associated with elevations of serum immunoreactive calcitonin. Using an immunoradiometric assay to detect only mature CT, we evaluated the basal CT level and its response to pentagastrin in 30 patients with CRF and compared these data with those obtained in 71 controls. Basal mature CT was significantly higher (p < 0.05) in patients with CRF (3.55 pg/mL) than in controls (2.00). Among these patients, 20% had basal CT levels more than 10 pg/mL with a maximum of 51 pg/mL. Peak CT values (highest value obtained 3 or 5 minutes after pentagastrin) were comparable in the two groups. Among patients with CRF, 10% had peak CT values greater than 30 pg/mL with a maximum of 53 pg/mL. In this group of patients, no correlation was found between CT (at any time during the test) and parathyroid hormone, calcium, phosphate, or creatinine clearance. Men had significantly higher CT values compared with women at each time point tested, including peak values. Patients with CRF, who have not yet undergone dialysis, have moderately elevated basal CT levels, but have normal pentagastrin-stimulated peak CT levels.

Calcitonin↗

Multiple endocrine neoplasia type 2: management of patients and subjects at risk. French Study Group on Calcitonin-Secreting Tumors (GETC).

Multiple endocrine neoplasia type 2 (MEN-2) is an inherited multiglandular disease with age-related penetrance and variable expression. The prognosis of MEN-2 is linked to the carcinological evolution of medullary thyroid cancer (MTC), which depends mainly on the stage of discovery, and to the incidents related to pheochromocytomas. The emphasizes the need for early diagnosis and management of MEN-2. Since 1993, mutations evidenced on the protooncogene RET have allowed subjects at risk to be identified, thus leading to a three-step management of these patients. (1) For all the potentially affected members of a MEN-2 family, screening by molecular genetics of the ret gene enables one to identify the subjects at risk who bear the mutation. When no mutation is observed, a linkage analysis study may be proposed. (2) In the subjects at risk, early screening for the various types of endocrine lesions may then start in childhood and be performed using specific biological markers of MTC, pheochromocytoma and primary hyperparathyroidism, and particularly, basal and pentagastrin-stimulated calcitonin measurement, which is known to be the most sensitive marker for the monitoring of MTC. (3) This step of biological investigations enables the earliest possible treatment of any endocrine lesion detected before it is expressed clinically, thus improving the prognosis of MEN-2. When genetic screening cannot be performed, only annual clinical and biological monitoring remain available in all members of a family affected with MEN-2.

Drosophila Proteins↗

Induction of glioma cell death by 1,25(OH)2 vitamin D3: towards an endocrine therapy of brain tumors?

The secosteroid 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3) is the major biologically active metabolite of vitamin D. Antitumor activity of this hormone has been observed on several cell lines and on breast cancer in vivo. The purpose of this in vitro study was to determine the possible effect of 1,25(OH)2D3 on glioma cells. Two glioma cell lines from rat (C6) or human (GHD) origin were cultured in the presence of 1,25(OH)2D3. The sensitivity of these cells to 1,25 (OH)2D3 was assessed with a colorimetric MTT assay. A cytotoxic effect of 1,25(OH)2D3 was detected at concentrations around 10(-8) M. A lag period of 3 days was required between the onset of the treatment and the observation of the effects. However, the continuous presence of 1,25(OH)2D3 is not required since cell death occurred even when C6 cells were challenged for 24 hr with 1,25(OH)2D3 and then cultured in the absence of the hormone. In addition, 1,25(OH)2D3 regulates the expression of its own receptors in C6 glioma. These results provide to our knowledge the first evidence for a cytotoxic effect of 1,25(OH)2D3 on rat and human glioma cells and could offer both an experimental model to study a programmed cell death in a brain-derived cell line and a new strategy for the inhibition of glioma growth in vivo.

Animals↗

Pentagastrin stimulation test and early diagnosis of medullary thyroid carcinoma using an immunoradiometric assay of calcitonin: comparison with genetic screening in hereditary medullary thyroid carcinoma.

A pentagastrin stimulation test using a calcitonin (CT) immunoradiometric assay was performed in 38 healthy subjects and in the following 50 patients: 25 subjects from families with at least 2 known cases of medullary thyroid carcinoma (MTC), 11 subjects from families with apparently sporadic MTC, 2 pheochromocytoma carriers, 1 primary hyperparathyroidism, 8 patients with thyroid nodules, and 3 others with various diseases. In healthy volunteers, basal CT values were always less than 10 ng/L; the response to pentagastrin was below 30 ng/L for 36, and for the remaining 2, the peaks reached 30 for 1 subject and 48 ng/L for the other. The pentagastrin-stimulated CT peak was above 30 ng/L in each of the patients presented here, and all were thyroidectomized. In screening the 25 relatives of patients with familial MTC, a CT peak level over 30 ng/L was constantly associated with C-cell disease (23 cases of MTC and 2 of C-cell hyperplasia). A response to pentagastrin above 100 ng/L was observed in 15 patients among the 23 with MTC. In 8 of the 10 patients with a peak CT level between 30-100 ng/L, pathological examination showed a MTC; the other 2 had C-cell hyperplasia and a negative linkage study analysis. In the 25 other patients in the study without familial MTC, the pentagastrin-stimulated CT level was over 100 ng/L in 11 of the 14 subjects with MTC. The abnormal CT response to pentagastrin, which has been used as a criterion for surgical treatment, is currently determined by an immunoradiometric assay. Our study confirms that subjects with a peak CT level above 100 ng/L should undergo surgery whatever the reason for the test. In the context of inherited MTC, our results suggest that for patients with a CT peak level between 30-100 ng/L, surgery may actually be postponed when their probability of being gene carriers is low. Recent progress with the characterization of specific mutations in affected individuals will make familial screening much easier in the next few months.

Adolescent↗

Use of plasma iodine assay for diagnosing thyroid disorders.

AIMS: To examine the advantage of systematic plasma iodine assays in establishing the thyroid function of patients with thyroid disorders. METHODS: Iodine was determined by inductively coupled plasma mass spectrometry (ICPMS) in the plasma of 799 patients consulting for possible thyroid disorders, indicated by FT4 and TSH assays. RESULTS: Plasma iodine was below 40 micrograms/l in 57 (7%) patients, most of whom had hypothyroidism; 40-80 micrograms/l in 439 (55%) patients, most of whom had normal thyroid hormone function; 80-250 micrograms/l in 240 (30%) patients, most of whom had hyperthyroidism; and above 250 micrograms/l in 63 (8%) patients, almost all of whom had iodine overload caused by iodinated drugs, particularly amiodarone, resulting in euthyroidism (24%), hyperthyroidism (36%), and hypothyroidism (16%). Sixty five (7%) had been treated with amiodarone and 27 (3%) with other iodinated drugs. More than 10% of patients with thyroid disorders therefore had an iodine overload. CONCLUSIONS: The determination of total plasma iodine using the simple, accurate ICPMS technique, should be carried out in patients consulting for thyroid disorders, particularly for the detection of an iodine overload.

Adult↗

Bromine and thyroid hormone activity.

AIMS: To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone. METHODS: Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared. RESULTS: The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02). CONCLUSION: An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity.

Bromine↗

MC903, an analogue of 1,25-dihydroxyvitamin D3, increases the synthesis of nerve growth factor.

The effect of MC903, an analogue of 1,25-dihydroxyvitamin D3, on the expression of the nerve growth factor (NGF) gene has been studied in L cells. MC903 induces an increase in both NGF mRNA and protein with a time course similar to that obtained with 1,25-dihydroxyvitamin D3. This finding points to the potential importance of 1,25-dihydroxyvitamin D3 derivatives in the treatment of NGF-sensitive disorders.

Animals↗

Antagonistic effects of dexamethasone and 1,25-dihydroxyvitamin D3 on the synthesis of nerve growth factor.

Dexamethasone is known to decrease the pool of nerve growth factor (NGF) mRNA in various experimental systems. The negative regulatory effect of the glucocorticoid was first observed in mouse fibroblast-like L929 cells, and was subsequently reported to take place in many experimental systems, including in vivo following sciatic nerve injury. Conversely, another steroid hormone, 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3) was recently reported to promote NGF synthesis in mouse L929 cells. The present work was undertaken to investigate the effect of the concomitant addition of both steroids to L929 cells. Measurements of NGF mRNA and assays of the mature protein secreted by the cells provide evidence that the negative regulation exerted by dexamethasone may be counteracted in a dose-dependent manner by the positive action of 1,25-(OH)2D3, and vice versa. Therefore, the expression of the NGF gene can be regulated in a subtle way by the balance between the two steroids. It may be expected on the basis of these observations that in tissues that are responsive to both hormones, administration of 1,25-(OH)2D3 should be able to reverse the down-regulation of NGF synthesis elicited by glucocorticoids.

Animals↗

[Chronic autoimmune thyroiditis and C-cell hyperplasia. Study of calcitonin secretion in 24 patients].

Serum calcitonin (CT) was determined by radioimmunoassay, using two monoclonal antisera, in 22 women and two men, who had Hashimoto's thyroiditis as confirmed by echographic, immunological or cytological criteria; in 23 patients, serum CT levels were measured after intravenous infusion of pentagastrin (Pg). In 21 cases, basal and Pg stimulated serum CT concentrations were normal. A 61-year-old woman and a 63-year-old man, both euthyroid, had high serum basal CT: 12 pg/ml and 35 pg/ml; infusion of Pg resulted in abnormal increases in serum CT levels: respectively 64 pg/ml and 115 pg/ml. Another patient, a 65-year-old woman with primary hypothyroidism had high serum basal CT: 90 pg/ml (the Pg stimulation test was not done because of ischemic heart disease). Each of these 3 patients had a total thyroidectomy. Pathological examination of the thyroid showed typical features of Hashimoto's thyroiditis and extensive C-cell hyperplasia. After surgery, serum CT levels fell to normal. Therefore, a high serum CT can be observed as the consequence of C-cell hyperplasia in Hashimoto's thyroiditis.

Adolescent↗

A case of male pseudohermaphroditism due to 17 alpha-hydroxylase deficiency and hormonal profiles in the nuclear family.

A genetic male with 17 alpha-hydroxylase deficiency is described. The patient, raised as a female, was seen at 17 yr of age for impuberism. She presented all the features of the classical severe form of the disease: complete female phenotype; hypertension; hypokalemia; elevated levels of plasma progesterone, 11-deoxycorticosterone, corticosterone (B), and ACTH; and suppression of renin and aldosterone production. Levels of 17-hydroxyprogesterone, 17-hydroxypregnenolone, and all androgens were barely detectable. Hormone steroid patterns were determined in basal conditions and after acute ACTH stimulation in the parents and the two unaffected brothers in order to identify the heterozygotes. Subtle abnormalities in B and aldosterone secretion were observed in the male members of the family. On the basis of an increased ratio of B to aldosterone the two brothers were assumed to be heterozygotes. The mother had normal basal and stimulated levels of B, deoxycorticosterone, and aldosterone. In the parents and two brothers the progesterone responses to ACTH were exaggerated. The most striking finding in the father and both brothers was the observation of increased basal plasma 17-hydroxyprogesterone, unresponsive to ACTH stimulation, suggesting a partial Leydig cell 17,20-lyase deficiency in the male heterozygotes of this family. This study shows that a short ACTH test can help to identify the heterozygotes in affected families, but the abnormalities found are more heterogeneous than previously suggested.

Adolescent↗

Retinoic acid increases the expression of NGF gene in mouse L cells.

Retinoic acid (RA), the acid form of vitamin A, is shown to enhance the synthesis of nerve growth factor (NGF) in cultures of mouse L cells. Maximal stimulation was observed in cells growing in a serum-free medium supplemented with 10(-6)M RA during 48 h. The drug increased both the level of NGF mRNA and the amount of mature NGF protein secreted by the cells. RA was previously reported to increase the number of NGF receptors on some neuroblastoma cells (Haskell et al., 1987 Cell and Tiss. Res., 247, 67-73). It seems, therefore, that RA may influence nerve cell differentiation by promoting both the synthesis of the neurotrophic factor and the responsiveness of target cells.

Animals↗