RESUMO
The clinical involvement and antifungal susceptibility of Aspergillus section Circumdati are poorly known. We analyzed 52 isolates, including 48 clinical isolates, belonging to 9 species inside the section Circumdati. The whole section exhibited, by the EUCAST reference method, a poor susceptibility to amphotericin B, but species/series-specific patterns were observed for azole drugs. This underlines the interest in getting an accurate identification inside the section Circumdati to guide the choice of antifungal treatment in clinical practice.
Assuntos
Antifúngicos , Aspergillus , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Anfotericina B/farmacologia , Azóis/farmacologiaRESUMO
OBJECTIVE: To validate and evaluate the performance metrics of the high-throughput semiconductor sequencing platform, Ion Proton®, in non-invasive prenatal genetic screening (NIPS) for common fetal aneuploidies in a clinical setting. METHODS: This prospective cohort study included 2505 pregnant women from eight academic genetics laboratories (695 high risk for trisomy 21 (risk ≥ 1/250) pregnancies in a validation study, and 1810 such pregnancies, without ultrasound anomalies, in a real-life NIPS clinical setting). Outcome was available for all cases in the validation cohort and for 521 in the clinical cohort. Cell-free DNA from plasma samples was sequenced using the Ion Proton sequencer, and sequencing data were analyzed using the open-access software, WISECONDOR. Performance metrics for detection of trisomies 21, 18 and 13 were calculated based on either fetal karyotype result or clinical data collected at birth. We also evaluated the failure rate and compared three methods of fetal fraction quantification (RASSF1A assay, and DEFRAG and SANEFALCON software). RESULTS: Results from both cohorts were consistent and their gestational age was not significantly different so their data were combined to increase the sample size for analysis. Sensitivities and specificities, respectively, were as follows: for trisomy 21, 98.3% (95% CI, 93.5-99.7%) and 99.9% (95% CI, 99.4-100%); for trisomy 18, 96.7% (95% CI, 80.9-99.8%) and 100% (95% CI, 99.6-100%); and for trisomy 13, 94.1% (95% CI, 69.2-99.7%) and 100% (95% CI, 99.6-100%). Our failure rate was 1.2% initially and as low as 0.6% after retesting some of the failed samples. Fetal fraction estimation by the RASSF1A assay was consistent with DEFRAG results, and both were adequate for routine diagnosis. CONCLUSIONS: We describe one of the largest studies evaluating Ion Proton-based NIPS and the first clinical study reporting pregnancy outcome in a large series of patients. This platform is highly efficient in detecting the three most common trisomies. Our protocol is robust and can be implemented easily in any medical genetics laboratory. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Ácidos Nucleicos Livres/sangue , Doenças Fetais/genética , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Diagnóstico Pré-Natal/métodos , Aneuploidia , Ácidos Nucleicos Livres/genética , Síndrome de Down/genética , Feminino , Doenças Fetais/sangue , Idade Gestacional , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Cariótipo , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Semicondutores , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/genéticaRESUMO
Animal models are fundamental to advance knowledge of disease pathogenesis and to test/develop new therapeutic strategies. Most of the current knowledge about the pathogenic mechanisms underpinning autoimmune demyelination processes implicating autoantigens has been obtained using the Experimental Autoimmune Neuritis (EAN) animal model. The most widely used EAN model is obtained by active immunization of Lewis rats using a peptide, P0 (180-199), issuing from the major peripheral nervous system myelin protein. But this model mimics only the classical monophasic acute form of demyelinating polyradiculoneuropathy, i.e. Guillain-Barré syndrome (GBS). We developed a new model by immunizing Lewis rats using the same immunodominant neuritogenic peptide P0 (180-199) but this time with its S-palmitoyl derivative, S-palm P0 (180-199). All of the animals immunized with the S-palm P0 (180-199) peptide developed a chronic relapsing-remitting form of the disease corresponding to the electrophysiological criteria of demyelination (slow sensory nerve conduction velocity, prolonged motor nerve latency, partial motor nerve conduction blocks) with axon degeneration. These findings were confirmed by immunohistopathology study and thus, appear to mimic human chronic inflammatory demyelinating polyradiculopathy (CIDP). This new model opens up new avenues of research for testing new anti-inflammatory and neuroprotective therapeutic strategies.
Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/induzido quimicamente , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Animais , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/fisiopatologia , Modelos Animais de Doenças , Imuno-Histoquímica , Neurônios Motores , Condução Nervosa , Neurite Autoimune Experimental , Ácido Palmítico/química , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Ratos , Ratos Endogâmicos LewRESUMO
The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell-specific markers. Cardiomyocytes undergo post-mitotic senescence in response to telomere damage, characterized by persistent DNA damage response and expression of the classical senescence markers p21 and p16, which are shared by many other cell types. In the present study, we used transcriptomic approaches to discover new markers specific for cardiomyocyte senescence. We identified Prominin2 (Prom2), encoding a transmembrane glycoprotein, as the most upregulated gene in cardiomyocytes of aged mice compared to young mice. We showed that Prom2 was upregulated by a p53-dependent pathway in stress-induced premature senescence. Prom2 expression correlated with cardiomyocyte hypertrophy in the hearts of aged mice and was increased in atrial samples of patients with HF with preserved ejection fraction. Consistently, Prom2 overexpression was sufficient to drive senescence, hypertrophy and resistance to cytotoxic stress while Prom2 shRNA silencing inhibited these features in doxorubicin-treated cardiac cells. In conclusion, we identified Prom2 as a new player of cardiac aging, linking cardiomyocyte hypertrophy to senescence. These results could provide a better understanding and targeting of cell-type specific senescence in age-associated cardiac diseases.
Assuntos
Envelhecimento , Senescência Celular , Miócitos Cardíacos , Miócitos Cardíacos/metabolismo , Animais , Senescência Celular/genética , Camundongos , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Envelhecimento/genética , Humanos , Antígeno AC133/metabolismo , Antígeno AC133/genética , Masculino , Camundongos Endogâmicos C57BL , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologiaRESUMO
Due to large outbreaks observed worldwide, Candida auris has emerged as a major threat to healthcare facilities. To prevent these phenomena, a systematic screening should be performed in patients transferred from regions where the pathogen is highly endemic. In this study, we recorded and analyzed French mycologists' current knowledge and practice regarding C. auris screening and diagnosis. Thirty-six centers answered an online questionnaire. Only 11 (30.6 %) participants were aware of any systematic screening for C. auris for patients admitted to their hospital. In the case of post-admission screening, axillae/groins (n = 21), nares (n = 7), rectum (n = 9), and mouth (n = 6) alone or various combinations were the body sites the most frequently sampled. Only six centers (8.3 %) reported using a commercially available plate allowing the differentiation of C. auris colonies from that of other Candida species, while five laboratories (13.8 %) had implemented a C. auris-specific qPCR. Considering the potential impact on infected patients and the risk of disorganization in the care of patients, it is crucial to remember to biologists and clinicians the utmost importance of systematic screening on admission.
Assuntos
Candida auris , Candidíase , Programas de Rastreamento , Humanos , França/epidemiologia , Inquéritos e Questionários , Candidíase/diagnóstico , Candidíase/epidemiologia , Candidíase/microbiologia , Programas de Rastreamento/métodos , Candida auris/efeitos dos fármacos , Candida auris/genética , Candida auris/isolamento & purificação , Conhecimentos, Atitudes e Prática em Saúde , Micologia/métodos , Sociedades Médicas , Candida/isolamento & purificação , Candida/efeitos dos fármacos , Candidíase InvasivaRESUMO
OBJECTIVE: To determine when the vesicourethral anastomosis (VUA) becomes tight after retropubic radical prostatectomy (RRP) and if an additional lateral view cystography provides significantly more information than the only anterior-posterior view. PATIENTS AND METHODS: Pressure-controlled cystography with anterior-posterior and lateral views was performed on postoperative days (POD) 3, 6 and 9 and evaluated in 100 consecutive patients after RRP. RESULTS: On POD 3, 6 and 9, 82, 80 and 82% of all VUA, respectively, were tight. 85% of all tight VUA on POD 3 remained tight on POD 6 and 9. Of the 52 extravasations in a total of 300 cystographies, 65% were recognizable in the anterior-posterior as well as in the lateral view cystography, 6% were seen only in the anterior-posterior view and 29% only in the lateral view. CONCLUSIONS: The VUA after RRP is tight in about 80% of the cases on POD 3, 6 and 9. A tight VUA on POD 3 does not exclude later extravasation on POD 6 and 9 (14%). About one third (29%) of all extravasations of VUA are seen only in the lateral view cystography after RRP.
Assuntos
Anastomose Cirúrgica/métodos , Prostatectomia/efeitos adversos , Idoso , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Pressão , Prostatectomia/métodos , Procedimentos Cirúrgicos Operatórios , Fatores de Tempo , Uretra/cirurgia , Bexiga Urinária/patologiaRESUMO
A survey of mycology laboratories for antifungal susceptibility testing (AFST) was undertaken in France in 2018, to better understand the difference in practices between the participating centers and to identify the difficulties they may encounter as well as eventual gaps with published standards and guidelines. The survey captured information from 45 mycology laboratories in France on how they perform AFST (number of strains tested, preferred method, technical and quality aspects, interpretation of the MIC values, reading and interpretation difficulties). Results indicated that 86% of respondents used Etest as AFST method, with a combination of one to seven antifungal agents tested. Most of the participating laboratories used similar technical parameters to perform their AFST method and a large majority used, as recommended, internal and external quality assessments. Almost all the participating mycology laboratories (98%) reported difficulties to interpret the MIC values, especially when no clinical breakpoints are available. The survey highlighted that the current AFST practices in France need homogenization, particularly for MIC reading and interpretation.
Assuntos
Antifúngicos/uso terapêutico , Laboratórios , Testes de Sensibilidade Microbiana , Micologia , Prática Profissional/estatística & dados numéricos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/normas , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/estatística & dados numéricos , Farmacorresistência Fúngica , França , História do Século XXI , Humanos , Laboratórios/normas , Laboratórios/estatística & dados numéricos , Ensaio de Proficiência Laboratorial/métodos , Ensaio de Proficiência Laboratorial/estatística & dados numéricos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Micologia/história , Micologia/métodos , Micologia/normas , Micologia/estatística & dados numéricos , Prática Profissional/normas , Controle de Qualidade , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND PURPOSE: Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney. EXPERIMENTAL APPROACH: Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry. KEY RESULTS: Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 x 10(-11) M) than in distal specimens (EC50=7.4 x 10(-10) M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney. CONCLUSIONS AND IMPLICATIONS: Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.
Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Músculo Liso/efeitos dos fármacos , Ureter/efeitos dos fármacos , Idoso , Animais , Ciclo-Oxigenase 1/biossíntese , Ciclo-Oxigenase 2/biossíntese , Interpretação Estatística de Dados , Diclofenaco/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Isoxazóis/farmacologia , Rim/efeitos dos fármacos , Rim/fisiologia , Cinética , Masculino , Contração Muscular/efeitos dos fármacos , Sulfonamidas/farmacologia , Suínos , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/fisiopatologiaRESUMO
Excell 2280 analyser is a new automated haematology analyser manufactured by Drew Scientific Inc, Texas, USA, and distributed in France by MAXMAT S.A., Montpellier. It can achieve 80 complete blood cell counts per hour, with leukocyte differential counts. Three sampling possibilities are included: a direct one (open tubes, 180 microL), a blood saver one (80 microL) and an automatic, through-the-cap one (180 microL). The analytic principles are: electrical impedance for cell counting (WBC, RBC, platelets, MCV) and RBC/platelet sizing; and a new multidimensional optical system using a laser light scattering flow cytometer for WBC counting and classification. We evaluated the Excell 2280 in our laboratory: we quantified intra-run and within-run variations, correlations between the automatic and the direct sampling method, stability of the results over time, linearity of the detections and finally correlation between results obtained with this analyzer and the Gen'S one from Beckman-Coulter Inc. The obtained results were within the theoretical ranges given by the manufacturer. The presence of any abnormal result, or of any flag, must systematically lead to check the blood smear. This new automated haematology analyser appears to be convenient for emergency room-related laboratories, and for routine small-to-medium laboratories.
Assuntos
Contagem de Células Sanguíneas/instrumentação , HumanosRESUMO
The oncoprotein SET participates in a diversity of cellular functions including cell proliferation. Its role on cell cycle progression is likely mediated by inhibiting cyclin B-cdk1 and the protein phosphatase 2A (PP2A). On identifying new SET cellular partners, we found that SET interacts in vitro and in vivo with the heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2); a protein involved in various aspects of mRNA biogenesis. The SET-binding region of hnRNPA2 is the RNP1 sequence that belongs to the RNA-binding domain (RBD) of this protein. We also found that hnRNPA2 has much higher affinity for single-standed DNA than for SET. On analysing the effect of hnRNPA2 on PP2A inhibition by SET, we observed that hnRNPA2 cooperates with SET on PP2A inhibition. This is because we found that hnRNPA2 is also a PP2A inhibitor. HnRNPA2 interacts with PP2A by the RNP1 sequence; however, to inhibit PP2A activity, the complete RBD is needed. We also observed that overexpression of hnRNPA2 inhibits PP2A activity and stimulates cell proliferation. Interestingly, the overexpression of the complete RBD is sufficient to stimulate proliferation. As hnRNPA2 is overexpressed in a variety of human tumors, our results suggest that hnRNPA2 might participate in oncogenesis by stimulating cell proliferation.
Assuntos
Proliferação de Células , Proteínas Cromossômicas não Histona/metabolismo , DNA de Cadeia Simples/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Fosfoproteínas Fosfatases/antagonistas & inibidores , Fosfoproteínas Fosfatases/metabolismo , Fatores de Transcrição/metabolismo , Animais , Células COS , Ciclo Celular , Células Cultivadas , Chlorocebus aethiops , Cromatografia de Afinidade , Proteínas Cromossômicas não Histona/genética , DNA de Cadeia Simples/genética , Proteínas de Ligação a DNA , Eletroforese em Gel Bidimensional , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Chaperonas de Histonas , Humanos , Imunoprecipitação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fosforilação , Plasmídeos , Ligação Proteica , Proteína Fosfatase 2 , RNA/metabolismo , RNA Mensageiro , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fatores de Transcrição/genéticaRESUMO
We carried out gain-of-function mutagenesis screening and identified a mutant in which GAL4 induction led to both hyperplasia and apoptosis. The gene involved was identified as stonewall (stwl), a myb-related gene involved in germ cell proliferation and differentiation during oogenesis. As observed with dmyb, the ectopic expression of stwl(UY823) inhibited endoreplication in salivary glands. We also found that stwl(UY823) overexpression, like overexpression of the wild-type gene, activated G1/S transition and apoptosis. The apoptosis triggered by stwl(UY823) expression is correlated to induction of the proapoptotic gene reaper. Finally, the death of flies induced by ectopic stwl(UY823) expression is efficiently prevented in vivo by triggering cell death in stwl(UY823)-expressing cells. Our results suggest that stwl(UY823) kills flies by causing inappropriate cell cycle entry, and that triggering the death of these overproliferating cells or slowing their proliferation restores viability.
Assuntos
Apoptose/genética , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila/citologia , Drosophila/genética , Genes de Insetos , Fatores de Transcrição/genética , Alelos , Animais , Sequência de Bases , Ciclo Celular , Proliferação de Células , DNA Complementar/genética , Drosophila/crescimento & desenvolvimento , Feminino , Expressão Gênica , Genes Letais , Teste de Complementação Genética , Vetores Genéticos , Hiperplasia , Masculino , Mutagênese , Fenótipo , Pupa/citologia , Pupa/crescimento & desenvolvimento , Pupa/metabolismo , Glândulas Salivares/citologia , Glândulas Salivares/crescimento & desenvolvimento , Glândulas Salivares/metabolismo , Asas de Animais/citologia , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismoRESUMO
The use of low-dose aspirin in pregnancy should remain a highly targeted indication since its long-term safety has not been established and should be restricted to women at high risk of vascular complications. Indications for which the benefit of aspirin has been shown are women with a history of preeclampsia responsible for a premature birth before 34 weeks, those having at least two history of preeclampsia, those with an antiphospholipid syndrome and those with lupus associated with positive antiphospholipid antibodies or renal failure. In all other cases, the level of evidence of the benefit of aspirin is insufficient to recommend its routine prescription.
Assuntos
Aspirina/efeitos adversos , Aspirina/uso terapêutico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/etiologia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Feminino , Humanos , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Nascimento Prematuro/prevenção & controle , Fatores de RiscoRESUMO
Postpartum hemorrhage (PPH) is one of the most common causes of mortality in obstetrics worldwide. The accuracy of estimated blood loss is a priority in determining appropriate treatment. Will the additional use of a visual aid improve physicians' accuracy in estimating blood loss compared to the use of a collector bag and baby scale alone? Simulation training sessions created three vaginal delivery scenarios for participants to estimate volumes of blood loss: firstly, using only a collector bag and a baby weight scale and secondly, adding a visual aid depicting known volumes of blood. The primary endpoint was to determine if participants could accurately evaluate blood loss within a 20% error margin. The addition of the visual estimator resulted in overestimation of blood loss. The rates of participants' estimations were significantly more accurate when using the collector bag with the baby weight scale without the addition of the visual aid; 85.5% versus 33.3% (p < 0.01) for 350 mL, 88.4% versus 50.7% (p < 0.01) for 1100 mL and 88.4% versus 78.3% (p < 0.01) for 2500 mL, respectively. Additional use of a visual aid with a collector bag does not seem to be useful in improving the accuracy in the estimation of blood loss.
Assuntos
Recursos Audiovisuais , Hemorragia Pós-Parto/diagnóstico , Manejo de Espécimes , Adulto , Parto Obstétrico , Educação de Graduação em Medicina , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodos , Adulto JovemRESUMO
Radiological protection is a matter of concern for members of the public and thus national authorities are more likely to trust the quality of radioactivity data provided by accredited laboratories using common standards. Normative approach based on international standards aims to ensure the accuracy or validity of the test result through calibrations and measurements traceable to the International System of Units. This approach guarantees that radioactivity test results on the same types of samples are comparable over time and space as well as between different testing laboratories. Today, testing laboratories involved in radioactivity measurement have a set of more than 150 international standards to help them perform their work. Most of them are published by the International Standardization Organization (ISO) and the International Electrotechnical Commission (IEC). This paper reviews the most essential ISO standards that give guidance to testing laboratories at different stages from sampling planning to the transmission of the test report to their customers, summarizes recent activities and achievements and present the perspectives on new standards under development by the ISO Working Groups dealing with radioactivity measurement in connection with radiological protection.
Assuntos
Exposição à Radiação , Proteção Radiológica , Meio Ambiente , Exposição Ambiental , Humanos , Laboratórios , Radioatividade , Padrões de ReferênciaRESUMO
OBJECTIVES: To determine the efficacy of the cervical pessary for the prevention of preterm delivery and to propose recommendations. MATERIALS AND METHOD: We searched the MedLine and the Cochrane Library and checked the international guidelines: ACOG and SOGC. RESULTS: The data concerning the efficacy of the cervical pessary for the prevention of preterm birth in a population of asymptomatic women with a singleton pregnancy with a short cervix≤25mm between 20 and 24 weeks 6 days of gestation and in a population of asymptomatic women with a twin pregnancy at high risk of preterm delivery defined by a short cervix are contradictory. More studies are necessary to recommend its use in these indications (Professional consensus). A cervical pessary placed before 22 weeks of gestation does not reduce the risk of preterm birth in the general population of asymptomatic women with a twin pregnancy (EL1). It is therefore not recommended to use the cervical pessary in order to prevent preterm delivery in the general population of asymptomatic women with a twin pregnancy (grade A). CONCLUSION: More studies are necessary to recommend the use of the cervical pesssary in singleton and in twin pregnancies with a short cervix.
Assuntos
Colo do Útero , Pessários , Gravidez de Gêmeos , Nascimento Prematuro/prevenção & controle , Feminino , Humanos , GravidezRESUMO
Pediatric visceral leishmaniasis is caused by Leishmania infantum, a dog parasite transmitted to humans by the bite of the female phlebotomine sand fly. The well-known clinical triad is fever, pallor, and splenomegaly. A secondary macrophage activation syndrome (MAS) can complicate this infection, which is lethal when not treated. When MAS is observed without any explanation, a visceral leishmaniasis is highly recommended. We report a case of visceral leishmaniasis in a 21-month-old child complicated by a macrophage activation syndrome without splenomegaly. No immunodeficiency was diagnosed that could explain this unusual clinical condition. To our knowledge, this is the first case of visceral leishmaniasis without splenomegaly reported to date.
Assuntos
Leishmaniose Visceral/diagnóstico , Feminino , Humanos , Lactente , EsplenomegaliaRESUMO
We evaluated the usefulness of a serum Aspergillus PCR assay for the diagnosis and prognosis of invasive aspergillosis in a study involving 941 patients for a total of 5146 serum samples. Fifty-one patients had proven/probable aspergillosis. We compared galactomannan (GM), PCR and mycologic analysis of pulmonary samples in both neutropenic and nonneutropenic patients. PCR performed in serum yielded 66.7% sensitivity, 98.7% specificity, 75.6% positive predictive value and 98.0% negative predictive value, while the GM index yielded 78.4% sensitivity, 87.5% specificity, 27% positive predictive value and 98.6% negative predictive value. The inclusion of PCR in the European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) mycologic criteria permitted the reclassification of nine other cases from possible to probable aspergillosis and increased the sensitivity to 71.7%. Combining the GM index with serum PCR increased the detection rate of invasive aspergillosis with 88.2% sensitivity. PCR was systematically negative in 16 patients with noninvasive forms of aspergillosis (namely aspergilloma and chronic aspergillosis). Remaining PCR positive after a period of 14 to 20 days of treatment was related to poor outcome at 30 and 90 days. Our results also indicate that, unlike the determination of the GM index, the initial fungus load as determined by PCR was highly predictive of 90-day mortality, with the rate of the latter being 15.8% for patients with <150 copies/mL vs. 73.2% for patients at or above that cutoff (p <0.0001). Therefore, PCR appears to be a powerful and interesting tool for the identification of patients with invasive aspergillosis who might benefit from more intense care.
Assuntos
Aspergillus/isolamento & purificação , Aspergilose Pulmonar Invasiva/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Soro/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspergillus/genética , Feminino , Galactose/análogos & derivados , Humanos , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Neoplasias/complicações , Neutropenia/complicações , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVES: To determine the measures to prevent spontaneous preterm birth (excluding preterm premature rupture of membranes)and its consequences. MATERIALS AND METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: In France, premature birth concerns 60,000 neonates every year (7.4 %), half of them are delivered after spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of smoking is associated to a decrease of prematurity (level of evidence [LE] 1). This is therefore recommended (grade A). Routine screening and treatment of vaginal bacteriosis in general population is not recommended (grade A). Asymptomatic women with single pregnancy without history of preterm delivery and a short cervix between 16 and 24 weeks is the only population in which vaginal progesterone is recommended (grade B). A history-indicated cerclage is not recommended in case of only past history of conisation (grade C), uterine malformation (Professional consensus), isolated history of pretem delivery (grade B) or twin pregnancies in primary (grade B) or secondary (grade C) prevention of preterm birth. A history-indicated cerclage is recommended for single pregnancy with a history of at least 3 late miscarriages or preterm deliveries (grade A).). In case of past history of a single pregnancy delivery before 34 weeks gestation (WG), ultrasound cervical length screening is recommended between 16 and 22 WG in order to propose a cerclage in case of length<25mm before 24 WG (grade C). Cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with a twin pregnancy (grade A) and in populations of asymptomatic women with a short cervix (Professional consensus). Although the implementation of a universal transvaginal cervical length screening at 18-24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In case of preterm labor, (i) it is not possible to recommend one of the methods over another (ultrasound of the cervical length, vaginal examination, fetal fibronectin) to predict preterm birth (grade B); (ii) routine antibiotic therapy is not recommended (grade A); (iii) prolonged hospitalization (grade B) and bed rest (grade C) is not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (grade B), contrary to betamimetics (grade C), can be used for tocolysis in spontaneous preterm labour without preterm premature rupture of membranes. Maintenance tocolysis is not recomended (grade B). Antenatal corticosteroid administration is recommended to every woman at risk of preterm delivery before 34 weeks of gestation (grade A). After 34 weeks, evidences are not consistent enough to recommend systematic antenatal corticosteroid treatment (grade B), however, a course might be indicated in the clinical situations associated with the higher risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (grade C). Repeated courses of antenatal corticosteroids are not recommended (grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended to women at high risk of imminent preterm birth before 32WG (grade A). Cesarean is not recommended in case of vertex presentation (Professional consensus). Both planned vaginal or elective cesarean delivery is possible in case of breech presentation (Professional consensus). A delayed cord clamping may be considered if the neonatal or maternal state so permits (Professional consensus). CONCLUSION: Except for antenatal corticosteroid and magnesium sulfate administration, diagnostic tools or prenatal pharmacological treatments implemented since 30 years to prevent preterm birth and its consequences have not matched expectations of caregivers and families.
Assuntos
Guias de Prática Clínica como Assunto , Nascimento Prematuro/prevenção & controle , Feminino , Humanos , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologiaRESUMO
Studies of apoptosis in C. elegans have allowed the identification of three genes, ced-3, ced-4 and ced-9. Their products constitute the components of an induction pathway of apoptosis conserved in the nematode and mammals. In Drosophila, homologues have been found for CED-3, CED-4 and CED-9. CED-9 belongs to the Bcl-2 family which includes negative (Bcl-2) and positive (Bax) regulators of apoptosis. The recently discovered Bcl-2 family member named Drob-1 acts as a positive regulator of cell death. To address whether a Bcl-2 anti-apoptotic pathway exists in the fly, we studied the effects of expressing the mammalian genes bcl-2 in Drosophila. In embryos, expression of bcl-2 inhibits developmental and X-ray-induced apoptosis. Expressing bcl-2 or the pro-apoptotic mammalian bax in the developing eye and wing alters these structures, bcl-2 increasing the number of cells, while bax reduces the number of cells. In addition, the functional interaction between Bcl-2 and Bax is conserved. These results indicate that factors necessary for the activity of bcl-2 and bax are present in Drosophila. Therefore, a Bcl-2 pathway for inhibition of cell death may exist in the fly.