Search

Study Design: A case report. Objectives: To report laminoplasty and recapping procedure of C7 for intradural tumor excision Summary of Literature Review: Various surgical techniques have been attempted to decrease postoperative axial neck pain. Material and Methods: Kurokawa laminoplasty of C7 was performed. Autogenous bone graft material was harvested from partial T1 laminectomy. Intradural tumor was removed without any complications. Four mini plates were applied at hinge sites of laminoplasty and one lag screw was fixed at the longitudinally splitted lamina of C7. Results: Early range of motion without braces was possible following laminoplasty and recapping procedure. Solid union was achieved at the hinge sites of laminoplasty at the 3-month postoperative follow-up. No instability was observed at the 2-year postoperative followup. The visual analog scale of axial neck pain at the 2-year postoperative follow-up was 2. Conclusions: Laminoplasty and recapping procedure might be a good option for intradural tumor excision to facilitate early range of motion and decrease postoperative axial neck pain.

Study Design: A Cross-sectional study Objective: This study evaluated the degree of osteoporosis of adolescent idiopathic scoliosis (AIS) and neuromuscular scoliosis (NMS) and compared bone mineral density. Literature Review: In osteoporosis, bone mineral density was not as dense even in the outer layer, and the cortex was thinner than normal. A larger screw doss not enhance the screw stability and can break the thin cortex in osteoporotic vertebrae. Materials and Methods: This study reviewed the cases of consecutive patients with scoliosis, who underwent an osteoporosis examination before surgery between August 2004 and June 2006. The osteoporosis examination included DEXA in lumbar vertebrae and proximal femur. The mean osteoporotic degree of both femurs was recorded. The data was analyzed using the BMD(bone mineral density, g/cm) and Z value of the BMD according to age, gender, and ethnicity. Results: The mean degree of the coronal deformity was 48.4 in AIS and 62.9 in NMS. A comparison of both groups revealed a significantly lower BMD and Z value of Femur, and BMD of the vertebra in the NMS patients (p�0.05). A comparison between AIS and non-ambulant NMS showed that all parameters were significantly lower in the non-ambulant NMS (p� 0.05). Neither the BMD and Z value of the AIS nor the NMS were associated with the severity of the spinal deformity. Conclusion: A lower BMD was measured in patients with non ambulant NMS than AIS. The degree of the osteoporosis, particularly of the non ambulant NMS patients need to be considered before undergoing surgery.

Study Design: An in vitro experiment. Objectives: To evaluate the mRNA expressions of matrix components, and analyze the cellular proliferation and proteoglycan synthesis of human intervertebral disc cells in response to dexamethasone and TGF-β1 Summary of Literature Review: Corticosteroids are responsible for the regulation of a diverse range of biological processes through modulation of the expression of target genes. The direct injection of methylprednisolone to the intervertebral disc (IVD) has been shown to cause degeneration and calcification of the disc in rabbits. Systemic administration of hydrocortisone induced degeneration of notochordal cells, which accelerated the aging process of the disc in mice. Transforming growth factor beta-1 (TGF-β1) is known as a potent agent for the proliferation, differentiation and matrix synthesis of IVD. Materials and Methods : IVD cells were isolated from ten patients, and subsequently cultured. Various doses of dexamethasone (DEX) and/or TGF-β1 were administered to the IVD cultures. DNA and proteoglycan syntheses were measured by the incorporation of [3H]-thymidine and [35S]-sulfate, respectively. RT-PCRs were performed for the expressions of aggrecan, collagen types I and II, and osteocalcin mRNA. R e s u l t s: Cultures with DEX showed increased cellular proliferation and decreased proteoglycan synthesis (p

Study design: An in vitro experiment. Objectives: To assess the effect of pulsed sinusoidal EMF on human intervertebral disc (IVD) cells. Literature Review Summary: Electromagnetic field (EMF) is known to modify some relevant physiological parameters of cells cultured in vitro, such as proliferation, synthesis, secretion of growth factors and transcription. EMF induces bone formation in delayed, non union and spinal fusion models. Also, the exposure of EMF has been shown to protect against the hazardous effect of smoking in the rabbit IVD. Materials and Methods: Human IVD cells were three-dimensionally cultured in alginate beads and exposed to a 650Ω, 1.8millitesla magnetic flux density, 60Hz sinusoidal wave of EMF. The cultures were divided into the control and EMF groups, with various exposure times. The cytotoxicity, and DNA and proteoglycan syntheses were measured by the MTT assay, and [3H]thymidine and [35S]-sulfate incorporation, respectively. RT-PCRs were performed for aggrecan, and collagen types I and II mRNA expressions. Results: There was no recognizable cytotoxicity in the EMF group, but cellular proliferation was stimulated (p

Study Design: In-vitro experiments using human mesenchymal stem cells (MSCs), intervertebral disc (IVD) cells and type 5 adenovirus/transforming growth factor-β1 construct (Ad/TGF-β1). Objectives: To determine the effect of MSC-based gene therapy for matrix regeneration of IVD cells. Summary of Literature Review: MSCs are known to be multipotent in tissue regeneration. In degeneration of IVD, cellular replacement with genetic modification other than that of IVD cells may prove an enhanced mechanism for the regeneration of IVD cells. Materials and Methods: MSCs and IVD cells were cultured and an adenovirus construct containing TGF-β1 cDNA (Ad/TGF-β 1) was also produced. In the first step, the MSCs were transduced with Ad/TGF-β1, then mixed with IVD cells in various proportions and three dimensionally cultured. [methyl-H]Thymidine and [ S]Sulfur incorporation for DNA and proteoglycan synthesis, respectively, were measured. RT-PCR was performed to assess the aggrecan and collagen types I and II mRNA expressions Results: Mixed cultures of MSC and IVD cells showed relatively similar amounts of newly synthesized proteoglycan compared with cultures of IVD cells only. In mixed cultures transduced with Ad/TGF-β1, there were significant decreases in newly synthesized proteoglycan with increasing the proportions of MSCs, which was also found with the aggrecan and collagen type II mRNA expressions. However, the collagen type I mRNA expression increased with increased proportions of MSCs transduced with Ad/TGF-β1. Conclusion: Cell therapy with MSCs and IVD cells provided a mechanism for cellular augmentation. However, MSC-based gene therapy coupled with IVD cells did not maintain a chondrogenic phenotype.

Objectives: To determine the dual roles of LF as an osteoinductive agent and carrier for ex-vivo gene transfer. Summary of Literature Review: LF is known to have osteogenic potential. Pathologically, ossified LF may cause myelopathy and radiculopathy. BMP-2 is known as an important factor in the differentiation, and maintenance, of osteoblast phenotypes. Ex-vivo gene transfer, using human LF for spinal fusion, has never been attempted before. Materials and Methods: The LF cells were cultured from the degenerated LF of spinal stenosis patients. An adenovirus construct, containing BMP-2 cDNA (Ad/BMP-2), was also produced. The LF cell cultures were exposed to the adenoviral construct. The Osteocalcin expression was analysed by Western blot analysis. The osteocalcin and BMP-2 mRNA expressions were analysed by RT-PCR. Bone formation was assessed by alkaline phosphatase and Von Kossa stains. Results: The LF cell cultures, with Ad/BMP-2, showed transgene expression in the Western blot analysis. Also, the cultures exhibited the mRNA expressions of both osteocalcin and BMP-2, in a dose-dependent manner. The LF cultures, with Ad/BMP-2, demonstrated alkaline phosphatase expression and bone nodule formations from the Von Kossa staining. Conclusion: The genetically modified LF strongly induced osteogenesis, which can be used during a spinal fusion, as an osteoinductive agent and carrier, for ex-vivo gene transfer.

‐ Abstract ‐ Study design: This was a retrospective study that analyzed and compared the results between a posterior lumbar interbody fusion, and a posterolateral fusion (PLIF+PLF), and PLF alone, in the treatment of spondyolytic spondylolisthesis in adults. O b j e c t i v e s: To evaluate the outcomes of two surgical treatment methods for spondylolytic spondylolisthesis-posterolateral fusion alone, and circumferential fusion, using posterior lumbar interbody fusion and posterolateral fusion. Summary of Literature Review: There have been many reports regarding the surgical treatment of spondylolisthesis. Posterior lumbar interbody fusions have certain distinct mechanical advantages over posterolateral ones. However, the clinical and radiological results do not usually correlate. Materials and Methods: Between January 1998 and December 2001, 38 patients, with spondylolytic spondylolisthesis, were operated on by a single surgeon. Nineteen patients underwent a posterolateral fusion alone (group I), with the same number undergoing an additional posterior lumbar interbody fusion (group II). These two groups were evaluated for their clinical outcomes, radiological measurements and fusion rates. Results: The losses in the slip reduction were 7.1 and 1.3% in the PLF and PLF+PLIF groups, respectively (P 0.05). Conclusions: Although the addition of a posterior lumbar interbody fusion, to an instrumented posterolateral fusion, following decompression, is more predictable in maintaining a correction and achieving union, a posterolateral fusion may have a better clinical outcome in patients with low grade spondylolytic spondylolisthesis. Therefore, careful patient selection is necessary for each operation.

Study Design : In-vitro experiment. Objectives : To determine the effect of bone morphogenetic protein-2 in the osteogenesis of human ligamentum flavum cells and test the feasibility of gene transfer to these cells. Summary of literature review : Bone morphogenetic protein-2 (BMP-2) is known to be an important factor in the differentiation and maintenance of the osteoblastic phenotype. Tissue engineering for osteogenesis in ligamentum flavum by BMP-2 and gene transfer has not been previously studied. Materials and Methods : Ligmentum flavum cells were harvested and cultured from surgical patients with spinal stenosis. BMP-2 was produced by transfecting pcDNA3.1/Hygro/BMP-2 into CHO cells using Lipofectamine 2000. Adenovirus-lacZ (Ad/lacZ) was also produced, and administered with BMP-2 to cell culture. The expression of lacZ was analyzed by X-gal staining. Bone formation was assessed by alkaline phosphatase, von Kossa, and alizarin Red-S staining, and the expression of osteocalcin was determined immunocytochemically. Results : Ligamentum flavum cell cultures with Ad/lacZ showed marker gene expression. BMP-2 induced osteogenesis in ligamentum flavum cells as evidenced by alkaline phosphatase, von Kosa, and alizarin Red-S staining. Also, cell culture with BMP-2 showed strong positivity with osteocalcin by immunocytochemistry. Conclusion : BMP-2 more strongly induced the osteogenesis of ligamentum flavum, and also its gene transfer to ligamentum flavum was found to be feasible. These results may open a new era of ligamentum flavum tissue engineering..

Study Design : A prospective study. Objective : To determine whether phospholipase A2(PLA2) activity in herniated lumbar disc is correlated with clinical, radiographic and anatomic signs of the patients with herniated nucleus pulposus. Summary of Literature Review : Several studies have suggested inflammation around nerve root as a mechanism of sciatica and PLA2 emerges as a key enzyme of the inflammation. However, consensus about association between PLA2 and sciatica has been lacking. In addition, there has been no report that investigated the relationship between cytosolic and membrane PLA2 in herniated disc and patient’s symptoms. Materials and Methods : Human intervertebral disc materials were obtained from 33 patients who underwent discectomy for HNP. The information was noted about smoking history, medication of NSAID, symptom duration, pain score on a visual analog scale(VAS), positive angle of straight leg raising test (SLR), neurologic deficits, Thompson grade of herniated disc, volume of herniation shown by the MRI and type of herniation based on the operative record. These data were matched to the PLA2 a c t i v i t y in herniated disc measured using Western blotting analysis. PLA2 activity was expressed as the relative percentage compared to that of a 33-year-old female disc obtained during an operation for spinal fracture. The analysis was carried out using MannWhitney test, Pearson correlation analysis, simple linear regression analysis. A value of p

Purpose : To elucidate host immune responses to intradiscal gene transfer. Materials and Methods : Twenty rabbits were utilized. Ad/luciferase (adenovirus construct) were injected into nucleus pulposus of lumbar vertebrae. Group 1 received intradiscal injection of Ad/luciferase only, Group 2 received subcutaneous and intradiscal injection simultaneously, Group 3 received subcutaneous injection then intradiscal injection with 2 weeks interval. Blood samples were obtained serially after injection. Animals were sacrificed at 7 weeks. Antibody to adenovirus in peripheral blood was measured with ELISA and transgene expression was measured with standard luciferase kits. Results : All rabbits in the Group 2 and 3 exhibited increased production of neutralizing antibody. There were clearly two subgroups in Group 1, three rabbits exhibited production of antibody but remaining three rabbits showed little or no production of antibody. All rabbits showed robust increase in transgene expression regardless of titer of neutralizing antibody. Conclusion : The intervertebral disc is favorable site for adenovirus-mediated gene transfer escaping from systemic immunity.

Study Design : In vitro experiment to determine the matrix synthesis of human intervertebral disc (IVD) cell to adenovirusmediated therapeutic gene transfer. Objectives : To elucidate proteoglycan and collagen synthesis of human IVD cells in vitro to adenovirus-mediated transfer of cDNA of transforming growth factor-beta 1(TGF-β1). Summary of Literature Review : Sophisticated method to delivery of growth factors, in continuous manner, is the genetic modification of disc cells through gene transfer. Confirming susceptibility of human IVD cell to adenovirus, anabolic response of human IVD cells to therapeutic gene transfer should be next step. Materials and Methods : IVD tissue was obtained from fourteen patients with grade III, IV degeneration. Isolation and culture of disc cells were performed. Disc cells were treated with either Ad/TGF-β1 exogenous TGF-β1. Control cultures were treated with either saline or Ad/luciferase. Newly synthesized proteoglycans were assessed by S-sulfate incorporation using chromatography on Sepadex G-25 in PD-10 columns. Uptake of H proline was used to measure synthesis of collagen and noncollagen protein. Results : Culture treated with Ad/TGF-β1 showed 3 fold increase in proteoglycan synthesis (p

Growth factor is a polypeptide regulating cell proliferation, maturation, activity, and apoptosis. Despite its small molecular weight, it exerts diverse and potent biologic effects on cellular function. With recent development of molecular biology and vector technology, it is now possible to administer recombinant growth factors in clinical dose and modify somatic cell with growth factor encoding gene. Research fields in spinal surgery can be divided into spinal fusion, disc regeneration and spinal cord regeneration. In this review, we discuss the action mechanism of growth factors and their possible clinical applications especially in the field of spinal fusion and disc regeneration.

Background : Genetic modification of cells through gene transfer gains popularity as a sophisticated delivery system in the management of musculoskeletal disease. Anabolic growth factors like IGF-1 BMP-2 OP-1, and TGF-s1 were candidate for therapeutic purposus for regenerating matrix of intervertebral disc. TGF-s1, OP-1 and BMP-2 share same pathway i.e. Smad while IGF-1 utilize P13K pathway. Accordingly it is logical to use two cytokine encoding genes which using different signal transduction pathway to upregulate matrix synthesis. Purpose : To elucidate the anabolic effect of the combination gene transfer(IGF-1 and TGF-s1 encoding gene) to human disc cells, cultured in alginate beads. Materials and Methods : Lumbar and cervical intervertebral disc tissue was obtained from surgical disc procedure from fifteen patients. After isolation and culture of the cells, cultures were transduced with first, Adenovirus-TGFs1 construct(Ad/TGF-s1) and Ad/IGF-1 respectively, second, with combination of two viral constructs(Ad/TGF-s1+Ad/IGF-1). Cultures treated with saline and Ad/luciferase served as control. Then cultures were incorporated into alginate beads. Exogenous TGF-s1(2 ng/ml) and IGF-1(100 ng/ml) were administered also. Newly synthesized proteoglycan was assessed using S35 incorporation using chromatography on Sephadex G-25 in PD-10 column Results : In cultures transduced with single therapeutic gene construct, there were statistically significant 2.9 fold(Ad/TGF-s1) and 1.8 fold(Ad/IGF-1) increase in newly synthesized proteoglycan comparing control(p

‐ Abstract ‐ Study Design : In vivo study to determine the immune effects to adenoviral vector encoding LMP-1 cDNA in rabbit. Objective : To quantify the immune effect of Ad5-LMP-1 in the rabbit during the therapeutic gene transfer. Summary of Literature Review : One of the major limitations in the use of adenoviral vector for gene therapy is the immune response and it made the poor transduction efficiency when re-administrated. Adenoviral antigen plus those derived from transgene expression in transduced cell contribute to cellular, humoral and non-specific immune response constitutes barriers to successful gene therapy. Therefore, the animal immune model will be mandatory to study the immune impact. Materials and Method : We i.v. injected Ad5-β Gal to total 24 adult NZW rabbits; 1x10 8