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1.
Chronic Obstr Pulm Dis ; 3(3): 636-642, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27547817

RESUMO

BACKGROUND: Commercially available pedometers have been used as tools to measure endpoints in studies evaluating physical activity promotion programs. However, their accuracy in patients recovering from COPD exacerbations is unknown. The objectives of this study were to 1) assess the relative accuracy of different commercially available pedometers in healthy volunteers and 2) evaluate the accuracy of the top-performing commercially available pedometer in patients recovering from COPD exacerbations following hospital discharge. METHODS: Twelve healthy volunteers wore 2 pedometers, 2 smartphones with pedometer apps and an accelerometer for 15 minutes of indoor activity. The top-performing device in healthy volunteers was evaluated in 4 patients recovering from COPD exacerbations following hospital discharge during 6 minutes of walking performed at home. Bland-Altman plots were employed to evaluate accuracy of each device compared with direct observation (the reference standard). RESULTS: In healthy volunteers, the mean percent error compared to direct observation of the various devices ranged from -49% to +1%. The mean percent error [95% confidence interval (CI)] of the top-performing device in healthy volunteers, the Fitbit Zip®, was +1% [-33 to +35%], significantly lower than that of the accelerometer (-13% [-56 to +29%], p=0.01). The mean percent error [95% CI] for the Fitbit Zip® in patients recovering from COPD exacerbations was -3% [-7 to +12%]. CONCLUSIONS: The accuracy of commercially available pedometers in healthy volunteers is highly variable. The top-performing pedometer in our study, the Fitbit Zip,® accurately measures step counts in both healthy volunteers and patients recovering from COPD exacerbations.

2.
J Allergy Clin Immunol ; 131(6): 1496-503, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23534973

RESUMO

BACKGROUND: We previously reported an interaction between maternal asthma and the child's HLA-G genotype on the child's subsequent risk for asthma. The implicated single nucleotide polymorphism at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect might be mediated by these miRs. OBJECTIVE: The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies. METHODS: We measured soluble HLA-G (sHLA-G) concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR-152 family (miR-148a, miR-148b, and miR-152) transcript levels in airway epithelial cells from the same subjects. RESULTS: miR-148b levels were significantly increased in airway epithelial cells from asthmatic subjects with an asthmatic mother compared with those seen in asthmatic subjects without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother but not among those with a nonasthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA). CONCLUSION: These combined results are consistent with +3142 allele-specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject's mother and the subject's genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of the mother's children persist into adulthood.


Assuntos
Asma/genética , Asma/imunologia , Antígenos HLA-G/imunologia , MicroRNAs/genética , Adulto , Negro ou Afro-Americano , Asma/metabolismo , Feminino , Genótipo , Antígenos HLA-G/sangue , Antígenos HLA-G/genética , Humanos , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Exposição Materna , Pessoa de Meia-Idade , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , População Branca , Adulto Jovem
3.
Am J Respir Crit Care Med ; 183(3): 379-87, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20833822

RESUMO

RATIONALE: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. OBJECTIVES: To determine the potential benefit versus risk of sirolimus in lung transplantation. METHODS: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infection was decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P < 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study. CONCLUSIONS: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Pulmão , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Azatioprina/efeitos adversos , Bronquiolite Obliterante/etiologia , Quimioterapia Combinada , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Sirolimo/efeitos adversos , Fatores de Tempo
4.
J Heart Lung Transplant ; 30(2): 175-81, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20947384

RESUMO

BACKGROUND: Sirolimus (rapamycin) is a potent anti-proliferative agent with immunosuppressive properties that is increasingly being used in solid-organ and hematopoietic stem cell transplantation. In addition, this drug is being investigated for treatment of a broad range of disorders, including cardiovascular disease, malignancies, tuberous sclerosis, and lymphangeioleiomyomatosis. In this study, we found an increased risk of venous thromboembolism (VTE) in lung transplant recipients treated with a sirolimus (SIR)-based immunosuppressive regimen. METHODS: One hundred eighty-one lung transplant recipients were enrolled in a prospective, multicenter, randomized, open-label trial comparing a tacrolimus (TAC)/SIR/prednisone immunosuppression regimen with a TAC/azathioprine (AZA)/prednisone immunosuppressive regimen. The differences in rates of VTE were examined. RESULTS: There was a significantly higher occurrence of VTE in the SIR cohort [15 of 87 (17.2%)] compared with the AZA cohort [3 of 94 (3.2%)] (stratified log-rank statistic = 7.44, p < 0.01). When adjusted for pre-transplant diagnosis and stratified by transplant center, this difference remained essentially unchanged (hazard ratio for SIR vs AZA = 5.2, 95% confidence interval 1.4 to 19.5, p = 0.01). CONCLUSION: Clinicians prescribing SIR should maintain a high level of vigilance for VTE, particularly among patients with other risk factors for this complication.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/efeitos adversos , Transplante de Pulmão/imunologia , Sirolimo/efeitos adversos , Tromboembolia Venosa/epidemiologia , Azatioprina/uso terapêutico , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico
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