Anastomotic tissue response associated with expanded polytetrafluoroethylene access grafts constructed by using nonpenetrating clips. (17/3384)

PURPOSE: The gross, light microscopic, and scanning microscopic appearance of arterial and venous anastomoses in expanded polytetrafluoroethylene (ePTFE) access grafts constructed with nonpenetrating clips were compared with that of those constructed with polypropylene suture. We hypothesized that clip-constructed anastomoses would provide controlled approximation of native vessel intimal and medial components with the ePTFE grafts. We further hypothesized that anastomotic healing with clips would involve primarily an intimal cellular response, as compared with suture-constructed anastomoses in which cells within the media and adventitia walls participate. METHODS: Femoral artery to femoral vein arteriovenous (AV) grafts were constructed in five dogs using 4-mm internal diameter ePTFE graft material. Each animal received one AV graft with anastomoses constructed by using polypropylene sutures in one leg and one AV graft with anastomoses constructed with Vascular Closure System clips in the contralateral leg. Animals were given aspirin for the duration of the study, and grafts were explanted at 5 weeks. At the time of explantation, graft segments were grossly evaluated and then underwent light and scanning electron microscopic analysis. RESULTS: At the time of explantation, all access grafts were patent. Joining the ePTFE grafts to the native vessels with clips resulted in minimal vessel wall damage. The lumenal contours of the discontinuous approximation were smooth and without gross endothelial disruption. These observations are in contrast to the lumenal compromise and endothelial disturbance associated with the sutured anastomoses. Furthermore, hemostasis was achieved immediately in the clipped grafts, decreasing the incidence of perianastomic hematoma. Finally, cellular reconstitution occurred at the anastomotic cleft in both the sutured and the clipped junctions. The neointima exhibited an endothelial cell lining on the lumenal surface and the presence of alpha-smooth muscle cell actin positive cells within the subendothelial layer. CONCLUSION: Vascular Closure System clips are a viable alternative to suture for the approximation of ePTFE AV access grafts to native blood vessels. The use of the clips resulted in a more streamlined anastomosis, with decreased vessel wall damage, immediate hemostasis, and a trend toward shorter procedure times.  (+info)

Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs. (18/3384)

PURPOSE: Short-term pattern electrical stimulation of the retina via multielectrode arrays in humans blind from photoreceptor loss has shown that ambulatory vision and limited character recognition is possible. To develop an implantable retinal prosthesis that would provide useful vision, these results need to be sustained over a prolonged period of retinal electrical stimulation. As a first step toward this goal, the biocompatibility and the feasibility of surgically implanting an electrically inactive electrode array onto the retinal surface was tested. METHODS: A 5 x 5 electrode array (25 platinum disc-shaped electrodes in a silicone matrix) was implanted onto the retinal surface using retinal tacks in each of the 4 mixed-breed sighted dogs. Color fundus photography, fluorescein angiography, electroretinography, and visual evoked potentials were obtained preoperatively, at 1-week intervals for 2 weeks postoperatively, then at 2-week intervals up to 2 months postoperatively, and thereafter at 1-month intervals. One dog was killed at 2 months after implantation and a second dog after 3 months of implantation. Histologic evaluation of the retinas was performed. The remaining two dogs continue to be followed beyond 6 months after the implantation surgery. RESULTS: No retinal detachment, infection, or uncontrolled intraocular bleeding occurred in any of the animals. Retinal tacks and the retinal array remained firmly affixed to the retina throughout the follow-up period. Hyperpigmentation of the retinal pigment epithelium was observed only around the site of retinal tack insertion. No fibrous encapsulation of the implant or intraocular inflammation was visible. A- and b-wave amplitudes of the electroretinogram were depressed at the first postoperative week testing but recovered over the ensuing 1 week and were not statistically different from the normal unoperated fellow eye throughout the postoperative period. N1 and P1 wave amplitudes of the visual evoked potentials were not significantly different from the normal fellow eyes at any of the postoperative test intervals. Fluorescein angiography showed that the entire retina including the area under the electrode array remained well perfused. Similarly, histologic evaluation revealed near total preservation of the retina underlying the electrode array. CONCLUSIONS: Implantation of an electrode array on the epiretinal side (i.e., side closest to the ganglion cell layer) is surgically feasible, with insignificant damage to the underlying retina. The platinum and silicone arrays as well as the metal tacks are biocompatible. With the success of implanting an electrically inactive device onto the retinal surface for prolonged periods, the effects of long-term retinal electrical stimulation are now ready to be tested as the next step toward developing a prototype retinal prosthesis for human use.  (+info)

Enhancement of osteogenesis in vitro and in vivo by a novel osteoblast differentiation promoting compound, TAK-778. (19/3384)

TAK-778 [(2R,4S)-(-)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4, 5-tetrahydro-4-methyl-7, 8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide; mw 505.53], a novel osteoblast differentiation promoting compound, was characterized in vitro and in vivo models. TAK-778 at doses of 10(-6) M and higher promoted potently bone-like nodule formation in the presence of dexamethasone in rat bone marrow stromal cell culture. This was accompanied by increases in cellular alkaline phosphatase activity, soluble collagen release, and osteocalcin secretion. Under the culture conditions, TAK-778 also stimulated the secretion of transforming growth factor-beta and insulin-like growth factor-I, indicating that TAK-778 may exert regulatory effects on osteoblast differentiation via autocrine/paracrine mechanisms. Furthermore, the in vivo osteogenic potential of TAK-778 was studied in bony defect and osteotomy animal models, using sustained release microcapsules consisted of a biodegradable polymer, poly (dl-lactic/glycolic) acid (PLGA). Single local injection of TAK-778/PLGA-microcapsules (PLGA-MC) (0.2-5 mg/site) to rat skull defects resulted in a dose-dependent increase in new bone area within the defects after 4 weeks. When the pellet containing TAK-778/PLGA-MC (4 mg/pellet) was packed into place to fill the tibial segmental defect in rabbit, this pellet induced osseous union within 2 months, whereas the placebo pellet did not. In addition, single local application of TAK-778/PLGA-MC (10 mg/site) to rabbit tibial osteotomy site enhanced callus formation accompanied by an increase in breaking force after 30 days. These results reveal for the first time that a nonendogenous chemical compound promotes potently osteogenesis in vitro and enhances new bone formation during skeletal regeneration and bone repair in vivo and should be useful for the stimulation of fracture healing.  (+info)

Coral grafting supplemented with bone marrow. (20/3384)

Limited success in regenerating large bone defects has been achieved by bridging them with osteoconductive materials. These substitutes lack the osteogenic and osteoinductive properties of bone autograft. A direct approach would be to stimulate osteogenesis in these biomaterials by the addition of fresh bone-marrow cells (BMC). We therefore created osteoperiosteal gaps 2 cm wide in the ulna of adult rabbits and either bridged them with coral alone (CC), coral supplemented with BMC, or left them empty. Coral was chosen as a scaffold because of its good biocompatibility and resorbability. In osteoperiosteal gaps bridged with coral only, the coral was invaded chiefly by fibrous tissue. It was insufficient to produce union after two months. In defects filled with coral and BMC an increase in osteogenesis was observed and the bone surface area was significantly higher compared with defects filled with coral alone. Bony union occurred in six out of six defects filled with coral and BMC after two months. An increase in the resorption of coral was also observed, suggesting that resorbing cells or their progenitors were present in bone marrow and survived the grafting procedure. Our findings have shown that supplementation of coral with BMC increased both the resorption of material and osteogenesis in defects of a clinical significance.  (+info)

Efficacious treatment of experimental leishmaniasis with amphotericin B-arabinogalactan water-soluble derivatives. (21/3384)

In this study, we tested the efficacy of amphotericin B (AmB)-arabinogalactan (AmB-AG) conjugates for the treatment of experimental leishmaniasis. Chemical conjugation of AmB to a water-soluble, biodegradable, and biocompatible polymer could present many advantages over presently available AmB formulations. Two conjugates were tested, a reduced (rAmB-AG) form and an unreduced (uAmB-AG) form. In vitro, the drug concentrations which lower the values of parasites (for promastigotes) or infected macrophages (for amastigotes) to 50% of the untreated values (ED(50)s) of uAmB-AG and rAmB-AG were 0.19 and 0.34 microg/ml, respectively, for Leishmania major promastigotes and 0.17 and 0.31 microg/ml, respectively, for amastigotes. The effect on Leishmania infantum-infected macrophages was more marked, with ED(50)s of 0.035 microg/ml for rAmB-AG and 0.027 microg/ml for uAmB-AG. In in vivo experiments, BALB/c mice injected with L. major were treated from day 2 onwards on alternate days for 2 weeks. Both conjugates, as well as liposomal AmB (all at 6 mg/kg of body weight) and Fungizone (1 mg/kg), significantly delayed the appearance of lesions compared to that in untreated mice. In addition, both conjugates, but not liposomal AmB, were significantly more effective than Fungizone. Subcutaneous injection of the conjugates (6 mg/kg) was significantly more effective than liposomal AmB in delaying the appearance of lesions. Higher AmB concentrations of up to 12 mg/kg could be administered by this route. When an established infection was treated, uAmB-AG was somewhat more effective than liposomal AmB. In summary, water-soluble polymeric AmB derivatives were found effective and safe for the treatment of leishmanial infections. The conjugates, which are stable and can be produced relatively cheaply (compared to lipid formulations), can be used in the future for the treatment of leishmaniasis infections.  (+info)

Rotational acetabular osteotomy using biodegradable internal fixation. (22/3384)

We used biodegradable poly-L-lactide screws in rotational acetabular osteotomy in 41 hips of 41 patients, and studied the complications after an average follow-up of 4.9 years (range 1.0-7.7 years). There were 39 females and 2 males, their average age at the time of the operation was 32 years (range 12-55 years). A small subcutaneous abscess appeared around the non-absorbable sutures in 2 patients after surgery. There was 1 case of thrombophlebitis and 1 of local dermatitis. The small subcutaneous abscess resolved after the removal of the suture material in the 2 cases, and the thrombophlebitis resolved with aspirin. The local dermatitis persisted but was cured by local steroid therapy over 5.8 years. The incidence of local dermatitis after the use of biodegradable implants should be further investigated.  (+info)

Poly-L-lysine improves gene transfer with adenovirus formulated in PLGA microspheres. (23/3384)

In vivo gene transfer with recombinant adenovirus vectors can be hindered by the immunogenicity of the adenovirus capsid proteins. Previous work showed that formulation of the vector with biodegradable polymers such as poly-lactic-glycolic acid (PLGA), polyethylene glycol (PEG), or lipids, may shield the virus from inhibition by neutralizing antibodies. Formulation of adenovirus in PLGA microspheres also allowed for extended release in vitro. In experiments described here, we found that the surfactant used in the formation of the primary emulsion could significantly improve the overall yield of virus released. We also tested the effects of adding poly-L-lysine to adenovirus before encapsulation with PLGA. Our results show that although PLL did not effect the yield of virus encapsulated or released from the microspheres, it significantly improved the efficiency of gene transfer after release from the polymer.  (+info)

Cell and protein adhesion studies in glaucoma drainage device development. The AGFID project team. (24/3384)

AIM: To examine in vitro whether phosphorylcholine coating of poly(methylmethacrylate) can reduce the adhesion of fibrinogen, fibrin, human scleral fibroblast and macrophage compared with current biomaterials used in the construction of glaucoma drainage devices. METHODS: Sample discs (n=6) of poly(methylmethacrylate), silicone, polypropylene, PTFE, and phosphorylcholine coated poly(methylmethacrylate) were seeded with fibrinogen, fibrin, fibroblast, and macrophages and incubated for variable lengths of time. The quantification was performed using radioactivity, spectrophotometry, ATP dependent luminometry, and immunohistochemistry respectively. RESULTS: Fibrinogen and fibrin adhesion to phosphorylcholine coated poly(methylmethacrylate) were significantly lower than PMMA (p=0.004). Phosphorylcholine coating of poly(methylmethacrylate) also significantly reduced the adhesion of human scleral fibroblast (p=0.002) and macrophage (p=0.01) compared with PMMA. All the other biomaterials showed either similar or insignificantly different levels of adhesion to all the proteins and cells tested compared with PMMA. CONCLUSION: Phosphorylcholine coating is a new material technology that offers considerable promise in the field of glaucoma drainage device development.  (+info)