Biomedical subjects

Todd J Albert

Publications and source records attributed to Todd J Albert.

At least 19 recordsLinked to original sources

PubMed2007

Galectin-3 expression in the intervertebral disc: a useful marker of the notochord phenotype?

STUDY DESIGN: Galectin-3 expression in rat intervertebral disc at different stages in postnatal life is evaluated. OBJECTIVE: To determine if galectin-3 expression is confined to cells of the nucleus pulposus in the postnatal rat intervertebral disc. SUMMARY OF BACKGROUND DATA: During embryonic development, the anulus fibrosus is derived from the sclerotome, whereas the nucleus pulposus is notochordal. Many authorities opine that in the postnatal disc, notochordal cells play a central role in controlling the development of degenerative disc disease. Surprisingly, unequivocal evidence supporting the existence of notochordal cells in the nucleus pulposus in postnatal life has yet to be demonstrated. Since the expression of galectin-3 is commonly used to identify notochordal cells, we evaluated its expression in tissues of the rat disc and in cultured cells. METHODS: Galectin-3 expression was studied in the nucleus pulposus and anulus fibrosus tissue of rat discs (2 days, 9 weeks, and 10 months old), and cultured cells using different biochemical and molecular biology methods. Rat sternal cartilage and cultured sternal chondrocytes were used as controls. RESULTS: Immunohistochemical studies indicated that galectin-3 was present in the nucleus pulposus and anulus fibrosus. In both discal tissues and cultured cells, studies confirmed that there was a robust expression of galectin-3 messenger ribonucleic acid and protein. Protein expression patterns were similar in neonatal, young, and mature rats. There was also evidence of intracellular and membrane expression of galectin-3 in the cultured disc cells. Finally, significant levels of galectin-3 were evident in rat sternal cartilage and cultured sternal chondrocytes. CONCLUSIONS: Results of the study indicate that galectin-3 is expressed in the neonatal, young, and mature rat disc, and its expression is not restricted to the cells of the nucleus pulposus. Because of its ubiquitous expression, this protein cannot be used as a marker of notochordal cells in the postnatal rat disc.

Aging↗

PubMed2006

Use of computed tomography to predict failure of nonoperative treatment of unilateral facet fractures of the cervical spine.

STUDY DESIGN: Retrospective review. OBJECTIVES: To determine whether radiographic measurements derived from standard computed tomography (CT) evaluation can be used to predict failure of nonoperative treatment in patients with unilateral facet fractures. SUMMARY OF BACKGROUND DATA: There is no consensus regarding treatment of unilateral cervical spine facet fractures. Management of this injury is based primarily on the presence of neurologic deficits and the degree of perceived spinal instability. CT-based criteria for predicting failure of nonoperative treatment in this patient population have not been examined. METHODS: Initial CT scans of all patients with unilateral cervical facet fractures were reviewed. Direct measurements included height and width of the facet fracture fragment, fracture displacement, and angulation. Calculated data included percent height and width of the fracture fragment based on the height and width of the contralateral intact facet. RESULTS: A total of 24 patients with 26 unilateral facet fractures were identified. Five patients with 5 facet fractures failed nonoperative management and required delayed surgical stabilization. Comparing patients successfully treated nonoperatively to those failing nonoperative management, a significant difference was found in absolute height of the fracture fragment (P = 0.0002), articular fracture height (P = 0.008), and height of the fracture fragment expressed as a percentage of the contralateral intact lateral mass (P = 0.026). CONCLUSION: The only significant risk factors identified for failure of nonoperative treatment were craniocaudal height of the fracture fragment and relative height of the fracture fragment expressed as a percentage of the intact lateral mass. This study suggests that patients with unilateral cervical facet fractures involving >40% of the absolute height of the intact lateral mass or an absolute height >1 cm are at increased risk for failure of nonoperative treatment. Failure of nonoperative treatment was not observed in any patient with a fracture involving less than 40% of the height of the lateral mass or an absolute height <1 cm.

Adolescent↗

PubMed2006

Osteogenic protein-1 induced gene expression: evaluation in a posterolateral spinal pseudarthrosis model.

STUDY DESIGN: Molecular study of gene expression in rabbit lumbar pseudarthrosis repairs using reverse transcriptase polymerase chain reaction. OBJECTIVE: To evaluate differential gene expression of no graft, autograft, and osteogenic protein-1 treated pseudarthroses. SUMMARY OF BACKGROUND DATA: Osteogenic protein-1 is a potential bone graft alternative that has achieved high fusion rates in a rabbit lumbar fusion model, including in the repair of nicotine-induced pseudarthroses. A previous study established a correlation between osteogenic protein-1 fusion outcomes and an enhanced level of cytokine gene expression. The expression of such cytokines is known to be decreased in nicotine-exposed rabbit fusion masses. METHODS: Messenger ribonucleic acid was isolated from nicotine-exposed New Zealand white rabbit lumbar pseudarthroses following attempted no graft, autograft, and osteogenic protein-1 pseudarthrosis repairs. Reverse transcriptase polymerase chain reaction was used to assess the expression of angiogenin, angiopoietin, intercellular adhesion molecule, platelet-derived growth factor-beta, vascular endothelial growth factor, bone morphogenetic proteins 2 and 7, type I collagen, and osteonectin. Glyceraldehyde-3-phosphate dehydrogenase was used as a constitutively expressed control. RESULTS: Levels of gene expression in the osteogenic protein-1 group were higher than those of the autograft group, which were higher than the no graft group for the majority of the genes studied. CONCLUSIONS: In the rabbit pseudarthrosis model, gene expression data supported the hypothesis that successful pseudarthrosis repair is related to the induction of osteogenic and angiogenic cytokines by osteogenic protein-1.

Animals↗

PubMed2006

Neurophysiological identification of position-induced neurologic injury during anterior cervical spine surgery.

This study was a retrospective review of 3,806 patients who underwent anterior cervical spine surgery with multi-modality neurophysiological monitoring consisting of transcranial electric motor evoked potentials, somatosensory evoked potentials and spontaneous electromyography between 1999-2003. The objectives of this study were twofold: (1) to evaluate the role of transcranial electric motor evoked potential tceMEP and ulnar nerve somatosensory evoked potential (SSEP) monitoring for identifying impending position-related stretch brachial plexopathy, peripheral nerve entrapment/compression or spinal cord compression and (2) to estimate the point-prevalence of impending neurologic injury secondary to surgical positioning effects. Sixty-nine of 3,806 patients (1.8% showed intraoperative evidence of impending neurologic injury secondary to positioning, prompting interventional repositioning of the patient. The brachial plexus was the site of evolving injury in 65% of these 69 cases. Impending brachial plexopathy was most commonly noted immediately following shoulder taping and the application of counter-traction. Brachial plexus stretch upon neck extension for optimal surgical access and visualization was second in frequency-of-occurrence. Evolving traction injury to the ulnar nerve attributed to tightly-wrapped or malpositioned arms was observed in 16% of alerted cases, whereas evolving spinal cord injury following neck extension accounted for an additional 19%. This study highlights the role of tceMEP and ulnar nerve SSEP monitoring for detecting emerging peripheral nerve injury secondary to positioning in preparation for and during anterior cervical spine surgery.

Adult↗

PubMed2006

Medical complications of surgical treatment of adult spinal deformity and how to avoid them.

STUDY DESIGN: Review article of medical complications related to adult spinal deformity surgery. OBJECTIVE: To identify medical complications related to surgery for adult spinal deformity and suggest ways to minimize their occurrence and to avoid them. SUMMARY OF BACKGROUND DATA: Medical complications are a major consideration in adult spinal deformity surgery. Few studies have been done to identify the medical complication rate in relation to these procedures. METHODS: We review the literature pertaining to medical complications regarding spinal deformity surgery. RESULTS: Urinary tract infections are the most frequently seen complication. Additionally, pulmonary complications are the most common life-threatening complication. Medical complications are a frequent occurrence with adult deformity spinal surgery. CONCLUSIONS: Awareness of the presentation, treatment, and prevention of medical complications of deformity surgery may allow minimization of their occurrence and optimize treatment should they occur.

Gastrointestinal Diseases↗

PubMed2006

Healos/recombinant human growth and differentiation factor-5 induces posterolateral lumbar fusion in a New Zealand white rabbit model.

STUDY DESIGN: Posterolateral lumbar spine fusions in New Zealand white rabbits. OBJECTIVE: To evaluate the efficacy of recombinant human growth and differentiation factor-5 (rhGDF-5) lyophilized to a Healos carrier (cross-linked type I collagen with hydroxyapatite coating; DePuy Spine, Inc., Raynham, MA) in inducing fusion. SUMMARY OF BACKGROUND DATA: Bone graft substitutes have become an area of considerable interest. rhGDF-5 is one such product. Limited lumbar preclinical studies have been performed with this product. METHODS: Single-level, intertransverse process fusions were performed in 67 rabbits using iliac crest autograft (n = 13), Healos alone (n = 13), or 0.5, 1.0, or 1.5 mg/cc rhGDF-5 lyophilized to Healos (n = 13 per group). At 8 weeks, the rabbits were euthanized. Fusion masses were assessed. RESULTS: There were 2 animals (3%) lost to complication. Manual palpation revealed fusion rates for autograft of 38% (5/13), Healos alone of 0% (0/13), and each of the Healos/rhGDF-5 groups of 100% (13/13). Histologic analyses were 95% sensitive and 95% specific for confirming fusion. Histologic differences were found among the treatment groups. CONCLUSIONS: In this rabbit fusion model, Healos/rhGDF-5 induced fusion in 100% of the rabbits studied. This rate was significantly higher than the fusion rate induced by autograft (38%). Overall, these results support continued research of Healos/rhGDF-5 as a potential bone graft alternative.

Animals↗

PubMed2006

Long-term magnetic resonance imaging evaluation of bioresorbable anterior cervical plate resorption following fusion for degenerative and traumatic disk disruption.

STUDY DESIGN: A retrospective magnetic resonance imaging (MRI) review of a series of patients who underwent a single-level anterior cervical discectomy and fusion followed by anterior plate stabilization using an anterior cervical resorbable mesh plate and screw system. OBJECTIVE: MRI evaluation of the long-term implant resorption properties of a bioresorbable anterior cervical plate and the adjacent peri-implant soft tissue environment. SUMMARY OF BACKGROUND DATA: The use of bioresorbable anterior cervical plates for immediate cervical stabilization following an anterior cervical discectomy and fusion presents several distinct advantages over metallic instrumentation. Bioresorbable polymers may diminish, by their resorbability, implant-related complications such as loosening, migration, and failure of instrumentation, as well as stress shielding of the underlying fusion. Information on the intermediate and long-term bony and soft tissue reaction to the resorption byproducts of these biomaterials is limited. METHODS: There were 9 consecutive patients who underwent single-level anterior cervical decompression and fusion using allograft cortical bone, followed by bioresorbable polylactide anterior mesh plate and screw fixation. Following institutional review board approval, 5 of the 9 patients agreed to postoperative MRI assessment of the peri-implant area. An independent radiologist then characterized implant degradation, and the presence of soft tissue inflammation and swelling during the resorption phase of the bioresorbable plate. RESULTS: At an average follow-up of 32 months, MRI assessment showed no evidence of soft tissue swelling or inflammation related to the resorption of a bioresorbable anterior plate in any of the 5 patients. In addition, none of the patients complained of any dysphagia or phonation difficulties. CONCLUSIONS: Based on MRI assessment, these devices, at more than 2-year follow-up, did not indicate any local chronic inflammation or swelling resulting from their degradation. Clinical symptoms of dysphagia or dysarthria, a common reported problem following anterior cervical spine procedures, were not observed in any patient.

Absorbable Implants↗

PubMed2006

Characterization of neurophysiologic alerts during anterior cervical spine surgery.

STUDY DESIGN: A retrospective review of neurophysiologic alerts during anterior cervical surgery. OBJECTIVES: To examine incidence and types of neurophysiologic alerts and their correlation with new postoperative neurologic deficits after anterior cervical discectomy or corpectomy procedures. SUMMARY OF BACKGROUND DATA: Although multimodality neurophysiologic monitoring has been shown to predict iatrogenic neurologic injuries in scoliosis surgeries, their role in degenerative or trauma-related anterior cervical spine surgery is still unclear. MATERIALS AND METHODS: We retrospectively reviewed 1,445 patients who underwent anterior cervical discectomy or corpectomy and arthrodesis with neurophysiologic monitoring that included transcranial electrical motor-evoked potentials (tceMEP), somatosensory-evoked potentials (SSEP), and spontaneous electromyography (EMG). Intraoperative alerts were analyzed for type, perceived cause, actions taken to reverse or minimize the possible spinal cord injury, and any new postoperative neurologic deficits. RESULTS: There were 267 (18.4%) procedures that had either minor (spontaneous, sustained EMG) or major (tceMEP/SSEP amplitude reduction) alerts. Patients who underwent corpectomies had 28% increased risk of having a major neurophysiologic alert compared with those who had discectomies. Diagnosis of cervical spondylotic myelopathy or trauma increased the risk of having a major neurophysiologic alert 30% and 76%, respectively, compared with cervical radiculopathy. Eight surgeries were aborted due to persistent tceMEP/SSEP amplitude loss, but none resulted in new postoperative neurologic deficits. Two patients had halo-vest applied due to early termination of surgery. One of these patients ultimately could not receive definitive surgical stabilization. DISCUSSION AND CONCLUSION: Diagnosis of cervical spondylotic myelopathy or trauma and cervical corpectomy procedures increase the risk for having major intraoperative alerts. In case of persistent tceMEP/SSEP amplitude loss, consider delaying potentially harmful interventions, such as premature termination of the procedure or methylprednisolone infusion, until a new neurologic deficit is verified with an awake-clinical examination.

Adult↗

PubMed2006

Quantitative prediction of spinal cord drift after cervical laminectomy and arthrodesis.

STUDY DESIGN: Retrospective review of radiographic parameters. OBJECTIVES: To identify preoperative radiographic parameters that may be quantitatively predictive of postoperative spinal cord drift after cervical laminectomy and arthrodesis. SUMMARY OF BACKGROUND DATA: Cervical laminectomy and arthrodesis can be an effective method to treat anterior compressions of the spinal cord if there is a sufficient posterior spinal cord drift after surgery. Preoperative cervical alignment has shown some correlations to the degree of spinal cord shift, but whether this and other preoperative radiographic parameters can be used to quantitatively predict the amount of spinal cord drift is unclear. MATERIALS AND METHODS: Preoperative and postoperative radiographs (radiographs, MRIs, and CT) of patients who had cervical laminectomy and arthrodesis were reviewed retrospectively. Various radiographic parameters, including sagittal alignment, longitudinal distance index, space available for the spinal cord at cephalad or caudad levels, and distance from apex of the lordosis to the C2-C7 vertical line were measured. In the first cohort of patients, these parameters were correlated with mean postoperative spinal cord shift to identify any relationships. In the second cohort of patients, the identified association was used on preoperative imaging studies to attempt quantitative prediction of the postoperative spinal cord shift. RESULTS: Space available for the spinal cord at the level immediately cephalad to the laminectomized segments had high correlations (R = 0.94) to the postoperative spinal cord shift. This association was used to quantitatively predict postoperative spinal cord shift within 11% +/- 6% of the measured value. If 4 mm of mean postoperative spinal cord shift is desired, the ratio to the available space and anterior posterior diameter of the spinal cord should be approximately 2.0. CONCLUSION: Relative stenosis at the level directly cephalad to the laminectomized level can affect the degree of postoperative spinal cord shift. Preoperative axial imaging studies should be closely scrutinized to ensure that adequate space is available at the cephalad adjacent level to allow sufficient cord shift after decompressive laminectomy and arthrodesis.

Cervical Vertebrae↗

PubMed2006

The effect of anterior cervical fusion on neck motion.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To precisely measure the effect of anterior cervical fusion on neck motion. SUMMARY OF BACKGROUND DATA: Anterior cervical decompression and stabilization procedures are successful in treating recalcitrant cervical radiculopathy and cervical myelopathy. Most assume that these "fusion" procedures result in a loss of neck motion, although changes in overall motion following anterior cervical fusion have never been precisely quantified. METHODS: Twenty-five consecutive patients undergoing anterior cervical fusion of one to four levels underwent cervical range of motion testing in three planes using an unconstrained instrumented linkage before surgery and more than 3 months after surgery. These data were compared with that of 10 volunteers with no prior history of neck complaints. Motion data were compared between patients and volunteers, and between the patients before surgery and at last follow-up, using RMANOVA and Fisher's PLSD post hoc test. RESULTS: Before surgery, the patients had significantly less motion than the volunteers in all directions. Following surgical fusion, patients gained a statistically significant amount of motion in all planes, although they did not achieve the motion seen among the volunteers. Gains in motion were seen among all patients, including those undergoing four-level fusions, and there was no correlation between postoperative motion and the number of levels fused. CONCLUSIONS: Patients undergoing anterior cervical fusion have diminished neck motion compared with normal volunteers. Following surgery, they may be expected to gain motion, even when undergoing multilevel fusions. However, these patients are unlikely to regain the neck motion seen among normal individuals without neck complaints.

Adult↗

PubMed2006

Agreement between surgeons and an independent panel with respect to surgical site fusion after single-level anterior cervical spine surgery: a prospective, multicenter study.

STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To assess the: (1) agreement between surgeon and independent review of fusion after single-level anterior cervical decompression and fusion, and (2) influence of surgeon impression of patient status on agreement. SUMMARY OF BACKGROUND DATA: Failure to achieve fusion can lead to poor functional outcome. Visual inspection of plain radiographs is used to assess fusion, but this assessment's reliability is not well understood. METHODS: Of 668 participants in the Cervical Spine Research Society Outcomes Study, 181 underwent single-level procedures. Three independent reviewers and each surgeon assessed fusion (i.e., radiographic trabecular bridging of the graft-vertebral body gap and absence of spinous process motion) on plain radiographs at 3 and 6 months after surgery. Agreement was evaluated with an intraclass correlation coefficient (ICC). The influence of surgeon impression of patient status on agreement was assessed with logistic regression analysis. RESULTS: Agreement was high among reviewers (ICC 0.822 to 0.892) but poor between reviewers and surgeons (ICC 0.308 to 0.484); disagreement was higher when the surgeon reported medical (odds ratio [OR] = 0.19, 95%; confidence interval [CI] 0.12, 0.30; P < 0.001), neurologic (OR = 0.13, 95% CI: 0.09, 0.21, P < 0.001), or functional (OR = 0.19, 95% CI: 0.12, 0.29, P < 0.001) improvement than when the surgeon did not report this improvement. CONCLUSIONS: The finding that surgeons and independent reviewers disagreed on fusion assessment highlights the need for objective and reproducible measures of fusion.

Adult↗

PubMed2006

TonEBP/OREBP is a regulator of nucleus pulposus cell function and survival in the intervertebral disc.

The nucleus pulposus is an aggrecan-rich hydrated tissue that permits the intervertebral disc to resist compressive loads. Adaptation to loading is achieved through an elevation in disc osmolarity mediated by the numerous charged glycosoaminoglycan side chains of the aggrecan molecule. The goal of this investigation was to determine the functional role of the osmo-regulatory protein, TonEBP, in cells of the nucleus pulposus. We found that TonEBP and its downstream target genes were robustly expressed in the tissues of the disc. Above 330 mosmol/kg, cultured nucleus pulposus cells up-regulated target genes TauT, BGT-1, and SMIT; above 450 mosmol/kg, there was raised expression of HSP-70. In hypertonic media there was activation of TauT and heat shock protein-70 (HSP-70) reporter activity and increased binding of TonEBP to the TonE motif. When cells were transfected with the dominant-negative form of TonEBP (DN-TonEBP) there was suppression of TauT and HSP-70 reporter gene expression; pTonEBP enhanced reporter gene expression. Moreover, in hypertonic media, forced expression of DN-TonEBP induced apoptosis. We suppressed TonEBP using small interfering RNA technique and noted a decrease in TauT reporter activity in isotonic as well as hyperosmolar media. Finally, we report that the aggrecan promoter contains two conserved TonE motifs. To evaluate the importance of these motifs, we overexpressed DN-TonEBP and partially silenced TonEBP using small interfering RNA. Both approaches resulted in suppression of aggrecan promoter activity. It is concluded that TonEBP permits the disc cells to adapt to the hyperosmotic milieu while autoregulating the expression of molecules that generate the unique extracellular environment.

Amino Acid Motifs↗

PubMed2006

Reliability of a novel classification system for thoracolumbar injuries: the Thoracolumbar Injury Severity Score.

STUDY DESIGN: Prospective study of 5 spine surgeons rating 71 clinical cases of thoracolumbar spinal injuries using the Thoracolumbar Injury Severity Score (TLISS) and then re-rating the cases in a different order 1 month later. OBJECTIVE: To determine the reliability of the TLISS system. SUMMARY OF BACKGROUND DATA: The TLISS is a recently introduced classification system for thoracolumbar spinal column injures designed to simplify injury classification and facilitate treatment decision making. Before being widely adopted, the reliability of the TLISS must be studied. METHODS: A total of 71 cases of thoracolumbar spinal trauma were distributed on CD-ROM to 5 attending spine surgeons, including clinical/radiographic data, details of the TLISS, and a scoring sheet in which cases would be scored using the system. The surgeons were later assigned the task with the cases reordered. Intraobserver and interobserver reliability was calculated for TLISS components, total score, and surgeon's treatment decision using the Cohen unweighted kappa coefficients and Spearman rank-order correlation. RESULTS: Interrater reliability assessed by generalized kappa coefficients was 0.33 +/- 0.03 for injury mechanism, 0.91 +/- 0.02 for neurologic status, 0.35 +/- 0.03 for posterior ligamentous complex status, 0.29 +/- 0.02 for TLISS total, and 0.52 +/- 0.03 for treatment recommendation. Respective results using the Spearman correlation were 0.35 +/- 0.04, 0.94 +/- 0.01, 0.48 +/- 0.04, 0.65 +/- 0.03, and 0.51 +/- 0.04. Surgeons agreed with the TLISS recommendation 96.4% of the time. Intrarater kappa coefficients were 0.57 +/- 0.04 for injury mechanism, 0.93 +/- 0.02 for neurologic status, 0.48 +/- 0.04 for posterior ligamentous complex status, 0.46 +/- 0.03 for TLISS total, and 0.62 +/- 0.04 for treatment recommendation. Respective results using the Spearman correlation were 0.70 +/- 0.04, 0.95 +/- 0.02, 0.59 +/- 0.05, 0.77 +/- 0.04, and 0.59 +/- 0.05. CONCLUSIONS: The TLISS has good reliability and compares favorably to other contemporary thoracolumbar fracture classification systems.

Lumbar Vertebrae↗

PubMed2006

Nucleus pulposus cells express HIF-1 alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment.

Nucleus pulposus (NP) cells of the intervertebral disc reside in an environment that has a limited vascular supply and generate energy through anaerobic glycolysis. The goal of the present study was to examine the expression and regulation of HIF-1alpha, a transcription factor that regulates oxidative metabolism in nucleus pulposus cells. Nucleus pulposus cells were isolated from rat, human, and sheep disc and maintained at either 21% or 2% oxygen for various time periods. Cells were also treated with desferrioxamine (Dfx), a compound that mimics the effects of hypoxia (Hx). Expression and function of HIF-1alpha were assessed by immunofluorescence microscopy, Western blot analysis, gel shift assays, and luciferase reporter assays. In normoxia (Nx), rat, sheep, and human nucleus pulposus cells consistently expressed the HIF-1alpha subunit. Unlike other skeletal cells, when maintained under low oxygen tension, the nucleus pulposus cells exhibited a minimal induction in HIF-1alpha protein levels. Electromobility shift assays confirmed the functional binding of normoxic HIF-1alpha protein to its putative DNA binding motif. A dual luciferase reporter assay showed increased HIF-1alpha transcriptional activity under hypoxia compared to normoxic level, although this induction was small when compared to HeLa and other cell types. These results indicate that normoxic stabilization of HIF-1alpha is a metabolic adaptation of nucleus pulposus cells to a unique oxygen-limited microenvironment. The study confirmed that HIF-1alpha can be used as a phenotypic marker of nucleus pulposus cells.

Adaptation, Physiological↗

PubMed2006

Toward an optimum system for intervertebral disc organ culture: TGF-beta 3 enhances nucleus pulposus and anulus fibrosus survival and function through modulation of TGF-beta-R expression and ERK signaling.

STUDY DESIGN: Rat lumbar discs comprising nucleus pulposus, annulus fibrosus, and cartilaginous endplates were cultured for 1 week in a specialized media containing either TGF-beta1 or TGF-beta3. Role of TGF-beta isoforms on cell function was evaluated. OBJECTIVE: To develop an in vitro organ culture of rat intervertebral disc and evaluate effects of TGF-beta3 on disc cell function. SUMMARY OF BACKGROUND DATA: An in vitro model system is of considerable value in understanding the cell biology of the intervertebral disc. Development of a useful organ culture model would enhance understanding of disc function in health and disease. MATERIALS AND METHODS: Rat lumbar intervertebral discs were maintained in organ culture in media supplemented with TGF-beta3 or TGF-beta1 for 1 week. Tissue morphology was studied using routine histologic, histochemical and immunohistochemical techniques. Cell function was assessed by gene expression, sulfate incorporation, and Western blot analysis. RESULTS: After 1 week in culture with TGF-beta3 and TGF-beta1, the gross morphology and tissue architecture of the disc were preserved. TUNEL analysis indicated that there was no evidence of cell death in the nucleus pulposus or the anulus fibrosus. The level of Alcian blue staining in the nucleus pulposus was similar to that of the freshly isolated disc. However, when compared with TGF-beta1, TGF-beta3 elevated the expression of critical matrix genes, enhanced [S] incorporation into proteoglycans, preserved the expression of TGF-beta receptors, and decreased aggrecan turnover. There was also increased activation (phosphorylation) of ERK, a critical signaling protein. Moreover, inhibition of ERK activity, in the presence TGF-beta3, resulted in suppression of collagen Type II, aggrecan, TGF-beta-RI, TGF-beta-RII and TGF-beta-RIII mRNA expression. CONCLUSIONS: TGF-beta3 maintains the phenotype of disc cells in organ culture. It exerts this effect, in part, by elevating the levels of activated ERK1/2, which in turn regulates the expression of TGF-beta-RI and TGF-beta-RII.

Activin Receptors, Type I↗

PubMed2006

The impact of four common lumbar spine diagnoses upon overall health status.

BACKGROUND CONTEXT: The Short Form 36 (SF-36) health survey has been shown to be a valid instrument when used to measure the self-reported physical and mental health of patients. The impact of lumbar spinal disorders can be assessed as the difference between the SF-36 scale scores and age- and gender-specific population norms. PURPOSE: To establish the impact upon the self-reported health status of patients with one of four common lumbar spinal diagnoses. STUDY DESIGN: A cross-sectional, observational assessment of the health status of spine patients. METHODS: Data from patients presenting to the participating centers of the National Spine Network with low back pain or leg pain were collected prospectively using the Health Status Questionnaire 2.0. A database search identified patients with either herniated nucleus pulposus with radicular pain (HNP), lumbar spinal stenosis without deformity (SPS), degenerative spondylolisthesis (DS), and painful disc degeneration/spondylosis (DDD). The mean SF-36 scale scores were generated for each of the diagnostic groups. The impact of these diagnoses on health status was determined as the calculated difference from the age- and gender-specific population norms for each of the eight health scale scores. These scores, usually negative in this population, represent how far below normal these patients are. The analysis was stratified according to the age of the patients (<40 years, 40-60 years, >60 years). Analysis of variance and pair-wise comparison with Bonferroni correction were used to assess the significance of differences across diagnosis and age groups. RESULTS: Data from a total of 4,442 patients were available for this study. All four diagnostic groups had large, negative impact scores for the eight general health scales with the greatest impact upon the three scales that best measure physical health. The greatest impact on these physical health scales (physical functioning, role-physical, and bodily pain) was seen in the HNP diagnostic group. The younger age groups (<40 years and 40-60 years) had the greatest physical impairment when compared with the age- and gender-specific population norms. Analysis of variance showed a significant relationship between diagnosis and SF-36 scores, and between age groups and SF-36 scores. CONCLUSIONS: All four lumbar spine disorders have a significant negative impact on all eight of the SF-36 scales. The greatest negative impact was seen in those scales that measure physical health (role limitations due to physical symptoms [RP], physical functioning [PF], and bodily pain [BP]). The HNP diagnostic group experienced a significantly greater impact upon these three scales. This diagnostic group had the youngest patients, whose baseline physical functional status would be expected to be the most optimal. When we stratified by age in all the diagnostic groups, the greatest negative impact scores for physical health were seen in the <40 years and 40-60 years age groups. These patients were also more likely to perceive their health as poor, experience decreased energy, and have more social impairment when compared with their age/gender norms.

Adult↗

PubMed2006

Osteogenic potential of adult human stem cells of the lumbar vertebral body and the iliac crest.

STUDY DESIGN: Marrow was aspirated from the vertebral body (VB) and iliac crest (IC) of patients undergoing lumbar spinal surgery, following an approved protocol. Progenitor cells were isolated using standard culture conditions and their osteogenic potential evaluated. OBJECTIVE: To evaluate the osteogenic potential of mesenchymal stem cells (MSCs) isolated from the bone marrow of the human VB. SUMMARY OF BACKGROUND DATA: IC marrow grafting during cervical discectomy and fusion procedure is associated with donor site morbidity. Since the VB contains marrow cells, it may be possible to circumvent this problem by using this tissue for osseous graft supplementation. However, there is paucity of information concerning the osteogenic potential of non-IC-derived progenitor cells. Herein, we address this issue. METHODS: Marrow samples from VB of patients undergoing lumbar spinal surgery were collected; marrow was also harvested from the IC. Progenitor cells were isolated and the number of colony forming unit-fibroblastic (CFU-F) determined. The osteogenic potential of the cells was characterized using biochemical and molecular biology techniques. RESULTS: Both the VB and IC marrow generated small, medium, and large sized CFU-F. Higher numbers of CFU-F were obtained from the VB marrow than the IC (P < 0.05). Progenitor cells from both anatomic sites expressed comparable levels of CD166, CD105, CD49a, and CD63. Moreover, progenitor cells from the VB exhibited an increased level of alkaline phosphatase activity. MSCs of the VB and the IC displayed similar levels of expression of Runx-2, collagen Type I, CD44, ALCAM, and ostecalcin. The level of expression of bone sialoprotein was higher in MSC from the IC than the VB. VB and IC cells mineralized their extracellular matrix to a similar extent. CONCLUSIONS: Our studies show that CFU-F frequency is higher in the marrow of the VB than the IC. Progenitor cells isolated from both sites respond in a similar manner to an osteogenic stimulus and express common immunophenotypes. Based on these findings, we propose that progenitor cells from the lumbar vertebral marrow would be suitable candidate for osseous graft supplementation in spinal fusion procedures. Studies must now be conducted using animal models to ascertain if cells of the VB are as effective as those of the IC for the fusion applications.

Bone Marrow Cells↗

PubMed2006

"Normal" prevertebral soft tissue swelling following elective anterior cervical decompression and fusion.

INTRODUCTION: Prevertebral soft tissue swelling (PSTS) has been evaluated in the setting of traumatic cervical spine injuries. However, no study to date has quantified the PSTS following elective anterior cervical decompression and fusion or the time course to resolution of that swelling. METHODS: From May 2002 to May 2005 the senior author performed 193 elective 1- or 2-level anterior cervical decompression and fusions. Patients who underwent corpectomies and anterior cervical fusions for trauma or tumor were excluded. Preoperative, 2-week postoperative and 6-week postoperative radiographs were available on 100 patients. The prevertebral soft tissue stripe was measured on the neutral lateral radiographs for the 3 time points. The mean swelling (mm) for each time point was calculated and stratified by cervical level. Repeated measures analysis of variance with the Tukey-Kramer multiple comparisons test was used to compare the measured swelling at the various time points. RESULTS: The average PSTS was calculated for each cervical level, for each of the 3 time points, preoperative, 2- and 6-week postoperative. There was a significant increase in PSTS between the preoperative and 2-week postoperative measurements at all levels. There is a significant decrease in PSTS between 2- and 6-week postoperatively at all cervical levels. There is no significant change in PSTS at C2, C3, and C5, when comparing the preoperative and 6-week postoperative measurements. There is significant PSTS at C4, C6, and C7, when comparing preoperative and 6-week postoperative measurements. CONCLUSIONS: The "normal" range for PSTS at 2 weeks and at 6 weeks after elective 1- and 2- level anterior cervical decompression and fusions is described. Our data demonstrates that edema persists at the 2-week follow-up. By 6 weeks postoperative, the increased PSTS has greatly dissipated.

Cervical Vertebrae↗