Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart.

OBJECTIVES: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF121 complementary deoxyribonucleic acid (AdGVVEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function. METHODS: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery. Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi and by echocardiography during rest and stress. AdGVVEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. RESULTS: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in AdGVVEFG121.10-treated animals compared with AdNull control animals (p = 0.005). Stress echocardiography at the same time demonstrated improved segmental wall thickening in AdGVVEGF121.10 animals compared with AdNull control animals (p = 0.03), with AdGVVEGF121.10 animals showing nearly normalized function in the circumflex distribution. Collateral vessel development assessed by angiography was also significantly greater in AdGVVEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in AdGVVEGF121.10 animals. CONCLUSIONS: An Ad vector expressing the VEGF121 cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function. Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.

Treatment of squamous carcinoma of the retromolar trigone.

Since squamous carcinoma of the retromolar trigone is unusual, there is a paucity of information in the world's literature to use as a reference for selecting treatment and determining pertinent factors affecting prognosis. Consequently, an analysis of the medical records of 110 patients with biopsy proven squamous carcinoma originating in the retromolar trigone, seen and treated entirely at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1965-1977, with at least 5 years of follow-up, was completed and constitutes the substance of this study. Local-regional control and survival were correlated with age, sex, presenting signs and symptoms, dental status, T and N classification, histologic grading, surgical findings, and the various modalities of treatment. Seventy lesions were staged T1-T2 and 77 patients had N0 necks. Thirty-five patients received a planned combination of surgery and x-ray therapy to the primary and/or neck. A composite resection was performed in 48 patients with the closure accomplished primarily or with a skin graft. The various surgical approaches are critiqued with a favorable emphasis on the marginal resection of the mandible and a modification of the radical neck dissection. The ultimate failure in the primary and the neck was 7% (8/110) and 10% (11/110) respectively. Single modality treatment whether it is surgery or irradiation appears equally adequate regardless of the T or N Stage. However, more T3-T4 cancers were treated initially with surgery. Thirty-six patients developed a second primary cancer of which 29 were in the upper aerodigestive tract. The low 5-year survival of 20% (29/110) reflects a poor salvage of the second primary and a high incidence of intercurrent disease in this elderly group of patients.

In vitro antioxidant activity of species collected in Paraná.

Hydroalcoholic extracts of 10 medicinally used species collected from the area covered by a reservoir due to a dam built for the Salto Caxias Hydro-electric power plant in the State of Paraná, Southern Brazil, and Casearia sylvestris, were investigated for their potential antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) free radicals and by the phosphomolybdenum method. The extract of Bauhinia microstachya was found to be the most potent in both models.

Salvage angiogenesis induced by adenovirus-mediated gene transfer of vascular endothelial growth factor protects against ischemic vascular occlusion.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis, and transgene expression from adenovirus vectors can provide in vivo delivery of proteins. On the basis of this knowledge, we hypothesized that local administration of a replication-deficient adenovirus vector expressing complementary DNA for VEGF (AdVEGF) would induce collateral vessel formation in the setting of ischemia that could protect against subsequent acute vascular occlusion. METHODS: Hindlimb ischemia was induced in Sprague-Dawley rats by means of unilateral ligation of the common iliac artery immediately followed by administration of 4 x 10(9)-plaque-forming units VEGF, the control vector AdNull, or phosphate-buffered saline solution into the iliofemoral adipose tissue and thigh muscles. Untreated rats with common iliac ligation were used as an additional control group. RESULTS: Local VEGF expression was observed for 5 days in AdVEGF-treated rats but not in controls. Three weeks after ligation and vector administration, the ipsilateral femoral artery was ligated for a model of an acute vascular occlusion in the setting of preexisting ischemia. Blood flow to the ischemic hindlimb relative to the contralateral hindlimb evaluated with color microspheres demonstrated significantly increased blood flow in the AdVEGF-treated rats compared with each control group (p < 0.0001). Relative blood flow assessed by means of 99mTc-sestamibi radionuclide scans also demonstrated increased blood flow to the ligated hindlimb of AdVEGF-treated rats compared with each control group (p < 0.002). AdVEGF-treated rats also demonstrated increased vascularity in the ligated limb compared with each control group as assessed by means of angiography (p < 0.0001) and histologic quantification of blood vessels less than 80 microm diameter in local adipose tissue and capillaries per muscle fiber (p < 0.0002). AdVEGF treatment prevented a rise in femoral venous lactate femoral venous concentrations 1 hour after femoral artery ligation in control rats (p < 0.04). CONCLUSIONS: An adenovirus vector expressing VEGF complementary DNA is capable of stimulating an angiogenic response that protects against acute vascular occlusion in the setting of preexisting ischemia, suggesting that in vivo gene transfer of VEGF complementary DNA might be useful in prophylaxis of advancing arterial occlusive disease.