G´en´etique Clinique dans le Service de P´ediatrie et de G´en´etique M´edicale 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 blood–testis 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/β-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/β-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 l’hopital baptiste biblique de Kpele-Tsiko (Togo)

But : Faire le point sur la morbidité et la mortalité néonatales précoces au sein dudit hôpital, afin de mieux cibler et de mieux orienter les actions à menées pour contribuer à la réduction de la mortalité infantile au Togo.Patients et méthodes : Il s’est agi d’une étude rétrospective portant sur 240 nouveau-nés âgés de 0 à 7 jours, du 1er Janvier 2002 au 31 Décembre 2006, soit une période de 5ans. Les registres d’hospitalisation, les dossiers de nouveau-nés de 0 à 7 jours hospitalisés et les dossiersdisponibles des mères de nouveau-nés hospitalisés étaient les sources d’informations. La collecte des données a été effectuée à l’aide de fiche d’enquête individuelle.Résultats : Sur les 240 nouveau-nés hospitalisés, 146 (60,8 %) étaient de sexe masculin et 94 (39,2 %), de sexe féminin. La majorité (57%) des nouveau-nés était née à terme, 40% étaient prématurés, et 3% étaientpost-matures. Un peu plus de la moitié (54,2%) des nouveau-nés avaient un faible poids de naissance (inférieur à 2500g). Sur les 240 nouveau-nés hospitalisés, 96 (40%) étaient des prématurés et pesaient moins de 2500 grammes, et 144 (60%) étaient nés après la 37e semaine d’aménorrhée (SA), dont 34 (14,2%) étaient des hypotrophes, pesant moins de 2500 grammes et 107 (44,6%) étaient eutrophiques, pesant 2500 grammes ou plus. Parmi les nouveau-nés dont le score d’Apgar avait pu être noté, soit 126 cas (52,5 %), le score à la première minute était inférieur ou égal à 3 dans 34,9% des cas, entre 4 et 7 (36,5%), et entre 8 et 10 (28,6%). Les principaux motifs d’hospitalisation de ces nouveau-nés étaient dominés par le faible poids de naissance, 130 cas (54,2%), la prématurité, 96 cas (40%). Les diagnostics retenus étaient surtout les infections néonatales, 65 cas (27,1%), l’anoxie périnatale, 49 cas (20,4%), et les malformations congénitales, 18 cas (7,5%). Le taux de mortalité hospitalière était de 23,3% dont 68% de nouveau-nés décédés de sexe masculin et 32% de sexe féminin. Parmi les 26 nouveau-nés décédés dont le score d’Apgar était connu, 17 (65,4%) avaient le score inférieur ou égal à 3 à la première minute, un seul nouveau-né décédé (3,8%) avait le score normal (8 à 10). La moitié (50%) des nouveau-nés décédés était née à terme, tandis que 46,4% étaient des prématurés. La majorité (62,5%) des nouveau-nés décédés avait un faible poids de naissance. Les principales causes de décès étaient la prématurité (41,1%), l’anoxie périnatale (32,1%), et les infections néonatales (21,4%). Les 24 premières heures de vie étaient les plus meurtrières avec 24 cas (42,8%).Conclusion : Dans les pays en voie de développement comme le Togo, la réduction de l’incidence de la prématurité, de la souffrance foetale, l’amélioration des conditions d’asepsie et de réanimation néonatale, et la mise en place d’une surveillance épidémiologique pourraient contribuer à une réduction substantielle du taux de la mortalité néonatale précoce.Mots clés : Morbidité et Mortalité néonatales précoces, Hôpital 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-Payr′s 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: Patients′ 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 knees′ 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