Morphometric comparison of the pedicle rib unit to pedicles in the thoracic spine.

STUDY DESIGN: A radiographic study of the pedicle rib unit morphology as compared with measurements of the pedicle in cadaveric thoracic spines. OBJECTIVE: To evaluate the morphology of pedicle rib units in the thoracic spine in normal thoracic human spines, with particular attention to T4-T9, and to compare the dimensions of the pedicle rib unit with corresponding dimensions of the adjacent pedicles. SUMMARY OF BACKGROUND DATA: Despite the clinical successes reported with thoracic pedicle screw-rod constructs, controversy exists as to the safety of this technique in pedicles that are anatomically too small for transpedicular fixation. An alternative method of extrapedicular screw fixation within the pedicle rib unit was evaluated in a previous study and found to be anatomically feasible. Although the morphology of the pedicle rib unit was described in two previous studies, the measurements were obtained in scoliotic spines. Therefore, no study has sought to define the transverse dimension and chord length of the pedicle rib unit, and compare it with the corresponding pedicle dimensions. MATERIAL AND METHODS: Six fresh unfixed adult cadavers were obtained randomly. No history of spine disease was noted, and cause of death was unrelated to spinal disorder or trauma. The mean age was 84, with a range of 76 to 90. There were two females and four males. Computerized tomographic (CT) images of the thoracic spine were obtained. For cadavers in which the gantry resulted in oblique axial sections, reformatting was performed for more accurate measurements. Measurements of the transverse diameter and chord length of the pedicle rib unit were obtained and compared with measurements of the transverse pedicle width and chord length. RESULTS: The transverse width and chord length of the pedicle rib unit were significantly larger than corresponding pedicle measurements at all levels, a consistent finding when comparing the mean of all levels, the mean of T4-T9, and the mean of each individual level T4-T7. CONCLUSION: This study confirms the marked difference in size of the pedicle rib unit as compared with the pediclein both transverse width and chord length. This allows for a space that accommodates much larger major screw diameters, longer screw lengths, and because of the nature of screw placement, a greater screw convergence. Thus, there is anatomic potential for extrapedicular vertebral body fixation in the thoracic spine. However, care must be taken in placement of screws following precisely our previously described method of extrapedicular screw insertion. Penetration of surrounding structures, most notably the aorta on the left, is a potential risk when deviating from the method. Biomechanical evaluations are presently being conducted to evaluate the use of extrapedicular thoracic screw fixation.

An extrapedicular approach to the placement of screws in the thoracic spine: an anatomic and radiographic assessment.

STUDY DESIGN: A radiographic and anatomic study of an extrapedicular method of screw placement in cadaveric thoracic spines. OBJECTIVE: To evaluate an alternative method of thoracic vertebral body screw fixation using an extrapedicular screw technique. To evaluate the anatomic safe zones and proper starting point for this alternative approach to the placement of screw fixation in the thoracic spine. SUMMARY OF BACKGROUND DATA: Despite the clinical successes reported with thoracic pedicle screw-rod constructs, controversy exists about the safety of this technique in pedicles that are anatomically too small for transpedicular fixation. An alternative method of extrapedicular screw fixation was evaluated in this present study. MATERIALS AND METHODS: Two fresh, unfixed, adult cadavers were obtained randomly; 6.0-mm AO Synthes pedicle screws were placed using an extrapedicular approach bilaterally from T3 to T10. The screws were placed according to one defined method described later. Computerized tomographic (CT) images were obtained. The position of each screw was analyzed. The cadavers were then dissected with the screw pathway exposed and the relation of the screw to surrounding anatomy documented. RESULTS: All screws did not penetrate the spinal canal. All screws were within the pedicle rib unit and did not penetrate the neural foramen or pleura. CONCLUSION: This study, although only introductory, indicates the potential for extrapedicular vertebral body fixation in the thoracic spine. Biomechanical evaluations are presently being conducted to evaluate the use of extrapedicular thoracic screw fixation.

Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice.

Tumor vasculature is hyperpermeable to macromolecules compared to normal vasculature; however, the relationship between tumor hyperpermeability and tumor progression is poorly understood. Here we show that a cell-permeable peptide derived from caveolin-1, termed cavtratin, reduces microvascular hyperpermeability and delays tumor progression in mice. These antipermeability and antitumor actions of cavtratin occur in the absence of direct cytostatic or antiangiogenic effects. Cavtratin blocks microvascular permeability by inhibiting endothelial nitric oxide synthase (eNOS), as the antipermeability and antitumor actions of cavtratin are markedly diminished in eNOS knockout mice. Our results support the concepts that hyperpermeability of tumor blood vessels contributes to tumor progression and that blockade of eNOS may be exploited as a novel target for antitumor therapy.

Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide synthase and NO release.

Protein-protein interactions with the molecular chaperone hsp90 and phosphorylation on serine 1179 by the protein kinase Akt leads to activation of endothelial nitric oxide synthase. However, the interplay between these protein-protein interactions remains to be established. In the present study, we show that vascular endothelial growth factor stimulates the coordinated association of hsp90, Akt, and resultant phosphorylation of eNOS. Characterization of the domains of hsp90 required to bind eNOS, using yeast 2-hybrid, cell-based coprecipitation experiments, and GST-fusion proteins, revealed that the M region of hsp90 interacts with the amino terminus of eNOS and Akt. The addition of purified hsp90 to in vitro kinase assays facilitates Akt-driven phosphorylation of recombinant eNOS protein, but not a short peptide encoding the Akt phosphorylation site, suggesting that hsp90 may function as a scaffold for eNOS and Akt. In vivo, coexpression of adenoviral or the cDNA for hsp90 with eNOS promotes nitric oxide release; an effect eliminated using a catalytically functional phosphorylation mutant of eNOS. These results demonstrate that stimulation of endothelial cells with vascular endothelial growth factor recruits eNOS and Akt to an adjacent region on the same domain of hsp90, thereby facilitating eNOS phosphorylation and enzyme activation.