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Importance of intervertebral disc size in low back pain.

AIM: To compare two anthropometrical methods for measuring the intervertebral disc size with computer tomography measurements and to develop a new anthropometric method for calculating intervertebral disc area. METHODS: Intervertebral disc size was measured using computer tomography and two anthropometric methods (Colombini and modified Colombini) in a sample of 40 subjects. The new calculation for intervertebral disc size was developed and used in a sample of male bus drivers with (n=65) and without (n=30) anamnestic low back pain to asses clinical usefulness. RESULTS: The modified anthropometric method for intervertebral disc size assessment correctly predicted intervertebral disc size in 89% of the cases and the determination error was diminished to an average of 4.1% for level L4-L5 and 4.4% for level L5-S1. The average size of the intervertebral discs in 65 subjects with anamnestic lower back problems was significantly smaller than in the control group of 30 subjects having no such problems (p<0.001). CONCLUSION: The use of the presented formulas for the calculation of the intervertebral disc in L4-5 and L5-S1 areas from the data obtained by simple anthropometrical measurements is sufficiently reliable and accurate. The method is economical and harmless.

Adult↗

Intervertebral disc extrusion in six cats.

Existing reports concerning intervertebral disc disease (IVDD) have focused almost exclusively on dogs, although a small number of individual case reports of IVDD of cats has been published. The medical records of six cats with IVDD were reviewed. Radiographic studies confirmed narrowed intervertebral disc spaces, mineralised intervertebral discs, and one or more extradural compressive lesions of the spinal cord in each cat. All disc extrusions were located in the thoracolumbar region. Surgical decompression of the spinal cord was achieved in all cats by means of hemilaminectomy and removal of compressive extradural material confirmed to be degenerative disc material. Good to excellent neurological recovery was noted in five of the six cats included in this report. Based on this review, it appears that IVDD of cats has many similarities to IVDD of dogs, and that healthy cats with acute intervertebral disc extrusion(s) respond favourably to surgical decompression of the spinal cord.

Animals↗

Neural elements in human cervical intervertebral discs.

This study attempted to characterize neural elements within the human cervical intervertebral disc. Cervical intervertebral discs were obtained from four adult human subjects at autopsy. Discs were stained in bulk with gold chloride, sectioned, and viewed with the light microscope. Nerve fibers appeared to enter the disc in the posterolateral direction and course both parallel and perpendicular to the bundles of the anulus fibrosus. Nerves were seen throughout the anulus but were most numerous in the middle third of the disc. Receptors resembling Pacinian corpuscles and Golgi tendon organs were seen in the posterolateral region of the upper third of the disc. These results provide further evidence that human cervical intervertebral discs are supplied with both nerve fibers and mechanoreceptors.

Adult↗

Glycosaminoglycan accumulation in primary culture of rabbit intervertebral disc cells.

STUDY DESIGN: With the heterogeneity of the intervertebral disc as the focus, intervertebral discs from normal young rabbits were separated into nucleus pulposus (NP), inner anulus fibrosus (IAF), and outer anulus fibrosus (OAF) zones. Disc cells from each zone were isolated and propagated under monolayer and within agarose gel culture. The metabolism of these cultured disc cells was examined in terms of glycosaminoglycan (GAG) accumulation. OBJECTIVES: The object was to study the metabolism of disc cells derived from each zone and characterize them on the basis of GAG accumulation and composition. SUMMARY OF BACKGROUND DATA: It has been shown that three-dimensional culture systems, such as within-agarose gels or in alginate beads, permit long-term maintenance of the articular chondrocyte phenotype in vitro. However, little has been reported on how the metabolism of intervertebral disc cells, especially GAG accumulation, is affected by different culture conditions. METHODS: Cells from each zone were subjected to monolayer or three-dimensional culture for up to 12 days. GAG accumulation in the different culture systems was analyzed using chemical, histologic, and immunohistologic methods. Differences of GAG and DNA content among NP, IAF, and OAF cells were statistically evaluated by analysis of variance. The data of keratin sulfate content in three-dimensional culture were compared with that in monolayer culture using nonparametric Mann-Whitney U test. RESULTS: Monolayer culture revealed that increases in GAG content were significantly higher in IAF cells than in OAF cells. However, in three-dimensional culture GAG content was similar in the two groups. AF cells in three-dimensional cultures showed immunohistochemical localization of chondroitin sulfate and keratan sulfate, suggesting the existence of pericellular matrix. High performance liquid chromatography confirmed the expression of keratan sulfate in cultured cells. CONCLUSIONS: GAG accumulation in cultures of cells from different zones of the intervertebral disc varied according to the culture conditions used. The importance of choosing the appropriate culture systems to meet the objectives of a study should be emphasized.

Analysis of Variance↗

Age-related changes in fibromodulin and lumican in human intervertebral discs.

STUDY DESIGN: An analysis of proteoglycans of the intervertebral disc using immunoblotting of tissue extracts. OBJECTIVES: To investigate the changes in structure and abundance of fibromodulin and lumican in human intervertebral discs during aging and degeneration. SUMMARY OF BACKGROUND DATA: Fibromodulin and lumican are keratan sulfate proteoglycan constituents of the disc's extracellular matrix, whose interaction with collagen fibrils may contribute to the mechanical properties of the tissue. Changes in their abundance and/or structure that occur with aging and degeneration therefore may have an impact on disc function. METHODS: Lumbar intervertebral discs were obtained from individuals of different ages, and extracts of anulus fibrosus and nucleus pulposus were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using antibodies specific for fibromodulin and lumican. RESULTS: The major changes in abundance observed with age were a decrease in fibromodulin in the adult nucleus pulposus and an increase in lumican in anulus fibrosus during early juvenile development. In addition, fibromodulin in the anulus fibrosus exhibited a structural change with increasing age, characterized by a shift toward the predominance of its glycoprotein form lacking keratan sulfate. Fibromodulin was more abundant in the anulus fibrosus than in nucleus pulposus at all ages, whereas lumican was much more abundant in nucleus pulposus than in anulus fibrosus in the young juvenile; in the adult, however, lumican was present in comparable levels in both tissues. With increasing degrees of degeneration, fibromodulin exhibited an increase in abundance. CONCLUSIONS: Growth, aging, and degeneration of the intervertebral disc are associated with changes in the abundance and structure of fibromodulin and lumican, which presumably influence the functional properties of the tissue.

Adolescent↗

A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology.

STUDY DESIGN: The progression of intervertebral disc degeneration following anterolateral "stab" of adult rabbit lumbar discs by 16-gauge hypodermic needle to a limited (5-mm) depth was studied for up to 24 weeks using magnetic resonance imaging, radiograph, and histologic outcome measures. OBJECTIVES: To develop a slowly progressive, reproducible rabbit model of intervertebral disc degeneration suitable for studying pathogenesis and pathophysiology of intervertebral disc degeneration and testing safety and efficacy of novel approaches to the treatment of intervertebral disc degeneration (e.g., growth factors, gene therapy, cell therapy, and tissue engineering). SUMMARY OF BACKGROUND DATA: Numerous animal models of intervertebral disc degeneration have been proposed in the literature, each with attendant advantages and disadvantages. The classic "stab model," involving full-thickness stab of anterior anulus fibrosus of adult rabbit lumbar discs by a number 11 scalpel blade, appears to produce changes in certain biochemical and histologic outcome measures that are similar to changes seen in human intervertebral disc degeneration. However, the immediate herniation of nucleus pulposus on full-thickness stab renders this model less suitable for 1) studying effects of less precipitous changes in nucleus pulposus and anulus fibrosus that may be important in the onset and progression of intervertebral disc degeneration and 2) testing novel therapeutic approaches that target the processes of early intervertebral disc degeneration. METHODS: The L2-L3, L3-L4, and L4-L5 lumbar intervertebral discs of 18 skeletally mature female New Zealand White rabbits were stabbed by 16-gauge hypodermic needle to a depth of 5 mm in the left anterolateral anulus fibrosus. Serial magnetic resonance imaging scans of the stabbed discs and intact L1-L2 and L5-L6 control discs were performed at 3, 6, 12, and 24 weeks post surgery and compared with preoperative magnetic resonance images. Supplemental radiograph and histologic analyses were performed. RESULTS: The stabbed discs exhibited a progressive decrease in "magnetic resonance imaging index" (the product of nucleus pulposus area and signal intensity from T2-weighted midsagittal plane images) starting at 3 weeks post stab and continuing through 24 weeks, with no evidence of spontaneous recovery or reversal of magnetic resonance imaging changes. Radiograph findings included early osteophyte formation by 6 weeks post stab and extensive, bridging osteophytes by 24 weeks. Histologic analysis revealed progressive loss of notochordal cells from the nucleus pulposus, filling of the nucleus pulposus space with fibrocartilage, and derangement of anulus fibrosus. CONCLUSIONS: Stabbing the anterolateral anulus fibrosus of adult rabbit lumbar discs with a 16-gauge hypodermic needle to a limited (5-mm) depth results in a number of slowly progressive and reproducible magnetic resonance imaging, radiograph, and histologic changes over 24 weeks that show a similarity to changes seen in human intervertebral disc degeneration. This model would appear suitable for studying pathogenesis and pathophysiology of intervertebral disc degeneration and testing safety and efficacy of novel treatments of intervertebral disc degeneration.

Animals↗

Water and electrolyte content of human intervertebral discs under variable load.

The human intervertebral disc acts as an osmotic system. Water, salt, and other low-molecular substances penetrate the cartilage plates and annulus fibrosus. The content of water, sodium, potassium, and ashes in different regions of 69 human lumbar intervertebral discs was examined before and after being loaded with certain weights. Under load, the disc loses water (annulus 11%, nucleus 8%) and gains sodium and potassium. The higher concentration of electrolytes in the disc after a long period of loading increases its osmotic absorption force and enables the disc to hold back the remaining water, even against a considerable pressure. After reduction of the pressure, water is quickly reabsorbed and the disc gains height and volume. The pumping mechanism maintains the nutrition and biomechanical function of the intervertebral disc.

Biomechanical Phenomena↗

Experimental study of intervertebral disc allografting in the dog.

STUDY DESIGN: An investigation of the use of intervertebral disc allografting as a potential alternative to intervertebral fusion was performed. In 13 adult mongrel dogs, intervertebral disc units cryopreserved after slow freezing were grafted. OBJECTIVES: To evaluate the morphologic and biosynthetic damage caused by cryopreserving the canine intervertebral disc before allografting. SUMMARY OF BACKGROUND DATA: Cryopreservation did not alter the normal histologic appearance. The metabolic activity, measured by 35S-sulfate incorporation, was observed to be 44% of the fresh control. METHODS: Transplanted intervertebral discs were examined histologically and radiographically at 12, 24, and 48 weeks after surgery. RESULTS: The allografted disc had preserved anular and nuclear architecture with moderate loss of chondrocytes 12 weeks after grafting. However, the intervertebral disc showed evidence of progressive disc degeneration 1 year after transplantation. CONCLUSIONS: More investigation of storage methods is needed to enhance the viability of the intervertebral disc for successful intervertebral disc allografting.

Animals↗

Matrix metalloproteinase-3 production by human degenerated intervertebral disc.

To assess its possible role in the pathophysiology of intervertebral disc degeneration, we investigated the production of matrix metalloproteinase-3 (MMP-3) using human intervertebral disc explant culture. Five normal and 10 degenerated disc specimens were used. The levels of MMP-3 released in the medium were measured with use of an enzyme immunoassay. The results showed that the level of MMP-3 in the degenerated group (0.57 microg/ml/mg wet weight; n = 10) was significantly higher than that of the control group (0.29 microg/ml/mg wet weight; n = 5) (p < 0.05). Immunostaining of MMP-3 revealed that the ratio of positive staining cells in the degenerated group was greater than that of the control group. These observations suggest that MMP-3 produced by human intervertebral disc may be involved in the intervertebral disc degeneration, particularly in the initiation of matrix degradation of intervertebral disc.

Adult↗

Evidence for the degradation of type XI collagen by bovine intervertebral disc- and articular cartilage extracts.

Bovine intervertebral disc- and articular cartilage extracts contain a metalloproteinase system capable of degrading type XI collagen. The collagen-degrading activity is rather low in unmodified extracts but increases considerably on metalloproteinase activation. The similarity between intervertebral disc and articular cartilage in their patterns of (casein-degrading) metalloproteinases and type XI and type II collagen degradation is believed to suggest a similarity in the events underlying the degradative disorders of articular cartilage and intervertebral disc.

Animals↗

In vitro method for measuring synthesis rates in the intervertebral disc.

A method for culturing intervertebral disc tissue in vitro under conditions that control changes in hydration and minimize loss of proteoglycans has been developed. Disc slices were enclosed in small-pore dialysis tubing and incubated in medium containing polyethylene glycol (PEG). By varying the PEG concentration, different external swelling pressures could be applied to the tissue. The rate of glycosaminoglycan synthesis in rabbit and dog disc was then measured using [35S]sulphate as a precursor. Synthesis rates varied with final hydration of the tissue, and the highest rates were found at hydrations close to those found in vivo. Under conditions of controlled hydration, rabbit nucleus has a higher rate of glycosaminoglycan synthesis than annulus. However, the rates measured in sagittal slices of dog disc decreased from the outer to the inner regions of the anterior annulus, reaching a minimum value in the nucleus and then increasing again in the posterior part of the annulus. The results show that in the intervertebral disc, measured rates depend on culture conditions.

Animals↗

[New surgical technique of anterior decompression for cervical disc disease: vertebral column autograft with the intervertebral disc after anterior cervical decompression].

The authors describe the surgical technique of vertebral column autograft with the intervertebral disc after anterior decompression for cervical disc disease. This series consisted of 41 patients with cervical disc disease suffering from cervical spondylotic radiculomyelopathy. There were 27 men and 14 women, ranging in age from 27 to 72 years (mean age 49 years). 33 patients were operated on at one level and 8 patients at two levels. The average postoperative follow-up period was one year 10 months and ranged from 6 months to 3 years 3 months. The patients were generally allowed out of bed wearing a soft collar within 1 day postoperatively. The collar was used for 2 months after surgery. The postoperative course of all patients was uneventful and neurological symptoms improved. Postoperative X-ray films showed some movement in the operated disc level in all patients. The authors think that this surgical procedure may be suitable for preserving mobility of the spine.

Adult↗

Age-related phenomena in the lumbar intervertebral discs. Lipofuscin and amyloid deposition.

In 69 lumbar intervertebral discs from 69 autopsies, lipofuscin was seen in discs from individuals older than 50 years of age and amyloids in the discs of individuals older than 40 years of age. In 261 intervertebral disc tissue specimens collected at the time of surgery for disc herniation, lipofuscin was seen in the discs of individuals older than 20 years of age and amyloids in the discs of individuals older than 15 years of age. It is speculated that amyloids and lipofuscin are a sign of aging in the intervertebral disc as in other tissues. Furthermore, amyloids and lipofuscin were seen in the operated discs of young individuals than in the autopsy cases.

Adolescent↗

Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement.

STUDY DESIGN: By the technique of tissue engineering, composite intervertebral disc implants were fabricated as novel materials for disc replacement, implanted into athymic mice, and removed at times up to 12 weeks. OBJECTIVES: The goal of this study was to construct composite intervertebral disc structures consisting of anulus fibrosus cells and nucleus pulposus cells seeded on polyglycolic acid and calcium alginate matrices, respectively. SUMMARY OF BACKGROUND DATA: Previous work has documented the growth of anulus fibrosus cells on collagen matrices and nucleus pulposus cells cultured on multiple matrices, but there is no documentation of composite disc implants. METHODS: Lumbar intervertebral discs were harvested from sheep spine, and the nucleus pulposus was separated from surrounding anulus fibrosus. Each tissue was digested in collagenase type II. After 3 weeks in culture, cells were seeded into implants. The shape of the anulus fibrosus scaffold was fabricated from polyglycolic acid and polylactic acid, and anulus fibrosus cells were pipetted onto the scaffold and allowed to attach for 1 day. Nucleus pulposus cells were suspended in 2% alginate and injected into the center of the anulus fibrosus. The disc implants were placed in the subcutaneous space of the dorsum of athymic mice and harvested at 4, 8, and 12 weeks. At each time point, 4 samples were stored in -70 degrees C for collagen typing and analysis of proteoglycan, hydroxyproline, and DNA. Other samples were fixed in 10% formalin for Safranin-O staining. RESULTS: The gross morphology and histology of engineered discs strongly resembled those of native intervertebral discs. Biochemical markers of matrix synthesis were present, increasing with time, and were similar to native tissue at 12 weeks. Tissue-engineered anulus fibrosus was rich in type I collagen but nucleus pulposus contained type II collagen, similar to the native disc. CONCLUSION: These results demonstrate the feasibility of creating a composite intervertebral disc with both anulusfibrosus and nucleus pulposus for clinical applications.

Animals↗

Cell cluster formation in degenerate lumbar intervertebral discs is associated with increased disc cell proliferation.

Healthy human intervertebral discs contain relatively few cells and these are sparsely distributed. A characteristic feature of disc degeneration, however, is the appearance of cell clusters, particularly in damaged areas. How these clusters form is currently unknown. We have examined excised pathological human discs for evidence of cell proliferation. Disc sections were immunostained for the proliferating cell nuclear antigen (PCNA) and the proliferation-associated Ki-67 antigen. PCNA immunopositive cells were observed within degenerate discs, commonly though not exclusively, in cell clusters. Cells immunopositive for the Ki-67 antigen were less prevalent than those for PCNA, but similarly were observed frequently within clusters in degenerate discs. In contrast, immunopositivity for these markers was not common in less degenerate discs or in areas of the disc where cell clusters were not observed. These observations suggest that disc cell proliferation is associated with disc degeneration and is the likely cause of cell cluster formation.

Adolescent↗

Accuracy of survey radiographic diagnosis of intervertebral disc protrusion in dogs.

To assess the diagnostic accuracy of survey radiography for canine thoracolumbar intervertebral disc protrusion, survey radiographs (lateral and ventrodorsal) of 64 dogs with surgically-confirmed thoracolumbar intervertebral disc protrusion, 51 dogs with negative myelograms and 29 dogs with various spinal conditions other than disc protrusion were reviewed by three independent observers who were unaware of any clinical information. There were marked differences in observer performance for diagnosis of intervertebral disc protrusion, although there were no significant differences in intraobserver diagnostic accuracy for small vs. large dogs. Accuracy of observers for determining sites of intervertebral disc protrusion using survey radiography was in the range 51-61%. All observers had low accuracy for identification of second sites of intervertebral disc protrusion. The most useful radiographic sign, narrowed intervertebral space, had only moderate sensitivity (range 64-69%) and moderate predictive value (range 63-71%) for intervertebral disc protrusion. Vacuum phenomenon was an infrequent but accurate sign of intervertebral disc protrusion. Recognition of multiple radiographic signs of intervertebral disc protrusion at one site was associated with increased accuracy of diagnosis. No observer was accurate enough to justify attempting targeted surgical treatment of intervertebral disc protrusion without myelography.

Animals↗

The structure and degradation of aggrecan in human intervertebral disc.

The ability of the intervertebral disc to resist compression is dependent on its high proteoglycan concentration. The disc proteoglycans are classified as aggregating or non-aggregating depending on their ability to interact with hyaluronan. The majority of the aggregating proteoglycans are derived from aggrecan, though their glycosaminoglycan substitution pattern has not been determined. In contrast, the origin of the non-aggregating proteoglycans is unclear, though it has been postulated that they are derived from aggrecan by proteolysis. The present work demonstrates that keratan sulfate (KS) in the glycosaminoglycan-binding region of disc aggrecan is confined to the KS-rich domain of the core protein and is not present in association with chondroitin sulfate (CS) in the CS1 and CS2 domains. It also shows that the non-aggregating disc proteoglycans are derived from aggrecan, with the large molecules possessing both the KS-rich and CS1 domains and the smaller molecules being generated from either the KS-rich or CS2 domain. The origin and spectrum of disc proteoglycan heterogeneity is the same in both the annulus fibrosus and nucleus pulposus.

Adult↗

Lumbar intervertebral disc heights in normal subjects and patients with disc herniation.

A method for the measurement of intervertebral disc heights from lateral radiographs obtained in controlled conditions was examined for intra- and interobserver errors. The use of a strict criterion for the positioning of marks on the images of the vertebrae was shown to enable reproducible measurements to be made with a maximum error of 0.7 mm. Measurements of anterior and posterior disc heights and disc depths were made for 11 normal subjects and ten male patients with prolapsed intervertebral discs, while standing upright. The level of the prolapsed discs were shown to have reduced height compared with normal before surgery, and further narrowing 3 months after surgery. The unaffected discs of the patients were the same height as those of the controls. The technique is proposed as suitable for the investigation of the effect on intervertebral discs of procedures such as the injection of chymopapain.

Adult↗