Therapeutic use of cephazolin to prevent complications of spine surgery.

Discitis, caused by pyogenic organisms, is a potential complication of any procedure which involves entering the intervertebral disc during open or percutaneous procedures. While there are wide variations in the severity of symptoms, the characteristic feature of discitis is the development of increasingly severe back pain, which is not relieved by rest, or narcotic analgesics. While there is a tendency to spontaneous resolution over time, a self-limiting course does not always eventuate. Serious complications resulting from spread of the infective process can lead to vertebral osteomyelitis or to the formation of an epidural abscess with further risk of neural compression. Clinical and experimental evidence now supports the prophylactic use of a suitable antibiotic, but some uncertainties exist about the benefits of antibiotic therapy in treating established discitis. While cephazolin is a widely favoured choice of antibiotic, the timing of its administration to prevent or treat discitis has been complicated by the lack of suitable methods for detecting and measuring the concentration of cephazolin in the plasma and disc in experimental and clinical conditions. This paper describes a high-performance liquid chromatography technique for detecting the antibiotic cephazolin. The results conclude cephazolin can be detected in the plasma and disc after administering an intravenous bolus dose. However, concentration of cephazolin in the outer disc was 12 times greater than that of the inner disc.

Mechanical and pathologic consequences of induced concentric anular tears in an ovine model.

STUDY DESIGN: Relations between induced concentric tears in the sheep disc and the mechanics of the intervertebral joint and vertebral body bone were analyzed. OBJECTIVE: To examine the effect of concentric disc tears on the mechanics of the spine. SUMMARY OF BACKGROUND DATA: Degeneration of the intervertebral disc results in changes to the mechanics and morphology of the spine, but the effect of concentric disc tears is unknown. METHODS: In this study, 48 merino wethers were subjected to surgery, and discs were randomly selected for either a needlestick injury or induction of a concentric tear in the anterior and left anterolateral anulus. Sheep were randomly assigned to groups for killing at 0, 1, 3, 6, 12, and 18 months. From each sheep, two spine segments were mechanically tested: one with a needlestick injury and one with a concentric tear. Macroscopic disc morphology was assessed by three axial slices of the disc. Sagittal bone slices were taken from cranial and caudal vertebral bodies for histologic analysis. RESULTS: Induced concentric tears decrease the stiffness of intact spine segments in left bending and the disc alone in flexion. In all other mechanical tests, the needlestick injury had the same effect as the induced concentric tear. In the isolated disc, the disc stiffness at 6 months was increased for right bending, as compared with the response at 1 month. This was associated with increased anterior lamellar thickening and increased vertebral body bone volume fraction. CONCLUSIONS: Concentric tears and needlestick injury in the anterior anulus lead to mechanical changes in the disc and both anular lamellar thickness and vertebral body bone volume fraction. A needlestick injury through the anulus parallel to the lamellae produces progressive damage.

Effect of global system for mobile communication (gsm)-like radiofrequency fields on vascular permeability in mouse brain.

The effect of global system for mobile communication (GSM) radiofrequency fields on vascular permeability in the brain was studied using a purpose-designed exposure system at 898.4 MHz. Mice (n= 30) were given a single far field, whole body exposure for 60 minutes at a specific absorption rate of 4 W/kg. Control mice were also sham-exposed (n = 10) or permitted free movement in a cage (n = 10) to exclude any stress-related effects. Vascular permeability changes were detected using albumin immunohistochemistry and the efficacy of this vascular tracer was confirmed with a positive control group exposed to a clostridial toxin known to increase vascular permeability in the brain. No significant difference in albumin extravasation was detected between any of the groups at the light microscope level using the albumin marker.

Early histologic changes in lower lumbar discs and facet joints and their correlation.

Biomechanical and histologic studies have highlighted the close functional relationship between lumbar discs and their associated facet joints, and it is conceivable that their degenerative changes are interdependent. However, separation of cause from effect remains controversial. Hitherto, no study in humans has correlated the changes histologically. The present study assessed histologic changes in lower lumbar discs and their associated facet joints in patients under the age of 40 years using classification systems developed for this investigation. A specific objective was to correlate changes in discs and facet joints. Data from 15 lower lumbar spine specimens were obtained. Three parasagittal sections per disc and one section per facet joint were graded histologically. The results were correlated with age, within the functional spinal unit (FSU), and with the adjacent level. Histologic changes were found in discs and facet joints from all FSUs. There was no correlation between the age of the subject and the degree of degeneration of the disc or facet joints at either level. The extent of disc degeneration at L4/5 correlated significantly with changes at L5/S1 (P < 0.01). There was no correlation between changes in discs and the associated facet joints at either level. The results of the study showed that microscopic changes are seen in the disc and facet joints from an early age and can be quite marked in some individuals before the age of 40 years. A correlation of degenerative changes within the FSU could not be established.

Osteoarthrosis of the facet joints resulting from anular rim lesions in sheep lumbar discs.

STUDY DESIGN: Facet joints from sheep lumbar spines were examined for histologic evidence of osteoarthrosis after anular incision. OBJECTIVES: To describe the sequence of changes in facet joints in an animal model of disc degeneration. SUMMARY OF BACKGROUND DATA: There are many studies with results showing a link between facet joint osteoarthrosis and disc degeneration, but the development of osteoarthrosis in facet joints has not been observed in a controlled study of disc degeneration. METHODS: Histologic features of facet joint degeneration were compared with established descriptions of human osteoarthrosis, and the sequence of changes was documented in a controlled prospective study of disc degeneration. RESULTS: Osteoarthrosis in sheep lumbar facet joints is similar to that described in human joints and develops in response to anular injury. Discs degenerate relatively soon after anular incision, but there is a long delay in the appearance of significant changes to the facet joints at the level of anular incision and adjacent levels. CONCLUSIONS: The results shows that facet joints in sheep undergo osteoarthrotic changes in response to disc degeneration and confirm the sheep as a suitable model for the study of degenerative spinal disorders.

Variation in cytokines induced by particles from different prosthetic materials.

Particles of prosthetic material stimulate macrophages to release cytokines, which may cause bone loss and loosening of the prosthesis. This study investigates the possibility that particles of different prosthetic materials may induce different cytokines and thus have different effects on bone remodeling. The in vitro response of human monocytes to particles of cast and forged cobalt chrome alloy, stainless steel, and titanium aluminum vanadium alloy were compared. There was no difference in the biologic response to cobalt-chrome particles derived from cast or forged material. Cobalt-chrome particles were toxic to the cells, but titanium aluminum vanadium particles did not affect cell viability. Stainless steel particles were approximately 10 times more toxic than were cobalt-chrome particles. All particles induced the release of tumor necrosis factor and interleukin 1 beta; stainless steel particles were the most potent stimulators of interleukin 1 beta; titanium aluminum vanadium particles were the strongest stimulators of interleukin 6 and prostaglandin 2. The study showed that particles derived from prosthetic materials of different metal compositions can elicit significantly different biologic responses. Understanding these different responses may help identify materials better suited for prostheses.

Calcium pyrophosphate dihydrate deposition in degenerate lumbar discs.

Calcium pyrophosphate dihydrate (CPPD) crystal deposition in lumbar intervertebral discs has been described, but its clinical significance remains unclear. The present study analyzed histological sections of lumbar discs that were obtained from patients undergoing anterior lumbar interbody fusion. Immunohistological staining was undertaken to identify neural elements and blood vessels. Patients with CPPD deposition were compared with a group without CPPD deposition undergoing the same operation. CPPD was found in 15.7% of investigated patients (12.6% of analyzed discs). Deposits were found in areas of the annulus and nucleus showing advanced degeneration. Two patterns were identified: one comprised sharply demarcated rounded deposits, while the other showed diffuse deposition of crystals. There was no association with ingrowth of vascular or neural tissue. Clinical data did not differ significantly in the two groups of patients. However, in all patients with CPPD deposition there was a history of trauma, previous surgery, or both. Isolated CPPD deposition in lumbar intervertebral discs appears to be an incidental finding that is not related to systemic diseases or general arthropathies.

A comparison of the disease-modifying and cytokine-regulating activities of tenidap, piroxicam and cyclosporin-A using the adjuvant-induced model of arthritis in rats.

This study compared the antiarthritic activity of tenidap, piroxicam and cyclosporin-A (CsA) using the model of adjuvant-induced arthritis in rats. The aim of the study was to correlate any disease-modifying effects of tenidap with its in-vivo regulation of cytokines.Both tenidap and piroxicam reduced arthritic disease when administered orally from the time the first signs of arthritis are expressed. Disease suppression correlated with a significant reduction in interleukin-6 production and a slight reduction in interleukin-1 and tumour necrosis factor production. When coadministered with the adjuvant, tenidap and CsA prevented disease in 50% and 100% of animals, respectively, whereas piroxicam had no effect. This disease prevention induced by tenidap and CsA coincided with reduced interferon-gamma and interleukin-2 production by lymph node cells one day following initiation of adjuvant disease. This inhibition of T-cell cytokines might be consistent with tenidap acting as a disease-modifying drug.

Pathogenesis of tears of the anulus investigated by multiple-level transaxial analysis of the T12-L1 disc.

STUDY DESIGN: Three transaxial slices, dividing each disc into four layers of equal thickness, were made in each of 19 T12-L1 discs. Naked-eye and stereoscopic examination was used to record abnormalities of the T12 (superior) surface of the upper slice, opposing surfaces of the central slice, and the L1 (inferior) surface of the lower slice. OBJECTIVES: To characterize and quantify structural abnormalities to determine their incidence and three-dimensional arrangement, and to test the hypotheses 1) that the frequency and location of tears of the anulus are related to age and nucleus condition; and 2) that rim lesions initiate the development of concentric tears. SUMMARY OF BACKGROUND DATA: Most previous studies of disc disease have been based on the examination of single sagittal slices, some on single transaxial slices, and a few have used both. This single-slice approach underrecords abnormalities that have not involved the disc center, and may inhibit the interpretation of magnetic resonance imaging and computed tomography images. METHODS: Spines from 19 human cadavers (mean age, 47.4 years; range, 20-79 years) were used. An initial transaxial slice through the center of the T12-L1 disc was followed by cranial and caudal transaxial slices midway between the center and endplate. Soft tissues were then removed to allow examination of the endplate. Abnormalities recorded at each stage were summated for all disc levels. The incidence of the abnormalities in each disc sector was analyzed using the Spearman-Rank correlation coefficient and the Bonferroni correction. RESULTS: With the exception of radiating tears, which most commonly affected the posterior disc, the right anterior quadrant tended to show abnormalities more frequently than the other quadrants. Although concentric tears (in 74%), rim lesions (in 47%), and radiating tears (in 47%) were frequent, no correlations were found between these three types of anulus tear. Concentric tears were present after approximately 10% of the anulus had undergone some delamination. Rim lesions correlated with focal thickening of anulus lamellae. One fifth of radiating tears extended to involve the outer anulus zone. CONCLUSIONS: Neither hypothesis was substantiated. Because lesions of the nucleus and anulus lack uniform shape and are three-dimensionally complex, it is inappropriate to interpret cadaver disc disease on single, mid-disc slices. The three different types of anulus tears appear to evolve independent of age and each other.

Elevated synthesis of biglycan and decorin in an ovine annular lesion model of experimental disc degeneration.

The aim of this study was to extend our earlier observations on the changes that occur in the proteoglycans (PGs) of discs subjected to experimental injury to the annulus fibrosus (AF). We employed the alginate bead culture method to examine the metabolism of the dermatan sulphate (DS) containing PGs by cells derived from different regions of ovine discs that had been subjected to experimental annular injury. This was compared with the metabolism of the DS-PGs by cells isolated from equivalent regions of normal sham-operated discs. Six months after induction of the annular lesion, AF cells isolated from the lesion produced significantly higher levels of decorin and biglycan in alginate bead culture than did cells from equivalent zones of the controls. Decorin and biglycan were identified in culture media samples by immunoblotting, using specific antibodies (6-B-6, LF-96), and also by positive identification of their de-glycosylated core proteins. The core protein of the DS-PGs has been shown to inhibit type I/II collagen fibrillogenesis, to negatively regulate the action of transforming growth factor-beta (TGF-beta) and to diminish cellular proliferation in vitro; events which may be detrimental to tissue repair. The findings are therefore consistent with our previous observation the annular lesions in the avascular inner annulus have no capacity to heal.

The origin and fate of herniated lumbar intervertebral disc tissue.

STUDY DESIGN: In a clinicopathologic study, disc tissue collected from surgery and from cadaveric spines was examined to test an hypothesis about the pathogenesis of herniation. OBJECTIVES: To determine the origin and fate of herniated lumbar intervertebral disc tissue. SUMMARY OF BACKGROUND DATA: Previous studies have ascribed herniated disc tissue to the nucleus, anulus, or endplate, or combinations of the three. One study describes it as newly synthesized fibrocartilage. Regardless of its origin, peripheral neovascularization of disc fragments has been described and may be related to pain symptoms. METHODS: Disc tissue was collected after extrusion and was examined histologically to determine its origin and fate. To test the hypothesis that sequestration results from migration of isolated, degenerate fragments of nucleus pulposus through preexisting tears in the anulus fibrosus, cadaveric lumbar disc were examined in detail. RESULTS: Ninety-eight percent of sequestrations contained some nuclear material indicating that nucleus pulposus is the principal substance extruded from the disc. None contained anulus alone. Although vascular repair was present in 89% of specimens, it did not correlate with several clinical parameters. CONCLUSIONS: The autopsy study confirmed the model of nuclear fragmentation, migration, and extrusion along radiating anular clefts. Neovascularization of extruded fragments bore no relationship with duration of sciatic pain symptoms or clinical outcome.

Remodeling of vertebral bone after outer anular injury in sheep.

STUDY DESIGN: This study uses semiautomated histoquantitative techniques to analyze subchondral bone architecture in adult merino sheep up to 2 years after outer anular cuts were created in lumbar discs. OBJECTIVES: To describe morphometric changes to the adjacent vertebral bone structure in the lumbar spine, and to discuss these in relation to the pathology of other spinal components SUMMARY OF BACKGROUND DATA: Disc degeneration has been observed in the sheep lumbar spine 4-6 months after surgery to the outer anulus, whereas biomechanical testing has shown earlier changes. METHODS: Lumber discs with adjacent subchondral trabecular bone were sectioned using standard histologic methods. An image-analyzing computer was used to measure morphometric indices of bone structure. RESULTS: Trabecular bone volume was elevated significantly by 2 months because of consolidation of existing trabeculae and formation of new elements. The changes were evident 2 years after surgery. CONCLUSION: Subchondral trabecular bone appears to be sensitive to changes in the disc after outer anular injury. There is evidence that these structural changes are influenced by changes in the biomechanical behavior of the incised disc.

Complete prevention of the clinical expression of adjuvant-induced arthritis in rats by cyclosporin-A and lobenzarit: the regulation of lymph node cell populations and cytokine production.

A single dose of either cyclosporin-A (CsA) or lobenzarit (CCA) given with an arthrogenic adjuvant completely prevented expression of experimental adjuvant arthritis in rats. The aim of this study was to understand how these drugs prevented the arthritis expression by studying the popliteal lymph nodes draining the arthritic joints at various times after adjuvant injection. Neither drug affected the proliferation in popliteal lymph nodes at the time arthritis was normally expressed, however, there was a marked change in the types of cells present. Immunofluorescence assays showed a reduction in the proportion of CD4+ cells, while the proportion of B-lymphocytes was almost doubled. This coincided with a marked elevation in the ability of these cells to produce interleukin (IL)-6. At the same time production of other cytokines (IL-2, tumour necrosis factor (TNF) and interferon (IFN)-gamma) was not greatly affected. However, one day after adjuvant injection IL-2 and IFN-gamma production was reduced. In vitro experiments showed that IL-6 production by lymphoid cells was relatively unaffected by CsA and CCA but IL-2, TNF and IFN-gamma were suppressed by CsA. The results indicate that CsA and CCA may modify the response to the arthritic adjuvant by specifically inhibiting IL-2, TNF and IFN-gamma production at the time of adjuvant injection. The lack of inhibition of IL-6 by these drugs reveals it may not play a key role in the initiation of this model of chronic inflammation.

Drug inhibition of the macrophage response to metal wear particles in vitro.

The wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses. It is thought that their ability to induce either cell death or the release of mediators that induce bone resorption contributes to this loosening. This study was designed to test the hypothesis that these adverse biologic effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages. Cobalt chrome alloy and titanium alloy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent peritoneal macrophages. Treatment of macrophages with drugs that prevent a drop in pH within phagosomes significantly reduced the toxicity of phagocytosed cobalt chrome alloy particles. The same drugs also reduced the levels of prostaglandin E2 and interleukin-6 release induced by phagocytosed titanium alloy particles. When both types of particles were incubated at a low pH, similar to that encountered by phagocytosed particles, soluble products were released that induced the same effects as the particles themselves. These results show that enhanced corrosion of wear particles by phagocytic cells may contribute significantly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.

Chondromatosis of the choroid plexus.

A case of chondromatosis of the choroid plexus in a 19 year old woman presenting with focal seizures is reported. Benign intracranial cartilaginous lesions are reviewed and the differential diagnosis of chondromatosis of the choroid plexus and intraventricular chondromas discussed.

Does plate fixation prevent disc degeneration after a lateral anulus tear?

STUDY DESIGN: The sheep model was used to investigate the development of disc degeneration after outer anular tearing. OBJECTIVES: The authors determined whether plate fixation promotes healing of peripheral anular tears and thereby minimizes disc degeneration. SUMMARY OF BACKGROUND DATA: A limited outer anular tear (similar to the rim lesion) in the sheep lumbar disc causes progressive and irreversible degeneration within 6 months. Incomplete healing of the tear may result from continued movement in the vicinity of the lesion. METHODS: In 15 sheep, a cut 4 x 10 mm was made in the lateral anulus of two nonadjacent lumbar discs, and a metal plate was fixed across one. Three sheep were killed immediately, and the remainder were killed after 6 months for histologic examination. RESULTS: There were no significant differences in propagation of the cut through the inner anulus, extent of healing, or extent of nuclear degeneration, between plated and nonplated motion segments after 6 months. Vascularization of the cartilage endplate was significantly increased on the operated side (P < 0.01), but remained unchanged on the nonoperated side. CONCLUSIONS: Disc degeneration was not prevented by this method of plate fixation, despite similar but limited healing of the outer anulus tear in both plated and nonplated levels.

The relationship between head-neck-shaft angle, calcar width, articular cartilage thickness and bone volume in arthrosis of the hip.

The thickness of articular cartilage and the macroscopic and morphometric characteristics of bone in the proximal femur were assessed in a group of 28 surgically-treated patients with advanced idiopathic osteoarthrosis, and compared with the findings in a group of 16 non-arthrotic femora obtained at autopsy. In arthrosis, the BMI was increased, cartilage thickness at two principal stress sites was found to be significantly reduced, and the femoral head-neck-shaft angle was reduced. The calcar width of the cortical bone in the femur was unchanged. Bone volume was increased at the principal compressive region and diminished at both of the tensile regions. Regression analysis showed that in arthrosis calcar width was dependent on BMI and bone volume in the medial principal compressive region of the proximal femur. Furthermore, the volume of bone medial to the greater trochanter was significantly correlated with BMI.

Mechanical consequences of annular tears and subsequent intervertebral disc degeneration.

The relationship between degeneration of the intervertebral disc and changes to its mechanics is unclear. The aim of this study was to examine, in a sheep model, the effect of creating a lesion in the outer, anterior annulus on the mechanics of the intervertebral joint complex and the disc. Forty-one 2-year-old Merino wethers were allocated randomly into a control group or an annular lesion group and additionally to non-survivors which were sacrificed immediately or survivors sacrificed 6 months later. The annular lesion group had incisions made in two non-adjacent intervertebral discs and a plate was secured across the vertebrae at one level. Mechanical tests were performed on specimens consisting of the two vertebrae, the intervening disc and associated ligaments. Stiffness of the specimens was measured in flexion, extension, and in pure torsion. The tests were conducted first on the intact intervertebral joints and then after removal of the zygapophyseal joints and the interspinous and supraspinous ligaments. The results showed that the creation of an annular lesion caused immediate changes to the mechanics of the disc. In torsion, where no axis of rotation was imposed on the joints, there was a clear reduction in stiffness compared with controls. After 6 months the discs in the lesion groups approached the stiffness of the controls. The plates had a marked effect on the stiffness of the joints in flexion and extension, but after 6 months this difference was not apparent. The mechanics of the intact joints were not affected immediately by the lesion but after 6 months they were less stiff than the controls. There was clear evidence of a progressive degenerative response in the nucleus in all discs with a lesion. The addition of a plate to limit movement did not markedly affect this biological response to the injury but there was some evidence that after 6 months there were fewer degenerative changes to the zygapophyseal joints in the plated specimens. Recovery of the mechanical integrity of the disc was more marked in the joints that were plated, supporting the concept that limiting motion of an injured intervertebral disc facilitates a healing response in the annulus.