Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease.

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe3O4-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe3O4-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7 days compared to the non-treated leg that showed no evidence of the blood recovery.

Applicability of handmade expanded polytetrafluoroethylene trileaflet-valved conduits for pulmonary valve reconstruction: An ex vivo and in vivo study.

OBJECTIVE: The handmade expanded polytetrafluoroethylene (ePTFE) trileaflet-valved conduit could potentially be used as a substitute pulmonary valve replacement material, especially in children. The current study investigated (1) the function of the ePTFE trileaflet-valved conduits in an ex vivo experimental system and (2) the short-term performance of the conduit in a porcine model to verify its clinical applicability. METHODS: The competency of the ePTFE trileaflet-valved conduits was estimated through ex vivo (using a pulmonary mock circulation loop) and in vivo (in a porcine model with a damaged pulmonary valve) experiments. Explants were examined by gross morphology and histopathologic examination. RESULTS: In the ex vivo experiment, the ePTFE trileaflet-valved conduits were determined to effectively increase mean pulmonary pressure from 10.2 to 14.4 mm Hg compared with defective silicon-valved conduits. In addition, the regurgitation fraction value of ePTFE trileaflet-valved conduits was 15.9% to 18.1%, which was significantly better than the defective valve conduits (regurgitation fraction = 73.5%-85.7%). In the in vivo experiment, the valved conduits were confirmed to be with good valve position maintenance, and the valve and leaflets showed no signs of thickening or peeling after a short-term implantation period. There were also no significant signs of inflammation reaction on histopathologic examination. CONCLUSIONS: The ePTFE trileaflet-valved conduits for pulmonary valve reconstruction showed acceptable performance and outcomes in the ex vivo and in vivo experiments. The ePTFE trileaflet-valved conduit may be clinically useful, although additional studies in animals should be conducted to determine its long-term outcomes.

Therapeutic efficacy of milrinone in the management of enterovirus 71-induced pulmonary edema.

Hand, foot, and mouth disease and herpangina are the major clinical manifestations of enterovirus 71 (EV71) infections. Brain-stem encephalitis and pulmonary edema are severe complications that can lead to death. This study was designed to evaluate the potential therapeutic effect of milrinone, a phosphodiesterase (PDE) inhibitor, in the treatment of patients with EV71-induced pulmonary edema. We conducted a historically controlled trial of 24 children with severe EV71-induced pulmonary edema from April 1998-June 2003 in southern Taiwan. Patients were divided into groups treated before and after the introduction of milrinone therapy. Etiological diagnosis was established by viral cultures and confirmed by specific immunofluorescence and neutralization tests. All 24 patients were below 5 years of age. The mortality was lower in the milrinone-treated vs. nontreated group (36.4% vs. 92.3%, P=0.005). Sympathetic tachycardia was decreased in patients treated with milrinone compared to controls (144 +/- 17/min vs. 206 +/- 26/min, P=0.004). A marked decrease in IL-13 (77 +/- 9 pg/ml vs. 162 +/- 88 pg/ml, P=0.001) was observed in milrinone-treated patients compared to controls. There was a significant reduction in white blood cell (10,838 +/- 4,537/mm3 vs. 19,475 +/- 7,798/mm3, P=0.009) and platelet (257 +/- 45 x 10(3)/mm3 vs. 400 +/- 87 x 10(3)/mm3, P=0.001) counts in milrinone-treated patients compared to controls. These results were associated with improvement in sympathetic regulation and decrease in IL-13 production. Milrinone therapy may provide a useful therapeutic approach for this highly lethal disorder.