References of "Bours, Vincent"
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See detailMaladies complexes: des interactions genes-environnement au probleme de sante publique.
SCHEEN, André ULg; Bours, Vincent ULg

in Revue Médicale de Liège (2012), 67(5-6), 217-9

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See detailATP-gated P2X1 ion channels protect from endotoxemia by dampening neutrophil activation
Lecut, Christelle ULg; Faccinetto, Céline ULg; Delierneux, Céline ULg et al

in Journal of Thrombosis and Haemostasis [=JTH] (2012), 10(3), 453-65

Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to ... [more ▼]

Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to their role in platelet activation, ATP-gated P2X1 ion channels are involved in promoting neutrophil chemotaxis. <br />Objectives: To elucidate the contribution of P2X1 ion channels to sepsis and associated disturbance of hemostasis. <br />Methods: We used P2X1-/- mice in a model of lipopolysaccharide (LPS)-induced sepsis. Hemostasis and inflammation parameters were analysed together with outcome. Mechanisms were further studied ex vivo using mouse and human blood or isolated neutrophils and monocytes. <br />Results: P2X1-/- mice were more susceptible to LPS-induced shock than wild-type mice despite normal cytokine production. Plasma levels of thrombin-antithrombin complexes were higher, thrombocytopenia was worsened and whole blood coagulation time was markedly reduced, pointing to aggravated hemostasis disturbance in the absence of P2X1. However, whole blood platelet aggregation occurred normally and P2X1-/- macrophages displayed normal levels of total tissue factor activity. We found that P2X1-/- neutrophils produced higher amounts of reactive oxygen species. Increased amounts of myeloperoxidase were released in the blood of LPS-treated P2X1-/- mice, and circulating neutrophils and monocytes expressed higher levels of CD11b. Neutrophil accumulation into the lungs was also significantly augmented, as was lipid peroxidation in the liver. Desensitization of P2X1 ion channels led to increased activation of human neutrophils and enhanced formation of platelet-leukocyte aggregates. [less ▲]

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See detailPartial trisomy 4q associated with young-onset dopa-responsive parkinsonism.
Garraux, Gaëtan ULg; CABERG, Jean-Hubert ULg; Vanbellinghen, Jean-Francois et al

in Archives of Neurology (2012), 69(3), 398-400

OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder ... [more ▼]

OBJECTIVE: To describe a patient who developed a young-onset, dopa-responsive parkinsonism linked to a de novo heterozygous interstitial duplication 4q. DESIGN: Case report. SETTING: Movement Disorder Outpatient Clinic at the University Hospital Centre, Liege, Belgium. Patient A 31-year-old woman. MAIN OUTCOME MEASURES: Clinical, neuroimaging, and genetic data. RESULTS: The duplicated region contains 150 known genes, including the alpha-synuclein (SNCA) gene locus. Motor and 6-[(18)F]fluoro-L-dopa positron emission tomography features are similar to those previously reported in heterozygote SNCA duplication carriers. Altered expression of other genes contained in the duplicated region may contribute to clinical features that are uncommon in the phenotypic spectrum of SNCA multiplications such as delayed developmental psychomotor milestones during infancy and musculoskeletal abnormalities. CONCLUSION: This case report provides new insights on the genetic basis of parkinsonism. [less ▲]

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See detailHuman glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection.
Kroonen, Jérôme ULg; Nassen, Jessica ULg; Boulanger, Yves-Gauthier et al

in International Journal of Cancer = Journal International du Cancer (2011), 129(3), 574-585

This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs ... [more ▼]

This study reports the subsequent isolation of human glioblatoma cells able to initiate experimental brain tumors, specifically and repeatedly found in the subventricular zones and olfactory bulbs following xenograft in the caudate putamen of immunodeficient mice.In patients with glioblastoma multiforme, recurrence is the rule despite continuous advances in surgery, radiotherapy and chemotherapy. Within these malignant gliomas, glioblastoma stem cells or initiating cells have been recently described and they were shown to be specifically involved in experimental tumorigenesis. In this study, we show that some human glioblastoma cells injected into the striatum of immunodeficient nude mice exhibit a tropism for the subventricular zones. There and similarily to neurogenic stem cells, these subventricular glioblastoma cells were then able to migrate towards the olfactory bulbs. Finally, the glioblastoma cells isolated from the adult mouse subventricular zones and olfactory bulbs display high tumorigenicity when secondary injected in a new mouse brain. Together, these data suggest that neurogenic zones could be a reservoir for particular cancer-initiating cells. [less ▲]

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See detailGenetic screening for AIP mutations in Young patients with sporadic and Familial Pituitary Macroadenomas
Yaneva, M.; Elenkova, A.; Daly, Adrian ULg et al

in Endocrinologia = Endokrinologiia (2011), 16(1), 41-48

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See detailHigh prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas.
Tichomirowa, Maria A; Barlier, Anne; Daly, Adrian ULg et al

in European Journal of Endocrinology (2011), 165(4), 509-15

BACKGROUND: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas ... [more ▼]

BACKGROUND: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS: Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION: Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management. [less ▲]

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See detailGenetic susceptibility in pituitary adenomas : from pathogenesis to clinical implications
Jaffrain-Rea, Marie-Lise; Daly, Adrian ULg; Angelini, Mariolina et al

in Expert Review of Endocrinology & Metabolism (2011)

Pituitary adenomas (PA) usually present sporadically, with a multifactorial pathogenesis including somatic mutational events in cancer-related genes. Genetic predisposition implies the presence of ... [more ▼]

Pituitary adenomas (PA) usually present sporadically, with a multifactorial pathogenesis including somatic mutational events in cancer-related genes. Genetic predisposition implies the presence of germline DNA alterations with a variety of impacts on pituitary cell biology, translating into a variable penetrance of the disease. Genetic causes must be considered in the presence of specific clinical settings, such as familial occurrence of PA, with or without extrapituitary diseases, and may also be suspected in young patients with macroadenomas. We <br />review the clinical implications of genetic predisposition, with special attention to Multiple Endocrine Neoplasia type 1 (MEN1), Carney’s complex (CNC) and FIPA (Familial Isolated Pituitary Adenoma), and the scenario of genetic screening in selected patients with an apparently sporadic disease is discussed. [less ▲]

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See detailLack of P2X1 ion channels increases endotoxemia associated coagulation and organ damage through neutrophil hyperresponsiveness.
Lecut, Christelle ULg; Faccinetto, Céline ULg; Evans, Richard J et al

in Journal of Thrombosis and Haemostasis [=JTH] (2011), 9(suppl S2),

ATP-gated P2X1 ion channels contribute to arterial thrombosis by amplifying platelet activation. In the search for novel anti-platelet strategies, targeting P2X1 ion channels is appealing. However, in ... [more ▼]

ATP-gated P2X1 ion channels contribute to arterial thrombosis by amplifying platelet activation. In the search for novel anti-platelet strategies, targeting P2X1 ion channels is appealing. However, in this study we found that lack or inhibition of P2X1 channels enhanced neutrophil respiratory burst activity ex vivo. <br />To study the consequence of P2X1 deficiency on neutrophil function in vivo, P2X1-/- mice were used in a model of endotoxin-induced sepsis. Upon injection of lipopolysaccharides (LPS), plasma myeloperoxidase (MPO) concentrations reached higher levels in the P2X1-/- mice, and circulating neutrophils expressed higher levels of surface CD11b compared to wild-type mice. Neutrophil relocalization into the lungs of LPS-treated P2X1-/- mice was also significantly augmented, reflecting a higher activation state of P2X1-/- neutrophils under conditions of sepsis. Accordingly, more extensive lipid peroxidation was observed in the liver of LPS-treated P2X1-/- mice, indicative of exaggerated oxidative damage. Concomitantly, the levels of thrombin-antithrombin complexes were higher in the plasma of LPS-treated P2X1-/- mice and thrombocytopenia was worsened as compared to wild type mice. Elevated numbers of microthrombi were also found in the lungs of these mice. These observations coincided with a higher susceptibility of P2X1-/- mice to LPS-induced septic shock than wild type animals. <br />Our results strongly suggest that P2X1 ion channels play a protective role in sepsis by negatively regulating systemic neutrophil activation, thereby limiting oxidative damage, activation of coagulation and platelet accumulation into the lungs. Therefore, since antagonists of P2X1 ion channels may not only target platelets but also affect neutrophils, inhibiting these channels in the highly inflammatory environment of severe sepsis or of acute coronary syndromes might be detrimental. [less ▲]

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See detail3-years experience review of neonatal screening for hemoglobin disorders using tandem mass spectrometry.
BOEMER, François ULg; Cornet, Yves ULg; LIBIOULLE, Cécile ULg et al

in Clinica Chimica Acta (2011), 412(15-16), 1476-9

BACKGROUND: Neonatal screening programs for sickle cell disease are common in North America and in some European countries. Isoelectric Focusing or High Performance Liquid Chromatography is the main ... [more ▼]

BACKGROUND: Neonatal screening programs for sickle cell disease are common in North America and in some European countries. Isoelectric Focusing or High Performance Liquid Chromatography is the main technique used for hemoglobin variant detection. METHODS: Since tandem mass spectrometry is being used for screening of inherited metabolic disorders and allows protein identification, we had developed an application to identify the most relevant hemoglobin mutations with this technology. RESULTS: This approach had been previously validated and has been routinely applied in our laboratory for the last three years. We report here our experience with this new method in the field, applied to our East-Belgian population. CONCLUSIONS: To conclude, mass spectrometry provides an efficient alternative approach for laboratories performing neonatal screening of hemoglobin disorders. [less ▲]

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See detailAspects moléculaires du cancer du sein triple négatif et les implications thérapeutiques
COLLIGNON, Joëlle ULg; Struman, Ingrid ULg; Tabruyn, Sébastien ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 393-396

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See detailInfluence of brain-derived neurotrophic factor val66met human polymorphism on declarative memory consolidation
Mascetti, Laura ULg; Foret, Ariane ULg; Matarazzo, Luca et al

Poster (2010, November 15)

The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which in the adult brain regulates long-term potentiation. In humans, valine (val) to methionine (met) substitution in the 5’ pro-region of ... [more ▼]

The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which in the adult brain regulates long-term potentiation. In humans, valine (val) to methionine (met) substitution in the 5’ pro-region of the BDNF protein is associated with poorer episodic memory. Neurons transfected with met-BDNF-Green Fluorescence Protein showed lower depolarization-induced secretion, while constitutive secretion is unchanged. Here, we hypothesized that the differences in BDNF release determined by this polymorphism would influence memory consolidation and that in comparison with the val/met (=val/met or met/met), val/val individuals would show higher memory performance and different brain responses during a 16h-delayed rather than immediate retrieval session. Participants encoded a series of neutral faces in the afternoon. Retrieval sessions took place one hour after the encoding session, and in the following morning, during the acquisition of functional Magnetic Resonance Imaging (fMRI) time series with a 3 Tesla Allegra scanner. During retrieval, studied faces and new ones were presented in random order. For each stimulus, the subjects indicated whether they could retrieve the encoding episode with (“Remember”), or without details (“Know”), or if they thought the item had not been presented during encoding (“New”). A repeated-measure ANOVA on discrimination index (d’) showed significant effects of group (F(1, 27)=8.65, p=0.007, n(val/val)=14, n(val/met)=15) and session (F(1, 27)=24.64, p=0.000), although the group by session interaction was not significant (F(1, 27)=1.29, p=0.267). fMRI results showed a significant genotype (val/val > val/met) by session (delayed > immediate retrieval) by memory type (Remember > Know) interaction in the right inferior occipital gyrus (x=42, y=-78, z=0, p=0.004, Z=3.77), the left inferior parietal lobule (x=-56, y=-40, z=48, p=0.013, Z=3.43), the posterior cingulate cortex (x=14, y=-42, z=42, p=0.019, Z=3.29) and the right hippocampus (x=28, y=-22, z=-22, p=0.03, Z=3.11). Val/val individuals demonstrate higher memory performance than met-carriers but the change in memory performance between immediate and delayed retests is similar in both allelic groups. In contrast, neural correlates of recollection change between sessions differently according to genotype: responses increase significantly more in val/val than in val/met individuals in brain areas involved in the retrieval, accumulation and binding of perceptual memory details during delayed, relative to immediate retest. These data suggest that activity-dependent BDNF release promotes memory consolidation during the first post-training hours. [less ▲]

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See detailInfluence of Brain-Derived Neurotrophic Factor val66met human polymorphism on declarative memory consolidation during sleep
Mascetti, Laura ULg; Foret, Ariane ULg; Matarazzo, Luca et al

Poster (2010, September 15)

Objectives The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which in the adult brain, regulates long-term potentiation and has been involved in the build up of the homeostatic sleep pressure ... [more ▼]

Objectives The Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which in the adult brain, regulates long-term potentiation and has been involved in the build up of the homeostatic sleep pressure in rodents. In humans, valine (val) to methionine (met) substitution in the 5’ pro-region of the BDNF protein is associated with poorer episodic memory. Neurons transfected with met-BDNF-Green Fluorescence Protein showed lower depolarization-induced secretion, while constitutive secretion is unchanged. Here, we hypothesized that the differences in BDNF release determined by this polymorphism would influence sleep-dependent memory consolidation and that in comparison with the met-carriers (val/met or met/met), val/val individuals would show higher memory performance after one night of sleep rather than an immediate retrieval session. Methods Participants encoded a series of neutral faces in the afternoon. Retrieval sessions took place one hour after the encoding session, and in the following morning, after a night of polysomnographic-monitored sleep. During retrieval, studied faces and new ones were presented in random order. For each stimulus, the subjects indicated whether they could retrieve the encoding episode with (“Remember” response), or without details (“know” response), or if they thought the item had not been presented during encoding (“New” response). Results A repeated-measure ANOVA on discrimination index (d’) showed significant effects of group (F(1, 22)=4.66, p=0.042) and session (F(1, 22)=12.21, df=1, p=0.002). Although the group by session interaction was not significant (F(1, 22)=1.84, p=0.188), exploratory planned comparisons showed that at immediate retrieval, d’ was not significantly different between groups (val/val, d’ = 1.94±0.16; met-carriers, d’= 1.61±0.14; p>0.5). In contrast, during the second retest (the next day) d’ in the val/val group (d’=2.56±0.23) was significantly higher than in the met-carriers group (d’=1.88±0.21; p=0.041). Likewise, a between-session enhancement in d’ was detected only in the val/val population (p=0.003). Conclusion Val/val individuals demonstrate higher memory performance than met-carriers after a night of sleep but not at immediate retest. These data suggest that activity-dependent BDNF release promotes memory consolidation during the first post-training hours. Further analysis of the present data set will assess the respective effect of sleep and time on the BDNF-associated delayed memory enhancement. This study was supported by FNRS-FRIA, the University of Liège, and the QEMF. [less ▲]

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See detailRecherche de la mutation du gène CDKN1B dans les adénomes hypophysaires familiaux isolés (FIPA): analyse de 86 familles
Beckers, Albert ULg; Tichomirowa, M.; Pellegata, N. et al

in Annales d'Endocrinologie (2010, September), 71(5), 398

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See detailCyclin dependent kinase inhibitor 1B (CDKN1B) gene mutations in FIPA
Tichomirowa, M. A.; Pellegata, N. S.; Barlier, A. et al

in European Neuroendocrine Association - Liège, 22-25 septembre 2010 (2010, September)

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See detailHigh Prevalence of AIP Gene Mutations Following Focussed Screening in Young Patients with Sporadic Pituitary Macroadenomas
Tichomirowa, M. A.; Barlier, A.; Daly, Adrian ULg et al

in European Neuroendocrine Association - Liège, 22-25 septembre 2010 (2010, September)

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See detailRecherche de la mutation du gène CDKN1B dans les adénomes hypophysaires familiaux isolés (FIPA) : analyse de 86 familles
Beckers, Albert ULg; Tichomirowa, M.; Pellegata, N. et al

in 27ème Congrès de la Société Française d'Endocrinologie - Deauville, 29 septembre - 2 octobre 2010 (2010, September)

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See detailSystematic chromosomal aberrations found in murine bone marrow-derived mesenchymal stem cells.
Josse, Claire ULg; Schoemans, R.; Niessen, Neville-Andrew ULg et al

in Stem Cells & Development (2010), 19(8), 1167-1173

Mesenchymal stem cells (MSCs) are studied as a cellular source for the treatment of various diseases. In this work, we isolated and cultivated murine bone marrow-derived MSCs. After a first observation of ... [more ▼]

Mesenchymal stem cells (MSCs) are studied as a cellular source for the treatment of various diseases. In this work, we isolated and cultivated murine bone marrow-derived MSCs. After a first observation of a solid tumour in a mouse injected with these cells, we systematically explored their chromosomal stability. We observed in all the cytogenetically analysed cases gross chromosomal alterations every time the MSCs went through the senescence crisis while the lymphocytes from the same animals showed a normal chromosome count. This observation was confirmed in different mouse strains, with different culture protocols, and even in short-term cultures after an hematopoietic cell negative immunodepletion performed in order to accelerate the isolation procedure. Therefore, we conclude that murine MSCs display high chromosomal instability, can generate tumours, and that care must be taken before using them for the evaluation of MSC therapeutic potential. [less ▲]

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See detailThe role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes.
Stratakis, C. A.; Tichomirowa, M. A.; Boikos, S. et al

in Clinical Genetics (2010)

The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. The prevalence of ... [more ▼]

The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex. [less ▲]

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See detailClinical characteristics and therapeutic responses in patients with Germ-line AIP mutations and pituitary adenomas : An international collaborative study
Daly, Adrian ULg; Tichomirowa, Maria A.; Petrossians, Patrick ULg et al

in Journal of Clinical Endocrinology and Metabolism (2010), 95(11),

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features ... [more ▼]

Context: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. <br />Objective: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. <br />Design: This study was an international, multicenter, retrospective case collection/database analysis. <br />Setting: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. <br />Patients: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. <br />Results: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. <br />Conclusions: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility. [less ▲]

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See detailFish and chips
DELVENNE, Philippe ULg; Deprez, Manuel ULg; BISIG, Bettina ULg et al

in Revue Médicale de Liège (2010), 65 Spec no.

Academic hospital laboratories should offer patients the possibility to have the most accurate diagnosis by the development of new analyses, such as molecular biology tests including FISH (Fluorescent In ... [more ▼]

Academic hospital laboratories should offer patients the possibility to have the most accurate diagnosis by the development of new analyses, such as molecular biology tests including FISH (Fluorescent In Situ Hybridization) and chips (microarrays,...). The purpose of this article is to describe the principles and the potential applications of these techniques. [less ▲]

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