AIM： To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor（VEGF） treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor...AIM： To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor（VEGF） treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor（VEGFR） expressions were evaluated following repeated bevacizumab treatments in hypoxic human umbilical vein endothelial cells（HUVECs） in vitro.METHODS： HUVECs were incubated under hypoxic conditions in two media of different bevacizumab concentrations（1.0 or 2.5 mg/m L） for 17 h, and then in a new medium without bevacizumab for 7h. This procedure was repeated twice more. A culture with an identical volume of excipients served as the control. Cytotoxicity and cell proliferation were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and Ki-67 assays, respectively. Levels of VEGF and VEGFR were assessed using enzyme-linked immunosorbent assay and Western blot respectively.RESULTS： Cytotoxic effects were not reported for either bevacizumab concentration. Cell proliferation was not reduced after anti-VEGF treatments. VEGF level after single treatment was significantly higher than that of the control and after repeated treatments. Phosphorylated VEGFR-2 expression increased significantly after singleand repeated bevacizumab treatments compared with the control. The 1.0 mg/m L bevacizumab induced significantly higher expressions of VEGFR-2 than the 2.5 mg/m L in single and repeated treatment groups.CONCLUSION： Bevacizumab treatment of HUVECs elevated VEGFR expression in both single and repeated treatments, indicating a mechanism for the reduced efficacy of anti-VEGF therapy in ocular neovascular disorders.展开更多
AIM: To determine the rate and yield of repeat esophagogastroduodenoscopy (EGD) for dyspepsia in clinical practice,whether second opinions drive its use,and whether it is performed at the expense of colorectal cancer ...AIM: To determine the rate and yield of repeat esophagogastroduodenoscopy (EGD) for dyspepsia in clinical practice,whether second opinions drive its use,and whether it is performed at the expense of colorectal cancer screening.METHODS: We performed a retrospective cohort study of all patients who underwent repeat EGD for dyspepsia from 1996 to 2006 at the University of California,San Francisco endoscopy service.RESULTS: Of 24 780 EGDs,5460 (22%) were performed for dyspepsia in 4873 patients.Of these,451 patients (9.3%) underwent repeat EGD for dyspepsia at a median 1.7 (interquartile range,0.8-3.1) years after initial EGD.Signif icant f indings possibly related to dyspepsia were more likely at initial (29%) vs repeat EGD (18%) [odds ratio (OR),1.45;95% confidence interval (CI): 1.20-1.75,P < 0.0001],and at repeat EGD if the initial EGD had reported such f indings (26%) than if it had not (14%) (OR,1.32;95% CI: 1.08-1.62,P = 0.0015).The same endoscopist performed the repeat and initial EGD in 77% of cases.Of patients aged 50 years or older,286/311 (92%) underwent lower endoscopy.CONCLUSION: Repeat EGD for dyspepsia occurred at a low but substantial rate,with lower yield than initial EGD.Optimizing endoscopy use remains a public health priority.展开更多
文摘AIM： To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor（VEGF） treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor（VEGFR） expressions were evaluated following repeated bevacizumab treatments in hypoxic human umbilical vein endothelial cells（HUVECs） in vitro.METHODS： HUVECs were incubated under hypoxic conditions in two media of different bevacizumab concentrations（1.0 or 2.5 mg/m L） for 17 h, and then in a new medium without bevacizumab for 7h. This procedure was repeated twice more. A culture with an identical volume of excipients served as the control. Cytotoxicity and cell proliferation were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and Ki-67 assays, respectively. Levels of VEGF and VEGFR were assessed using enzyme-linked immunosorbent assay and Western blot respectively.RESULTS： Cytotoxic effects were not reported for either bevacizumab concentration. Cell proliferation was not reduced after anti-VEGF treatments. VEGF level after single treatment was significantly higher than that of the control and after repeated treatments. Phosphorylated VEGFR-2 expression increased significantly after singleand repeated bevacizumab treatments compared with the control. The 1.0 mg/m L bevacizumab induced significantly higher expressions of VEGFR-2 than the 2.5 mg/m L in single and repeated treatment groups.CONCLUSION： Bevacizumab treatment of HUVECs elevated VEGFR expression in both single and repeated treatments, indicating a mechanism for the reduced efficacy of anti-VEGF therapy in ocular neovascular disorders.
文摘AIM: To determine the rate and yield of repeat esophagogastroduodenoscopy (EGD) for dyspepsia in clinical practice,whether second opinions drive its use,and whether it is performed at the expense of colorectal cancer screening.METHODS: We performed a retrospective cohort study of all patients who underwent repeat EGD for dyspepsia from 1996 to 2006 at the University of California,San Francisco endoscopy service.RESULTS: Of 24 780 EGDs,5460 (22%) were performed for dyspepsia in 4873 patients.Of these,451 patients (9.3%) underwent repeat EGD for dyspepsia at a median 1.7 (interquartile range,0.8-3.1) years after initial EGD.Signif icant f indings possibly related to dyspepsia were more likely at initial (29%) vs repeat EGD (18%) [odds ratio (OR),1.45;95% confidence interval (CI): 1.20-1.75,P < 0.0001],and at repeat EGD if the initial EGD had reported such f indings (26%) than if it had not (14%) (OR,1.32;95% CI: 1.08-1.62,P = 0.0015).The same endoscopist performed the repeat and initial EGD in 77% of cases.Of patients aged 50 years or older,286/311 (92%) underwent lower endoscopy.CONCLUSION: Repeat EGD for dyspepsia occurred at a low but substantial rate,with lower yield than initial EGD.Optimizing endoscopy use remains a public health priority.
