Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 90
Filtrar
1.
Proc Natl Acad Sci U S A ; 121(6): e2317756121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38300868

RESUMO

Fibroblast growth factor receptor (FGFR) kinase inhibitors have been shown to be effective in the treatment of intrahepatic cholangiocarcinoma and other advanced solid tumors harboring FGFR2 alterations, but the toxicity of these drugs frequently leads to dose reduction or interruption of treatment such that maximum efficacy cannot be achieved. The most common adverse effects are hyperphosphatemia caused by FGFR1 inhibition and diarrhea due to FGFR4 inhibition, as current therapies are not selective among the FGFRs. Designing selective inhibitors has proved difficult with conventional approaches because the orthosteric sites of FGFR family members are observed to be highly similar in X-ray structures. In this study, aided by analysis of protein dynamics, we designed a selective, covalent FGFR2 inhibitor. In a key initial step, analysis of long-timescale molecular dynamics simulations of the FGFR1 and FGFR2 kinase domains allowed us to identify differential motion in their P-loops, which are located adjacent to the orthosteric site. Using this insight, we were able to design orthosteric binders that selectively and covalently engage the P-loop of FGFR2. Our drug discovery efforts culminated in the development of lirafugratinib (RLY-4008), a covalent inhibitor of FGFR2 that shows substantial selectivity over FGFR1 (~250-fold) and FGFR4 (~5,000-fold) in vitro, causes tumor regression in multiple FGFR2-altered human xenograft models, and was recently demonstrated to be efficacious in the clinic at doses that do not induce clinically significant hyperphosphatemia or diarrhea.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hiperfosfatemia , Humanos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/química , Ductos Biliares Intra-Hepáticos/metabolismo , Diarreia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química
2.
Cancer Discov ; 13(9): 2012-2031, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37270847

RESUMO

Oncogenic activation of fibroblast growth factor receptor 2 (FGFR2) drives multiple cancers and represents a broad therapeutic opportunity, yet selective targeting of FGFR2 has not been achieved. Although the clinical efficacy of pan-FGFR inhibitors (pan-FGFRi) validates FGFR2 driver status in FGFR2 fusion-positive intrahepatic cholangiocarcinoma, their benefit is limited by incomplete target coverage due to FGFR1- and FGFR4-mediated toxicities (hyperphosphatemia and diarrhea, respectively) and the emergence of FGFR2 resistance mutations. RLY-4008 is a highly selective, irreversible FGFR2 inhibitor designed to overcome these limitations. In vitro, RLY-4008 demonstrates >250- and >5,000-fold selectivity over FGFR1 and FGFR4, respectively, and targets primary alterations and resistance mutations. In vivo, RLY-4008 induces regression in multiple xenograft models-including models with FGFR2 resistance mutations that drive clinical progression on current pan-FGFRi-while sparing FGFR1 and FGFR4. In early clinical testing, RLY-4008 induced responses without clinically significant off-isoform FGFR toxicities, confirming the broad therapeutic potential of selective FGFR2 targeting. SIGNIFICANCE: Patients with FGFR2-driven cancers derive limited benefit from pan-FGFRi due to multiple FGFR1-4-mediated toxicities and acquired FGFR2 resistance mutations. RLY-4008 is a highly selective FGFR2 inhibitor that targets primary alterations and resistance mutations and induces tumor regression while sparing other FGFRs, suggesting it may have broad therapeutic potential. See related commentary by Tripathi et al., p. 1964. This article is featured in Selected Articles from This Issue, p. 1949.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Mutação , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico
3.
Artigo em Francês | AIM (África) | ID: biblio-1264307

RESUMO

Introduction. Nous décrivons un cas d'agénésies dentaire multiples associées à une ectopie bilatérale des troisièmes molaires ainsi de la deuxième prémolaire mandibulaire gauche. Cas clinique: Une patiente de 30ans était référée par son médecin gastroentérologue pour une prise en charge odontologique. La patiente décrit de ne jamais avoir bénéficié d'avulsion dentaire et ne souffrait d'aucun douleur ou gène au niveau orofacial. Une exploration clinique suivie d'examens radiologiques était réalisé. L'examen clinique révèle l'absence de plusieurs dents. La radiographie panoramique avait permis de confirmer le diagnostic d'agénésies multiples de huit dents. Les deux troisièmes molaires mandibulaires incluses en position verticale au niveau de la branche mandibulaire. La 35 aussi incluse en position apicale de la 38. L'examen CBCT montre une déhiscence des corticales des faces interne et externe du ramus en regarde des couronnes des troisièmes molaires. Discussion. L'oligodontie associée à une inclusion dentaire multiple reste un cas rare. Les éléments de l'examen clinique associés à la radiographie panoramique permettent de confirmer le diagnostic d'agénésie et d'ectopie dentaires. La radiologie tri dimensionnelle est capitale dans la prise de décision thérapeutique des dents ectopiques en position condy lienne.Conclusion. Sans symptomatologie clinique et radiologique, la décision thérapeutique était de s'abstenir de traitement chirurgical et de surveiller


Assuntos
Tomografia Computadorizada de Feixe Cônico , Radiografia Panorâmica , Senegal , Dente não Erupcionado
4.
Med Sante Trop ; 29(2): 200-205, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31379349

RESUMO

Knowledge of the factors of non-use of modern contraceptive methods should help to reduce the number of infants born after short interpregnancy intervals, which are associated with adverse effects for mothers, children, and families. For this reason, this study aimed to determine the factors associated with this non-use among mothers of infants aged 12 to 23 months. This case-control study included a sample of mothers of children aged 12 to 23 months. The case mothers were users of modern contraceptive methods and the control mothers were non-users. Data were collected from January 1 through March 31, 2018. Six factors were significantly associated with the use of modern contraceptive methods: age younger than 25 years, lack of gainful activity, desire for a family size ≥ 4 children, BMI greater than 25, opposition by husband, and failure to attend the 45-day postnatal consultation. Modifiable socio-economic factors were significantly associated with the non-use of modern contraceptive methods by mothers of children aged 12 to 23 months.


Assuntos
Comportamento Contraceptivo/estatística & dados numéricos , Anticoncepção/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Mães/estatística & dados numéricos , Adulto , Burkina Faso , Estudos de Casos e Controles , Feminino , Hospitais Universitários , Humanos , Lactente , Adulto Jovem
5.
Rev Epidemiol Sante Publique ; 66(3): 181-185, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29625861

RESUMO

BACKGROUND: Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive. METHODS: From 2010 to 2012, in Bamako, Mali, West Africa, 2489 newborns were routinely screened for sickle cell anemia at the umbilical cord or heel by isoelectrofocusing and, if necessary, by high-performance liquid chromatography. These newborns were born from 2420 mothers whose hemoglobin was studied by isoelectrofocusing. The data was recorded and processed using Excel software version 14.0.0. We calculated the frequency of the sickle cell gene in mothers and newborns as well as the number of SCA newborns from heterozygous or C homozygous mothers. RESULTS: Of the 2489 newborns, 16 had sickle cell anemia (6 SS and 10 SC); 198 had the sickle cell trait; 139 were AC and 1 was CC. Of the 10 newborns with SC profile, 3 were born from mothers not carrying the S gene but the C gene of hemoglobin and in which an Emmel test would have been negative. CONCLUSION: Targeted newborn screening, based on the results of sickling test in pregnant women, would misdiagnose more than one of six sickle cell anemia newborns who would not benefit from early care. Cost-effectiveness studies of routine newborn screening for sickle cell anemia should lead to a better screening strategy in contexts where hemoglobin S and other hemoglobin defect genes coexist.


Assuntos
Anemia Falciforme/diagnóstico , Testes Hematológicos/métodos , Triagem Neonatal/métodos , Vigilância da População/métodos , Complicações Hematológicas na Gravidez/diagnóstico , Diagnóstico Pré-Natal , Adulto , África Ocidental/epidemiologia , Anemia Falciforme/sangue , Feminino , Testes Hematológicos/normas , Testes Hematológicos/estatística & dados numéricos , Hemoglobina Falciforme/análise , Humanos , Recém-Nascido , Limite de Detecção , Masculino , Mali/epidemiologia , Mães , Valor Preditivo dos Testes , Gravidez , Complicações Hematológicas na Gravidez/sangue , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/normas
6.
Artigo em Francês | AIM (África) | ID: biblio-1271838

RESUMO

L'objectif était d'étudier la connaissance des signes de danger de la mère et du nouveau-né ainsi que les facteurs associés parmi les femmes du district sanitaire de Sig-Noghin. Il s'est agi d'une étude transversale analytique menée du 1er avril au 30 mai 2016. Elle a concerné un échantillon de 429 femmes. L'entretien a été la technique d'enquête utilisée. Pour l'identification des facteurs associés, une régression logistique fut réalisée. Parmi les participantes 16,5 % ; 11,1 % et 6,3 % ont pu citer au moins trois (3) signes de danger respectivement de la grossesse, du postpartum et du nouveau-né. L'âge de la femme (OR aj 6,14 [1,06-35,61]), le niveau d'instruction (OR aj 3,19 [1,59-6,38]), le nombre de grossesses (OR aj 3,30 [1,13-9,62]) et le nombre de consultations prénatales (OR aj 1,77 [1,09-3,46]) étaient les facteurs statistiquement associés à la connaissance des signes de danger de la mère. Aucun des facteurs étudiés n'était associé à la connaissance des signes de danger du nouveau-né. En somme, le niveau de connaissance des signes de danger de la mère et du nouveau-né reste faible. Il est impératif de promouvoir davantage la sensibilisation des femmes enceintes et accouchées tout en impliquant la communauté dans laquelle celles-ci vivent


Assuntos
Burkina Faso , Recém-Nascido , Condições Patológicas, Sinais e Sintomas , Período Pós-Parto , Gravidez de Alto Risco
7.
ACS Med Chem Lett ; 8(2): 151-156, 2017 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-28197303

RESUMO

High throughput screening and subsequent hit validation identified 4-isopropyl-3-(2-((1-phenylethyl)amino)pyrimidin-4-yl)oxazolidin-2-one as a potent inhibitor of IDH1R132H. Synthesis of the four separate stereoisomers identified the (S,S)-diastereomer (IDH125, 1f) as the most potent isomer. This also showed reasonable cellular activity and excellent selectivity vs IDH1wt. Initial structure-activity relationship exploration identified the key tolerances and potential for optimization. X-ray crystallography identified a functionally relevant allosteric binding site amenable to inhibitors, which can penetrate the blood-brain barrier, and aided rational optimization. Potency improvement and modulation of the physicochemical properties identified (S,S)-oxazolidinone IDH889 (5x) with good exposure and 2-HG inhibitory activity in a mutant IDH1 xenograft mouse model.

8.
Rev Med Interne ; 38(9): 572-577, 2017 Sep.
Artigo em Francês | MEDLINE | ID: mdl-28237127

RESUMO

INTRODUCTION: Retinopathy is a chronic complication with severe functional consequences in patients with sickle cell disease. Its prevalence is not well known in sub-Saharan Africa because of the absence of screening. We report here the results of a routine screening for sickle retinopathy in a Comprehensive Sickle Cell Center in Sub-Saharan Africa. METHODS: Screening of sickle retinopathy was carried out in all sickle cell patients aged 10 and over, followed between 2010 and 2012. Retinopathy was screened by dilated indirect fundoscopic examination and retinal angiography, if necessary. The gender, age and hematological parameters of patients with sickle retinopathy were compared with those of controls randomly selected from the cohort of sickle cell patients without retinopathy followed during the same period. RESULTS: The overall prevalence of sickle cell retinopathy was 8.8% (142/1604): 12.4% (91/731) in SC, 5.2% (38/734) in SS, 9.4% (5/53) in Sß°-thalassemia patients and 9.3% (8/86) in Sß+-thalassemia patients. Proliferative retinopathy was more common in SC patients (P<0.01). High levels of hemoglobin or of hematocrit were associated with retinopathy in all patients and with proliferative retinopathy in SC patients. In SS or Sß0thalassemia patients, high leukocyte count was associated with proliferative retinopathy. Low fetal hemoglobin level was associated with retinopathy in all groups. CONCLUSION: The prevalence of sickle cell retinopathy is high and negatively associated to the level of fetal hemoglobin. The efficiency of a routine screening for sickle cell retinopathy must be assessed in Africa as well as the benefit of phlebotomy and hydroxyurea therapy as a preventive treatments.


Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Doenças Retinianas/epidemiologia , Doenças Retinianas/etiologia , Adolescente , Adulto , África Subsaariana/epidemiologia , Feminino , Hospitais Especializados , Humanos , Masculino , Prevalência , Fatores de Risco , Adulto Jovem
9.
J Med Chem ; 60(5): 2155-2161, 2017 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-28186750

RESUMO

While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improving the kinase selectivity of type II maternal embryonic leucine zipper kinase inhibitors by applying these two complementary approaches together, which clearly demonstrates the powerful synergy between them.


Assuntos
Inibidores Enzimáticos/farmacologia , Zíper de Leucina , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Cristalografia por Raios X , Inibidores Enzimáticos/química
10.
Structure ; 25(3): 506-513, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28132785

RESUMO

Oncogenic IDH1 and IDH2 mutations contribute to cancer via production of R-2-hydroxyglutarate (2-HG). Here, we characterize two structurally distinct mutant- and isoform-selective IDH1 inhibitors that inhibit 2-HG production. Both bind to an allosteric pocket on IDH1, yet shape it differently, highlighting the plasticity of this site. Oncogenic IDH1R132H mutation destabilizes an IDH1 "regulatory segment," which otherwise restricts compound access to the allosteric pocket. Regulatory segment destabilization in wild-type IDH1 promotes inhibitor binding, suggesting that destabilization is critical for mutant selectivity. We also report crystal structures of oncogenic IDH2 mutant isoforms, highlighting the fact that the analogous segment of IDH2 is not similarly destabilized. This intrinsic stability of IDH2 may contribute to observed inhibitor IDH1 isoform selectivity. Moreover, discrete residues in the IDH1 allosteric pocket that differ from IDH2 may also guide IDH1 isoform selectivity. These data provide a deeper understanding of how IDH1 inhibitors achieve mutant and isoform selectivity.


Assuntos
Inibidores Enzimáticos/farmacologia , Isocitrato Desidrogenase/química , Isocitrato Desidrogenase/genética , Neoplasias/genética , Bibliotecas de Moléculas Pequenas/farmacologia , Regulação Alostérica , Sítio Alostérico , Cristalografia por Raios X , Glutaratos/metabolismo , Humanos , Isocitrato Desidrogenase/antagonistas & inibidores , Ligação Proteica , Conformação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética
11.
Odontostomatol Trop ; 40(157): 39-44, 2017 Mar.
Artigo em Francês | MEDLINE | ID: mdl-30240558

RESUMO

The Stafne defect is a benign, asymptomatic, non-progressive and rare bone depression, mainly discovered by chance in the posterior mandibular region. It is described radiographically as an oval radiolucency located below the mandibular canal, in the molar region, close to the submandibular gland. Sialography is a traditional technique in the radiographic examination of salivary glands that involves the injection of an iodine-based contrast medium into the main salivary duct. The Cone Beam Computed Tomography (CBCT) is a 3D imaging technique that has modernized the dental and maxillofacial practice with its advantages such as high speed, good spatial resolution and low radiation exposure. The CBCT Sialography that consists in a 3D Sialography with cone beam offers the same benefits as traditional sialography and allows three-dimensional viewing. It is a new imaging test for an accurate anatomical study of the major salivary glands and their relationships with their environments. The aim of this report is to present a case of Stafne bone cavity containing right submandibular gland tissue, occurring in a 58-year-old man and diagnosed by using CBCT sialography.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Mandíbula/anormalidades , Doenças Mandibulares/diagnóstico por imagem , Sialografia , Diagnóstico Diferencial , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade
12.
Angew Chem Int Ed Engl ; 55(46): 14218-14238, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27723189

RESUMO

Can classical and modern chemical C-H oxidation reactions complement biotransformation in the synthesis of drug metabolites? We have surveyed the literature in an effort to try to answer this important question of major practical significance in the pharmaceutical industry. Drug metabolites are required throughout all phases of the drug discovery and development process; however, their synthesis is still an unsolved problem. This Review, not intended to be comprehensive or historical, highlights relevant applications of chemical C-H oxidation reactions, electrochemistry and microfluidic technologies to drug templates in order to access drug metabolites, and also highlights promising reactions to this end. Where possible or appropriate, the contrast with biotransformation is drawn. In doing so, we have tried to identify gaps where they exist in the hope to spur further activity in this very important research area.


Assuntos
Preparações Farmacêuticas/química , Elementos de Transição/química , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Carbono/química , Catálise , Técnicas Eletroquímicas , Hidrogênio/química , Técnicas Analíticas Microfluídicas , Oxirredução , Preparações Farmacêuticas/metabolismo
13.
J Med Chem ; 59(10): 4711-23, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27187609

RESUMO

MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.


Assuntos
Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/normas , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Relação Estrutura-Atividade
14.
J Mycol Med ; 26(4): 317-322, 2016 Dec.
Artigo em Francês | MEDLINE | ID: mdl-27198757

RESUMO

INTRODUCTION: Endodontic flora is dominated in the apical part of the channels by strict anaerobic and some facultative anaerobic bacteria but also by Candida yeasts, especially Candida albicans species that are involved in the maintenance and persistence of endodontic infections. Their elimination of the canal system in practice by chemo-mechanical methods of disinfection is not always guaranteed. Thus, this in vitro study was performed to determine the sensitivity of C. albicans with sodium hypochlorite (NaOCl) dosed at 2.5 %, the chlorhexidine digluconate 0.5 % and calcium hydroxide used in inter-session medication. METHODS: The diffusion method was used initially to test the sensitivity of C. albicans strains with the above products. Then a dilution technique has allowed us to determine the minimum inhibitory concentration of these active products on C. albicans. RESULTS: Strains from infected pulp teeth of patients showed a sensitivity of C. albicans to sodium hypochlorite to a minimum inhibitory concentration less than 70µg/mL and 30µg/mL for chlorhexidine. CONCLUSION: This study demonstrated a sensitivity of C. albicans to sodium hypochlorite and chlorhexidine.


Assuntos
Hidróxido de Cálcio/farmacologia , Candida albicans/efeitos dos fármacos , Clorexidina/análogos & derivados , Desinfetantes/farmacologia , Hidróxido de Sódio/farmacologia , Anti-Infecciosos Locais/farmacologia , Candida albicans/crescimento & desenvolvimento , Candida albicans/isolamento & purificação , Clorexidina/farmacologia , Combinação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Mucosa Bucal/microbiologia
15.
J Mycol Med ; 26(2): 111-115, 2016 Jun.
Artigo em Francês | MEDLINE | ID: mdl-26924766

RESUMO

INTRODUCTION: Endodontic infections are characterized by their microbial polymorphism with the presence of pathogenic agents such as bacteria. The aim of this study was to investigate the presence of yeast in the root canals of teeth with pulp necrotic with or without apical periodontitis and to study the sensibility of these at disinfection at sodium hypochlorite to 2.5 %. METHODS: Root canal samples, taken with paper points before and after disinfection with sodium hypochlorite dosed at 2.5 % on 50 single rooted teeth in 38 patients, were seeded in petri dishes containing Sabouraud Chloramphenicol (SC) (Conda Laboratories, Madrid). These stains were incubated in an incubator at 37°C for 48hours. The presence of yeast was confirmed by white colonies on the entire circumference of the tip paper. The identification of species was done by macroscopic and microscopic examinations associated with Blastese test. RESULTS: The yeast colonies were isolated from 7 teeth (14 %) out of 50. All positive samples were from teeth with an open necrotic pulp (P<0.001). The only species found was Candida albicans. Immediate disinfection with sodium hypochlorite at 2.5 % did not show a complete elimination of yeasts. CONCLUSION: The results of this study show that the canal of necrotic teeth with or without apical periodontitis may shelter yeasts even after immediate disinfection with sodium hypochlorite 2.5 %.


Assuntos
Necrose da Polpa Dentária/microbiologia , Periodontite Periapical/microbiologia , Hipoclorito de Sódio/farmacologia , Leveduras/efeitos dos fármacos , Leveduras/isolamento & purificação , Adolescente , Adulto , Idoso , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Criança , Desinfecção/métodos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Senegal , Irrigação Terapêutica , Adulto Jovem
17.
Med. Afr. noire (En ligne) ; 63(10): 533-537, 2016.
Artigo em Francês | AIM (África) | ID: biblio-1266151

RESUMO

La leucémie primitive à plasmocytes est une pathologie agressive rare, caractérisée par une plasmocytose sanguine supérieure à 20% des leucocytes circulants. C'est une entité clinique proche du myélome multiple dans sa présentation clinique et biologique. Il n'y a pas de schéma thérapeutique bien codifié, mais des cas de rémission complète sont rapportés sous chimiothérapies spécifiques du myélome. Dans ce travail, nous rapportons le cas d'une leucémie primitive à plasmocytes agressive de diagnostic tardif chez un homme de 42 ans, d'origine malienne. La symptomatologie inaugurale était faite d'une bicytopénie expressive avec blastose circulante. Le caractère atypique des cellules et les difficultés techniques n'ont pas permis de poser rapidement le diagnostic, qui fût retenu à l'issue de l'immuno-phénotypage cellulaire réalisée en France. Les cellules exprimaient le CD38, mais étaient négatives pour le CD45, le CD56 et le CD138. Aucune chimiothérapie spécifique n'a pu être initiée devant l'évolution rapide vers le décès 5 mois après le premier contact avec notre service. Ce cas clinique rare incite à améliorer le plateau technique par l'introduction de la cytométrie en flux dans le diagnostic des hémopathies malignes en général, celui des leucémies aiguës atypiques en particuliers. A cause de son pronostic péjoratif en l'absence de thérapeutique précoce, la leucémie à plasmocytes doit être évoquée devant toute blastose sanguine atypique associées ou non à une symptomatologie clinique évocatrice du myélome multiple

18.
Arch Pediatr ; 22(3): 260-6, 2015 Mar.
Artigo em Francês | MEDLINE | ID: mdl-25636211

RESUMO

Cerebral vasculopathy exposes patients to a high risk of stroke, a major complication of sickle cell disease (SCD) associated with a high risk of death and disability. Transcranial doppler (TCD) ultrasonography used to identify SCD patients at risk of stroke may contribute to significantly reducing morbidity and mortality in these patients by indicating appropriate treatment. From March 2008 to February 2013, we conducted systematic screening for cerebral vasculopathy using TCD in 572 SCD patients (including 375 SS, 144 SC, 26 S/ß(0), and 27 S/ß(+) thalassemia patients) aged 1-17 years in a comprehensive center for follow-up and research on sickle cell disease in Bamako, Mali. After exclusion of 30 inadequate results and one case of abnormal TCD observed in a multiple organ failure patient, we found an abnormal or conditional TCD in 18% of 541 children examined in a steady state. The highest prevalence of abnormal cases concerned homozygous SS patients (8.1%). No case of abnormal or conditional TCD was observed in children with S/ß(+) thalassemia. Hemoglobin concentrations were significantly lower in patients with conditional or abnormal TCD (P<0.01). In a subgroup of 68 patients with conditional TCD, nine (13%) converted to abnormal TCD over 1 year. In this subgroup of 68 conditional TCD patients, a decrease or increase in baseline hemoglobin concentration was predictive of conditional or abnormal TCD at the follow-up visit. Progression towards conditional TCD was observed in four patients (0.9%) who initially had normal TCD. Children with abnormal TCD had, whenever possible, a monthly exchange transfusion program. One case of transient stroke in the context of P. falciparum malaria with low hemoglobin concentration and one death were observed. These findings highlight the need for systematic TCD in sickle cell disease monitoring and implementing regular blood transfusion programs in the context of limited access to regular and secure blood transfusions.


Assuntos
Anemia Falciforme/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Ultrassonografia Doppler Transcraniana , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
19.
Artigo em Francês | AIM (África) | ID: biblio-1263926

RESUMO

Objectif : Decrire l'experience du departement de gynecologie obstetrique du CHU-YO dans la determination echographique du sexe fotal au premier trimestre de la grossesse Patientes et methodes : Il s'agissait d'une etude prospective de type descriptif pendant une periode de 30 mois allant du 1er fevrier 2013 au 30 juin 2014 au sein de l'unite d'echographie gynecologique et obstetricale du CHU-YO de Ouagadougou. L'echantillon d'etude a ete constitue de 311 fotus. Ont ete incluses dans cet echantillon toute les gestantes venue pour une echographie obstetricale en dehors de toute situation d'urgence dont l'age gestationnel etait compris entre la 11eme et la 14eme semaine d'amenorrhee et ayant exprime le desir de connaitre le sexe fotal. Les methodes decrites par Mazza et par Efrat ont ete utilisees pour la determination du sexe fotal. Les patientes ont ete suivies jusqu'a leur accouchement apres verification clinique du sexe des nouveau-nes. Le recueil des donnees a ete fait sur une fiche de collecte individuelle de donnees. La participation a l'etude a ete conditionnee a la signature d'un consentement eclaire par les patientes.Resultats : La determination du sexe fotal a ete possible chez 280 des 311 fotus; soit un taux de faisabilite de 89;7%. Chez les 31 autres cas; il n'a pas ete possible de determiner le sexe fotal; la position du fotus ne permettant pas de bien voir le bourgeon genital. Au niveau de la fiabilite; des 238 fotus qui ont ete suivis; la determination du sexe fotal a ete correcte chez 204 fotus soit un taux de succes de 85;7%. L'exactitude etait meilleure lorsque la determination du sexe etait faite apres 12 semaines d'amenorrhee. Il n'y avait pas de difference significative dans les mesures selon que la grossesse etait monofoetale ou multiple. Conclusion : La determination echographique du sexe fotal au premier pourrait etre une option efficace; simple; disponible et peu couteuse dans les pays en voie de developpement


Assuntos
Centros Médicos Acadêmicos , Relatos de Casos , Primeiro Trimestre da Gravidez
20.
Med Sante Trop ; 24(4): 430-1, 2014.
Artigo em Francês | MEDLINE | ID: mdl-24919210

RESUMO

OBJECTIVE: to determine the specific antimicrobial activity of the drugs proposed in the national algorithm for treatment of vaginal infections. METHOD: Over a three-month period, the bacteriological laboratory of the Yalgado-Ouédraogo University Hospital in Ouagadougou analyzed vaginal swabs from women seen at 5 health-care facilities in that city. RESULT: The study included 404 women with a mean age of 29 years. The microbes with the highest incidence rates were various species of Candida (20%), Gardnerella and/or Mobiluncus (18.8%), and Ureaplasma/Mycoplasma (10.9%). The agents isolated were highly susceptible to ciprofloxacin, erythromycin, fluconazole, miconazole, and nystatin. CONCLUSION: This study demonstrated the continuing efficacy of the drugs in the national algorithm for treatment of vaginal infections, which is associated with compliance with the recommended diagnostic procedure and therapeutic protocol.


Assuntos
Vaginite/microbiologia , Adolescente , Adulto , Algoritmos , Burkina Faso , Feminino , Humanos , Pessoa de Meia-Idade , Vaginite/tratamento farmacológico , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...