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Articles by P. F Fedullo
Total Records ( 8 ) for P. F Fedullo
  W Yao , A. L Firth , R. S Sacks , A Ogawa , W. R Auger , P. F Fedullo , M. M Madani , G. Y Lin , N Sakakibara , P. A Thistlethwaite , S. W Jamieson , L. J Rubin and J. X. J. Yuan

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle -actin (SM-A)-positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34+Flk-1+) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34+Flk-1+CD133+ cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45+) and collagen-secreting cells (procollagen-1+) were detected in the proximal vascular wall. Some of the CD34+ cells in CTEPH cells isolated from proximal regions were also positive for SM-A. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.

  K. W Jensen , K. M Kerr , P. F Fedullo , N. H Kim , V. J Test , O Ben Yehuda and W. R. Auger

Background— The currently recommended treatment for chronic thromboembolic pulmonary hypertension is pulmonary thromboendarterectomy (PTE). No convincing evidence for the use of pulmonary hypertensive medical therapy (PHT) exists in operable candidates. We sought to determine the prevalence of the use of PHT on referral for PTE and the effects on pre-PTE hemodynamics and post-PTE outcomes/hemodynamics.

Methods and Results— We performed a retrospective analysis of chronic thromboembolic pulmonary hypertension patients referred for PTE during 2005–2007. The prevalence of PHT was determined for all patients referred to our institution. Hemodynamic and outcomes analysis involved only those undergoing PTE. Data included baseline demographics, PHT medication(s), dosage, duration of therapy, and time to referral. Hemodynamic data were acquired from the time of diagnosis, the time of referral visit, and after PTE. Outcomes included intensive care unit, hospital, and ventilator days; bleeding and infection rates; incidence of reperfusion lung injury; and in-hospital mortality. The control group (n=244) was compared with the PHT group (n=111); subgroups included monotherapy with bosentan, sildenafil, or epoprostenol and combination therapy. The prevalence of PHT significantly increased from 19.9% in 2005 to 37% in 2007. There was minimal benefit of treatment with PHT on pre-PTE mean pulmonary artery pressure, but its use was associated with a significant delay in time to referral for PTE. Both groups experienced significant improvements in hemodynamic parameters after PTE. The 2 groups did not differ significantly in any post-PTE outcome. Similar results were obtained for each subgroup.

Conclusions— Our results suggest that PHT use has minimal effect on pre-PTE hemodynamics and no effect on post-PTE outcomes/hemodynamics.

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