Enrico Ascher

p53 gene transfer to the injured rat carotid artery decreases neointimal formation

PURPOSEnWe studied the effect of adenovirus-mediated p53 gene transfer on the injured rat carotid artery to determine its ability to decrease the formation of neointima.nnnMETHODSnIn vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus containing the gene encoding for wild-type p53 (AdWTp53) was applied in three concentrations: 8 x 10(10), 1.6 x 10(10), and 8 x 10(9) pfu/mL. Control rats received either adenovirus null (AdNull), 8 x 10(10) pfu/mL, or Medium-199 solution (vehicle). Expression of p53 was determined 4 days after gene transfer by Western blotting. Neointimal formation was assessed after 14 days by harvesting carotid arteries and determining the intima/media (I/M) ratio based on cross-sectional area measurement. Simultaneously, immunohistochemistry was done to detect the presence of p53 on smooth muscle cell nuclei.nnnRESULTSnP53 expression was confirmed by Western blotting. There was a significant reduction in neointimal formation on all treated animals compared with controls. The highest dose of AdWTp53 (8 x 10(10) pfu/mL) resulted in a near-total arrest of neointimal formation (I/M = 0.09 +/- 0.03, mean +/- SEM) with P <. 0001 versus vehicle (I/M = 2.23 +/- 0.15) or AdNull (I/M = 2.12 +/-. 12). The intermediate dose of AdWTp53 (1.6 x 10(10) pfu/mL) resulted in an I/M value of 1.04 +/- 0.18, with P <.001 versus vehicle and P =.001 versus AdNull. The lowest dose (8 x 10(9) pfu/mL) resulted in an I/M value of 1.12 +/- 0.18, with P <.001 versus vehicle and P <. 002 versus AdNull. The immunohistochemistry was positive for the presence of p53 in rats infected with AdWTp53.nnnCONCLUSIONSnAdenovirus-mediated gene transfer of p53 protein significantly decreases the formation of neointima in the rat carotid injury model. This may represent a potential therapy for restenosis in humans.

Chapter 63 – Inferior Vena Cava Filter Placement

Your body can develop a blood clot in the vein in your legs which is called a deep vein thrombosis (DVT). This blood clot, or a piece of this clot, can move from your leg to your heart and lungs. A clot in your lung is called a pulmonary embolism. If you have one or two of these problems and cannot take blood thinners, you are a candidate for an inferior vena cava (IVC) filter. The filter will trap any clot or pieces of the clot to keep them from your heart or lungs.

Bypass to the Infrapopliteal Arteries for Chronic Critical Limb Ischemia

An 85-year-old male with a history of diabetes, hypertension, hypercholesterolemia, coronary artery bypass, and active tobacco use presented with a gangrenous right first toe. The patient stated that he had no history of trauma to the area, and complained of rest pain in the foot. The patient had been in otherwise good health since his coronary artery bypass 12 years ago. On physical examination, the patient was in no physical distress. The patient had a well-healed median sternotomy scar. Auscultation of the heart revealed a regular rate without any murmurs. He was obese. Abdominal examination revealed no palpable masses. The patient had bilateral femoral and popliteal pulses but no pedal pulses. The patient had bilateral, well-healed scars from the greater saphenous vein harvest sites. The right gangrenous toe was dry without any evidence of infection.