ABSTRACT
OBJECTIVES/HYPOTHESIS: To evaluate the efficacy and safety of bevacizumab administered at a concentration of 50 mg as an intranasal spray in the treatment of epistaxis in patients suffering from Rendu-Osler disease. STUDY DESIGN: Prospective. METHODS: A preliminary, prospective, review board-approved study was conducted on six patients with Rendu-Osler disease who received 10 treatment courses of 50 mg bevacizumab. Monthly follow-up was based on the epistaxis severity score (ESS), with adverse effects being reported. RESULTS: Ten treatment courses were administered to six patients, with a mean follow-up period of 2.8 months. A statistically significant decrease in mean ESS was observed at 1 month (P < .001) and 2 months (P < .005), whereas a nonsignificant decrease was found at 3 months (P = .07). A nonsignificant decline in mean ESS was detected at 1 month in patients with ESS ≥7 at baseline. No adverse effects were reported. CONCLUSIONS: The intranasal spray application of 50 mg bevacizumab was found to be an effective symptomatic treatment over a period of 2 months for patients with a pretreatment ESS of <7, with no adverse effects being noted.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Epistaxis/drug therapy , Telangiectasia, Hereditary Hemorrhagic/complications , Administration, Intranasal , Aerosols , Angiogenesis Inhibitors/administration & dosage , Bevacizumab , Dose-Response Relationship, Drug , Epistaxis/etiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nasal Sprays , Prospective Studies , Quality of Life , Treatment Outcome , Vascular Endothelial Growth Factor AABSTRACT
UNLABELLED: In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants. METHODOLOGY/PRINCIPAL FINDINGS: A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.8±2.2 µm vs. 36.7±11.4 µm, p≤0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA. CONCLUSIONS: In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure.
