47 research outputs found
GÂŽenÂŽetique Clinique dans le Service de PÂŽediatrie et de GÂŽenÂŽetique MÂŽedicale du Centre National Hospitalier et Universitaire de Cotonou : Etat des Lieux et Perspectives
Il s’agissait d’une ´etude r´etrospective descriptive portant sur les patients rec¸us en consultation de g´en´etique m´edicale de Septembre 2004 `a Aoˆut 2007. Les patients b´en´eficiaient des examens dysmorphologique et physique, des bilans cytog´en´etiques et/ou mol´eculaires, des interventions th´erapeutiques et un suivi `a long terme. Les variables ´etudi´ees ´etaient les donn´ees sociod´emographiques et cliniques. Soixante et seize patients ont ´et´e rec¸us durant la p´eriode avec une pr´edominance masculine (57,89%). Les motifs de consultation ´etaient domin´es par le retard psychomoteur (38,15%), la dysmorphie faciale (30,26%) et les malformations (19,73%). Les principales malformations portaient sur les extr´emit´es et la face. Les pathologies confirm´ees comprenaient des aberrations chromosomiques (46,05%) avec une pr´edominance de la trisomie 21 et des maladies monog´eniques (7,89%). Le rendement de nos recherches pourrait ˆetre am´elior´e par l’acc`es `a la technique FISH. C’est une exp´erience quasi unique en Afrique de l’ouest et permet d’apporter des r´eponses aux personnes souffrant d’affections h´er´editaires.Mots Cl´es g´en´etique clinique ; retard psychomoteur ; dysmorphie ; malformation ; aberration chromosomique ; maladie monog´eniqu
Intra aortic balloon pump: literature review of risk factors related to complications of the intraaortic balloon pump
The increasing use of the intra aortic balloon pump is attributed to the relatively easy percutaneous insertion and the low threshold of use over the past few years, especially in elderly patients with multi-vessel diseases and an affected ejection fraction
Brief review on systematic hypothermia for the protection of central nervous system during aortic arch surgery: a double-sword tool?
Antegrade selective cerebral perfusion in conjunction with hypothermia attenuate postoperative neurological injury, which in turn still remains the main cause of mortality and morbidity following aortic arch surgery. Hypothermic circulatory arrest however could be a useful tool during arch surgery, surgery for chronic thromboembolic disease, air on the arterial line during CPB, during cavotomy for extraction of renal cell carcinoma with level IV extension, or when dealing with difficult trauma to the SVC or IVC. Cerebral protective effects with hypothermic procedures including inhibition of neuron excitation, and discharge of excitable amino acids, and thereby, prevention of an increase in intercellular calcium ions, hyperoxidation of lipids in cell membranes, and free radical production
A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer
BackgroundHistone deacetylases (HDACs) are crucial components of the oestrogen receptor (ER) transcriptional complex. Preclinically, HDAC inhibitors can reverse tamoxifen/aromatase inhibitor resistance in hormone receptor-positive breast cancer. This concept was examined in a phase II combination trial with correlative end points.MethodsPatients with ER-positive metastatic breast cancer progressing on endocrine therapy were treated with 400 mg of vorinostat daily for 3 of 4 weeks and 20 mg tamoxifen daily, continuously. Histone acetylation and HDAC2 expression in peripheral blood mononuclear cells were also evaluated.ResultsIn all, 43 patients (median age 56 years (31-71)) were treated, 25 (58%) received prior adjuvant tamoxifen, 29 (67%) failed one prior chemotherapy regimen, 42 (98%) progressed after one, and 23 (54%) after two aromatase inhibitors. The objective response rate by Response Evaluation Criteria in Solid Tumours criteria was 19% and the clinical benefit rate (response or stable disease >24 weeks) was 40%. The median response duration was 10.3 months (confidence interval: 8.1-12.4). Histone hyperacetylation and higher baseline HDAC2 levels correlated with response.ConclusionThe combination of vorinostat and tamoxifen is well tolerated and exhibits encouraging activity in reversing hormone resistance. Correlative studies suggest that HDAC2 expression is a predictive marker and histone hyperacetylation is a useful pharmacodynamic marker for the efficacy of this combination
Action Mechanism of Inhibin α-Subunit on the Development of Sertoli Cells and First Wave of Spermatogenesis in Mice
Inhibin is an important marker of Sertoli cell (SC) activity in animals with impaired spermatogenesis. However, the precise relationship between inhibin and SC activity is unknown. To investigate this relationship, we partially silenced both the transcription and translation of the gene for the α-subunit of inhibin, Inha, using recombinant pshRNA vectors developed with RNAi-Ready pSIREN-RetroQ-ZsGreen Vector (Clontech Laboratories, Mountain View, Calif). We found that Inha silencing suppresses the cell-cycle regulators Cyclin D1 and Cyclin E and up-regulates the cell-cycle inhibitor P21 (as detected by Western blot analysis), thereby increasing the number of SCs in the G1 phase of the cell cycle and decreasing the amount in the S-phase of the cell cycle (as detected by flow cytometry). Inha silencing also suppressed Pdgfa, Igf1, and Kitl mRNA levels and up-regulated Tgfbrs, Inhba, Inhbb, Cyp11a1, Dhh, and Tjp1 mRNA levels (as indicated by real-time polymerase chain reaction [PCR] analysis). These findings indicate that Inha has the potential to influence the availability of the ligand inhibin and its antagonist activin in the SC in an autocrine manner and inhibit the progression of SC from G1 to S. It may also participate in the development of the bloodâtestis barrier, Leydig cells, and spermatogenesis through its effect on Dhh, Tjp1, Kitl, and Pdgfa. Real-time PCR and Western blot analyses of Inha, Inhba, and Inhbb mRNA and Inha levels over time show that Inha plays an important role in the formation of round spermatid during the first wave of spermatogenesis in mice
Multifaceted roles of GSK-3 and Wnt/ĂĆœĂÂČ-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention
Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex array of critical cellular processes. It was initially identified in rat skeletal muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen synthase. This versatile protein is involved in numerous signaling pathways that influence metabolism, embryogenesis, differentiation, migration, cell cycle progression and survival. Recently, GSK-3 has been implicated in leukemia stem cell pathophysiology and may be an appropriate target for its eradication. In this review, we will discuss the roles that GSK-3 plays in hematopoiesis and leukemogenesis as how this pivotal kinase can interact with multiple signaling pathways such as: Wnt/ĂÂČ-catenin, phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), Ras/Raf/MEK/extracellular signal-regulated kinase (ERK), Notch and others. Moreover, we will discuss how targeting GSK-3 and these other pathways can improve leukemia therapy and may overcome therapeutic resistance. In summary, GSK-3 is a crucial regulatory kinase interacting with multiple pathways to control various physiological processes, as well as leukemia stem cells, leukemia progression and therapeutic resistance. GSK-3 and Wnt are clearly intriguing therapeutic targets
Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry
OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc).
METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers.
RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group.
CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies
Morbidite et mortalite neonatales precoces dans un hopital rural : Cas de lâhopital baptiste biblique de Kpele-Tsiko (Togo)
But : Faire le point sur la morbiditĂ© et la mortalitĂ© nĂ©onatales prĂ©coces au sein dudit hĂŽpital, afin de mieux cibler et de mieux orienter les actions Ă menĂ©es pour contribuer Ă la rĂ©duction de la mortalitĂ© infantile au Togo.Patients et mĂ©thodes : Il sâest agi dâune Ă©tude rĂ©trospective portant sur 240 nouveau-nĂ©s ĂągĂ©s de 0 Ă 7 jours, du 1er Janvier 2002 au 31 DĂ©cembre 2006, soit une pĂ©riode de 5ans. Les registres dâhospitalisation, les dossiers de nouveau-nĂ©s de 0 Ă 7 jours hospitalisĂ©s et les dossiersdisponibles des mĂšres de nouveau-nĂ©s hospitalisĂ©s Ă©taient les sources dâinformations. La collecte des donnĂ©es a Ă©tĂ© effectuĂ©e Ă lâaide de fiche dâenquĂȘte individuelle.RĂ©sultats : Sur les 240 nouveau-nĂ©s hospitalisĂ©s, 146 (60,8 %) Ă©taient de sexe masculin et 94 (39,2 %), de sexe fĂ©minin. La majoritĂ© (57%) des nouveau-nĂ©s Ă©tait nĂ©e Ă terme, 40% Ă©taient prĂ©maturĂ©s, et 3% Ă©taientpost-matures. Un peu plus de la moitiĂ© (54,2%) des nouveau-nĂ©s avaient un faible poids de naissance (infĂ©rieur Ă 2500g). Sur les 240 nouveau-nĂ©s hospitalisĂ©s, 96 (40%) Ă©taient des prĂ©maturĂ©s et pesaient moins de 2500 grammes, et 144 (60%) Ă©taient nĂ©s aprĂšs la 37e semaine dâamĂ©norrhĂ©e (SA), dont 34 (14,2%) Ă©taient des hypotrophes, pesant moins de 2500 grammes et 107 (44,6%) Ă©taient eutrophiques, pesant 2500 grammes ou plus. Parmi les nouveau-nĂ©s dont le score dâApgar avait pu ĂȘtre notĂ©, soit 126 cas (52,5 %), le score Ă la premiĂšre minute Ă©tait infĂ©rieur ou Ă©gal Ă 3 dans 34,9% des cas, entre 4 et 7 (36,5%), et entre 8 et 10 (28,6%). Les principaux motifs dâhospitalisation de ces nouveau-nĂ©s Ă©taient dominĂ©s par le faible poids de naissance, 130 cas (54,2%), la prĂ©maturitĂ©, 96 cas (40%). Les diagnostics retenus Ă©taient surtout les infections nĂ©onatales, 65 cas (27,1%), lâanoxie pĂ©rinatale, 49 cas (20,4%), et les malformations congĂ©nitales, 18 cas (7,5%). Le taux de mortalitĂ© hospitaliĂšre Ă©tait de 23,3% dont 68% de nouveau-nĂ©s dĂ©cĂ©dĂ©s de sexe masculin et 32% de sexe fĂ©minin. Parmi les 26 nouveau-nĂ©s dĂ©cĂ©dĂ©s dont le score dâApgar Ă©tait connu, 17 (65,4%) avaient le score infĂ©rieur ou Ă©gal Ă 3 Ă la premiĂšre minute, un seul nouveau-nĂ© dĂ©cĂ©dĂ© (3,8%) avait le score normal (8 Ă 10). La moitiĂ© (50%) des nouveau-nĂ©s dĂ©cĂ©dĂ©s Ă©tait nĂ©e Ă terme, tandis que 46,4% Ă©taient des prĂ©maturĂ©s. La majoritĂ© (62,5%) des nouveau-nĂ©s dĂ©cĂ©dĂ©s avait un faible poids de naissance. Les principales causes de dĂ©cĂšs Ă©taient la prĂ©maturitĂ© (41,1%), lâanoxie pĂ©rinatale (32,1%), et les infections nĂ©onatales (21,4%). Les 24 premiĂšres heures de vie Ă©taient les plus meurtriĂšres avec 24 cas (42,8%).Conclusion : Dans les pays en voie de dĂ©veloppement comme le Togo, la rĂ©duction de lâincidence de la prĂ©maturitĂ©, de la souffrance foetale, lâamĂ©lioration des conditions dâasepsie et de rĂ©animation nĂ©onatale, et la mise en place dâune surveillance Ă©pidĂ©miologique pourraient contribuer Ă une rĂ©duction substantielle du taux de la mortalitĂ© nĂ©onatale prĂ©coce.Mots clĂ©s : MorbiditĂ© et MortalitĂ© nĂ©onatales prĂ©coces, HĂŽpital rural, Togo
Iatrogenic retractile quadriceps fibrosis within children in Benin: Epidemiological, clinical, therapeutical aspects
Background: In tropical countries, iatrogenic retractile quadriceps fibrosis (IRQF), the cause of walking handicap in children, is often the result of intraquadricipital injection of quinine salts. The aim of this review was to analyse the epidemiological, clinical, therapeutic aspects and outcome of IRQF in children admitted in three hospitals in Benin Republic. Patients and Methods: It was a 10-year retrospective, descriptive and analytic survey of IRQF, involving 81 children aged from 8 months to 15 years. Iterative mobilization of the knee (IMK) or modified distal quadriceps plasty by Thompson-PayrâČs technique (MDQTPT), with a POP on the knee in flexion position, was performed with additional functional rehabilitation. The results were evaluated on knee flexion gain and walking quality. Data were processed using Epi Info 3.2 software. Results: PatientsâČ average age was 7.60 years. Children of 6-10 years were most affected; sex ratio was 1.02. Lesions were unilateral (71.6%) and bilateral (28.4%). The kneesâČ stiffness was in flexion (10.57%), rectitude (64.42%) and recurvatum (25%). The amyotrophy of the thigh was found in 79.42 %. The IMK was successful in eight cases (7.69 %) and the MDQTPT was done in 98 cases (94.23%) associated with femoral osteotomy in 13 cases (12.50%). In post-surgical period, skin necrosis and fractures occurred respectively in 15.31% and 5.10%. Results were good in 92.31% of cases. Conclusions: IRQF in children do exist in our settings. The treatment that is based on MDQTPT associated to rehabilitation leads to acceptable outcome