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Pseudoenhancement of intervertebral disc herniation.

Two patients with intervertebral disc herniation appeared to demonstrate abnormally diffuse and intense enhancement of the disc after intravenous administration of gadolinium-DTPA for MRI. Surgery disclosed a dilated epidural venous plexus in one and vascular granulation tissue in the other, associated with the herniated disc material. The mechanism of this "pseudoenhancement" of the disc appears to be a partial volume effect of disc material and the adjacent veins or granulation tissue. Pseudoenhancement of a herniated disc should be included in the differential diagnosis of a diffusely enhancing epidural mass.

Aged↗

Cellular, but not matrix, immunolocalization of SPARC in the human intervertebral disc: decreasing localization with aging and disc degeneration.

STUDY DESIGN: Human intervertebral disc anulus tissue was obtained in a prospective study of immunolocalization of SPARC (secreted protein, acidic and rich in cysteine) (osteonectin). Experimental studies were approved by the authors' Human Subjects Institutional Review Board. Discs were obtained from surgical specimens and from control donors. OBJECTIVES: To determine whether SPARC could be detected in the disc with immunohistochemistry and to determine the incidence of SPARC-positive cells. SUMMARY OF THE BACKGROUND DATA: SPARC is a glycoprotein that has an important role in modulating interactions between cells and matrix. It influences remodeling, collagen fibrillogenesis, metalloproteinase expression, and cytokine expression. Little is known about SPARC in the disc, and one previous study reported the absence of its immunolocalization in fetal and adult disc tissue. METHODS: Eight normal human discs from subjects aged newborn to 10 years, and 11 disc specimens from control donors or surgical patients aged 15to 76 years were examined for immunolocalization of SPARC. Anulus cells were also tested for the presence of SPARC in vitro in monolayer or three-dimensional agarose culture. RESULTS: In discs of subjects aged newborn to 0.19 years, SPARC was present in all cells in the outer anulus, in 76.4% of inner anulus cells, and 76.0% of nucleus cells. Localization was significantly lower in anulus cells of study participants aged 4.7 to 76 years (66.7%, P = 0.04). Anulus cells cultured in agarose or monolayer showed positive localization in all cells. CONCLUSIONS: Findings show decreased presence of SPARC in disc cells of older subjects with disc degeneration and point to the importance of future studies designed to elucidate the unrecognized role of SPARC in disc remodeling, aging, and degeneration.

Adolescent↗

Versican G3 domain enhances cellular adhesion and proliferation of bovine intervertebral disc cells cultured in vitro.

The functional role of versican in influencing intervertebral disc cell adhesion and proliferation was analyzed in bovine intervertebral disc. We have previously demonstrated the C-terminal globular G3 (or selectin-like) domain of versican to influence mesenchymal chondrogenesis and fibroblast proliferation in vitro. For this study, a versican G3 expression construct was generated to examine the role of the G3 domain of versican. Nucleus pulposus and annulus fibrosus cells were isolated from adult bovine caudal discs using sequential enzymatic digestion and versican expression characterized by RT-PCR. In cell proliferation assays, we observed that there was greater cellular proliferation in the presence of versican G3 for both disc cell types. The higher proliferation rate of annulus fibrosus cells when compared to nucleus pulposus cells seeded in monolayer supports heterogeneity of intervertebral disc cell populations. The presence of versican G3 construct enhanced the adhesion of isolated nucleus pulposus and annulus fibrosus cells approximately 4 to 6 fold, respectively. Cellular adhesion was greater in the presence of versican G3 in a dose dependent manner. G3 product was purified using affinity columns, and the purified G3 also enhanced cell adhesion.

Animals↗

Exposure to pulsed low intensity ultrasound stimulates extracellular matrix metabolism of bovine intervertebral disc cells cultured in alginate beads.

STUDY DESIGN: In vitro study on the effects of pulsed low intensity ultrasound on the cellular metabolism of bovine intervertebral disc cells. OBJECTIVE: To determine whether pulsed low intensity ultrasound has effects on cell proliferation and extracellular matrix metabolism by bovine intervertebral disc cells. SUMMARY OF BACKGROUND DATA: The application of pulsed low intensity ultrasound is known to be effective in stimulating fracture and cartilage repair. However, the effects of pulsed low intensity ultrasound on intervertebral disc cells are not known. METHODS: Cells of the nucleus pulposus and inner and outer anulus fibrosus were enzymatically isolated from bovine coccygeal tissue and precultured in alginate beads for 14 days. In the ultrasound group, pulsed low intensity ultrasound was administered to the culture for 20 minutes daily for an additional 20 days. The control group was cultured in the same way but without administration of ultrasound. Cell viability, DNA content, proteoglycan and collagen synthesis, and proteoglycan content at days 10 and 20 after the initiation of treatment were evaluated. Characterization of newly synthesized collagen and proteoglycan was performed. RESULTS: No significant differences in cell viability and DNA content were observed between the two groups. On day 20, proteoglycan synthesis was increased by the application of pulsed low intensity ultrasound in nucleus pulposus and inner and outer anulus fibrosus cells (24%-26% increase, P < 0.001). The application of pulsed low intensity ultrasound increased proteoglycan content in alginate beads containing inner and outer anulus fibrosus cells (P < 0.05). Collagen synthesis by cells isolated from all three zones of the intervertebral disc was increased by the application of pulsed low intensity ultrasound (16%-19% increase, P < 0.05-0.0001). CONCLUSIONS: The application of pulsed low intensity ultrasound stimulated extracellular matrix metabolism in intervertebral disc cells. Pulsed low intensity ultrasound may prove useful for the physical stimulation of cell metabolism for tissue engineering of intervertebral disc tissue.

Animals↗

Antibiotic prophylaxis in surgery of the intervertebral disc. A comparison between gentamicin and cefuroxime.

Antibiotics are often administrated prophylactically in spinal procedures to reduce the risk of infection of the disc space. It is still not known which antibiotics are able to penetrate the intervertebral disc effectively. In a prospective, randomised, double-blind clinical study, we examined the penetration of the intervertebral discs of two commonly used antibiotics, cefuroxime and gentamicin. The patients, randomised into two groups, received either 1.5 g of cefuroxime or 5 mg/kg of gentamicin prophylactically two hours before their intervertebral discs were removed. A specimen of blood, from which serum antibiotic levels were determined, was obtained at the time of discectomy. Therapeutic levels of antibiotic were detectable in the intervertebral discs of the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had a quantifiable level of antibiotic in their discs although therapeutic serum levels of cefuroxime were found in all ten patients. Our results show that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin. It is possible that the charge due to ionisable groups on the antibiotics can influence the penetration of the antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures in order to reduce the risk of discitis.

Adult↗

Accumulation of platinum in the intervertebral discs and vertebrae of ovarian tumor-bearing patients treated with cisplatin.

Platinum was determined by the inductively coupled plasma mass spectrometry (ICP-MS) in the intervertebral discs and vertebrae of ovarian tumor bearing patients treated with cis-diamminedichloro-platinum (II) (cisplatin). Platinum was 0.05 ng/mL at the absolute detection limit, and platinum was undetectable in the intervertebral discs and vertebrae of human specimens without cisplatin treatments. On the other hand, platinum was detected in the intervertebral discs and vertebrae of patients administered cisplatin, and platinum concentration was at levels of 1.06-10.31 micrograms/g dry tissue in the intervertebral discs and 0.60-1.28 micrograms/g dry tissue in the vertebrae, respectively. The platinum level of intervertebral discs was 4.3-fold higher than that of the vertebrae. Thus, platinum accumulates greatly in the intervertebral discs and somewhat in the vertebrae after administering cisplatin to patients for therapy.

Adenocarcinoma↗

Intervertebral disc cells produce tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model.

STUDY DESIGN: A new hernia model that simulates human disc herniations was developed in rabbits. The herniated discs were examined by gross appearance and histology and production of tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 was investigated. OBJECTIVES: To clarify the early mechanism of spontaneous herniated disc resorption. SUMMARY OF BACKGROUND DATA: Macrophage infiltration in herniated discs is essential for disc resorption. However, surgically removed human herniated disc tissues and existing animal hernia models are not suitable for analyzing the mechanism of macrophage infiltration. Recently, we have demonstrated that intervertebral disc cells are capable of producing monocyte chemoattractant protein-1, a potent macrophage chemoattractant, after stimulation with tumor necrosis factor alpha and interleukin-1beta. METHODS: Intervertebral disc herniations were surgically developed in rabbits using a new technique. The herniated discs were excised at appropriate time intervals after the surgery, and the size and histologic findings were examined. Expressions of tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 in herniated discs were investigated immunohistochemically. RESULTS: A new rabbit model of disc herniation was established. The herniated discs spontaneously reduced in size by 12 weeks postsurgery. Infiltrating cells, mainly composed of macrophages, were observed from day 3. Immunohistochemically, intervertebral disc cells in the herniated discs produced tumor necrosis factor alpha and interleukin-1beta on day 1, followed by monocyte chemoattractant protein-1 on day 3. CONCLUSIONS: The new hernia model appears to be very useful for studying herniated disc resorption. Intervertebral disc cells may produce inflammatory cytokines/chemokine immediately after the onset of disc herniation, possibly triggering subsequent macrophage infiltration that leads to disc resorption.

Animals↗

Finite element study of a novel intervertebral disc substitute.

STUDY DESIGN: A new type of composite device with a similar structure to a natural lumbar intervertebral disc was modeled, and its mechanical interaction with a L3-L5 lumbar spine segment was studied by a finite element analysis. OBJECTIVE: To identify the influence of the prosthesis on the biomechanical changes induced in a L3-L4 lumbar spine segment model after having substituted the physiologic L4-L5 intervertebral disc by the implant. SUMMARY OF BACKGROUND DATA: In our societies, the large number of back pain cases highly motivates the investigation of intervertebral disc prostheses. Postoperative complications induced by spinal fusion showed that the mechanical properties of the novel components and its interactivity with the rest of the spine are a critical point. METHODS: The prosthesis replaced the L4-L5 intervertebral disc within a previously developed L3-L5 lumbar spine segment physiologic model. The effect of loads in compression, flexion, extension, and axial rotation was simulated, and two types of vertebrae-implant contact were compared to the physiologic model. RESULTS: Models with disc substitute are much stiffer than the physiologic model. In case of perfect contact with the adjacent vertebrae, the implant behaves like a physiologic intervertebral disc and respects the surrounding motion segment biomechanics. Although no traumatic loads were calculated within the adjacent vertebrae, bone remodeling would be expected in the trabecular bone. CONCLUSION: By using numerical methods, this study allows prediction of the static mechanical behavior of a new device within a lumbar spine structure, which appears very useful for preclinical study.

Biomechanical Phenomena↗

Lumbar intervertebral disc prosthesis. An experimental study.

To provide a more effective treatment and improve the outcome of surgical treatment of lumbar intervertebral disc protrusion, the values of lumbar intervertebral disc prosthesis (LIDP) were investigated. LIDP was specially designed and made of silicone rubber. The properties of material mechanics were investigated by compressive test and damage test of LIDP specimens. The biocompatibilities of LIDP were observed experimentally in monkeys. The surgical applicabilities were studied by in vitro experiments of fresh human lumbar spine. The results showed that LIDP has the advantages of good biomechanical applicability, biocompatibility and surgical applicability. LIDP is able to maintain the intervertebral space, stress balance and stability of the lumbar spine. after lumbar intervertebral disc excision, the replacement of LIDP could restore the functions of the lumbar spine and improve the curative results of disc excision.

Adult↗

[Histopathological study on the intervertebral discs of idiopathic scoliosis (author's transl)].

To elucidate morphologic events, 74 intervertebral discs removed by Dwyer instrumentation from 15 scoliotic patients and 10 intervertebral discs by anterior spinal wedge osteotomy from 10 patients were examined, along with 33 intervertebral discs from autopsy cases. Paraffin sections were stained with PAS, toluidine blue and alcian blue in addition to routine stainings. The results obtained are as follows: (1) Noticeable differences in stainability of cartilaginous plate, cleft and vacuolation of the matrix of annulus fibrosus and cellular decrease were obtained in nucleus pulposus in scoliotic patients as compared with controls. Chordal cells in nucleus pulposus were found in 30% of scoliotic patients and 9% of controls. (2) In the apical discs, ossification gap of cartilaginous plate decreased, while cleft and vacuolation of annulus fibrosus and formation of cartilage cell cluster in nucleus pulposus were increased. (3) Irregular fiber running, cleft and vacuolation of annulus fibrosus were found in scoliotic patients with the curvature of the spine by more than 60 degrees. Matrix degeneration of cartilaginous plate and irregular fiber running of annulus fibrosus were common in scoliotic patients with higher rotation than grade III of Nash & Moe classification. Conversely, chordal cells in nucleus pluposus were not common in higher rotation cases. Chordal cell remnants were prominent in nucleus pulposus in scoliotic patients. This suggests that some abnormalities occurring during the maturation process of nucleus pulposus are related to the evolution of scoliosis.

Adolescent↗

Elastic fibres in the anulus fibrosus of the adult human lumbar intervertebral disc. A preliminary report.

Two intervertebral discs were removed at autopsy from the lumbar region of the spine from male or female adult human cases at the following ages: 26, 34, 43, 50 and 62 years. The discs were prepared by paraffin wax embedding, sectioned serially and stained with haematoxylin and eosin or by Verhoff's elastic fibre method. Four light microscopy photomicrographs were made of randomly selected 400 micron 2 areas of anulus fibrosus matrix (two each from different levels of a single disc). Each photomicrograph was examined for elastic fibres, and the areas occupied by them were quantitated by manual planimetry. Elastic fibres were observed in all lamellae of the anulus fibrosus at lumbar levels and they were circularly, obliquely and vertically oriented. Approximately 10% of the matrix of the anulus fibrosus consisted of elastic fibres and their numbers tended to decrease slightly with increasing age of the individual.

Adult↗

Biomechanics of the SB Charité lumbar intervertebral disc endoprosthesis.

The SB Charité intervertebral disc prostheses consist of two metal end-plates and an interposed polyethylene slide core. These were subjected to static and dynamic testing in a servohydraulic test rig. When embedded in polypropylene, the prostheses were found to function adequately under a high static load, and under a lighter dynamic load for a long time. When tested in a cadaveric vertebral segment, a large end-plate surface area proved to be of critical importance in preventing collapse of the prosthesis into the vertebral body.

Biomechanical Phenomena↗

Biomechanical, radiologic, and histopathologic correlations in the pathogenesis of experimental intervertebral disc disease.

STUDY DESIGN: The desert sand rat, an animal model for spinal degenerative disc disease, was studied for biomechanical, histologic, and radiographic characteristics. Load deformation curves with peak force and force decay, hematoxylin-eosin-stained sections, and lateral radiographs were correlated. OBJECTIVES: The hypothesis that the subchondral bone response preceded or contributed to the degenerative disc disease seen in the desert sand rat was tested. SUMMARY OF BACKGROUND DATA: Intervertebral disc disease spontaneously develops in the desert sand rat during its lifetime. Approximately 50% will have significant disc disease by age 18 months. Previous studies have found metabolic and histologic changes associated with intervertebral disc degeneration in the sand rat. METHODS: Desert sand rats were killed at 3-, 9-, 15-, and 18-month intervals and tested in Rheometrics Solid Analyzer with nondestructive step strain loading to obtain a load deformation curve. Radiographs and histologic sections of each animal were compared. Peak force and force decay were analyzed by level and by age. Analysis of variance and Tukey's methods were applied to data. RESULTS: There were no statistically significant differences in biomechanical data. No histologic changes were noted in the study groups up to 18 months of age. Radiographic differences characterized by subchondral bony sclerosis were noted by 18 months of age. No trends were noted when radiographic grades were compared with force data. CONCLUSIONS: The absence of biomechanical histologic changes in the intervertebral disc per se from 3 through 18 months, with radiographic changes in the subchondral bone, supports the hypothesis that the earliest changes in intervertebral disc disease in this animal model are related to the subchondral bone response.

Animals↗

Pathological studies on calcification of the intervertebral discs.

Calcified deposits in the intervertebral discs of 35 cadavers microradiographically appeared as linear of flake-like densities composed of calcium pyrophosphate dihydrate (CPPD) crystals and as multiple punctates possibly composed of dicalcium phosphate dihydrate (DCPD) crystals. Calcium deposits were found in 57% of the cadavers by microradiography and 63% by light microscopy, without known metabolic or familial history related to articular chondrocalcinosis. By scanning electron microscopy, CPPD crystals were mainly rod-like, rectangular and cuboid and were about 4 to 10 mu in length while DCPD crystals were prismatic and about 20 to 60 microns in length.

Adolescent↗

Kinetics of tissue and serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 in intervertebral disc degeneration and disc herniation.

We have evaluated the correlation between disc herniation or degeneration and the levels of matrix metalloproteinase-3 (MMP-3) or tissue inhibitor of metalloproteinases-1 (TIMP-1). The lumbar discs obtained from 22 autopsied cadavers and 21 patients with lumbar disc herniation were examined. Immunohistochemical study: The number of MMP-3-producing and TIMP-1-producing cells increased as disc herniation or degeneration progressed. Zymography: Activated type MMP-3 was observed in the normal and herniated intervertebral disc excluding the intervertebral disc with protrusion-type herniation. RT-PCR: The MMP-3 gene was expressed in all groups. However, the expression of the TIMP-1 gene was weak in the normal group as well as in the protrusion type disc herniation. Determination of tissue and serum levels of MMP-3 and TIMP-1 was increased as disc degeneration or herniation progressed. There were positive correlations between the number of MMP-3-producing or TIMP-1-producing cells in the intervertebral disc and the tissue or serum levels of MMP-3 and TIMP-1. These results suggested that MMP-3 and TIMP-1 were closely related to the progression of disc degeneration or herniation. The results also suggested that MMP-3 and TIMP-1 exhibited similar kinetics. Moreover, the serum levels of MMP-3 and TIMP-1 reflected the progression of disc degeneration and herniation.

Adolescent↗

[Mineral changes in the intervertebral disc and facet joints during aging].

The mineralogic examinations of intervertebral disc and cartilages of facet joints, taken from corps of the accidents victims, from the level L4-L5, were performed. At the moment of accident the middle age of victim was 41.2 years (4-87 years). Scanning microscopy, atom absorption, chemical analyses and electron microprobe analyses were used in the examinations. As the result of examinations we found: demineralisation of nucleus pulposus in the intervertebral disc and two kinds of mineralisation of anulus fibrosus--invisible and visible. Invisible mineralization was found as the initial stage of visible mineralization. In the cartilages of fact joints, similarly as in the anulus fibrosus, the visible mineralization was found, characterised by the presence of the different shaped mineral deposits in the microscope. The invisible mineralization characterised by increased content of Ca and P and by changes in the chemical composition of basic cartilage substance Fe, Cu, Pb, Zn, Sr, Na, K. It was detected with very sensitive methods. The very close relations between mineralogic changes in the intervertebral disc and facet joints cartilages were also found. Mineralogic changes in degenerative changes of vertebral column outstrip the radiologic ones.

Adolescent↗

Injury mechanisms of the cervical intervertebral disc during simulated whiplash.

STUDY DESIGN: A kinematic analysis of cervical intervertebral disc deformation during simulated whiplash using the whole cervical spine with muscle force replication model was performed. OBJECTIVES: To quantify anulus fibrosus fiber strain, disc shear strain, and axial disc deformation in the cervical spine during simulated whiplash. SUMMARY OF BACKGROUND DATA: Clinical studies have documented acute intervertebral disc injury and accelerated disc degeneration in whiplash patients, although there has been no biomechanical investigation of the disc injury mechanisms. METHODS: A bench-top sled was used to simulate whiplash at 3.5, 5, 6.5, and 8 g using six specimens. The 30 degrees and 150 degrees fiber strains, disc shear strains, and axial disc deformations during whiplash were compared with the sagittal physiologic levels. RESULTS: Increases over sagittal physiologic levels (P < 0.05) were first observed during the 3.5 g simulation. Peak fiber strain was greatest in the posterior 150 degrees fibers (running posterosuperiorly), reaching a maximum of 51.4% at C5-C6 during the 8 g simulation. Peak disc shear strain was also greatest at the posterior region of C5-C6, reaching a maximum of 1.0 radian due to posterior translation during the 8 g simulation. Axial deformation at the anterior disc region exceeded physiologic levels at 3.5 g and above, while axial deformation at the posterior region exceeded physiologic limits only at C5-C6 at 6.5 g and 8 g. CONCLUSIONS: The cervical intervertebral discs may be at risk for injury during whiplash because of excessive 150 degrees fiber strain, disc shear strain, and anterior axial deformation.

Aged↗

Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica.

Intervertebral disc disease (IDD) characterized by sciatica is a common disorder affecting about 5% of individuals. Environmental factors can predispose to this disease, but IDD has a strong genetic background. Recent evidence suggests that inflammation is one of the key factors in the etiology of IDD. Here, a possible role of the inflammatory mediator genes was studied in 155 patients with IDD-related sciatica and 179 controls. Forty-eight patients were analyzed for mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10 candidate cytokine genes (IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10, IFNG) were genotyped from all subjects. No disease-causing mutations were identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however, significantly different between the two groups for IL6 SNP, T15A in exon 5 (P=0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more common in the patients (P=0.011; OR=4.4, 95% CI=1.2-15.7; AR=7.5%, 1.6-13.1%). Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C, G-174C, and T15A in exon 5. Haplotype GGGA was more common in the patients (P=0.011; OR=4.8, 95% CI=1.6-14.5). To evaluate attributable risk, haplotype pairs were assigned for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR of 5.4 (95% CI=1.5-19.2). Association of GGGA with disease was highly significant (P=0.0033), and the associated AR was 6.8% (1.9-11.5%). These findings support the role of IL-6 genetic variations in discogenic pain.

Adult↗