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Biomedical subjects

J Lefebvre

Publications and source records attributed to J Lefebvre.

At least 289 records · Page 16Linked to original sources

[Postpartum thyroiditis. 31 cases].

Postpartum thyroiditis. 31 cases. Between 1977 and 1986, 29 women consulted in three internal medicine and endocrinology departments for clinical disorders which could be ascribed to 31 episodes of thyroiditis developed within 9 months of giving birth. Thyroiditis was diagnosed clinically on the basis of acute diffuse (11 cases) or nodular (7 cases) goitre formation, signs of dysthyroidism (16 cases) revealed by menstrual disturbances and/or galactorrhoea (11 cases). A thyrotoxic episode was observed in 9 patients; it was either without sequelae (5 cases) of followed by transient hypothyroidism (4 cases). In other patients transient hypothyroidism was observed in 11 cases and permanent hypothyroidism in 5 cases. Six patients showed no sign of dysthyroidism, and the diagnosis was made by immunological, cytological and/or histological examination of the thyroid gland. Circulating anti-thyroid antibodies were present in two-thirds of the patients. The results of radioisotope scanning varied according to the stage of the disease. In these patients, only the absence of goitre was predictive, in 4 out of 5 cases, of subsequent permanent hypothyroidism; in all other patients the prognosis was highly favourable, even without specific treatment.

Adult↗

Psychologic morbidities prior to loop electrosurgical excision procedure in the treatment of cervical intraepithelial neoplasia.

The objective of this study was to assess and compare anxiety and distress in patients undergoing colposcopic examinations and loop electrosurgical excision procedure (LEEP). Patients seen for evaluation of cervical intraepithelial neoplasia (CIN) and LEEP were recruited. All patients received further teaching with respect to their abnormality right after the colposcopic evaluation by nursing staff. The Hospital anxiety and Depression Scale (HADS) and the Psychosocial Effects of Abnormal Pap Smears (PEAPS) questionnaires were used to measure and compare distress between the two groups. Linear regression models were built to identify significant predictive variables for psychologic morbidities. Twenty-one colposcopy and 20 LEEP patients participated in this study. No significant demographic differences were noted. Eighty-one percent of patients having colposcopy and 65% of those undergoing LEEP can be classified as having significant anxiety and depression based on the HADS questionnaire. Patients undergoing LEEP scored significantly better than colposcopy patients on the mean total PEAPS score and on the self-belief/cancer concern and effects on sexual relationship dimension scores. Significant psychologic morbidities exist in patients diagnosed with CIN. Face-to-face individualized education and support after colposcopy can decrease patients' distress at subsequent treatment visits.

Adult↗

[Production rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)].

The adrenocortical function was studied in 23 patients with hyperthyroidism. The half-life of tritiated cortisol was significantly shortened; metabolic clearance rate was about twice increased, and production rate of cortisol was significantly increased in hyperthyroidism. The mean plasma concentration was unmodified. After return to euthyroid state, all the values were normalized in 7 patients.

17-Hydroxycorticosteroids↗

[Atrial natriuretic hormone and endocrine functions].

The atrial natriuretic hormone (ANP) is a cardiac hormone which gene and receptors are widely present in the body. Its main function is to lower blood pressure and to control electrolyte homeostasis. Its main targets are the kidney and the cardiovascular system but ANP interacts with many other hormones in order to regulate their secretion. The adrenal glands are the first endocrine target. Steroidogenesis, especially mineralocorticoid synthesis, is inhibited by ANP, but glucocorticoid production seems to be depressed too. As ANP synthesis is enhanced by the latter, it suggests a regulatory loop. Moreover ANP inhibits the thyroid synthesis whereas its production is enhanced by thyroid hormone. The hypothalamo-hypophyseal axis is another important target. ANP inhibits ACTH release and arginine vasopressin secretion. Vasopressin enhances ANP synthesis while GH decreases it. Finally the endocrine effects of ANP strengthen the cardiovascular and renal effects of the hormone, antagonizing the salt and water retention due to aldosterone and AVP. Because of a local production, ANP may also act as a paracrine hormone that influences the function of many endocrine systems (ovarian function for instance). In the central nervous system, ANP acts as a neurotransmitter in order to regulate pituitary and vegetative functions. Plasma ANP levels are impaired in several endocrine diseases : the plasma hormone levels increase in hypercortisolism, hyperaldosteronism, thyrotoxicosis and inappropriate antidiuretic hormone secretion; it decreases in hypothyroidism. In case of Addison's disease, ANP may be used to assess the quality of mineralocorticoid treatment, in association with the other biological criteria.

Adrenal Glands↗

Human pancreatic ductal cells: large-scale isolation and expansion.

The in vitro differentiation of pancreatic stem cells has recently been shown to represent a new source of beta cells for cell therapy in diabetes. Human ductal cell differentiation, in vitro, has been documented in three-dimensional (3D) culture and recently substantiated. Although encouraging, the optimization of the ductal cell source, expansion and differentiation ex vivo are mandatory for clinical relevance. We compared three sources of human ductal cells (hDC) (method A1-2, B, and C). The classical main duct isolation of hDC by explant (A1), or enzymatic digestion (A2), was compared with two indirect methods: from 3D cultured human islet/duct-enriched fractions (B) and dedifferentiated exocrine fractions (C). Method A: few viable hDC were obtained from the main duct. Method B: embedding islet/duct rich fraction in 3D collagen gels expands the cytokeratin 19 (CK19)-positive ductal component in the form of ductal cysts, as we described previously; monolayers derived from digested cysts were 80% ductal (CK19). Method C: initially adherent amylase-positive exocrine clusters contained 12% (CK19) to 22% (CK7) ductal cells. One-week exocrine cultures were amylase negative and 46% (CK19) to 63% (CK7) ductal. Cell viability varied: <20% (A1), 81+/-12% (B), 91+/-2% (C). Extrapolating total yields we obtained (+/-SEM): 10.5+/-4.6 x 10(3) (A1), 36+/-18 x 10(3) (A2), 292+/-50 x 10(6) (B), 1696+/-526 x 10(6) (C) viable hDC per pancreas. A secondary monolayer expansion of cyst-derived hDC (method B) was achieved with NuSerum (4.2-fold on plastic, 2.6-fold on 804G matrix; p < 0.05 vs. control cells on plastic). First passage exocrine-derived ductal cells also responded to matrix and to growth factors, albeit not significantly. In conclusion, this study demonstrated that an abundant hDC supply can be obtained from islet/duct or exocrine fractions followed by monolayer expansion with NuSerum. If their differentiation capacity is confirmed, in particular exocrine-derived ductal cells may represent a promising abundant source of islets for allogenic and autologous diabetes cell therapy.

Cell Differentiation↗

[Proceeding: Production rate, metabolic clearance rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)].

The adrenocortical function was studied in 23 patients with hyperthyroidism and compared with a group of 15 normal subjects. Parameters of adrenal function were determined with 1,2(3)H-cortisol. The half-life of cortisol is significantly shortened in hyperthyroidism, as compared to normal subjects (49,5 +/- 6,6 min vs 68,3 +/- 10,5 min) and metabolic clearance rate is increased (418,5 +/- 89,5 L/24 h vs 237,5 +/- 48,5 L/24 h, for normal subjects). The production rate of cortisol, calculated from specific and cumulate activities of THE and THF is increased in hyperthyroidism expressed as mg/24 h or mg/m2/24 h (respectively : 26,7 +/- 7,8 mg/24 h vs 15,7 +/- 3 mg/24 h and 16,9 +/- 4,6 mg/m2/24 h vs 9,5 +/- 1,8 mg/m2/24 h). The mean plasma concentration, calculated as the radio (see article) is not statiscally different in hyperthyroid and normal subjects (6,8 +/- 2,1 microg/100 ml vs 7,3 +/- 1,9 microg/100 ml). 7 patients were reinvestigated after treatment of thyrotoxicosis when they were clinically and biologically in euthyroid state. All the values were normalized, without statistically significant difference from control (T 1/2 = 65,4 +/- 18 min, Metb Cl. Rate : 255 +/- 64,5 L/24 h, production rate : 15,6 +/- 1,8 mg/24 h and 9 +/- 1,4 mg/m2/24 h. mean plasma concentration : 6,8 +/- 2,8 microg/100 ml). Shortened cortisol half life, increased metabolic clearance rate and production rate, and normal mean plasma concentration have been reported in hyperthyroidism (Peterson, Copinschi, Gallagher). These changes, secondary to thyroid hormone excess, are the consequences of increased hepatic catabolism of cortisol. The activity of 11 OH steroid deshydrogenase is increased, as demonstrated by increased ratio (see article) in normal subjects (0,001 less than p less than 0,005). There is a high proportion of 17 kéto metabolites (E, DHE, THE) whose feed-back effect is weak as compared to 17 OH metabolites (F, DHF, THF). The hypothalamo-hypophyso-adrenal system is stimulated to maintain a normal plasma concentration. The fact that the mean plasma concentration is normal despite the increased production rate suggest that changes are rather due to increased catabolism than to central effect of thyroid hormones.

Hydrocortisone↗

[Proceedings: Plasma renin activity in management of Addison's disease (author's transl)].

13 patients with Addison's disease, 7 men and 6 women, 19 to 61 years old, were investigated. Plasma Renin Activity (P.R.A.) is measured by radioimmunoassay of Angiotensin I (ng/ml/h) in the supine (S) and the upright (U) position. These patients are studied before treatment and under normal sodium diet in 11 cases: the P.R.A. value is constantly increased [5 men: MS = 10,09 (range: 6,2-12,5) and MU = 23,22 (range : 17,1-31,09), 6 women : MS = 24,48 (range : 3,46-45,04) and MU = 42,23 (range : 42,23 (range 17,37-69,34), to be compared with our normal values (M +/- S.D.) : MS = 1,02 +/- 0,39 and MU = 2,56 +/- 0,99 for men - MS = 0,82 +/- 0,14 and MU = 2,32 +/- 0,93 for women in follicular phase - MS = 1,45 +/- 0,56 and MU = 4,59 +/- 1,63 for women in luteinic phase. After dietary sodium restriction (10 mEq/24 h) in 2 cases, the P.R.A. is significantly increased with respect to the basal value]. Under Hydrocortisone alone (25 to 30 mg/24 h) and normal sodium diet, 4 patients kept significantly increased P.R.A. values. Under Hydrocortisone (20 to 40 mg/24 h) and 9-alpha-fluorohydrocortisone (50 to 100 microgrammes/24 h) for 6 days to 14 months, the P.R.A. value decrease into the normal range [men : MS = 1,02 (range : 0,54-1,92) and MU = 1,68 (RNAGE : 0,81-2,57) - 2 Menopausal women : MS = 1,55 and MU - 1,16. The P.R.A. measurement seems useful in the adaptation of Addision's disease treatment.

Addison Disease↗

Beta-adrenergic receptors in human breast cancer: identification, characterization and correlation with progesterone and estradiol receptors.

Besides the variety of other cellular processes in which beta-adrenergic compounds have been involved, their effect on the second messenger cAMP is thought to be related to the growth and differentiation of malignant cells. Because beta-adrenergic receptor could be an easy target for a new combination treatment, we attempted to identify and characterize adrenergic receptor in breast tumor and sought for correlations with estradiol and progesterone receptors. Using L[3H]-dihydroalprenolol, a potent beta-adrenergic antagonist, we demonstrated in human breast tumor the presence of beta-adrenergic receptors with high affinity (Kd 1-3 nM) as shown by Scatchard analyses. Natural and synthetic agonists and antagonists inhibited the [3H] DHA binding, mainly in the order of beta 2-subtype potency. We verified that these receptors were normally coupled with G-protein. A slight correlation was shown between adrenergic and progesterone receptors, and no correlation between adrenergic and estrogen receptors. The presence of specific beta-adrenergic receptors functionally coupled with G protein incited us to study their physiological regulation, since it is tempting to speculate that circulating or locally released catecholamines or other natural compounds may participate in the process of growth and differentiation of the mammary gland through adrenergic receptors.

Biomarkers, Tumor↗

C-myc overexpression, c-mil, c-myb expression in a breast tumor cell line. Effects of estrogen and antiestrogen.

In breast tumor cell lines, c-myc amplification is frequently associated with estrogen unresponsiveness. We, however, succeeded in characterizing an estrogen-responsive cell line VHB1 derived from a duct cell carcinoma, which exhibits c-myc amplification and overexpression. We therefore studied the effects of estrogen and antiestrogen on c-myc expression in this particular cell line. We also investigated these effects on the expression of c-mil and c-myb oncogenes, also expressed but not amplified in VHB1 cells. Short-(1 h) and long-(72 h) term stimulations were performed. Our experiments showed that estradiol (E2 10(-8) M) was still able to stimulate c-myc expression equally either after short or long-term treatment. In the same way, the antiestrogen 4-hydroxytamoxifen equally decreased c-myc expression but the reversal effect of E2 after long-term antiestrogen treatment was more pronounced than after short-term treatment. The effects of E2 and 4-OH Tam on the expression of the not-amplified c-mil and c-myb oncogenes were stronger than those observed on c-myc expression; however, the E2 reversal effect was identical either after short or long-term antiestrogen treatment. Our results may enlighten some aspects of the complex action of some of the early- and late-growth regulated genes in breast cancer.

Blotting, Northern↗

[Post-operative hyperaldosteronism and related endocrine perturbations (author's transl)].

Electrolytes disturbances during operative period are believed to be related to an hyperaldosteronism produced by anaesthetic management and surgery. Effects of ethrane anaesthesia and surgery on hydroelectrolytic metabolism and endocrin function were investigated in 11 patients submitted to an abdominal surgery. Plasma and urinary levels of aldosterone were increased (x3) significantly (p less than or equal to 0.001) during operation, then decreased gradually in post-operative period, and return to normal values when Na/K ratio is reversed in urines. Relationship between hyperaldosteronism and other changes in endocrine function are established by determination of following hormones: A.C.T.H., cortisol, plasma renin activity (P.R.A.) catecholamines in plasma and urinary levels of 17-ceto, 17-hydroxysteroids and catecholamines. Ethrane anesthesia give a good neurovegetative stability since plasma catecholamines levels are not affected significatively. Plasma aldosterone level is correlated with urinary aldosterone and plasma renin activity. Plasma A.C.T.H. is much more increased at the operative time and decreases rapidly instead of plasma cortisol which decreases more slowly. Relationship of this hyperaldosteronism with anesthetic management, surgical stress intestinal transit disturbances, other endocrine function changes is discussed.

17-Hydroxycorticosteroids↗

Cell kinetics (SAMBA 200) of estradiol stimulated long-term phenol red withdrawn cultured breast cancer cells.

When estradiol stimulation was performed on hormone-responsive MCF-7 human breast cancer cells maintained in phenol red-containing medium until 24h before experiments, the cell number and the cell surface transferrin receptor level, an early marker of estradiol stimulation, were strongly increased. In contrast, similar treatment performed on MCF-7 cells grown in phenol red-free medium up to 12 months before experiments induced no stimulating effect on the cell number, although transferrin receptors were still enhanced. Since the appearance of transferrin receptors occurs before the cells begin DNA synthesis in late G1 phase, we assumed that the discrepancy between cell counts and cell surface transferrin receptors might involve cell kinetic perturbations. The proportion of cells in the (S + G2) phases and the duration of the cell cycle phases were analysed using the SAMBA 200 cell image processor. The data presented in this study failed to indicate any block in the cell cycle and the duration of the S and G2 phases were found to be unchanged. The lack of effect of estradiol stimulation on the growth of MCF-7 cells maintained several months without phenol red is not thus a consequence of cell cycle perturbations.

Breast Neoplasms↗

Involvement of cell surface transferrin receptor in the assessment of estradiol stimulating effect on cultured breast cancer cells.

In order to find the reasons for the conflicting results depicted during the estradiol stimulations of cultured MCF7, breast cancer cells we investigated, besides cell counts, the cell surface transferrin receptor as an additional means of assessing the effect of estradiol. In this study we report results obtained using different culture conditions, i.e. short-term or long-term phenol-red withdrawn cells grown either in calf-serum supplemented media or defined media. Our results point out concurrent variations of cell counts and transferrin receptors when short-term phenol-red withdrawn cells were grown in defined media. Discrepancies were, however, observed when short-term phenol-red withdrawn cells were grown in serum-supplemented media or when long-term phenol-red withdrawn cells were grown in defined media. In both cases, only transferrin receptors account for estradiol stimulation. These results highlight the importance of transferrin receptor measurement in cultured breast cancer cell experiments and suggest cell kinetic perturbations due, in all likelihood, to serum factors or factors secreted by long-term phenol-red withdrawn cells.

Breast Neoplasms↗

[A rare cause of heart failure: hypocalcemic cardiopathy].

In this paper, the authors present the case of hypocalcemic cardiopathy observed in a female patient who underwent thyroidectomy which was complicated post-operatively by the development of hypoparathyroidism. Two attacks of heart failure experienced by this patient were improved by the administration of calcium in combination with digitalis treatment. A study of cases published in the medical literature reveals that this condition is a rare cause of heart failure which develops only in the course of chronic hypocalcemia, with few neuromuscular clinical manifestations. The dual negative inotropic and hypovolemic effects caused by hypocalcemia explain the efficacy observed with the administration of calcium therapy, while the usual symptomatic treatment of this condition is inadequate.

Calcium↗