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A Evrard

Publications and source records attributed to A Evrard.

At least 19 recordsLinked to original sources
PubMed2002

Altered regulation of the 5-HT system in the brain of MAO-A knock-out mice.

Genetic deficiency of monoamine oxidase-A (MAO-A) induces major alterations of mood and behaviour in human. Because serotonin (5-HT) is involved in mood regulation, and MAO-A is responsible for the catabolism of 5-HT, we investigated 5-HT mechanisms in knock-out mice (2-month-old) lacking MAO-A, using microdialysis, electrophysiological, autoradiographic and molecular biology approaches. Compared to paired wild-type mice, basal extracellular 5-HT levels were increased in ventral hippocampus (+202%), frontal cortex (+96%) and dorsal raphe nucleus (DRN, +147%) of MAO-A mutant mice. Conversely, spontaneous firing rate of 5-HT neurons in the DRN (recorded under chloral hydrate anaesthesia) was approximately 40% lower in mutants. Acute 5-HT reuptake blockade by citalopram (0.2 and 0.8 mg/kg i.v.) produced a much larger increase in extracellular 5-HT levels (by approximately 4 fold) and decrease in DRN neuronal firing (with a approximately 4.5 fold decrease in the drug's ED50) in MAO-A knock-out mice, which expressed lower levels of the 5-HT transporter throughout the brain (-13 to -34% compared to wild-type levels). The potency of the 5-HT1A agonist 8-OH-DPAT to produce hypothermia and to reduce the firing of DRN serotoninergic neurons was significantly less in the mutants, indicating a desensitization of 5-HT1A autoreceptors. This was associated with a decreased autoradiographic labelling of these receptors (-27%) in the DRN. Altogether, these data indicate that, in MAO-A knock-out mice, the enhancement of extracellular 5-HT levels induces a down-regulation of the 5-HT transporter, and a desensitization of 5-HT1A autoreceptors which allows the maintenance of tonic activity of 5-HT neurons in the DRN.

Action Potentials↗
PubMed2001

Fluoropyrimidine sensitivity of human MCF-7 breast cancer cells stably transfected with human uridine phosphorylase.

The relationship between uridine phosphorylase (UP) expression level in cancer cells and the tumour sensitivity to fluoropyrimidines is unclear. In this study, we found that UP overexpression by gene transfer, and the subsequent efficient metabolic activation of 5-fluorouracil (5-FU) by the ribonucleotide pathway, does not increase the fluoropyrimidine sensitivity of MCF-7 human cancer cells.

Antimetabolites, Antineoplastic↗
PubMed2001

Regulation of protein degradation and protease expression by mannose in maize root tips. Pi sequestration by mannose may hinder the study of its signaling properties.

The effects of mannose (Man) and glucose (Glc) on central metabolism, proteolysis, and expression of the root starvation-induced protease (RSIP; F. James, R. Brouquisse, C. Suire, A. Pradet, P. Raymond [1996] Biochem J 320: 283-292) were investigated in maize (Zea mays L. cv DEA) root tips. Changes in metabolite concentrations (sugars, ester-phosphates, adenine nucleotides, and amino acids) were monitored using in vivo and in vitro (13)C- and (31)P-NMR spectroscopy, in parallel with the changes in respiration rates, protein contents, proteolytic activities, and RSIP amounts. The inhibition of proteolysis, the decrease in proteolytic activities, and the repression of RSIP expression triggered by Man, at concentrations usually used to study sugar signaling (2 and 10 mM), were found to be related to a drop of energy metabolism, primarily due to a Man-induced Pi sequestration. However, when supplied at low concentration (2 mM) and with the adequate phosphate concentration (30 mM), energy metabolism was restored and Man repressed proteolysis similarly to Glc, when provided at the same concentration. These results indicate that Man should be used with caution as a Glc analog to study signalization by sugars in plants because possible signaling effects may be hindered by Pi sequestration.

Endopeptidases↗
PubMed2001

Combination of thymidine phosphorylase gene transfer and deoxyinosine treatment greatly enhances 5-fluorouracil antitumor activity in vitro and in vivo.

We reported previously that 5-fluorouracil (FUra) efficacy could be enhanced by increasing tumoral thymidine phosphorylase (TP) activity. Potentiated TP yield was achieved by either transfecting cells with human TP gene (A. Evrard et al., Br. J. Cancer, 80: 1726-1733, 1999) or associating FUra with 2'-deoxyinosine (d-Ino), a modulator providing the tumors with TP cofactor deoxyribose 1-phosphate (J. Ciccolini et al., Clin. Cancer Res., 6: 1529-1535, 2000). The purpose of the present work was to study the effects of a combined modulation (TP gene transfer + use of d-Ino) on the sensitivity to FUra of the LS174T human colorectal cell line. Results showed a near 4000 times increase of cell sensitivity in vitro after double (genetic + biochemical) modulation. This potentiation of tumor response was accompanied by a total change in the FUra anabolic pathway with a 5000% increase of cytosolic fluorodeoxyuridine monophosphate, a stronger and longer inhibition of thymidylate synthase, and 300% augmentation of DNA damage. Besides, whereas thymidine failed to inhibit FUra cytotoxicity in LS174T wild-type cells, the potentiation of the antitumor activity observed in the modulating regimen was partly reversed by thymidine, indicative of thymidylate synthase as the main drug target. The impact of this double modulation was next investigated in xenograft-bearing nude mice. Results showed that whereas FUra alone was completely ineffective on wild-type tumor growth, the size of TP-transfected tumors in animals treated with the FUra/d-Ino combination was reduced by 80% (P < 0.05). Our results suggest that FUra exhibits stronger antiproliferative activity when activated via TP through the DNA pathway and that high tumoral TP activity therefore leads to enhanced sensitivity to fluoropyrimidines.

Animals↗
PubMed2000

Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter.

By taking up serotonin (5-hydroxytryptamine, 5-HT) released in the extracellular space, the 5-HT transporter (5-HTT) regulates central 5-HT neurotransmission. Possible adaptive changes in 5-HT neurotransmission in knock-out mice that do not express the 5-HT transporter were investigated with special focus on 5-HT1A and 5-HT1B receptors. Specific labelling with radioligands and antibodies, and competitive RT-PCR, showed that 5-HT1A receptor protein and mRNA levels were significantly decreased in the dorsal raphe nucleus (DRN), increased in the hippocampus and unchanged in other forebrain areas of 5-HTT-/- vs. 5-HTT+/+ mice. Such regional differences also concerned 5-HT1B receptors because a decrease in their density was found in the substantia nigra (-30%) but not the globus pallidus of mutant mice. Intermediate changes were noted in 5-HTT+/- mice compared with 5-HTT+/+ and 5-HTT-/- animals. Quantification of [35S]GTP-gamma-S binding evoked by potent 5-HT1 receptor agonists confirmed such changes as a decrease in this parameter was noted in the DRN (-66%) and the substantia nigra (-30%) but not other brain areas in 5-HTT-/- vs. 5-HTT+/+ mice. As expected from actions mediated by functional 5-HT1A and 5-HT1B autoreceptors, a decrease in brain 5-HT turnover rate after i.p. administration of ipsapirone (a 5-HT1A agonist), and an increased 5-HT outflow in the substantia nigra upon local application of GR 127935 (a 5-HT1B/1D antagonist) were observed in 5-HTT+/+ mice. Such effects were not detected in 5-HTT-/- mice, further confirming the occurrence of marked alterations of 5-HT1A and 5-HT1B autoreceptors in these animals.

Animals↗
PubMed2000

Enhanced antitumor activity of 5-fluorouracil in combination with 2'-deoxyinosine in human colorectal cell lines and human colon tumor xenografts.

We investigated the effects of 2'-deoxyinosine (d-Ino), a modulator yielding thymidine phosphorylase activity, on cellular pharmacology of 5-fluorouracil (FUra) in various human colorectal cell lines and its antitumoral activity when combined with FUra in human xenografts. Associating d-Ino with FUra increased by 38 up to 700 times the sensitivity of HT29 and FUra-resistant SW620 lines, respectively, but not of CaCO2 cells, although high levels of intracellular FdUMP and subsequent higher thymidylate synthase inhibition were observed. Cell death studies confirmed the ability of d-Ino to enhance both early and late apoptosis induced by FUra in HT29 and SW620 but not in CaCo2. Similarly, we showed that associating d-Ino increased by 68 up to 101% the Fas overexpression induced by FUra in HT29 and SW620 but not in CaCo2 cells. Anti-Fas and anti-FasL antibodies both partly reversed this increase of cell sensitivity, thus confirming the role Fas plays in the modulation of FUra toxicity by d-Ino. This Fas component could explain the discrepancy between the lines because CaCO2 has been described as insensitive to Fas-mediated apoptosis. Antitumor activity of the combination was next investigated in nude mice transplanted with SW620. Results showed that although FUra alone has little effect on SW620 xenografts (P > 0.05), associating d-Ino significantly reduced the tumor growth by 57% (P < 0.05). This study suggests that it is possible to reduce both in vitro and in vivo resistance to FUra by modulating the way the drug is converted after cellular uptake.

Analysis of Variance↗
PubMed1999

[Relationship between corticotropin and arginine vasopressin in endocrine diseases].

VASOPRESSIN: The action of vasopressin (AVP) is not limited to regulating water excretion but also plays an essential role in regulating the corticotropic axis during stress. PHYSIOLOGY: Vasopressin is synthesized in the hypothalamus and stored in the posterior pituitary. It acts on 3 types of receptors (RV). RV1a are vascular receptors mediating the vasoconstrictor and glycogenolytic effects of the hormone. Anterior pituitary RV1b or V3 mediate stimulating effects on the corticotropic axis. Renal RV2 regulate water and urea excretion. Hypothetical extrarenal RV2 would be responsible for the vasodilator and procoagulant effects of the hormone. MODIFICATIONS IN ENDOCRINE DISEASES: Pituitary or adrenal hypocorticism syndromes include hyponatremia with secondary plasma hypoosmolality and reduced glomerular filtration due to the direct effect of glucocorticoids and also the effect of vasopressinism. Certain endogenous hypercorticisms appear to be related to an overexpression of RV: in ACTH-independent Cushingís syndrome, adrenal overexpression of eutopic RV1a, and in ACTH-dependent Cushingís syndrome, pituitary overexpression of eutopic RV1b or ectopic RV2. In addition, inappropriate secretion of antidiuretic hormone is frequent after transphenoidal surgery, particularly for corticotropic adenomas. DYNAMIC TESTS: The physiological response of ACTH and also AVP to corticotropin releasing hormone (CRH) in the petrous sinus, the unusual responses of certain corticotropic tumors to dDAVP, or certain forms of ACTH-independent hypercortisolism to lysine vasopressin (LVP) suggest excessive or ectopic expression of RV in corticotropic or adrenal cells: tumorgenesis of these cells could also depend, at least partially, on AVP.

Adrenocorticotropic Hormone↗
PubMed1999

Enhancement of 5-fluorouracil cytotoxicity by human thymidine-phosphorylase expression in cancer cells: in vitro and in vivo study.

Transferring a gene into cancer cells in order to sensitize them to drugs is an important approach in human cancer gene-therapy research. Thymidine phosphorylase (TP) is the first enzyme in the metabolic activation pathway of 5-fluorouracil (5-FU) to fluorodeoxyribonucleotides, thus, it could be used to increase the sensitivity of cancer cells to this anti-pyrimidine agent. In this study, an expression vector containing the human TP cDNA was transfected into C26 murine colon-carcinoma cells. Stable transfectants were selected; all showed increased TP activity, ranging from 2- to 10-fold when compared with wild-type cells. The in vitro sensitivity of transfectants to 5-FU and 5'-deoxy-5-fluorouridine (5'-DFUR) was enhanced, in agreement with the observed increase in TP activity. Then, tumors were generated by s.c. injection of TP-transfected or wild-type C26 cells in syngeneic BALB/c mice. 5-FU (25 mg/kg, i.p.) induced a growth delay of TP-transfected C26 tumors as compared with C26 wild-type tumors. These data suggest that TP could be transfected in tumor cells to increase the sensitivity to 5-FU for subsequent cancer gene therapy.

Animals↗
PubMed1999

Transient pseudo-hypoaldosteronism following resection of the ileum: normal level of lymphocytic aldosterone receptors outside the acute phase.

Pseudo-hypoaldosteronism (PHA) is due to mineralocorticoid resistance and manifests as hyponatremia and hyperkalemia with increased plasma aldosterone levels. It may be familial or secondary to abnormal renal sodium handling. We report the case of a 54-year-old woman with multifocal cancer of the colon, who developed PHA after subtotal colectomy, ileal resection and jejunostomy. She was treated with 6 g of salt daily to prevent dehydration, which she stopped herself because of reduced fecal losses. One month later she was admitted with signs of acute adrenal failure, i.e. fatigue, severe nausea, blood pressure of 80/60 mmHg, extracellular dehydration, hyponatremia (118 mmol/l); hyperkalemia (7.6 mmol/l), increased blood urea nitrogen (BUN) (200 mg/dl) and creatininemia (2.5 mg/dl), and decreased plasma bicarbonates level (HCO3-: 16 mmol/l; N: 27-30). However, the plasma cortisol was high (66 microg/100 ml at 10:00 h; N: 8-15) and the ACTH was normal (13 pg/ml, N: 10-60); there was a marked increase in plasma renin activity (>37 ng/ml/h; N supine <3), active renin (869 pg/ml; N supine: 1.120), aldosterone (>2000 pg/ml; N supine <150) and plasma AVP (20 pmol/l; N: 0.5-2.5). The plasma ANH level was 38 pmol/l (N supine: 5-25). A urinary steroidogram resulted in highly elevated tetrahydrocortisol (THF: 13.3 mg/24h; N: 1.4+/-0.8) with no increase in tetrahydrocortisone (THE: 3.16 mg/24h; N: 2.7+/-2.0) excretion, and with low THE/THF (0.24; N: 1.87+/-0.36) and alpha THF/THF (0.35; N: 0.92+/-0.42) ratios. The number of mineralocorticoid receptors in mononuclear leukocytes was in the lower normal range for age, while the number of glucocorticoid receptors was reduced. Small-bowel resection in ileostomized patients causes excessive fecal sodium losses and results in chronic sodium depletion with contraction of the plasma volume and severe secondary hyperaldosteronism. Nevertheless, this hyperaldosteronism may be associated with hyponatremia and hyperkalemia suggesting PHA related to the major importance of the colon for the absorption of sodium. In conclusion, this case report emphasizes 1) the possibility of a syndrome of acquired PHA with severe hyperkalemia after resection of the ileum and colon responding to oral salt supplementation; 2) the major increase in AVP and the small increase in ANH; 3) the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios; 4) the normal number of lymphocytic mineralocorticoid receptors outside the acute episode.

Colectomy↗
PubMed1999

Increased cytotoxicity and bystander effect of 5-fluorouracil and 5-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase.

5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, are anticancer agents activated by thymidine phosphorylase (TP). Transfecting the human TP cDNA into cancer cells in order to sensitize them to these pyrimidine antimetabolites may be an important approach in human cancer gene therapy research. In this study, an expression vector containing the human TP cDNA (pcTP5) was transfected into LS174T human colon carcinoma cells. Eight stable transfectants were randomly selected and analysed. The cytotoxic effects of 5-FU and 5'-DFUR were higher in TP-transfected cells as compared to wild-type cells. The maximal decreases in the IC50 were 80-fold for 5-FU and 40-fold for 5'-DFUR. The increase in sensitivity to these pyrimidines of TP-transfected cells significantly correlated with the increase in both TP activity and TP expression. Transfected clone LS174T-c2 but not wild-type cells exhibited formation of [3H]FdUMP from [3H]5-FU. In addition the LS174T-c2 clone enhanced the cytotoxic effect of 5'-DFUR, but also that of 5-FU, towards co-cultured parental cells. For both anti-cancer agents, this bystander effect did not require cell-cell contact. These results show that both 5-FU or 5'-DFUR could be used together with a TP-suicide vector in cancer gene therapy.

Adenocarcinoma↗
PubMed1999

31P nuclear magnetic resonance study of the flavoprotein component of the Escherichia coli sulfite reductase.

SiR-FP60, the monomeric form of the Escherichia coli sulfite reductase flavoprotein component (SiR-FP), has been analysed by 31P-NMR spectroscopy. This protein was reported previously as a reliable simplified model for native SiR-FP [Zeghouf, M., Fontecave, M., Macherel, D., & Covès, J. (1998) Biochemistry 37, 6117-6123]. SiR-FP60 was examined in its native form, as a complex with NADP+ and after monoelectronic reduction either with NADPH or dithionite. In these latter cases, the stabilized FMN semiquinone radical offers a natural and internal paramagnetic probe. The paramagnetic effect of added manganese was also studied. In each case, the NMR parameters were extracted from digitalized data by a deconvolution procedure and compared with those obtained previously with cytochrome P450 reductase. Evolution of the NMR parameters and of calculated relaxation rate constants upon biochemical modifications of SiR-FP60 led us to propose that the reactive center is more compact than the one of cytochrome P450 reductase, with the redox components, FMN, FAD and NADPH, in a tighter spatial arrangement, close to the protein surface. This underlies some subtle differences between the two proteins for which a very similar overall structure is likely considering their common genetic origin and common operating cycle.

Binding Sites↗
PubMed1999

5-HT1A and 5-HT1B receptors control the firing of serotoninergic neurons in the dorsal raphe nucleus of the mouse: studies in 5-HT1B knock-out mice.

The characteristics of the spontaneous firing of serotoninergic neurons in the dorsal raphe nucleus and its control by serotonin (5-hydroxytryptamine, 5-HT) receptors were investigated in wild-type and 5-HT1B knock-out (5-HT1B-/-) mice of the 129/Sv strain, anaesthetized with chloral hydrate. In both groups of mice, 5-HT neurons exhibited a regular activity with an identical firing rate of 0.5-4.5 spikes/s. Intravenous administration of the 5-HT reuptake inhibitor citalopram or the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induced a dose-dependent inhibition of 5-HT neuronal firing which could be reversed by the selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xane carboxamide (WAY 100635). Both strains were equally sensitive to 8-OH-DPAT (ED50 approximately 6.3 microgram/kg i.v.), but the mutants were less sensitive than wild-type animals to citalopram (ED50 = 0.49 +/- 0.02 and 0.28 +/- 0.01 mg/kg i.v., respectively, P < 0.05). This difference could be reduced by pre-treatment of wild-type mice with the 5-HT1B/1D antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carbox yli c acid [4-methoxy-3-(4-methyl-piperazine-1-yl)-phenyl]amide (GR 127935), and might be accounted for by the lack of 5-HT1B receptors and a higher density of 5-HT reuptake sites (specifically labelled by [3H]citalopram) in 5-HT1B-/- mice. In wild-type but not 5-HT1B-/- mice, the 5-HT1B agonists 3-(1,2,5, 6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94253, 3 mg/kg i.v.) and 5-methoxy-3-(1,2,3, 6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 0.6 mg/kg i.v.) increased the firing rate of 5-HT neurons (+22.4 +/- 2.8% and +13.7 +/- 6.0%, respectively, P < 0.05), and this effect could be prevented by the 5-HT1B antagonist GR 127935 (1 mg/kg i.v.). Altogether, these data indicate that in the mouse, the firing of 5-HT neurons in the dorsal raphe nucleus is under both an inhibitory control through 5-HT1A receptors and an excitatory influence through 5-HT1B receptors.

Animals↗
PubMed1999

[Nephrogenic diabetes insipidus].

Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by polyuro-polydipsic syndrome (> 30 ml/kg/day in adult) related to an inability to concentrate the urine secondary to resistance to the antidiuretic action of vasopressin (AVP) or to its V2 agonist, dDAVP. NDI may be congenital or acquired. Congenital NDI, familial in most cases, are related in 90% of cases to mutations of the gene coding for V2 receptor of AVP (X-linked recessive disease), and in 10% of cases, to mutations of the gene encoding for aquaporin 2 (autosomic recessive disease). This water channel is expressed at the apical membrane of principal cells of collecting ducts and mediates water transport across the apical plasma membrane of these cells. It is regulated by AVP in two ways. First, AVP has a short term effect in triggering translocation of aquaporin-2-containing intracytoplasmic vesicles to the apical membrane. Second, AVP has a long term effect in increasing the expression of aquaporin-2 in collecting duct. Acquired NDI are iatrogenic (lithium), or related to electrolytic (hypokalemia) or renal abnormalities. The mechanism of these acquired NDI is a decrease of aquaporin 2 abundance in the renal collecting duct.

Aquaporin 2↗
PubMed1996

An in vitro nucleoside analog screening method for cancer gene therapy.

Suicide genes that sensitize cells to drugs that are normally nontoxic at therapeutic levels represent an important approach in human gene therapy research. We have developed an in vitro screening assay to assess the modulation of nucleoside analogs after transfection of a vector expressing the herpes simplex virus thymidine kinase gene (HSV-TK). The thymidine kinase gene enhances nucleoside phosphorylation to nucleotides that kill cells by blocking DNA elongation. Cells lines used are 3T3-NIH fibroblasts (parental cells) and 3T3-TKc3 (HSV-TK gene-transfected 3T3-NIH). Two types of analysis are performed: a cytotoxicity assay, the neutral red uptake assay to assess the IC50 on the two cell lines, and an HPLC analysis coupled to a radiochemical flow detector to evaluate metabolic profiles after incubation of cells with tritiated analogs. Results show that cells expressing the HSV-TK gene are more sensitive than the parent cells to the effect of acyclovir or ganciclovir, the reference purine analog drugs, and also to the effect of pyrimidine analogs, bromodeoxyuridine, bromovinyldeoxyuridine, and ethyldeoxyuridine. Promising nucleoside analogs for gene therapy that can be achieved by HSV-TK could be evaluated using this model.

3T3 Cells↗
PubMed1996

[Thyreotropic adenoma: review of the literature. Apropos of 2 cases].

TSH-secreting adenoma is a rare entity; a series of 69 cases has been collected by Faglia in 1989 and 78 new cases were published from 1987 to 1994. We report two new cases which have been explored by octreotide scintigraphy before treatment with the SRIH analogue. An in vitro SRIH receptor study was also performed in the first patient. This patient, a young man, suffered from hyperthyroidism with enhanced FT3 and FT4 concentrations without decreased TSH values. Plasma alpha subunit level was slightly increased. He had a pituitary tumor, positive in Octreoscan but responded partially to treatment by SRIH analogue. The tumor was in part surgically removed and the SRIH receptors revealed a homogeneous density; their number was equal to those of GH-secreting tumor but their affinity was lower. The second patient, an elderly woman was not surgically treated because the octreotide treatment dramatically improved both tumor volume and thyroid hormone or alpha subunit levels. The tumor, associated to a probable meningioma, was also positive in Octreoscan and was characterized by a highly increased alpha subunit plasma level. These results are discussed by comparison with those of the literature.

Adenoma↗
PubMed1996

[Gonadotropi adenoma linking labeled somatostatin analogs. Lack of relationship with therapeutic effect].

Somatotropin- and thyrotropin-secreting adenomas are well known for positive uptake of radio-labeled octreotide in vivo, this fact is not so well assessed for gonadotropin-secreting adenomas (GSA). We report one case of positive somatostatin receptor scintigraphy in a woman suffering from histologically proven GSA. This 63 year old patient has been suffering for two years of akinetic syndrome when the outcome of diplopia led to the discovery of a large hypophyseal tumor spreading till V3 floor and in left cavernous sinus by resonance magnetic imaging (RMI). Clinical examination showed anterior hypopituitarism and bitemporal hemianopsia. Biologically, blood gonadotropins were decreased more on LH (0.6 UI/l, N > 15) than on FSH (10 UI/l; N > 20). A lack of response of gonadotropins to LHRH with low blood estradiol concentration (< 10 pg/ml) was noticed. Basal blood measurement of alpha subunit was at 0.17 microgram/l (N = 0.10-1.6) and increased at 0.39 microgram/l after stimulation by LHRH. Although in low range of normal values, other hypophyseal hormones were normal except prolactinemia (45 mg/L; N < 20), however stimulated by TRH and related to dopaminergic deconnection; Indium 111 labeled octreotide scintigraphy showed an over uptake of the tumor. Three month treatment by octreotide (100 micrograms x 3/day subcutaneously) did not allow to decrease significantly FSH concentration or to reduce the tumoral mass. Incomplete removal of the tumor was performed by transphenoidal route. Immunohistochemical analysis revealed positive immunostaining for alpha subunit and FSH beta on numerous cells while the labeling was slightly less strong for LH beta. These data evoked a GSA. This case record depicts the possibility of detection of GSA by somatostatin receptor imaging. However a positive result does not preclude of somatostatin analog therapeutic efficiency.

Adenoma↗
PubMed1984

[Genital hemorrhage in girls before puberty. Apropos of 33 cases].

Vaginal bleeding in young girls without other signs of precocious sexual development is rare. We report a series of 33 cases observed during a 21 year period in the departments of pediatrics of the University of Lyon. Among the various etiologies, vaginal foreign bodies (10 cases, 30%) and vaginitis (10 cases, 30%) were the most frequent. There were 3 cases of benign vulvar tumors (9%) and 3 cases of malignant vaginal tumors (9%). In 3 cases the vaginal bleeding remained apparently idiopathic leading to the diagnosis of premature menarche. A retrospective evaluation of each case showed that history, physical examination and colposcopy would have rapidly established the correct diagnosis in 80 to 85% of cases; it is therefore concluded that laboratory and complex gynecologic investigations should be considered only after negative findings from these simple clinical tools in the evaluation of vaginal bleeding in prepubertal girls.

Child↗