Multipotential differentiation of human anulus fibrosus cells: an in vitro study.

BACKGROUND: The existence of fibrocartilage, bone-like tissues, nerves, and blood vessels in the anulus fibrosus during intervertebral disc degeneration has been well documented. Migration of differentiated cells from outside the intervertebral disc has been hypothesized as a possible mechanism for the formation of these tissues. We hypothesized that the normal anulus fibrosus tissue contains multipotent progenitor cells, which are able to differentiate into cartilage and/or fibrocartilage cells, osteoblasts, neurons, and blood vessel cells. METHODS: We isolated anulus fibrosus cells from the nondegenerative intervertebral discs of adolescent (thirteen to sixteen-year-old) patients with idiopathic scoliosis and cultured the cells in vitro in induction media containing different stimuli. Immunophenotypic analysis of cell surface markers was performed by flow cytometry. Expression of markers of adipogenesis, osteogenesis, chondrogenesis, neurogenesis, and differentiation into endothelial lineages was determined with use of immunostaining, cytohistological staining, and reverse transcription-polymerase chain reaction. RESULTS: Anulus fibrosus cells expressed several of the cell surface antigens that are sometimes associated with mesenchymal stem cells, including CD29, CD49e, CD51, CD73, CD90, CD105, CD166, CD184, and Stro-1, and two neuronal stem cell markers, nestin and neuron-specific enolase. Furthermore, varying the stimulants added to the induction media determined whether anulus fibrosus cells differentiated into adipocytes, osteoblasts, chondrocytes, neurons, or endothelial cells. CONCLUSIONS: Anulus fibrosus cells isolated from nondegenerative intervertebral discs can differentiate into adipocytes, osteoblasts, chondrocytes, neurons, and endothelial cells in vitro.

Narrative-based intervention for word-finding difficulties: a case study.

BACKGROUND: Children with word-finding difficulties manifest a high frequency of word-finding characteristics in narrative, yet word-finding interventions have concentrated on single-word treatments and outcome measures. AIMS: This study measured the effectiveness of a narrative-based intervention in improving single-word picture-naming and word-finding characteristics in narrative in a case study. METHODS & PROCEDURES: A case study, quasi-experimental design was employed. The participant was tested on picture naming and spoken word to picture matching on control and treatment words at pre-, mid-, and post-therapy and an 8-month maintenance point. Narrative samples at pre- and post-therapy were analysed for word-finding characteristics and language production. A narrative-based language intervention for word-finding difficulties (NBLI-WF) was carried out for eight sessions, over 3 weeks. The data were subjected to a repeated-measures trend analysis for dichotomous data. OUTCOMES & RESULTS: Significant improvement occurred for naming accuracy of treatment, but not for control words. The pattern of word-finding characteristics in narrative changed, but the frequency did not reduce. CONCLUSIONS & IMPLICATIONS: NBLI-WF was effective in improving naming accuracy in this single case, but there were limitations to the research. Further research is required to assess the changes that may occur in language production and word-finding characteristics in narrative. Community clinicians are encouraged to refine clinical practice to ensure clinical research meets quality indicators.

Implications of lumbar plexus anatomy for removal of total disc replacements through a posterior approach.

STUDY DESIGN: An anatomic study in which the lumbar plexuses of 14 embalmed cadavers were dissected bilaterally and measured using a posterior approach. OBJECTIVE: To determine the cephalocaudal (root-to-root) distances and the mediolateral (root-to-tether) distances within the lumbar plexus and determine the feasibility for removal of a lumbar total disc replacement (TDR) through these anatomic spaces using a posterior approach. SUMMARY OF BACKGROUND DATA: Currently, lumbar TDRs are implanted primarily through an anterior retroperitoneal or transperitoneal approach. However, revision surgeries through these approaches can be complicated by significant adhesions, with potential injuries to intra- and retroperitoneal contents. Advancements in accessing anterior column structures through a posterior lumbar extracavitary approach suggest that posterior removal of TDRs may be an alternative. Unlike the thoracic extracavitary approach in which ligation of the thoracic nerve rarely leaves significant morbidity, the lumbar extracavitary approach cannot rely on the analogous ligation of the lumbar root to achieve access. Therefore, feasibility of the lumbar extracavitary approach depends on the presence of sufficient anatomic space between the tethered nerves of the lumbar plexus. METHODS: Fourteen adult cadavers (5 M/9F) were dissected through a posterior approach to expose the lumbar plexus bilaterally. The root-to-root distances at levels L2-S1 and corresponding root-to-tether distances at levels L3-L5 were measured bilaterally. RESULTS: Root-to-root distance was smallest at the male L5-S1 interval (11.7 +/- standard deviations 4.1 mm). Root-to-tether distance was smallest at the female L5 (43.1 +/- standard deviations 8.4 mm). These plexus measurements compare favorably with the CHARITE TDR components, in which the thickest sliding core is 11.0 mm in height and the largest endplate is 42.0 mm in width. CONCLUSION: This anatomic study suggests that posterior TDR removal is possible in the lumbar spine without undue risk to the surrounding nervous structures.

The use of an expandable cage for corpectomy reconstruction of vertebral body tumors through a posterior extracavitary approach: a multicenter consecutive case series of prospectively followed patients.

BACKGROUND CONTEXT: Posterior decompressions in the form of laminectomies for vertebral body tumors have poor outcomes. Surgical management typically requires anterior decompression and reconstruction; however, these procedures can be associated with significant morbidity and mortality. PURPOSE: To evaluate the feasibility of anterior spinal column reconstruction using an expandable cage through a posterior approach. STUDY DESIGN/SETTING: Multicenter consecutive case series of 21 prospectively followed patients. PATIENT SAMPLE: Twenty-one patients with vertebral body tumors treated with anterior and posterior resection and reconstruction from a single posterior approach were followed prospectively. OUTCOME MEASURES: Pre- and postoperative neurologic status, number of levels instrumented and fused, length of surgery, length of stay after surgery, and complications related directly or indirectly to surgery were analyzed. In addition, pre- and postoperative radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) scans were evaluated for involvement of the vertebral body and associated posterior elements. Particular attention was paid to the presence of either unilateral or bilateral pedicle and/or middle column involvement. METHODS: Patients were placed in a prone position on a rotating radiolucent table. Corpectomy was performed from an extracavitary approach, and anterior column reconstruction was completed with an expandable cage. The posterior tension band and spinal fusion was completed with segmental pedicle screw fixation and performed through the same posterior exposure. No patient required a separate anterior procedure. RESULTS: Patients' average age was 60.3 years (range, 17-78); there were 12 women and 9 men. Eighteen underwent single-level corpectomies (11 thoracic and 7 lumbar), and 3 underwent two-level corpectomies (T4-T5, T11-T12, and T12-L1). Average estimated blood loss (EBL) and length of surgery per level were 1,360 cc (range, 200-2,500) and 5.3 hours (range, 2.7-8.6), respectively. Average postoperative stay was 4.7 days. Nine patients had at least one partial motor grade improvement. One patient had postoperative left lower extremity weakness after surgical decompression and reconstruction secondary to iatrogenic nerve root traction but remained ambulatory. No chest tubes or postoperative bracing was required. At the most recent follow-up, six patients were alive at an average of 16.1 months (range, 3-33). For the 15 patients who died, the average life span after surgery was 6.8 months (range, 1-16). In addition to the iatrogenic nerve root injury, one cage required repositioning on postoperative Day 2 and one cage demonstrated radiographic evidence of settling but did not require surgical intervention; there were no deep venous thromboses (DVTs), pneumothoraces, pneumonias, ileus, or other complications, with a total complication rate of 14.3%. CONCLUSIONS: This is the largest study that specifically examines the use of an expandable cage through a posterior extracavitary approach for reconstruction after vertebral body tumor resection. The use of an expandable cage combined with an extracavitary approach is feasible and allows the surgeon to address both the anterior and posterior columns through a single incision. Although technically challenging, both one- and two-level corpectomies in the thoracic and/or lumbar spine can be performed with this technique. Furthermore, insertion of the expandable cage in the collapsed position and then expansion in situ after implantation allowed for all lumbar reconstructions to be completed without sacrificing any of the lumbar nerve roots. Our 14.3% complication rate is similar to those reported in anterior-alone and circumferential spinal procedures.

A novel "four-rod technique" for lumbo-pelvic reconstruction: theory and technical considerations.

STUDY DESIGN: Surgical technique with case example. OBJECTIVE: To report on a novel technique that allows for the placement of 4 separate longitudinal rods across the lumbo-pelvic junction. SUMMARY OF BACKGROUND DATA: Despite advances in surgical techniques and instrumentation, lumbo-pelvic fixation remains a significant challenge. Fusions to the pelvis create long lever arms and generate high forces across the lumbosacral junction, resulting in high rates of screw pullout and implant fracture. In the attempt to achieve better bony fixation, techniques described include the use of bone cement, hydroxyapatite, and expandable screws. Although this process has decreased the incidence of screw pullout, it has not addressed the problem of rod fracture at the lumbo-pelvic junction. METHOD: There are 4 separate longitudinal rods placed across the lumbo-pelvic junction that couples proximal lumbar screw anchors to 4 separate pelvic fixation points. Proximal lumbar fixation anchors are based on alternating Roy-Camille "straight ahead" screws and Magerl "lateral to medial converging" pedicle screws. There are 4 distal pelvic fixation anchors used based on 1 pair of Galveston-like screws and 1 pair of proximal iliac wing screws. RESULTS: Early results of both ex vivo and in vivo reconstruction show that careful insertion of the lumbar and pelvic screws allows for divergent placement of the pedicle screw heads in a manner that 2 longitudinal rods can be placed per side, resulting in a total of 4 longitudinal rods across the lumbo-pelvic junction. Selection of cross-links in various combinations allows for additional axial and torsional stability, depending on the desired reconstruction. CONCLUSION: Longer follow-up is necessary, and biomechanical and finite element studies are needed to show long-term efficacy of this technique, however, early results indicate that such a construct is feasible. Furthermore, depending on the general medical condition of the patient, immediate postoperative weight bearing is possible and reasonable.

Identification of phenyl-pyridine-2-carboxylic acid derivatives as novel cell cycle inhibitors with increased selectivity for cancer cells.

Ro 41-4439, a phenyl-pyridine-2-carboxylic acid derivative, was identified by a cell-based screening approach that exploits the differences between normal and cancer cells in their sensitivity to cytotoxic agents. This compound showed low micromolar antiproliferative activity and cytotoxicity against a broad panel of human cancer cell lines in vitro, and over 10-fold selectivity to cancer cells when tested in parallel with a panel of proliferating normal human cells. Cytotoxicity of Ro 41-4439 is due to arrest of cell cycle progression in mitosis followed by induction of apoptosis. Four-week treatment of nude mice bearing established mammary tumor xenografts (MDA-MB-435) with well-tolerated doses of the compound showed 73% inhibition of tumor growth. Limited exploration of structure-activity relationships involving side chain length, and aryl and pyridine rings allowed for the identification of more potent analogs.