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1.
Dig Dis Sci ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166622

RESUMO

BACKGROUND: Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules. AIM: To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI. METHODS: We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design. RESULTS: Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4-96.8%; I2 15.6%), capsule 92.1% (CI 88.6-95.0%; I2 7.1%), enema 87.2% (CI 83.4-90.5%; I2 0%), and NGT/NDT 78.1% (CI 71.6-84.1%; I2 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%. CONCLUSION: CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.

2.
Dig Dis Sci ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052215

RESUMO

BACKGROUND: In the USA, fibrolamellar hepatocellular carcinoma (FLC) accounts for 1-2% of all cases of hepatocellular carcinoma. FLC remains poorly understood. AIM: We aim to investigate the incidence, demographics, tumor characteristics, treatment, and prognosis of patients with FLC. METHODS: Data on FLC between 2000 and 2016 were extracted from the SEER database and analyzed. RESULTS: A total of 300 patients with FLC were identified where 126 were male. Median age at diagnosis was 27 ± 22 years. The overall age-adjusted incidence of FLC between 2000 and 2016 was 0.02 per 100,000 per year. A bimodal distribution was observed where the highest incidences occurred between 15-19 years and 70-74 years. Most tumors on presentation were moderately differentiated (20.7%), while the most common stage at presentation was stage 1 (21.7%) followed by stages 3 and 4 (20.0% and 20.3%, respectively); 50.3% of these tumors were surgically resected, while 8.0% received radiation and 45.3% received chemotherapy. One- and 5-year cause-specific survival for FLC was 72.0% and 32.9%, respectively, with a median survival of 32.9 months. HCC had a median survival time of 11.7 months. Patients who were not treated with surgical intervention had about 3 times increased risk for death (HR 2.8, 95% CI 1.68-4.72, P = 0.000). Radiation and chemotherapy did not significantly affect outcomes. CONCLUSION: FLC presents with a bimodal distribution in both early and elderly individuals. Compared to HCC, FLC has a higher recurrence rate but better survival outcome. Surgical intervention is superior to chemotherapy and radiation.

3.
J Clin Gastroenterol ; 53(9): 627-634, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31403982

RESUMO

Esophageal cancer represents one of the most lethal forms of malignancy. The growing incidence of esophageal adenocarcinoma represents an emerging public health concern. This review article summarizes current diagnostic, management, and therapeutic practices of premalignant conditions of the esophagus including Barrett's esophagus, tylosis, granular cell tumors, achalasia, and the ingestion of caustic substances. Our report provides clinicians and academics with a global clinical perspective regarding presentation, surveillance guidelines, and therapeutic management of these esophageal conditions.

4.
Am J Gastroenterol ; 114(9): 1496-1501, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31335362

RESUMO

OBJECTIVES: Combined hepatocellular cholangiocarcinoma (CHC) is a rare form of primary liver cancer with features of hepatocellular carcinoma and cholangiocarcinoma. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with CHC. METHODS: Data on CHC between 2004 and 2014 were extracted from the Surveillance, Epidemiology, and End Results Registry and analyzed. RESULTS: Five hundred twenty-nine patients with CHC were identified; 367 were male. Median age at diagnosis was 62.5 ± 12 years. The overall incidence of CHC between 2004 and 2014 was 0.05 per 100,000 per year. Incidence increased with age, with the highest incidence in men occurring between 60 and 64 years and 75-79 years for women. Women had a higher incidence of CHC compared to men (0.08 vs 0.03 per 100,000 per year). Most tumors were poorly differentiated (30.8%) while the most common stage at presentation was stage 4 (26.8%). 39.5% of these tumors were resected while 6.8% received radiation and 34% received chemotherapy. One- and 5-year cause-specific survival for CHC was 41.9% and 17.7%, respectively, with a median survival of 8 months. Worse outcomes were noted among patients with tumor stage 3 (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.44-2.87, P = 0.000), stage 4 (HR 1.71, 95% CI 1.06-2.75, P = 0.027), those not treated with surgery (HR 4.94, 95% CI 3.64-6.68, P = 0.000), those who did not receive radiation (HR 1.71, 95% CI 1.08-2.70, P = 0.021), those who did not receive chemotherapy (HR 1.54, 95% CI 1.20-1.99, P = 0.001), and those with increasing tumor size on chemotherapy (HR 1.00, 95% CI 1.00-1.00, P = 0.013). DISCUSSION: CHC is the combined presentation of 2 malignancies. Incidence appears to be increasing and is associated with age and male gender. While surgery, radiation, and chemotherapy are associated with improved outcomes, patients who did not undergo surgery are at highest risk for death.

6.
Behav Brain Res ; 342: 43-50, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29339005

RESUMO

A host of scholarly work has characterized the positive effects of exercise and environmental enrichment on behaviour and cognition in animal studies. The purpose of this study was to investigate the uptake and longitudinal impact of exercise and enrichment on the behavioural phenotype of male and female CD-1 mice. CD-1 mice housed in standard (STD) or exercise and enrichment (EE) conditions post-weaning were tested in the 3-chamber sociability test, open field, and elevated plus maze and exercise activity was monitored throughout the enrichment protocol. Male and female EE mice both showed reduced anxiety and activity in the open field and elevated plus maze relative to sex-matched STD mice. EE altered social behaviours in a sex-specific fashion, with only female EE mice showing increased social preference relative to female STD mice and a preference for social novelty only present in male EE mice. This sexual dimorphism was not observed to be a product of exercise uptake, as CD-1 mice of both sexes demonstrated a consistent trend of wheel rotation frequencies. These findings suggest the importance of considering variables such as sex and strain on experimental design variables in future work on environmental enrichment.


Assuntos
Ansiedade/prevenção & controle , Comportamento Animal/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Meio Ambiente , Comportamento Exploratório/fisiologia , Feminino , Abrigo para Animais , Masculino , Camundongos , Fatores Sexuais , Comportamento Social
7.
Autism Res ; 10(8): 1436-1447, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28383156

RESUMO

Individuals with Autism Spectrum Disorder (ASD) have a range of health, community, and social support needs across the lifespan that create age-specific challenges in navigating service sectors. In this study, we set out to identify the priority needs of individuals with ASD across the lifespan, and the factors that predict receiving priority services. Participants included 3,317 individuals with ASD from a Canada-wide online caregiver survey, stratified into five age groups (preschool, elementary school age, adolescence, emerging adulthood, adulthood). Priority receipt was calculated as a ratio of current services that corresponded to individualized priority need. Age-stratified Poisson regression analyses were used to identify the sociodemographic, clinical and systemic predictors of priority receipt. Results indicate that the distribution of priority need varied by age, except for social skills programming, which was a high across all groups. The number of high and moderate priority needs diversified with age. Overall, 30% of individuals had none of their priority needs met and priority receipt decreased with age. Systemic factors were most consistently related to priority receipt across the lifespan. Understanding patterns and correlates of priority needs and use that currently exist in different age groups can inform policies to improve service access. Autism Res 2017, 10: 1436-1447. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


Assuntos
Transtorno do Espectro Autista/terapia , Pesquisas sobre Serviços de Saúde/estatística & dados numéricos , Acesso aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Canadá , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto Jovem
8.
J Comp Neurol ; 524(4): 807-28, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26235839

RESUMO

Neuroligins and neurexins are transsynaptic proteins involved in the maturation of glutamatergic and GABAergic synapses. Research has identified synaptic proteins and function as primary contributors to the development of fragile X syndrome. Fragile X mental retardation protein (FMRP), the protein that is lacking in fragile X syndrome, binds neuroligin-1 and -3 mRNA. Using in situ hybridization, we examined temporal and spatial expression patterns of neuroligin (NLGN) and neurexin (NRXN) mRNAs in the somatosensory (S1) cortex and hippocampus in wild-type (WT) and fragile X knockout (FMR1-KO) mice during the first 5 weeks of postnatal life. Genotype-based differences in expression included increased NLGN1 mRNA in CA1 and S1 cortex, decreased NLGN2 mRNA in CA1 and dentate gyrus (DG) regions of the hippocampus, and increased NRXN3 mRNA in CA1, DG, and S1 cortex between female WT and FMR1-KO mice. In male mice, decreased expression of NRXN3 mRNA was observed in CA1 and DG regions of FMR1-KO mice. Sex differences in hippocampal expression of NLGN2, NRXN1, NRXN2, and NRXN3 mRNAs and in S1 cortex expression of NRXN3 mRNAs were observed WT mice, whereas sex differences in NLGN3, NRXN1, NRXN2, and NRXN3 mRNA expression in the hippocampus and in NLGN1, NRXN2 and NRXN3 mRNA expression in S1 cortex were detected in FMR1-KO mice. These results provide a neuroanatomical map of NLGN and NRXN expression patterns over postnatal development in WT and FMR1-KO mice. The differences in developmental trajectory of these synaptic proteins could contribute to long-term differences in CNS wiring and synaptic function.


Assuntos
Molécula de Adesão de Leucócito Ativado/metabolismo , Região CA1 Hipocampal/crescimento & desenvolvimento , Giro Denteado/crescimento & desenvolvimento , Síndrome do Cromossomo X Frágil/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Córtex Somatossensorial/crescimento & desenvolvimento , Animais , Autorradiografia , Região CA1 Hipocampal/metabolismo , Giro Denteado/metabolismo , Feminino , Hibridização In Situ , Masculino , Camundongos Knockout , RNA Mensageiro/metabolismo , Caracteres Sexuais , Córtex Somatossensorial/metabolismo
9.
Behav Brain Res ; 259: 119-30, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24211451

RESUMO

The fmr1 knock out (KO) mouse has been a useful animal model to understand pathology and treatment of FXS, both anatomically and behaviorally. Ultrasonic vocalizations (USVs) are a behavioral tool to assess early life communication deficits in mice. Here, we report on the temporal and spectral features of USVs emitted after maternal separation in wild type (FVB/N) and fmr1 KO pups at postnatal days (P) P4, P7 and P10. The results show changes in the number and duration of calls in fmr1 KO pups and wild type pups were dependent on age and call type. Fmr1 KO pups showed an increased number of USVs at P7 but not at P4 or P10. This increase was specific to Frequency Jump calls. In addition, fmr1 KO mice showed a developmental shift in the temporal distribution of calls, with P10 mice calling in distinct bout patterns. Overall, these findings provide evidence that changes in USV outcomes were specific to certain call types and ages in fmr1 KO mice. Because early postnatal life is a window during which multiple neural systems activate and become established, behavioral measures such as using USVs as a measure of communication, may be useful as a predictor of brain changes and later developmental behavioral changes. Work is needed to better understand the functional outcomes of altered development of USVs and how these changes contribute to later emergence of autistic-like behaviors in animal models of autism.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Deficiências do Desenvolvimento/genética , Proteína do X Frágil de Retardo Mental/genética , Vocalização Animal/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Proteína do X Frágil de Retardo Mental/metabolismo , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Privação Materna , Camundongos , Camundongos Knockout
10.
Neurotoxicol Teratol ; 36: 47-56, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23395807

RESUMO

Valproic acid (VPA) is both an anti-convulsant and a mood stabilizer. Clinical studies over the past 40 years have shown that exposure to VPA in utero is associated with birth defects, cognitive deficits, and increased risk of autism. Two recent FDA warnings related to use of VPA in pregnancy emphasize the need to reevaluate its use clinically during child-bearing years. The emerging clinical evidence showing a link between VPA exposure and both cognitive function and risk of autism brings to the forefront the importance of understanding how VPA exposure influences neurodevelopment. In the past 10 years, animal studies have investigated anatomical, behavioral, molecular, and physiological outcomes related to in utero VPA exposure. Behavioral studies show that VPA exposure in both rats and mice leads to autistic-like behaviors in the offspring, including social behavior deficits, increased repetitive behaviors, and deficits in communication. Based on this work VPA maternal challenge in rodents has been proposed as an animal model to study autism. This model has both face and construct validity; however, like all animal models there are limitations to its translation to the clinical setting. Here we provide a review of clinical studies that examined pregnancy outcomes of VPA use as well as the related animal studies.


Assuntos
Transtorno Autístico/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ácido Valproico/uso terapêutico , Animais , Transtorno Autístico/fisiopatologia , Transtorno Autístico/psicologia , Comportamento Animal/efeitos dos fármacos , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ácido Valproico/administração & dosagem , Ácido Valproico/efeitos adversos
11.
PLoS One ; 6(5): e19768, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21611190

RESUMO

Pluripotent stem cell lines have been generated in several domestic animal species; however, these lines traditionally show poor self-renewal and differentiation. Using canine embryonic stem cell (cESC) lines previously shown to have sufficient self-renewal capacity and potency, we generated and compared canine neural stem cell (cNSC) lines derived by lineage selection with epidermal growth factor (EGF) or Noggin along the neural default differentiation pathway, or by directed differentiation with retinoic acid (RA)-induced floating sphere assay. Lineage selection produced large populations of SOX2+ neural stem/progenitor cell populations and neuronal derivatives while directed differentiation produced few and improper neuronal derivatives. Primary canine neural lines were generated from fetal tissue and used as a positive control for differentiation and electrophysiology. Differentiation of EGF- and Noggin-directed cNSC lines in N2B27 with low-dose growth factors (BDNF/NT-3 or PDGFαα) produced phenotypes equivalent to primary canine neural cells including 3CB2+ radial progenitors, MOSP+ glia restricted precursors, VIM+/GFAP+ astrocytes, and TUBB3+/MAP2+/NFH+/SYN+ neurons. Conversely, induction with RA and neuronal differentiation produced inadequate putative neurons for further study, even though appropriate neuronal gene expression profiles were observed by RT-PCR (including Nestin, TUBB3, PSD95, STX1A, SYNPR, MAP2). Co-culture of cESC-derived neurons with primary canine fetal cells on canine astrocytes was used to test functional maturity of putative neurons. Canine ESC-derived neurons received functional GABA(A)- and AMPA-receptor mediated synaptic input, but only when co-cultured with primary neurons. This study presents established neural stem/progenitor cell populations and functional neural derivatives in the dog, providing the proof-of-concept required to translate stem cell transplantation strategies into a clinically relevant animal model.


Assuntos
Proteínas de Transporte/farmacologia , Linhagem da Célula/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Fator de Crescimento Epidérmico/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Sinapses/metabolismo , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Forma Celular/efeitos dos fármacos , Técnicas de Cocultura , Cães , Humanos , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Sinapses/efeitos dos fármacos , Tretinoína/farmacologia
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