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1.
Science ; 366(6469): 1143-1149, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31780560

RESUMO

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.


Assuntos
Enterococcus/crescimento & desenvolvimento , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/microbiologia , Transplante de Células-Tronco Hematopoéticas , Lactose/metabolismo , Idoso , Animais , Disbiose , Enterococcus/genética , Enterococcus/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Intestinos/microbiologia , Masculino , Camundongos , Microbiota , Pessoa de Meia-Idade , RNA Ribossômico 16S , Análise de Sequência de RNA , Transplante Homólogo
2.
Front Neural Circuits ; 11: 89, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29225569

RESUMO

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency "burstlet" activity that probably is analogous to the previously described in vitro "fast rhythm", which is thought to represent lamprey locomotor activity. However, "burstlet" activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; "burstlet" activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, "burstlet" activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations.


Assuntos
Geradores de Padrão Central/fisiologia , Lateralidade Funcional/fisiologia , Locomoção/fisiologia , Medula Espinal/fisiologia , Animais , Encéfalo/fisiologia , Simulação por Computador , Eletromiografia , Lampreias , Modelos Neurológicos , Músculos/fisiologia , Vias Neurais/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia
3.
J Perinatol ; 37(2): 157-161, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27853322

RESUMO

OBJECTIVE: The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. STUDY DESIGN: We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS. RESULTS: EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)). CONCLUSION: Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.


Assuntos
População Negra , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Idade Materna , Complicações Infecciosas na Gravidez/prevenção & controle , Infecções Estreptocócicas/epidemiologia , Adolescente , Adulto , Antibioticoprofilaxia , Bases de Dados Factuais , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , North Carolina/epidemiologia , Razão de Chances , Gravidez , Diagnóstico Pré-Natal , Estudos Retrospectivos , Fatores de Risco , Streptococcus agalactiae/isolamento & purificação , Adulto Jovem
4.
J Perinatol ; 37(7): 853-856, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28383537

RESUMO

OBJECTIVE: To characterize in-hospital outcomes of premature infants diagnosed with severe bronchopulmonary dysplasia (BPD). STUDY DESIGN: Retrospective cohort study including premature infants with severe BPD discharged from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2015. RESULTS: There were 10 752 infants with severe BPD, and 549/10 752 (5%) died before discharge. Infants who died were more likely to be male, small for gestational age, have received more medical interventions and more frequently diagnosed with surgical necrotizing enterocolitis, culture-proven sepsis and pulmonary hypertension following 36 weeks of postmenstrual age compared with survivors. Approximately 70% of infants with severe BPD were discharged by 44 weeks of postmenstrual age, and 86% were discharged by 48 weeks of postmenstrual age. CONCLUSIONS: A majority of infants diagnosed with severe BPD were discharged home by 44 weeks of postmenstrual age. These results may inform discussions with families regarding the expected hospital course of infants diagnosed with severe BPD.


Assuntos
Displasia Broncopulmonar/fisiopatologia , Enterocolite Necrosante/epidemiologia , Hipertensão Pulmonar/epidemiologia , Sepse/epidemiologia , Displasia Broncopulmonar/complicações , Registros Eletrônicos de Saúde , Enterocolite Necrosante/cirurgia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Unidades de Terapia Intensiva Neonatal , Masculino , North Carolina , Alta do Paciente , Estudos Retrospectivos , Fatores de Risco , Sepse/diagnóstico , Fatores Sexuais
5.
Clin Microbiol Infect ; 23(8): 544-549, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28159672

RESUMO

OBJECTIVES: Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. METHODS: All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal ß-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. RESULTS: Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). CONCLUSIONS: In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal ß-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , beta-Lactamas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Reação em Cadeia da Polimerase Multiplex , Estudos Prospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Análise de Sobrevida , Resultado do Tratamento , Fatores de Virulência/genética
6.
Acta Psychiatr Scand ; 53(2): 119-38, 1976 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1251758

RESUMO

This paper considers data on hysterical neurosis, conversion type from the Monroe County (New York) Cumulative Psychiatric Case Register, from the Psychiatric Case Register in Iceland, and from a psychiatric consultation service in a university teaching general hospital in Monroe County (New York) during the period 1960 to 1969. The rate of hysterical neurosis, conversion type in Monroe County during this period was 22 per 100,000 per year, whereas in Iceland it was 11 per 100,000 per year. It was highest for women, non-whites and those of low social economic status. The rate of hysterical neurosis, conversion type and "probable" hysterical neurosis, conversion type combined among patients seen in psychiatric consultation was 4.5%. The most often noted diagnostic criteria were inconsistency with somatic process and precipitation of symptoms by psychological stress. Most patients had more than one conversion symptom at the same time. Pain was the most common symptom. The majority of patients had an accompanying organic or functional illness.


Assuntos
Histeria , Adolescente , Adulto , Idoso , População Negra , Transtorno Conversivo/diagnóstico , Transtorno Conversivo/epidemiologia , Feminino , Humanos , Histeria/diagnóstico , Histeria/epidemiologia , Islândia , Masculino , Pessoa de Meia-Idade , New York , Fatores Sexuais , População Branca
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