Improved adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in a canine model.

PURPOSE: A significant limitation to using genetically modified endothelial cells (ECs) to seed prosthetic grafts before implantation has been poor cell adherence to the graft lumen. Methodologic changes to improve cell adherence were evaluated in a canine carotid interposition graft model using 4 mm interior diameter expanded polytetrafluoroethylene. METHODS: ECs harvested from external jugular veins were grown in culture, with 80% of the cells from each culture transduced by incubation with an LXSN-type retroviral vector carrying a gene for human prourokinase and a neomycin resistance gene for selection in antibiotic G418. Control grafts had passive luminal coating with fibronectin and were seeded with transduced ECs immediately after G418 selection; these grafts were incubated for 2 days before implantation. Experimental grafts had fibronectin forcefully squeezed through the interstices and were seeded with ECs that had recovered in culture for 5 days after G418 selection; these grafts were incubated for 4 days before implantation. For each control (n = 9) and experimental (n = 12) graft, a graft prepared in the same fashion but seeded with the remaining autologous nontransduced cells was placed in the contralateral carotid artery. Grafts were explanted after 30 days and were evaluated for patency, thrombus-free surface area, and cell-free surface area. RESULTS: No significant differences in patency rates were seen between any groups. The thrombus-free surface area was improved for experimental grafts (90%) compared with control grafts (76%), but this improvement did not achieve statistical significance. The cell-free surface area for transduced cells on experimental grafts was 65% compared with 96% for control grafts (p = 0.021) and was comparable with that for nontransduced cells on both control grafts (62%) and experimental grafts (51%; p = 0.201). CONCLUSIONS: Adherence of genetically modified endothelial cells to small-diameter expanded polytetrafluoroethylene grafts in an in vivo physiologic flow model is significantly improved when cells have a more prolonged recovery from G418 selection, when the graft lumen is more uniformly coated with fibronectin before EC seeding, and when seeded grafts are left longer in culture before implantation to develop cell lining stability. The short-term patency rate of these seeded grafts is not affected by increased cell retention; long-term graft patency data and luminal healing require further evaluation.

Gastro-aortic fistula: an uncommon complication of Nissen fundoplication.

We report a case of and review the literature concerning primary gastro-aortic fistula secondary to erosion of a gastric ulcer into the thoracic aorta in a patient with a previous Nissen fundoplication. Treatment consisted of excision of the fistula with closure of the gastric and aortic defects. This rare cause of upper gastrointestinal bleeding is life threatening, and a high level of suspicion is necessary to make the diagnosis and initiate early, aggressive surgical treatment.

Bedside tracheostomy in the intensive care unit.

OBJECTIVE: To prove that tracheostomy performed at the bedside in the intensive care unit is a safe, cost-effective procedure. DESIGN: Retrospective review of all adult patients undergoing elective bedside tracheostomy in the intensive care unit between January 1983 and December 1988. Two hundred four patients were identified. SETTING: A private 1200-bed tertiary care center with a 120-bed critical care facility. MAIN OUTCOME MEASURES: Major and minor perioperative complications, cost savings, and comparison of risk between bedside tracheostomy and that performed in the operating room. RESULTS: There were six major complications (2.9%): one death due to tube obstruction, two bleeding episodes requiring reoperation, one tube entrapment requiring operative removal, one nonfatal respiratory arrest, and one bilateral pneumothorax; and seven minor complications (3.4%): five episodes of minor bleeding, one tube dislodgement in a tracheostomy with a well-developed tract, and one episode of mucus plugging. One late complication (tracheal stenosis) was identified. CONCLUSIONS: Bedside tracheostomy in the intensive care unit can be performed with morbidity and mortality rates comparable to operative tracheostomy. In addition, it provides a significant cost savings for the patient.

The management of patients on chronic Coumadin therapy undergoing subsequent surgical procedures.

Coumadin, a long-acting antagonist of Vitamin K-dependent clotting factors, is commonly used for prevention of thromboembolism and potentially lethal clotting of mechanical heart valves. When patients require surgery for subsequent problems, inadequate perioperative management of coagulation may result in hemorrhage or thrombosis. Reversal with Vitamin K makes subsequent anticoagulation therapy difficult, and normalization of coagulation with fresh frozen plasma exposes the patient to the risk of fatal valvular thrombosis. In addition, third party payers and governmental reimbursement policies discourage most, if not all, preoperative hospitalization. Twenty-one patients on chronic Coumadin therapy required surgery for diseases unrelated to their original need for anticoagulation. Seven patients had hemorrhagic complications, and 14 did not. In these two groups, sex, current operation, reason for anticoagulation, other drugs, admitting CBC, and platelet count were similar. Preoperative hospital days averaged 5.2 days in both groups. Statistically significant differences were noted in age, preoperative Coumadin dose, admitting prothrombin times, and postoperative stays (P = 0.05). Although the perioperative prothrombin times, partial thromboplastin times, and perioperative heparin doses were similar, more patients in the bleeding group were operated with a prothrombin time > 13.0 seconds. The current evolved protocol is to discontinue Coumadin 5 days before surgery, and begin intravenous heparin @ 1000 u/hr with adjustment to keep partial thromboplastin times at therapeutic levels. Heparin is stopped early on the morning of surgery and restarted at 200-400 units/hr at 4 to 6 hours after surgery. Coumadin is restarted as soon as the patient can tolerate it. It is considered safe to operate only when the prothrombin time is less than 13 seconds.(ABSTRACT TRUNCATED AT 250 WORDS)