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Howard S An

Publications and source records attributed to Howard S An.

At least 19 recordsLinked to original sources
PubMed2007

Mechanical neck pain and cervicogenic headache.

Mechanical neck pain is a very common symptom that may occur with cervical spondylosis. It can be associated with cervical radiculopathy and myelopathy or can occur in isolation. Neck pain can result from a variety of causes, including trauma, tumor, infection, and degeneration. The presentation of axial neck pain varies. This article highlights the presentation, differential diagnosis, and appropriate work-up for the patient who presents with mechanical neck pain.

Cervical Vertebrae↗
PubMed2006

Effects of growth differentiation factor-5 on the intervertebral disc--in vitro bovine study and in vivo rabbit disc degeneration model study.

STUDY DESIGN: In vitro studies on the effects of recombinant human growth and differentiation factor-5 (rhGDF-5) on matrix metabolism of bovine intervertebral disc cells and an in vivo study on the effect of rhGDF-5 in the rabbit anular puncture model. OBJECTIVE: To determine the reparative capacity of rhGDF-5 on the intervertebral disc. SUMMARY OF BACKGROUND DATA: The in vitro and in vivo effects of rhGDF-5, a crucial protein in the developing musculoskeletal system, on repair of the degenerated intervertebral disc remain unidentified. METHODS: In vitro, bovine nucleus pulposus and anulus fibrosus cells were cultured with or without rhGDF-5 (100 or 200 ng/mL). On days 7, 14, and 21, the contents of deoxyribonucleic acid and proteoglycan, and the synthesis of proteoglycan and collagen were assessed. In vivo, 16 adolescent New Zealand white rabbits received anular punctures in 2 lumbar discs. Four weeks later, phosphate buffered saline or rhGDF-5 (10 ng, 1 and 100 mug) was injected into the nucleus pulposus. The rabbits were followed up for 16 weeks for disc height, magnetic resonance imaging, and histologic grading. RESULTS: In vitro, rhGDF-5 increased the deoxyribonucleic acid and proteoglycan contents of both cell types significantly after day 14. rhGDF-5 at 200 ng/mL significantly stimulated proteoglycan synthesis (nucleus pulposus: +138%, anulus fibrosus: +24%) and collagen synthesis (nucleus pulposus: +95%, anulus fibrosus: +23%) at day 21. In vivo, the injection of rhGDF-5 resulted in a restoration of disc height, improvement of magnetic resonance imaging scores, and histologic grading scores with statistical significance (P < 0.05-0.001). CONCLUSION: A single injection of rhGDF-5 has a reparative capacity on intervertebral discs, presumably based on its effects to enhance extracellular matrix production in vitro.

Animals↗
PubMed2006

Intradiscal injections of osteogenic protein-1 restore the viscoelastic properties of degenerated intervertebral discs.

BACKGROUND CONTEXT: Using biochemical, histological, and radiological parameters in a rabbit model of intervertebral disc (IVD) degeneration, the intradiscal injection of a growth factor, such as osteogenic protein-1 (OP-1), has been shown to regenerate the IVD. However, very little is known about how such a biological therapeutic approach affects the biomechanical properties of the degenerated IVD. PURPOSE: To investigate the effects of an intradiscal injection of OP-1 on the biomechanical properties of IVDs in the rabbit annular-puncture disc degeneration model and to determine their relationship to biochemical properties. STUDY DESIGN/SETTING: In vivo study on the effects of intradiscally administered OP-1 on the biomechanical and biochemical properties of IVDs in the rabbit annular-puncture disc degeneration model. METHODS: New Zealand White rabbits (n=16) underwent annulus fibrosus (AF) puncture, using an 18-gauge needle, at L2-L3 and L4-L5 (L3-L4: nonpunctured control). Four weeks later, the punctured discs received an injection of either 5% lactose (10 microL) or OP-1 (100 microg/10 microL of 5% lactose) into the nucleus pulposus (NP). The disc height was radiographically monitored biweekly. After sacrifice and removal of bone-disc-bone complexes 8 weeks postinjection, the dynamic viscoelastic properties of the IVDs were tested by applying a cycle of sinusoidal strain in uniaxial compression at six loading frequencies (0.05 to 2 Hz). The biochemical properties of the dissected IVDs were then analyzed and correlated with the biomechanical properties. RESULTS: A single injection of OP-1 significantly restored disc height when compared with the lactose-injected discs (OP-1 vs. lactose, p<.001). The elastic modulus of the IVDs in the OP-1-injected discs was significantly higher than that in the lactose-injected discs at all frequencies (mean: +43%, p<.001). The viscous modulus in the OP-1-injected discs was significantly higher at 0.05, 0.2, 0.5, and 1 Hz (mean: +55%, p<.001) and showed higher tendencies at other frequencies (p=.08-.09). For both moduli, no significant differences were observed between the OP-1-injected and the nonpunctured control discs. The OP-1 injection significantly increased the proteoglycan (PG) content in the NP and AF, and the collagen content in the NP (p<.001-.05). Both elastic and viscous moduli showed significant positive correlations with PG content in the NP and collagen content in the NP and AF (Rho=.357-.466, p=.010-.047). CONCLUSIONS: We have shown for the first time that an injection of the growth factor, OP-1, restored the biomechanical properties of IVDs in a rabbit model of IVD degeneration. Comparing biomechanical with biochemical data suggests that the OP-1-induced biomechanical restoration was a consequence of increased activities of anabolic pathways that resulted in biochemical changes in the IVD.

Animals↗
PubMed2006

Comparative effects of bone morphogenetic proteins and sox9 overexpression on extracellular matrix metabolism of bovine nucleus pulposus cells.

STUDY DESIGN: An in vitro biologic study of the effects of adenovirus expressing bone morphogenetic proteins (BMPs) and adenovirus expressing Sox9 on extracellular matrix metabolism by bovine nucleus pulposus cells. OBJECTIVE: To compare the effects of recombinant adenoviral vectors expressing various BMPs (2, 3, 4, 5, 7, 8, 10, 11, 12, 13, 14, and 15) and Sox9 on extracellular matrix accumulation by bovine nucleus pulposus cells. SUMMARY OF BACKGROUND DATA: Nucleus pulposus matrix production may be promoted by transducing the cells with genes that permit the sustained expression of growth factors. The choice of the particular factors or BMPs to be studied for these applications has been largely based on the commercial availability of such products. To our knowledge, this study is the first effort to evaluate systematically the relative effectiveness of the various members of the BMP family in promoting intervertebral disc matrix repair. METHODS: Adult bovine nucleus pulposus cells cultured in monolayer were transduced with adenoviruses expressing human BMP-2, 3, 4, 5, 7, 8, 10, 11, 12, 13, 14, and 15, and adenovirus expressing Sox9. Proteoglycan and collagen accumulation, and cell proliferation were measured 6 days after viral transduction. As a positive control, cells were cultured without any exogenous gene in the presence of recombinant human (rh)BMP-7. RESULTS: Nucleus pulposus cells transduced with adenoviruses expressing BMP-2, 3, 4, 5, 7, 8, 10, 13, 15, and Sox9 accumulated more proteoglycans than nucleus pulposus cells transduced with adenovirus expressing green fluorescent protein (control). It is noteworthy that nucleus pulposus cells transduced with adenoviruses expressing BMP-2 and 7 resulted in essentially as great a stimulation of proteoglycan accumulation as nucleus pulposus cells maintained in the presence of rhBMP-7 (adenoviruses expressing BMP-2: 104% increase; adenoviruses expressing BMP-7: 162% increase; and rhBMP-7: 120% increase). Nucleus pulposus cells transduced with BMP-2, 4, 5, 7, 8, 10, 14, 15, and Sox9 accumulated significantly more collagen compared to nucleus pulposus cells transduced with adenovirus expressing green fluorescent protein; adenoviruses expressing BMP-4 and 14 were the most effective (552% and 661% increase, respectively). Nucleus pulposus cells also proliferated, as measured by deoxyribonucleic acid content, when transduced with adenoviruses expressing BMP-2 and 8. CONCLUSIONS: To our knowledge, for the first time, we have shown the relative effectiveness of 12 different BMPs and Sox9 in stimulating proteoglycan and collagen production by nucleus pulposus cells. Adenoviruses expressing BMP-2 and 7 were the most effective in stimulating proteoglycan accumulation, while adenoviruses expressing BMP-4 and 14 were the most effective in stimulating collagen accumulation. To our knowledge, this study is the first to compare the relative effectiveness of various BMPs and Sox9 on extracellular matrix accumulation by nucleus pulposus cells, and could help to develop more efficacious approaches to the treatment of degenerating intervertebral discs.

Adenoviridae↗
PubMed2006

Three-dimensional in vivo measurement of lumbar spine segmental motion.

STUDY DESIGN: Fifteen asymptomatic volunteers were externally rotated and CT scanned to determine lumbar segmental motion. OBJECTIVES: To measure three-dimensional segmental motion in vivo using a noninvasive measurement technique. SUMMARY OF BACKGROUND DATA: Spinal instability has been implicated as a potential cause of low back pain, especially, axial rotational instability. Typically, flexion-extension lateral radiographs were used to quantify instability, but inaccurately measured translations and inability to capture out-of-plane rotations are limitations. METHODS: Using a custom-calibrated rotation jig, L1-S1 CT reconstructions were created of volunteers in each of 3 positions: supine and left and right rotations of the torso with respect to the hips. Segmental motions were calculated using Euler angles and volume merge methods in three major planes. RESULTS: Segmental motions were small (< 4 degrees or 6 mm) with the greatest motions seen in axial rotation (range, 0.6 degrees to 2.2 degrees ), lateral bending (range, -3.6 degrees to 3.0 degrees ), and frontal translation (-1.2 mm to 5.4 mm). Largest motions were in the levels: L1-L2 to L3-L4. CONCLUSIONS: Complex coupled motions were measured due to external torsion and could be indicative of instability chronic patients with low back pain. The presented data provide baseline segmental motions for future comparisons to symptomatic subjects.

Adult↗
PubMed2006

Prevention of disc degeneration with growth factors.

Clinically, a large number of patients have persistent low back pain attributable to intervertebral disc (IVD) degeneration. After the concept of biologically regenerating the degenerated IVD using growth factor injection was first proposed in early 1990, the advancement of molecular technology to produce recombinant proteins, including growth factors, on an industrial scale accelerated research in this field. The purpose of this review is to summarize the most recent findings of the in vitro and in vivo effects of growth factors on the IVD and, further, to discuss the limitations of growth factor therapy and its clinical implications. In vitro data showed that stimulation of matrix synthesis by growth factors alters the balance of homeostasis by shifting cellular metabolism to the anabolic state. In vivo data using small animals has shown the possibility of using growth factors as a "structural modifying therapy". Based on in vitro and in vivo data previously reported, the clinical application of growth factors by direct injection of protein into the nucleus pulposus or anulus fibrosus was shown to be feasible as a new therapeutic intervention for treatment of disc degeneration. Stimulation of the biological repair process will create a new category of therapy to treat disc degeneration, where no active treatment currently exists, between conservative therapies and more aggressive therapies such as fusion or disc replacement. However, it should be noted that there are several important factors to be taken into consideration. In a relatively advanced degenerative condition, the supply of nutrients is disturbed and stimulation of cellular activity by growth factors may result in an increased demand for nutrients, eventually inducing an adverse event. Further investigations of the optimal environment for growth factor stimulation should be pursued. Growth factor therapy, which has experimental evidence supporting it to be a "structural modifying therapy", may not be a "symptom modifying therapy" that is able to resolve the symptoms associated with pathologic changes. Therefore, further studies on the effect of growth factor therapy on pain are essential to shed light on its therapeutic usefulness for degenerative disc disease.

Extracellular Matrix↗
PubMed2006

Novel model to analyze the effect of a large compressive follower pre-load on range of motions in a lumbar spine.

A 3-D finite element model (FEM) of the lumbar spine (L1-S1) was used to determine the effect of a large compressive follower pre-load on range of motions (ROM) in all three planes. The follower load modeled in the FEM produced minimal vertebral rotations in all the three planes. The model was validated by comparing the disc compression at all levels in the lumbar spine with the corresponding results obtained by compressing 10 cadevaric lumbar spines (L1-S1) using the follower load technique described by Patwardhan et al. [1999. A follower load increases the load-carrying capacity of the lumbar spine in compression. Spine 24(10), 1003-1009]. Further validation of the model was performed by comparing the lateral bending and torsion response without pre-load and the flexion-extension response without pre-load and with an 800 N follower pre-load with those obtained using cadaver lumbar spines. Following validation, the FEM was subjected to bending moments in all three planes with and without compressive follower pre-loads of up to 1200 N. Disc compression values and the flexion-extension range of motion under 800 N follower pre-load predicted by the FEM compared well with in vitro results. The current model showed that compressive follower pre-load decreased total as well as segmental ROM in flexion-extension by up to 18%, lateral bending by up to 42%, and torsion by up to 26%.

Adaptation, Physiological↗
PubMed2006

Comparison of cellular response in bovine intervertebral disc cells and articular chondrocytes: effects .of lipopolysaccharide on proteoglycan metabolism.

Lipopolysaccharide (LPS) induces matrix degradation and markedly stimulates the production of several cytokines, i.e., interleukin-1beta, -6, and -10, by disc cells and chondrocytes. We performed a series of experiments to compare cellular responses of cells from the bovine intervertebral disc (nucleus pulposus and annulus fibrosus) and from bovine articular cartilage to LPS. Alginate beads containing cells isolated from bovine intervertebral discs and articular cartilage were cultured with or without LPS in the presence of 10% fetal bovine serum. The DNA content and the rate of proteoglycan synthesis and degradation were determined. In articular chondrocytes, LPS strongly suppressed cell proliferation and proteoglycan synthesis in a dose-dependent manner and stimulated proteoglycan degradation. Compared with articular chondrocytes, nucleus pulposus cells responded in a similar, although less pronounced manner. However, treatment of annulus fibrosus cells with LPS showed no significant effects on proteoglycan synthesis or degradation. A slight, but statistically significant, inhibition of cell proliferation was observed at high concentrations of LPS in annulus fibrosus cells. Thus, LPS suppressed proteoglycan synthesis and stimulated proteoglycan degradation by articular chondrocytes and nucleus pulposus cells. The effects of LPS on annulus fibrosus cells were minor compared with those on the other two cell types. The dissimilar effects of LPS on the various cell types suggest metabolic differences between these cells and may further indicate a divergence in pathways of LPS signaling and a differential sensitivity to exogenous stimuli such as LPS.

Animals↗
PubMed2006

Platelet-rich plasma (PRP) stimulates the extracellular matrix metabolism of porcine nucleus pulposus and anulus fibrosus cells cultured in alginate beads.

STUDY DESIGN: In vitro assessment of the effects of platelet-rich plasma on the extracellular matrix metabolism of porcine intervertebral disc cells. OBJECTIVES: To determine whether platelet-rich plasma is effective in stimulating cell proliferation and extracellular matrix metabolism by porcine disc cells cultured in alginate beads. SUMMARY OF BACKGROUND DATA: Platelet-rich plasma is used to accelerate wound healing and tissue regeneration. Activated platelets release multiple growth factors that regulate cell proliferation, differentiation, and morphogenesis. Individual growth factors present in platelet-rich plasma have been demonstrated to affect the metabolism of intervertebral disc cells. METHODS: Platelet-poor and platelet-rich plasma was isolated from fresh porcine blood using a commercially available platelet concentration system. After preculture for 7 days and serum starvation for 24 hours, the beads containing nucleus pulposus and anulus fibrosus cells were then cultured for another 72 hours in serum-free medium, 10% fetal bovine serum, 10% platelet-poor plasma, or 10% platelet-rich plasma. The synthesis of proteoglycans and collagen, the accumulation of proteoglycans, and the DNA content were biochemically assessed. RESULTS: Platelet-rich plasma had a mild stimulatory effect on cell proliferation of intervertebral disc cells. Platelet-rich plasma treatment significantly upregulated proteoglycan and collagen synthesis and proteoglycan accumulation when compared with platelet-poor plasma. CONCLUSIONS: Platelet-rich plasma was effective in stimulating cell proliferation and extracellular matrix metabolism. The response to platelet-rich plasma was greater in the case of anulus fibrosus cells than of nucleuspulposus cells. The local administration of platelet-rich plasma might stimulate intervertebral disc repair. In addition, given the risks of using animal serum for tissue engineering, autologous blood may gain favor as a source of growth factors and serum supplements needed for stimulating cells to engineer intervertebral disc tissues.

Animals↗
PubMed2006

Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit anular puncture model.

STUDY DESIGN: In vivo study of the effect of injection of osteogenic protein-1 (OP-1) on a rabbit anular needle puncture model of intervertebral disc (IVD) degeneration. OBJECTIVE: To study radiographic, magnetic resonance imaging (MRI), biochemical, and histologic changes in the rabbit IVD after injection of OP-1 into the nucleus pulposus in a needle puncture disc degeneration model. SUMMARY OF THE BACKGROUND DATA: Growth factors, such as OP-1, have the ability to stimulate synthesis of proteoglycans and collagen in vitro. The in vivo injection of OP-1 into the normal rabbit IVD has increased disc height and proteoglycan content in the anulus fibrosus and nucleus pulposus. However, to our knowledge, no attempts have yet been made to determine the effects of these growth factors in an in vivo model of disc degeneration. METHODS: New Zealand adolescent white rabbits (n = 90, 8 for baseline evaluation, 82 at 8 times) received an anular puncture in 2 noncontiguous discs with an 18-gauge needle to induce disc degeneration. Four weeks later, either 5% lactose (10 microL) or OP-1 (100 microg in 10 microL 5% lactose) was injected into the center of the nucleus pulposus. The disc height was followed radiographically for up to 24 weeks after the injections. At the 2, 4, 8, 12, and 24-week times after the injection, rabbits were euthanized, and MRI of the harvested spinal columns was obtained to grade the degeneration. The discs injected with OP-1 or lactose and noninjected discs were subjected to biochemical and histologic analysis. The specimens at the 24-week time were limited to histologic evaluation. RESULTS: The anular puncture with a needle induced a consistent disc narrowing within 4 weeks. The injection of OP-1 induced a restoration of disc height at 6 weeks, which was sustained for the entire experimental period, up to 24 weeks after the injection. The injection of lactose alone did not change the course of disc narrowing over the same time. MRI grading score showed significant differences between the OP-1 and lactose groups at the 8, 12, and 24-week times, suggesting an increase in water content in the nucleus pulposus of the OP-1 group. The proteoglycan content of the nucleus pulposus and anulus fibrosus was significantly higher in the OP-1 group than in the control group. The degeneration grades of the punctured discs in the OP-1 group were significantly lower than those in the lactose group. CONCLUSION: The results of this study show the feasibility of restoring degenerative rabbit discs by a single injection of OP-1 into the nucleus pulposus. Importantly, the effects of the OP-1 injection on disc height were sustained for up to 24 weeks. The metabolic changes in the cells, following a single injection, might be sustained and, thus, induce long-term changes in disc structure. An efficacy study in large animals is required to show further that the intradiscal injection of OP-1, or bone morphogenetic proteins or growth factors with similar properties would be useful for the structural restoration of the IVD in humans.

Animals↗
PubMed2006

Anti-adhesion properties of a thrombin-based hemostatic gelatin in a canine laminectomy model: a biomechanical, biochemical, and histologic study.

STUDY DESIGN: An in vivo study on the effects of an agent for scar prevention in a dog laminectomy model. OBJECTIVE: To examine the anti-adhesion properties of a thrombin-based hemostatic gelatin (FLOSEAL; Baxter International Inc., Deerfield, IL). SUMMARY OF BACKGROUND DATA: Postlaminectomy dural adhesion sometimes causes symptomatic problems. Although a new type of hemostatic agent, a thrombin-based hemostatic gelatin, has been developed, its effect on postlaminectomy scar prevention is unknown. METHODS: A 4-level lumbar laminectomy was performed on 11 adult mongrel dogs. There were 2 levels randomly chosen to receive the thrombin-based hemostatic gelatin treatment, while the remaining levels were untreated (control). Dogs were euthanized 8 weeks after surgery. To assess the tenacity of adhesion between the dura and scar, peel-off testing was performed. Gross, biochemical, and histologic analyses were then used to examine the samples. RESULTS: Peel-off stiffness was significantly decreased in the treatment group (64.8% of the control, P = 0.032; 2-tailed unpaired t test). Histologically, there was significantly less scar tissue formation in the treatment group (P = 0.04). The gross analyses showed a trend toward a smaller amount of scar tissue and tenacity of adhesion between the dura and scar in the treatment group. Biochemically, there was a trend toward a lower collagen cross-links content in the treatment group (P = 0.07). CONCLUSIONS: The thrombin-based hemostatic gelatin decreases the tenacity of adhesion between the dura and scar at laminectomy sites.

Animals↗
PubMed2006

Spinal infections: diagnostic tests and imaging studies.

UNLABELLED: Clinical signs and symptoms caused by spinal infections often are subtle and insidious; therefore, clinical suspicion in patients with nonmechanical pain is important in making the correct diagnosis in the early stage of disease. Serologic tests such as erythrocyte sedimentation rate and C-reactive protein are quite sensitive, but specificity is relatively low. Imaging tests include plain radiographs, radionuclide studies, computed tomography scan, and magnetic resonance imaging. Changes on plain radiographs appear at least 3 to 4 weeks after the onset of disease. Bone scan is a sensitive but not a specific test. Computed tomography provides structural details in the bone and intervertebral disc but magnetic resonance imaging is a superior imaging test for diagnosing infections earlier and more accurately. In many patients, percutaneous or open biopsy is required to make the definitive diagnosis of discitis or osteomyelitis and the organism responsible for the infection. Early and accurate diagnosis of spinal infections will lead to less invasive treatment for the patient. LEVEL OF EVIDENCE: Level V (Expert Opinion). Please see the Guidelines for Authors for a complete description of levels of evidence.

Bacterial Infections↗
PubMed2006

Sensory neurons and fibers from multiple spinal cord levels innervate the rabbit lumbar disc.

OBJECTIVE: To establish the neurotransmission pathway from the lumbar L5/6 intervertebral disc (IVD) to the spinal cord in the rabbit. DESIGN: Fluorogold particles injected into the posterior portion of the rabbit L5/6 IVD were traced by examining gold-positive neurons and fibers in the dorsal root ganglion (DRG) and spinal cord at various root levels. RESULTS: Fluorogold-labeled neurons were observed bilaterally in primary afferent DRG neurons from the L3 through L5 segments; a small number of gold-labeled neurons were found at the L1 level. Fluorogold-labeled neurons were predominantly present in the ipsilateral DRG (the side of the injection) at the L5 level, but they were more equally distributed (on both sides) at the L4 and L3 levels. In the posterior horn of the spinal cord, Fluorogold particles were found in nerve fibers as rostral as the T12 level. CONCLUSIONS: Our study has shown that Fluorogold particles injected into the rabbit L5/6 IVD are taken up by primary sensory neurons in the DRGs and primary sensory fibers in the posterior horn of the spinal cord at multiple levels. This diffuse innervation pattern of the lumbar disc may help explain why discogenic back pain in humans is often poorly localized.

Animals↗
PubMed2006

Relevance of in vitro and in vivo models for intervertebral disc degeneration.

Models available for the study of intervertebral disc degeneration are designed to answer many important questions. In vitro biologic models employ a variety of cell, tissue, or organ culture techniques with culture conditions that partially mimic the cellular environment of the degenerated human intervertebral disc. In vitro biomechanical models include intervertebral disc or motion-segment loading experiments as well as finite element modeling techniques. The literature describes numerous in vivo animal models for use in the study of intervertebral disc degeneration, each of which has its own advantages and disadvantages. Human-subject studies have included the use of magnetic resonance imaging and other techniques to assess diffusion into the intervertebral disc, to measure intradiscal pressure, to conduct kinematic or stiffness studies of lumbar motion segments, and to evaluate muscular forces on the spine. Although all of these studies are helpful in answering specific questions, their relevance in assessing disc degeneration in patients with symptoms of discogenic pain must be carefully considered.

Age Factors↗