Endothelial implants inhibit intimal hyperplasia after porcine angioplasty.
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The perivascular implantation of tissue-engineered endothelial cells around injured arteries offers an opportunity to study fundamental vascular physiology as well as restore and improve tissue function. Cell source is an important issue because the ability to implant either xenogeneic or allogeneic cells would greatly enhance the clinical applications of tissue-engineered grafts. We investigated the biological and immunological responses to endothelial cell xenografts and allografts in pigs 4 weeks after angioplasty of the carotid arteries. Porcine or bovine aortic endothelial cells were cultured within Gelfoam matrices and implanted in the perivascular space of 42 injured arteries. Both porcine and bovine endothelial cell grafts reduced the restenosis index compared with control by 54% and 46%, respectively. Perivascular heparin release devices, formulated to release heparin at twice the rate of release of heparan sulfate proteoglycan from endothelial cell implants, produced no significant reduction in the restenosis index. Endothelial cell implants also reduced occlusive thrombosis compared with control and heparin release devices. Host immune responses to endothelial implants were investigated by immunohistochemical examination of explanted devices and by immunocytochemistry of serum samples. The bovine cell grafts displayed infiltration of leukocytes, consisting primarily of lymphocytes, and caused an increase in antibodies detected in serum samples. Reduced cellular infiltration and no humoral response were detected in animals that received allografts. Despite the difference in immune response, the biological effects of xenografts or allografts did not differ significantly. (+info)
Role of the C-C chemokine, TCA3, in the protective anticryptococcal cell-mediated immune response.
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Activated T lymphocytes play a crucial role in orchestrating cellular infiltration during a cell-mediated immune (CMI) reaction. TCA3, a C-C chemokine, is produced by Ag-activated T cells and is chemotactic for neutrophils and macrophages, two cell types in a murine CMI reaction. Using a gelatin sponge model for delayed-type hypersensitivity (DTH), we show that TCA3 is a component of the expression phase of an anticryptococcal CMI response in mice. TCA3 mRNA levels are augmented in anticryptococcal DTH reactions at the same time peak influxes of neutrophils and lymphocytes are observed. Neutralization of TCA3 in immunized mice results in reduced numbers of neutrophils and lymphocytes at DTH reaction sites. However, when rTCA3 is injected into sponges in naive mice, only neutrophils are attracted into the sponges, indicating TCA3 is chemotactic for neutrophils, but not lymphocytes. We show that TCA3 is indirectly attracting lymphocytes into DTH-reactive sponges by affecting at least one other chemokine that is chemotactic for lymphocytes. Of the two lymphocyte-attracting chemokines assessed, monocyte-chemotactic protein-1 and macrophage-inflammatory protein-1alpha (MIP-1alpha), only MIP-1alpha was reduced when TCA3 was neutralized, indicating that TCA3 affects the levels of MIP-1alpha, which attracts lymphocytes into the sponges. TCA3 also plays a role in protection against Cryptococcus neoformans in the lungs and brains of infected mice, as evidenced by the fact that neutralization of TCA3 results in increased C. neoformans CFU in those two organs. (+info)
Hypervascular spinal tumors: influence of the embolization technique on perioperative hemorrhage.
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BACKGROUND AND PURPOSE: Corporectomy is an effective treatment for vertebral metastases; however, massive perioperative hemorrhage is often associated with this procedure. We compared preoperative particle, particle-coil, and coil embolizations of hypervascular spinal tumors prior to vertebral body replacement to determine which prevented perioperative hemorrhage most effectively. METHODS: The vertebral tumors of 59 patients were embolized prior to corporectomy. In 26 cases, only coils were used for the proximal occlusion of feeding segmental arteries. Twenty-four patients received a combination of polyvinyl alcohol (PVA) particles and coils, and nine tumors were embolized with particles alone. We compared intraoperative blood loss between the three groups and 10 other patients who did not undergo embolization prior to corporectomy. RESULTS: Estimation of intraoperative hemorrhage showed a median value of 4350 mL in patients without embolization, 2650 mL in cases of coil embolization, 1850 mL in cases of particle-coil embolization, and 1800 mL in cases of particle embolization. The difference between unembolized patients and those who underwent coil embolization was not statistically significant. Particle and particle-coil embolizations showed very similar results, and reduced hemorrhage significantly as compared to unembolized and proximal coil occlusion cases. Residual bleeding came from the venous system and the neighborhood of the embolized region. CONCLUSION: Particle embolization prior to corporectomy can reduce perioperative hemorrhage. The additional benefit of proximal coil occlusion of arterial feeders is questionable. (+info)
Hemostatic efficacy of fibrin sealant (human) on expanded poly-tetrafluoroethylene carotid patch angioplasty: a randomized clinical trial.
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PURPOSE: The efficacy of solvent-detergent-treated fibrin sealant (human [FSH]) for controlling anastomotic bleeding from expanded polytetrafluoroethylene (ePTFE) patch angioplasty during carotid endarterectomy was evaluated, and FSH was compared with thrombin-soaked gelatin sponge (Gelfoam; TSG). METHODS: The study was of a randomized, open-label, single-site, single-treatment, parallel design that took place in a referral center with hospitalized patients. Forty-seven adult patients (33 men, 14 women) underwent elective carotid endarterectomy. Patients were randomized to receive either FSH (N = 24) or TSG (N = 23). FSH was obtained as an investigational new drug. FSH was applied as a liquid by means of a dual-syringe technique. Heparin anticoagulation, patch thickness, and suture type were standardized. Two different needle sizes were used (CV-6, PT-13: N = 21 [FSH: N = 10, TSG: N = 11]; CV-6, PT-9: N = 26 [FSH: N = 14, TSG: N = 13]). The FSH or TSG was applied to the ePTFE patch, and then blood flow was restored through the carotid artery. Degree of anticoagulation was assessed by anti-factor Xa activity. The time from restoration of carotid blood flow until achieving hemostasis was recorded. The blood loss from patch suture hole bleeding was measured. Completion intraoperative duplex ultrasound scanning was performed in all cases. Heparin was reversed with protamine sulfate. The primary end point was successful hemostasis within 15 minutes of restoration of carotid blood flow. The secondary end points were the amount of blood loss caused by suture line bleeding and the time to achieve hemostasis. RESULTS: There was no difference in the number of patients with complete hemostasis at 15 minutes (TSG, 13 of 23; FSH, 12 of 24; P =.77). The measured blood loss was 99.0 +/- 119.9 (SD) mL for TSG, and 105.0 +/- 107.9 mL for FSH (P =.86). The time to hemostasis was the same for both groups (TSG, 16.5 +/- 16.5 minutes; FSH, 16.6 +/- 14.2 minutes; P =.97). Within both treatment groups, the use of larger needles (PT-13) was associated with greater blood loss (FSH, 169.7 +/- 124.2 mL; TSG, 172.7 +/- 151.5 mL) than was the use of smaller needles (PT-9; FSH, 58.8 +/- 66.3 mL; TSG, 34.1 +/- 25.6 mL; P =.036, P =.001, respectively). There were no postoperative strokes or bleeding complications in either group. No abnormalities were shown in either group by means of completion carotid duplex ultrasound scanning. CONCLUSION: FSH was equivalent, but not superior to, TSG in achieving hemostasis during carotid endarterectomy performed with ePTFE patch angioplasty. Adhesion properties of FSH to ePTFE are possibly different than those to native tissue and warrant additional investigation. (+info)
Survival and function of bioengineered cardiac grafts.
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INTRODUCTION: Patients with congenital heart disease frequently require graft material for repair of cardiac defects. However, currently available grafts lack growth potential and are noncontractile and thrombogenic. We have developed a viable cardiac graft that contracts spontaneously in tissue culture by seeding cells derived from fetal rat ventricular muscle into a biodegradable material. We report our investigations of the in vitro and in vivo survival and function of this bioengineered cardiac graft. METHODS AND RESULTS: A cardiomyocyte-enriched cell inoculum derived from fetal rat ventricular muscle was seeded into a piece of Gelfoam (Upjohn, Ontario, Canada), a biodegradable gelatin mesh, to form the graft. For in vitro studies, growth patterns of the cells within the graft were evaluated by constructing growth curves and by histologic examination; in in vivo studies, the graft was cultured for 7 days and then implanted either into the subcutaneous tissue of adult rat legs or onto myocardial scar tissue in a cryoinjured rat heart. Five weeks later, the graft was studied histologically. The inoculated cells attached to the gelatin mesh and grew in 3 dimensions in tissue culture, forming a beating cardiac graft. In both the subcutaneous tissue and the myocardial scar, blood vessels grew into the graft from the surrounding tissue. The graft implanted into the subcutaneous tissue contracted regularly and spontaneously. When implanted onto myocardial scar tissue, the cells within the graft survived and formed junctions with the recipient heart cells. CONCLUSIONS: Fetal rat ventricular cells can grow 3-dimensionally in a gelatin mesh. The cells in the graft formed cardiac tissue and survived and contracted spontaneously both in tissue culture and after subcutaneous implantation. Future versions of this bioengineered cardiac graft may eventually be used to repair cardiac defects. (+info)
A giant intramural gastric hematoma successfully treated by transcatheter arterial embolization.
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We describe a case of intramural gastric hematoma with hemorrhagic shock caused by the formation of a large hematoma. Computed tomographic and angiographic examinations confirmed the presence of active bleeding into the hematoma. Transcatheter arterial embolization (TAE) was performed for hemostasis. To our knowledge, although 21 cases of intramural gastric hematoma have been reported in the literature, this is apparently the first case treated by TAE. We conclude that TAE is a safe and effective treatment option for intramural gastric hematoma confirmed to be associated with active bleeding into the hematoma. (+info)
Cutting edge: restoration of the ability to generate CTL in mice immune to adenovirus by delivery of virus in a collagen-based matrix.
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Viruses are commonly used for the delivery of genes coding for tumor-associated Ags to elicit tumor-specific immune responses. The success of viral vectors has been limited in preclinical and clinical trials in part because of antiviral immunity. We investigated the ability of a collagen-based matrix (Gelfoam; Pharmacia and Upjohn, Kalamazoo, MI) to improve CTL activation by recombinant adenovirus. The data show that coinjection of Gelfoam with type 5 adenovirus recombinant for prostate-specific Ag (Ad5-PSA) enhanced CTL activation. Ad5-PSA priming in Gelfoam also abrogated the inhibitory effects of adenoviral immunity on CTL activation in mice naive to PSA but immune to adenovirus. Finally, Gelfoam enhanced immunization in a self-Ag model using type 5 adenovirus recombinant for membrane-bound OVA (Ad5-mOVA) in rat insulin promoter (RIP)-mOVA-transgenic mice. Thus, Gelfoam enhances CTL activation by recombinant viral vectors in a setting where preformed Ab to the virus is present and also in a tolerant self-Ag model. (+info)
Colonic necrosis subsequent to catheter-directed thrombin embolization of the inferior mesenteric artery via the superior mesenteric artery: a complication in the management of a type II endoleak.
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The optimal management of endoleaks after endovascular repair of abdominal aortic aneurysms remains to be established. In this report, we describe a persistent side-branch, or type II, endoleak 1 year after endograft implantation treated with catheter-directed embolization of the aneurysm sac and the inferior mesenteric artery via the superior mesenteric artery, with embolization agents including thrombin, lipiodol, and gelfoam powder. Shortly after the embolization procedure, colonic necrosis developed in the patient, manifested by peritonitis, which necessitated a partial colectomy. This case underscores the devastating complication of colonic ischemia as a result of catheter-directed embolization of the inferior mesenteric artery in the management of an endoleak. (+info)