Minimally invasive reconstruction of lateral tibial plateau fractures using the jail technique: a biomechanical study

Background: This study described a novel, minimally invasive reconstruction technique of lateral tibial plateau fractures using a three-screw jail technique and compared it to a conventional two-screw osteosynthesis technique. The benefit of an additional screw implanted in the proximal tibia from the anterior at an angle of 90° below the conventional two-screw reconstruction after lateral tibial plateau fracture was evaluated. This new method was called the jail technique. Methods: The two reconstruction techniques were tested using a porcine model (n = 40). Fracture was simulated using a defined osteotomy of the lateral tibial plateau. Load-to-failure and multiple cyclic loading tests were conducted using a material testing machine. Twenty tibias were used for each reconstruction technique, ten of which were loaded in a load-to-failure protocol and ten cyclically loaded (5000 times) between 200 and 1000 N using a ramp protocol. Displacement, stiffness and yield load were determined from the resulting load displacement curve. Failure was macroscopically documented. Results: In the load-to-failure testing, the jail technique showed a significantly higher mean maximum load (2275.9 N) in comparison to the conventional reconstruction (1796.5 N, p  0.05). In cyclic testing, the jail technique also showed better trends in displacement that were not statistically significant. Failure modes showed a tendency of screws cutting through the bone (cut-out) in the conventional reconstruction. No cut-out but a bending of the lag screws at the site of the additional third screw was observed in the jail technique. Conclusions: The results of this study indicate that the jail and the conventional technique have seemingly similar biomechanical properties. This suggests that the jail technique may be a feasible alternative to conventional screw osteosynthesis in the minimally invasive reconstruction of lateral tibial plateau fractures. A potential advantage of the jail technique is the prevention of screw cut-outs through the cancellous bone.<br

Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans

BACKGROUND AND AIMS: In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (Fabs) and gastrointestinal extraction (EGI) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. METHODS: Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. RESULTS: The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for Fabs) (F/Fabsd3-verapamil240 min versus d0-verapamil15 min, 0.24 0.10 versus 0.20 0.09; P < .05). Accordingly, the EGI value for d3-verapamil240 min was 0.50 0.18 compared with 0.59 0.14 for d0-verapamil15 min (P < .05). In vivo, EGI(d0-verapamil15 min) correlated strongly with EGI(d3-verapamil240 min) (r = 0.94, P < .005). Moreover, intrinsic clearance of CYP3A4-mediated verapamil metabolism in homogenates of simultaneously collected shed enterocytes correlated with in vivo EGI of d0-verapamil15 min/d3-verapamil240 min (r = 0.62, P = .03). CONCLUSIONS: Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.Hartmut Glaeser, Siegfried Drescher, Ute Hofmann, Georg Heinkele, Andrew A. Somogyi, Michel Eichelbaum and Martin F. From