The use of the O-arm in combination with a navigation system increases the accuracy of pedicle screw placement. The accuracy of the surgeon's perception and the need to limit the radiation dose for the patient justify an additional CT scan only after careful assessment of the potential additional value.
Blocking angiogenesis is an attractive strategy to inhibit tumor growth, invasion, and metastasis. We describe here the structure and the biological action of a new cyclic peptide derived from vascular endothelial growth factor (VEGF). This 17-amino acid molecule designated cyclopeptidic vascular endothelial growth inhibitor (cyclo-VEGI, CBO-P11) encompasses residues 79 -93 of VEGF which are involved in the interaction with VEGF receptor-2. In aqueous solution, cyclo-VEGI presents a propensity to adopt a helix conformation that was largely unexpected because only -sheet structures or random coil conformations have been observed for macrocyclic peptides. Cyclo-VEGI inhibits binding of iodinated VEGF 165 to endothelial cells, endothelial cells proliferation, migration, and signaling induced by VEGF 165 . This peptide also exhibits anti-angiogenic activity in vivo on the differentiated chicken chorioallantoic membrane. Furthermore, cyclo-VEGI significantly blocks the growth of established intracranial glioma in nude and syngeneic mice and improves survival without side effects. Taken together, these results suggest that cyclo-VEGI is an attractive candidate for the development of novel angiogenesis inhibitor molecules useful for the treatment of cancer and other angiogenesis-related diseases.Angiogenesis takes place during embryonic development and in the adult during wound healing and the female ovulatory cycle. In pathological states, angiogenesis is observed during solid tumor growth and metastasis, diabetic retinopathy, and chronic inflammatory disorders. A number of angiogenic regulators such as vascular endothelial growth factors (VEGFs),
Preclinical evaluation of spinal implants is a necessary step to ensure their reliability and safety before implantation. The American Society for Testing and Materials reapproved F1717 standard for the assessment of mechanical properties of posterior spinal fixators, which simulates a vertebrectomy model and recommends mimicking vertebral bodies using polyethylene blocks. This set-up should represent the clinical use, but available data in the literature are few. Anatomical parameters depending on the spinal level were compared to published data or measurements on biplanar stereoradiography on 13 patients. Other mechanical variables, describing implant design were considered, and all parameters were investigated using a numerical parametric finite element model. Stress values were calculated by considering either the combination of the average values for each parameter or their worst-case combination depending on the spinal level. The standard set-up represents quite well the anatomy of an instrumented average thoracolumbar segment. The stress on the pedicular screw is significantly influenced by the lever arm of the applied load, the unsupported screw length, the position of the centre of rotation of the functional spine unit and the pedicular inclination with respect to the sagittal plane. The worst-case combination of parameters demonstrates that devices implanted below T5 could potentially undergo higher stresses than those described in the standard suggestions (maximum increase of 22.2% at L1). We propose to revise F1717 in order to describe the anatomical worst case condition we found at L1 level: this will guarantee higher safety of the implant for a wider population of patients.
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In a prospective study, we aimed to evaluate the potential use of kyphoplasty (KP) and vertebroplasty (VP) as complementary techniques in the treatment of painful osteoporotic vertebral compression fractures (VCFs). After 1 month of conservative treatment for VCFs, patients with intractable pain were offered treatment with KP or VP according to a treatment algorithm that considers time from fracture (Dt) and amount of vertebral body collapse. Bone biopsy was obtained intra-operatively to exclude patients affected by malignancy or osteomalacia. 164 patients were included according to the above criteria. Mean age was 67.6 years. Mean follow-up was 33 months. 10 patients (6.1%) were lost to follow-up and 154 reached the minimum 2-year follow-up. 118 (69.5%) underwent VP and 36 (30.5%) underwent KP. Complications affected five patients treated with VP, whose one suffered a transient intercostal neuropathy and four a subsequent VCF (two at adjacent level). Results in terms of visual analogue scale and Oswestry scores were not different among treatment groups. In conclusion, at an average follow-up of almost 3 years from surgical treatment of osteoporotic VCFs, VP and KP show similar good clinical outcomes and appear to be complementary techniques with specific different indications.
The present study proposes a semiautomatic software approach to reconstruct 3D subject-specific musculoskeletal model of thoracolumbar spine from radiographic digitized images acquired with EOS system. The approach is applied to evaluate the intervertebral loads in 38 standing adolescents with mild idiopathic scoliosis. For each vertebra, a set of landmarks was manually identified on radiographic images. The landmark coordinates were processed to calculate the following vertebral geometrical properties in the 3D space (i) location (ii) dimensions; and (iii) rotations. Spherical joints simulated disks, ligaments, and facet joints. Body weight distribution, muscles forces, and insertion points were placed according to physiological–anatomical values. Inverse static analysis, calculating joints’ reactions in maintaining assigned spine configuration, was performed with AnyBody software. Reaction forces were computed to quantify intervertebral loads, and correlation with the patient anatomical parameters was then checked. Preliminary validation was performed comparing the model outcomes with that obtained from other authors in previous modeling works and from in vivo measurements. The comparison with previous modeling works and in vivo studies partially fulfilled the preliminary validation purpose. However, minor incongruities were pointed out that need further investigations. The subjects’ intervertebral loads were found significantly correlated with the anatomical parameters in the sagittal and axial planes. Despite preliminary encouraging results that support model suitability, future investigations to consolidate the proposed approach are necessary. Nonetheless, the present method appears to be a promising tool that once fully validated could allow the subject-specific non-invasive evaluation of a deformed spine, providing supplementary information to the routine clinical examination and surgical intervention planning.
Purpose:We investigated the ability of the combinatorial administration of different inhibitors with activities on glioma angiogenesis, migration, and proliferation to produce a prolonged inhibition of glioma growth.
Experimental Design: We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF, cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX, PF-4/DLR).Results: When administered in combination, these drugs produced a prolonged and increased inhibition of glioma growth independently from the type of inhibitor used. The combinatory administration was more effective than the administration of a single inhibitor alone, and a strong therapeutic response was reached with a significantly lower amount of protein. The strongest inhibition was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis and invasion by separate mechanisms, were combined.Conclusions: This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.
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