Microsurgical repair after crush-avulsion injury of the femoral vein in rats: prevention of microvascular thrombosis with recombinant human tissue-type plasminogen activator (rt-PA).

Vein thrombosis is often encountered in microsurgery, especially in the case of crush-avulsion injuries. The aim of this study was to investigate the effect of systemic administration of recombinant tissue-type plasminogen activator (rt-PA) on the patency of the femoral vein of the rat, which had previously sustained a crush-avulsion injury. The study consisted of 3 groups of male Wistar rats, 20 animals each. A standardized crush-avulsion injury model was used. After microvascular repair of the femoral vein, the animals received either normal saline (group A), heparin 100 U/kg body weight (group B), or rt-PA 3.5 mg/kg body weight (group C) systemically. Patency tests were performed at 20 minutes, 48 hours, and 1 week after blood flow reestablishment. According to our results, the patency rate of the rt-PA group was significantly higher than in both the control and heparin groups.

Microvascular repair with 1-mm polytetrafluoroethylene (PTFE) grafts: effect of recombinant tissue-type plasminogen activator (rt-PA) on the patency rate and healing process.

The present study assesses the effect of recombinant tissue-type plasminogen activator (rt-PA) on the patency rate and healing process of microvascular polytetrafluoroethylene (PTFE) grafts. Wistar rats were used, divided into four groups of 25 animals each. After dissection of the carotid artery a segment of the vessel, 1 cm long, was resected and replaced by equal length graft. Two different type fibril length (30- or 60-microm) grafts of the same wall thickness (0.18 mm) were used. Normal saline or 3 mg/kg of body weight of rt-PA was applied locally in each group of different fibril length grafts. Patency tests were performed at 15 min and 4 weeks after blood flow was reestablished. All grafts were harvested and examined histologically. The results showed that local application of rt-PA improves patency statistically significantly in both types of fibril length grafts. Patency in 60-microm fibril length grafts was statistically significantly higher than that of 30-microm fibril length grafts, whether rt-PA was used or not. The use of rt-PA had no influence on the healing process of either type of graft.

Prefabrication of an axial bio-synthetic flap for circumferential tracheal defect reconstruction.

The aim of this study was to prefabricate an axial bio-synthetic flap for reconstruction of circumferential tracheal defects in a rabbit model. Two series of experiments were performed. In the first set of experiments axial island bio-synthetic flaps were prefabricated. These consisted of an inner island de-epithelialised fasciocutaneous flap from a rabbit's ear and an outer polytetrafluoroethylene vascular graft. The flaps were buried at the base of the rabbit's ear for periods of 1, 2 and 3 weeks (groups A, B and C, respectively), 10 flaps per group. Only one flap in group C failed to survive. Clinical and histological assessment, at the completion of each time period, showed that only the viable flaps of group C developed all the characteristics needed for a tracheal substitute. In the second set of experiments the prefabricated bio-synthetic flaps were transferred to the rabbit's neck by means of microvascular anastomoses. Ten such free flaps were buried at the rabbit's neck for 3 weeks (group D). Eight of the flaps remained viable and all the viable flaps had characteristics similar to those of group C. These results demonstrate the feasibility of creating a prefabricated axial bio-synthetic flap (island or free), over a 3-week period, possessing the characteristics needed for a tracheal substitute in a rabbit model.

Microvascular repair following a modified crush-avulsion injury in a rat model: effect of recombinant human tissue-type plasminogen activator on the patency rate.

The failure rate of replantations following a crush-avulsion type injury is high. This study has been designed to reproduce an effective standardized crush-avulsion injury model to the femoral artery of the rat and evaluate the antithrombotic efficacy of systemic intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA). The crush-avulsion injury was reproduced by using a bulldog clamp and two hemostats and followed by microvascular repair. The animals were divided into three groups of 20 rats each and received either normal saline, heparin 100 U/kg body weight, or rt-PA 3.5 mg/kg body weight intravenously. Patency tests were performed 20 min and 48 h after blood flow reestablishment. Results showed that this experimental crush-avulsion injury model ensures low patency in the control group, whereas systemic rt-PA administration improves the patency rate statistically significantly compared to control and heparin groups at both 20 min and 48 h postrevascularization.

Interferon-gamma in the prevention of severe burn-related infections: a European phase III multicenter trial. The Severe Burns Study Group.

OBJECTIVES: To determine the efficacy and tolerance of interferon-gamma-1b (IFN-gamma) for the prevention of death related to infection in patients with burn injury who were at risk for infection. The positive anti-infective effects of IFN-gamma observed in animal models and in clinical studies provided the rationale for this study. DESIGN: Randomized, double-blind, placebo-controlled, phase III multicenter trial, with a group sequential design, conducted at 23 European burn centers. PATIENTS: Two hundred sixteen patients with major critical burn (Abbreviated Burn Severity Index score of > or = 7). INTERVENTION: Patients were randomized to receive IFN-gamma (100 microg) or placebo daily by subcutaneous injection for up to 90 days. MEASUREMENT AND MAIN RESULTS: The primary end point (the incidence of death related to infection within 90 days from the start of treatment) was similar in the two treatment groups. There were no significant differences between the two treatments in any of the secondary end points (all causes of mortality at 90 days, incidence of infectious complications, duration of intensive care unit or hospital stay, and scar formation at 90 days). CONCLUSION: IFN-gamma did not protect burn patients from infections or decrease the mortality from infections.

Rationale, design and performance of a clinical trial to investigate interferon-gamma (Imukin) in the prophylactic treatment of severe burns-related infections.

Recent advances in resuscitation therapy have increased the survival rate of patients with severe burns in the burn shock phase. Infectious complications represent the major cause of death in patients with extensive burns, however, in spite of the application of early and aggressive interventions. Extensive burn injury causes profound alterations in various essential elements of the normal host immune response and the main aim of treatment after resuscitation is to maintain or even improve host resistance. The positive anti-infective effects of interferon (IFN)-gamma observed in animal models and in clinical studies, for example in chronic granulomatous disease, provided the rationale for a study to investigate its use in patients with severe burns. A study was therefore designed to determine the efficacy and tolerance of IFN-gamma in preventing death related to infection in patients with severe burn injury who are at risk of infection. In order to avoid unnecessary risk for patients and reduce the cost, a sequential design was chosen. The primary end-point was reviewed in a group sequential manner after every 60 patients through an independent monitoring board. The study was a randomised, double-blind, Phase III multi-centre trial, conducted at 23 European Burn Centres. An interval censored survival time approach was taken, using information collected at days 8, 15, 30, 60, and 90. The trial is still blinded, but the rationale for conducting the study and its design are discussed.

Use of free flaps in the aesthetic reconstruction of face and neck deformities.

Three cases of face and neck deformities, reconstructed with free flaps in order to obtain better aesthetic results, are presented here. Nasal tip, cartilage, and soft tissue defects as well as facial burn contractures were reconstructed with a free radial forearm flap, latissimus dorsi myocutaneous flap, and groin flap, respectively. Case specifics are discussed.