Biomechanical comparison of five different atlantoaxial posterior fixation techniques.

STUDY DESIGN: Five different reconstructions of the atlantoaxial complex were biomechanically compared in vitro in a nondestructive test. OBJECTIVES: To determine whether non-bone graft-dependent one-point fixation affords stability levels equivalent to three-point reconstructions. SUMMARY OF BACKGROUND DATA: Previous investigations have demonstrated that three-point fixation, using bilateral transarticular screws in combination with posterior wiring, provide the most effective resistance to minimize motion around C1-C2. However, placement of transarticular screws is technically demanding. Posterior wiring techniques affording one-point fixation have failure rates of approximately 15%, with failure considered to be secondary to structural bone graft failures. One-point, non-bone graft-dependent fixations have not been tested. METHODS: Eight human cervical specimens, C0-C3 were loaded nondestructively. Unconstrained three-dimensional segmental motion was measured. The reconstructions tested were two one-point fixations, one two-point fixation, and two three-point fixations. RESULTS: Under axial rotation two and three-point reconstructions provided better stiffness than the one-point reconstructions (P < 0.05). During flexion-extension, higher stiffness levels were observed in one- and three-point fixations when compared with the intact spine (P < 0.05). In lateral bending no significant differences were observed among the six groups, although the trend was that reconstructions including transarticular screws provided greater stability than one-point fixations. CONCLUSION: The current findings substantiate the use of three-point fixation as the treatment of choice for C1-C2 instability. [l: atlantoaxial fixation, biomechanics, cervical spine, instability, spinal instrumentation, transarticular screws]

1,2,4-Benzotriazine 1,4-dioxides. An important class of hypoxic cytotoxins with antitumor activity.

Tirapazamine (1,2,4-benzotriazin-3-amine 1,4-dioxide, SR 4233, WIN 59075) is the lead compound representing this class of anticancer drugs. It is also the first compound to be introduced in the clinic as a pure bioreductive cytotoxic agent. Tirapazamine represents a completely novel approach to the treatment of solid tumors and has generated considerable interest, with research being carried out on all aspects of the its anticancer activity. Phase III trials of tirapazamine in combination with cisplatin (cDDP) have recently been concluded, and phase II trials of triapazamine in combination with irradiation are presently being performed. We developed a drug discovery program into this class of compounds designed to produce derivatives with improved in vivo activity against solid tumors. Based on the hypothesis that these compounds require bioreductive activation for antitumor activity, the research was primarily directed at producing analogues with greater electron affinity and improved aqueous solubility. The in vitro and in vivo data for a variety of structural analogues clearly show that 1,2,4-benzotriazine 1,4-dioxides have considerable potential as anticancer agents. When their activity is compared directly with the activity observed for triapazamine, the most promising series of analogues appears to be the 3-alkyl-substituted derivatives, especially the 3-ethyl- and 3-(2'-methoxyethyl)-derivatives, SR 4895 and SR 4941 respectively.