In vivo macrophage recruitment by murine intervertebral disc cells.

SUMMARY: An in vivo murine experiment was conducted to measure the capacities of viable intervertebral disc cells to recruit inflammatory cells. The objective was to determine whether compounds secreted from viable cells induce inflammation or whether inflammation in disc herniation simply requires exposure to structural cell or matrix components. Three tissue preparations were inserted into the right lower peritoneal cavity of male mice: tissue with viable annulus fibrosus and nucleus pulposus cells, tissue with viable annulus fibrosus cells, or devitalized annulus fibrosus and nucleus pulposus tissue. Controls included sham-operated and nonoperated groups. Mice were killed 1, 2, or 7 days after surgery. Macrophage recruitment occurred after exposure to viable disc tissue but not after exposure to devitalized disc components; recruitment increased over time. Viable disc cells play a role in the etiology of inflammation in disc herniation.

Chondrocyte differentiation is modulated by frequency and duration of cyclic compressive loading.

As part of a program of research aimed at determining the role of mechanical forces in connective tissue differentiation, we have developed a model for investigating the effects of dynamic compressive loading on chondrocyte differentiation in vitro. In the current study, we examined the influence of cyclic compressive loading of chick limb bud mesenchymal cells to a constant peak stress of 9.25 kPa during each of the first 3 days in culture. Cells embedded in agarose gel were subjected to uniaxial, cyclic compression at 0.03, 0.15, or 0.33 Hz for 2 h. In addition, load durations of 12, 54, or 120 min were evaluated while holding frequency constant at 0.33 Hz. For a 2 h duration, there was no response to loading at 0.03 Hz. A significant increase in chondrocyte differentiation was associated with loading at 0.15 Hz, and an even greater increase with loading at 0.33 Hz. Holding frequency constant at 0.33 Hz, a loading duration of 12 min elicited no response, whereas chondrocyte differentiation was enhanced by loading for either 54 or 120 min. Although not statistically significant from the 120 min response, average cartilage nodule density and glycosaminoglycan synthesis rate were highest in the 54 min duration group. This result suggests that cells may be sensitive to the level of cumulative (nonrecoverable) compressive strain, as well as to the dynamic strain history.

Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption.

Herniated disc (HD) is a common health problem that is resolved by surgery unless spontaneous resorption occurs. HD tissue contains abundant macrophage infiltration and high levels of matrix metalloproteinases (MMPs) MMP-3 and MMP-7. We developed a model system in which disc tissue or isolated chondrocytes from wild-type or MMP-null mice were cocultured with peritoneal macrophages and used this system to investigate the role of MMPs and chondrocyte/macrophage interactions in disc resorption. We observed a marked enhancement of MMP-3 protein and mRNA in chondrocytes after exposure to macrophages. Chondrocytic MMP-3, but not MMP-7, was required for disc resorption, as determined by assaying for a reduction in wet weight and proteoglycan content after 3 days of coculture. Surprisingly, chondrocyte MMP-3 was required for the generation of a macrophage chemoattractant and the subsequent infiltration of the disc tissue by proteolytically active macrophages. We conclude that macrophage induction of chondrocyte MMP-3 plays a major role in disc resorption by mechanisms that include the generation of a bioactive macrophage chemoattractant.

Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption.

Herniated disc (HD), one of the major causes of low back pain, is often resolved spontaneously without surgical intervention. Resorption is associated with a marked increase in infiltrating macrophages, and the matrix metalloproteinases (MMP) MMP-3 and MMP-7 have been implicated in this phenomenon. We developed a murine organ culture model in which intact intervertebral discs were cocultured with peritoneal macrophages to investigate the role of MMPs in HD resorption. Using macrophages isolated from MMP-null mice, we report that macrophage-produced MMP-7 was required for proteoglycan degradation, loss of wet weight, and macrophage infiltration of cocultured discs. The inability of MMP-7-deficient macrophages to infiltrate discs could not be attributed to a defect in macrophage migration. MMP-7 was required for the release of the cytokine TNF-alpha from peritoneal macrophages. The generation of soluble TNF-alpha was essential for the induction of MMP-3 in disc cocultures, which in turn is required for the generation of a macrophage chemoattractant and subsequent macrophage infiltration. TNF-alpha release from macrophages was necessary but insufficient for disc resorption, which required macrophage infiltration. We conclude that there is extensive communication between macrophages and chondrocytes in HD resorption and that an essential component of this communication is the requirement for MMPs to release soluble bioactive factors.

Risk factors associated with methicillin-resistant staphylococcal wound infection after spinal surgery.

We used the data from a retrospective case controlled study to identify risk factors for methicillin-resistant staphylococcal wound infection after spinal surgery. Thirty-five cases and 35 uninfected control patients were matched for indication for initial surgery and approximate operative date. Preoperative, intraoperative, and postoperative risk factors were examined. At our institution between 1989 and 1995, 35 adult patients developed spinal wound infection requiring operative debridement; 16 infections were caused by methicillin-resistant staphylococci (MRS). Significant risk factors for MRS infection were lymphopenia, history of chronic infections, alcohol abuse, recent hospitalization, and prolonged postoperative wound drainage. Patients with MRS infections were also somewhat less likely to have received vancomycin prophylaxis. In contrast, the only factor associated with infection caused by other pathogens was alcohol abuse. A number of preoperative risk factors were significantly associated with subsequent MRS spinal wound infection. Chemoprophylaxis with vancomycin should be targeted to patients at increased risk, because overuse may promote the emergence of vancomycin-resistant pathogens.

Up-regulated expression of matrilysin and neutrophil collagenase in human herniated discs.

Spontaneous resorption of herniated nucleus pulposus (HNP) is commonly observed when there is substantial contact of the disc with the spinal canal. We already demonstrated the expression of matrix metalloproteinase (MMP)-3 (stromelysin-1) in the granulation tissues of HNP, suggesting its role in the resorption process of HNP. Recent studies of osteoarthritic cartilages reported an up-regulated expression of metalloproteinases including MMP-7 (matrilysin) and MMP-8 (neutrophil collagenase), suggesting their roles in the matrix degradation. To clarify the expression of MMP-7 and MMP-8 in HNP, immunohistological analysis of various types of HNP was performed. We found MMP-7 was expressed in infiltrated mononuclear cells and chondrocytes, whereas MMP-8 was specifically expressed in chondrocytes. The positive rate for both MMP-7 and MMP-8 significantly increased when HNP was exposed to the epidural space (p < 0.01). Our data suggest that not only MMP-3 but also MMP-7 and MMP-8 may play a role in the resorption process of HNP.

Results of elective lumbar discectomy for patients involved in the workers' compensation system.

We compared the outcomes from lumbar discectomy for patients who were workers' compensation claimants and/or who were involved in active litigation with patients who underwent elective lumbar discectomy, but who were not involved with either compensation or litigation. Eighty-two consecutive patients who underwent elective lumbar discectomy by the senior author were identified from 1989 through 1994. Those patients who underwent a primary discectomy with a minimum of 6 months' follow-up were studied. Patients were excluded if a spinal fusion was performed or if a multilevel laminectomy procedure was required. Patients were classified as compensation patients if they were involved in either worker's compensation claims or active litigation at the time of the lumbar discectomy. The compensation group was further divided into three subsets of patients: those involved in active litigation without compensation, those involved in both compensation and litigation, and those pursuing workers' compensation claims without litigation. The control group was comprised of patients who were not in any way involved with compensation or litigation. Outcome assessment and ratings were determined independently by the coauthors, not the primary surgeon. Outcome was based on pain, employment status, analgesic use, and level of activity. Fifty-four patients met the inclusion criteria. Average follow-up for the compensation patients was 40 weeks. Follow-up for the noncompensation patients averaged 51 weeks. Eighty-one percent of our patients in the noncompensation group achieved a good result. Only 1 of 27 patients was categorized as having a poor outcome. Conversely, patients who were actively involved in the compensation and/or litigation process had significantly poorer outcomes, with only 29% of the patients receiving a good outcome evaluation (p = < 0.0002). Legal involvement was associated with poorer outcome in compensation patients (p = < 0.001).

Needle tract recurrences after closed biopsy for sarcoma: three cases and review of the literature.

BACKGROUND: Percutaneous closed needle biopsy of musculoskeletal neoplasms has gained in popularity. However, it remains controversial whether or not to resect the needle tract for fear of a local recurrence. A single published case report exists, noting the lone tract recurrence of an extremity skeletal osteosarcoma. METHODS: We report on three additional individuals who demonstrated that tract local recurrences may occur after a closed needle biopsy for nonosteosarcoma, nonextremity sarcomas. For perspective, the world literature is reviewed to identify tract recurrences for other malignancies and the results of needle biopsy in musculoskeletal neoplasms. RESULTS: Eighty-nine percent of needle tract local recurrences occur when carcinomas are subjected to biopsy, as reported in the literature. Forty-seven cases since 1950 are described representing essentially all tumor types. The nature of musculoskeletal neoplasms makes closed biopsy more difficult than for softer, more homogeneous, and easier to access neoplasms. CONCLUSIONS: Local recurrences of sarcoma may occur in closed needle biopsy tracts. Strong consideration should be given to open biopsy and tract resection.

Stretch-induced nerve injury as a cause of paralysis secondary to the anterior cervical approach.

The anterior approach to the cervical spine, first described 40 years ago, has become a popular and widely used procedure by spine surgeons to expose the anterior vertebral bodies from C3 to T1. A significant complication of this procedure is transient or permanent ipsilateral recurrent laryngeal nerve paralysis. In a previous review at our institution of patients with hoarseness after an anterior cervical approach, 15 of 16 patients demonstrated right-sided paralysis. The asymmetry in the anatomic courses and lengths of the recurrent laryngeal nerves are proposed to place the right recurrent laryngeal nerve at an increased risk of stretch-related injury during this surgical procedure. We developed a cadaver model to evaluate the in-line stretch on the recurrent laryngeal nerve during the right- and left-sided approaches to the C4 and C7 vertebral bodies. To assess the difference in risk of injury to the two recurrent laryngeal nerves, we performed the anterior approach to the cervical spine in four anatomic positions: the left neck and right neck at the levels of C4 and C7 on 10 fresh human cadavers during the immediate postmortem period. The blades of a Cloward retractor were progressively spread to 2, 3, and 4 cm in the four anatomic positions while the corresponding degrees of ipsilateral recurrent laryngeal nerve stretch resulting from retraction were simultaneously measured. The left recurrent laryngeal nerve had sufficient redundancy in its course within the tracheoesophageal groove in 10 of 10 cadavers such that it exhibited no in situ stretch during the left-sided approach to either the C4 or C7 vertebrae. In contrast, the right recurrent laryngeal nerve has little redundancy in its course and is not protected within the tracheoesophageal groove. The right-sided approach to C7 resulted in an average in situ stretch on the ipsilateral recurrent laryngeal nerve of 12% and 24%, with 3 cm and 4 cm of Cloward retraction, respectively. The right-sided approach to C4 resulted in significant levels of stretch in 3 (30%) of 10 cadavers and no stretch in 7 (70%) of 10 cadavers. The relevance of these data is demonstrated by the review of numerous studies demonstrating the potential for significant neural damage with nerve stretch greater than 12%.

Web client and ODBC access to legacy database information: a low cost approach.

A new method has been developed for the Department of Orthopaedics of Vanderbilt University Medical Center to access departmental clinical data. Previously this data was stored only in the medical center's mainframe DB2 database, it is now additionally stored in a departmental SQL database. Access to this data is available via any ODBC compliant front-end or a web client. With a small budget and no full time staff, we were able to give our department on-line access to many years worth of patient data that was previously inaccessible.

Integrating and presenting clinical and treatment outcome data for cost-effective case management.

The broad objective was to develop an information system which integrates various sources of clinical data and facilities outcome assessment for patients evaluated in a lumbar spine service. During a patient encounter, the physician formulates a hypothesis regarding appropriate forms of treatment and he or she may then use this system to explore previous treatment outcomes for similar cases. The availability of a clinical tool that presents information in an outcome-oriented format may be highly relevant to the delivery of cost-efficient, high-quality health care and also create a formal mechanism for detecting practice variability.

An analysis of the posterior epidural ligament role on the cervical spinal cord.

STUDY DESIGN: Laminectomy was performed on cats to destroy the posterior epidural ligament. Evoked potentials and spinal cord blood flows quantified the spinal cord function before and after cervical flexion. OBJECTIVES: This work describes a relationship between the loss of the posterior epidural ligaments and cervical spinal cord injury. SUMMARY OF BACKGROUND DATA: The posterior epidural ligaments of the human cervical spine have been recently described. These ligaments theoretically prevent injury to the spinal cord by resisting collapse of the dura during cervical flexion. METHODS: The animals were divided into three experimental groups: 1) control: no laminectomy and standard position, 2) flexion control: no laminectomy and known imposed flexion, 3) laminectomy (C3-C7) and flexion. Motor-evoked potentials and evoked spinal cord potentials were recorded to quantify the spinal cord functions. Radioactive microspheres were used to quantify ischemia in the spinal cord. RESULTS: Control subjects showed blood flows of 36 mL/100 g/min (C3-C4) to 46 mL/100 g/min (C7-C8). Flexion control subjects did not experience significant reductions in blood flows or substantial change in evoked potentials. The laminectomy plus flexion group experienced reduced blood flows and substantial motor-evoked potentials and slight evoked spinal cord potential changes with 50 degrees, 60 degrees, and 70 degrees flexion. Blood flow reduction was greater in the anterior half of the C7-C8 segments compared with the posterior half at 60 degrees flexion. Evoked spinal cord potentials were less vulnerable than motor-evoked potentials. CONCLUSIONS: The role of the posterior cervical epidural ligaments is to anchor the posterior dura mater to the ligamentum flavum. Loss of the ligaments allows anterior displacement of the posterior dura mater in flexion. Abnormal distribution of or lack of the cervical posterior epidural ligaments may lead to flexion myelopathy.

The spinal nail: a new implant for short-segment anterior instrumentation of the thoracolumbar spine.

The biomechanics of a new spinal implant were evaluated and its dependence on an anterior strut graft was determined. Six fresh-frozen adult porcine spines were used. An L3 corpectomy was created. The spinal nail was inserted intraosseously into the middle column of the L2-L4 vertebral bodies in a trough. Implant drill holes were made for proximal and distal locking bolts in L2 and L4. A locking plate bridged the L2 and L4 trough and anchored the exposed ends of the locking bolts. Testing was performed in axial compression, torsion, and flexion. The axial and torsional stability of the spine instrumented with the spinal nail are similar to results with other devices when used with anterior strut grafting. The axial and flexural stiffnesses of the instrumented spine are independent of strut grafting. This study suggests that this device may be useful for reconstruction of the anterior spine because of instability.

Relationship between vertical ground reaction force and speed during walking, slow jogging, and running.

OBJECTIVE: To obtain descriptive information between vertical ground reaction force (GRF)-time histories and gait speed, running style, and gender. DESIGN: GRF-time history measurements were obtained from male and female subjects during walking, slow jogging, jogging and running on an indoor platform. BACKGROUND: Previous studies have established GRF descriptor variables for male subjects running at speeds from 3 to 6 m s(-1), but very little descriptive data exists for slower or faster running, nor have previous studies reported GRF descriptors separately for female subjects. METHODS: GRF-time histories were recorded for 13 male and 10 female recreational athletes during walking and slow jogging at speeds between 1.5 and 3.0 m s(-1), and running at speeds between 3.5 and 6.0 m s(-1). Vertical GRF-time data for trials with speeds within 0.2 m s(-1) of the prescribed speed were analysed to determine thrust maximum GRF (F(z)) and loading rate (G(z)). RESULTS: In both male and female subjects, F(z) increased linearly during walking and running from 1.2 BW to approximately 2.5 BW at 6.0 m s(-1), remaining constant during forward lean sprinting at higher speeds. F(z) was linearly correlated to G(z), the latter ranging from 8 to 30 BW s(-1) over this speed range. Slow jogging was associated with a > 50% higher F(z) and G(z) in comparison to walking or fast running. CONCLUSIONS: Similar GRF descriptor data and velocity relationships were obtained for male and female subjects. Impact forces were greatest when the subjects adopted a higher, less fixed centre of gravity during slow jogging. RELEVANCE: These results suggest that vertical GRF norms can be established for male and female subjects alike, and that slow or fast running with a lower, fixed centre of gravity decreases impact forces.

A biomechanical model of the lumbar spine during upright isometric flexion, extension, and lateral bending.

STUDY DESIGN: Task-specific and subject-specific lumbar trunk muscle function, muscle geometry, and vertebral density data were collected from 16 men. A biomechanical model was used to determine muscle strength and the compressive forces acting on the lumbar spine. OBJECTIVES: To develop an anatomic biomechanical model of the low back that could be used to derive task-specific muscle function parameters and to predict compressive forces acting on the low back. Several model-specific constraints were examined, including the notion of bilateral trunk muscle anatomic symmetry, the influence of muscle lines of action, and the use of density-derived vertebral strength for model validation. SUMMARY OF BACKGROUND DATA: Clinical and basic science investigators are currently using a battery of diverse biomechanical techniques to evaluate trunk muscle strength. Noteworthy is the large variability in muscle function parameters reported for different subjects and for different tasks. This information is used to calculate forces and moments acting on the low back, but limited data exist concerning the assessment of subject-specific, multiaxis, isometric trunk muscle functions. METHODS: A trunk dynamometer was used to measure maximum upright, isometric trunk moments in the sagittal (extension, flexion) and coronal (lateral flexion) planes. Task- and subject-specific trunk muscle strength or "gain" was determined from the measured trunk moments and magnetic resonance image-based muscle cross-sectional geometry. Model-predicted compressive forces obtained using muscle force and body force equilibrium equations were compared with density-derived estimates of compressive strength. RESULTS: Individual task-specific muscle gain values differed significantly between subjects and between each of the tasks they performed (extension > flexion > lateral flexion). Significant differences were found between left side and right side muscle areas, and the lines of action of the muscles deviated significantly from the vertical plane. Model-predicted lumbar compressive forces were 38% (lateral flexion) to 73% (extension) lower that the L3 vertebral compressive strength estimated from vertebral density. CONCLUSION: The present study suggests that biomechanical models of the low back should be based on task-specific and subject-specific muscle function and precise geometry. Vertebral strength estimates based upon vertebral density appear to be useful for validation of model force predictions.

Isolated muscle atrophy of the distal upper extremity in cervical spinal cord compressive disorders.

The purpose of this article is to clarify one mechanism of muscular atrophy of the distal upper extremity that we attribute to cervical compression (Hirayama-type amyotrophy) by medical imaging and anatomical studies of the cervical spine. Five young male patients (mean age: 22.6 years) with this disorder showed characteristic findings to include an abnormal anterior displacement of the posterior dura wall in flexion that resulted in an anteroposterior compression of the spinal cord segment from C7 to C8. To identify an anatomical relationship to this disorder, the lower cervical spine was studied using 11 embalmed adult human cadavers. Abundant posterior epidural ligaments were observed between the posterior dura mater and the ligamentum flavum. Posterior epidural ligaments in the cervical spine have not been reported previously. The anterior displacement of the dura mater may be attributed to a lack of and/or insufficiency of the posterior epidural ligaments.

Multiplanar variations in the structural characteristics of cancellous bone.

A quantitative serial sectioning technique and a video-imaging procedure were used to obtain precise (20-microns voxels, in a 5 mm x 6 mm x 7 mm test volume) digital images of lumbar vertebral cancellous bone specimens. Conventional stereological image analyses were performed on this data to determine multiplanar (bulk) and surface planar variations in cancellous structural properties. Based upon an error analysis of subgroups of the complete serial planar images, our findings suggest that, for a plane resolution of 20 microns, sectioning at an increment < or = 100 microns along an axis is necessary to obtain accurate data of bulk structural properties of cancellous bone. Planar structural variations obtained from the serial sections of cancellous bone revealed a high degree of complexity and heterogeneity of the bone architecture. Bone area centers deviated from the section centroid and showed a helical variation along the primary or superior--inferior loading axis of samples. In comparison with the base planes (perpendicular to the superior-inferior axis), the lateral planes (parallel to the superior-inferior axis) of spine samples showed smaller mean values of structural indices and a more oriented structure. This structural anisotropy may be related to the functional mechanical anisotropy of the samples.

Effects of specimen load-bearing and free surface layers on the compressive mechanical properties of cellular materials.

The influence of load-bearing surface layers on Young's modulus was determined for cancellous bone and polyurethane foam specimens of three different heights cut from each material: 16, 9, and 5 mm for bone specimens (cross-sectional area A = 81 mm2) ranging in density from 0.04 to 0.32 g cm-3; 20, 10, and 5 mm for foam specimens (A = 100 mm2) ranging in density from 0.064 to 0.64 g cm-3. The compressive elastic modulus of the 5 mm bone specimens was significantly smaller (42%) than that of the 16 mm bone specimens. A similar change in elastic modulus was also observed for the foam specimens, but the height effect diminished in a relatively linear manner as the foam density increased. For a height change from 20 to 5 mm, the foam modulus difference ranged from a 41% decrease for the lowest density specimens (p = 0.064 g cm-3) to an insignificant change (< 1.8%) for the highest foam density specimens (p = 0.64 g cm-3). The specimen height effect on elastic modulus was hypothesized to result from a higher deformation (compliance) of the cellular materials in the load-bearing or contacting surface layer than in the bulk. A mathematical formula was derived to predict the variation in measured elastic modulus (E) caused by the contacting surface layer modulus (Ecs) to bulk modulus (Eb) ratio (Y = Ecs/Eb) and contacting surface layer height (hcs) to sample height (h) ratio (t = hcs/h): E/Eb = Y/[Y(1-t)+t]. Predicted differences in the measured modulus associated with graduated specimen heights were verified experimentally by regional strain measurements of the foam and bone samples using an optical microscope. The influence of free-surface layers was also determined for the foam specimens with cross-sectional areas 1.21 and 10 times the load-bearing area of a load platen, but the measured differences were small (< 10%) compared to that of the load-bearing surface layer influence. In future compressive mechanical testing of cellular materials, specimens < 10 mm in height should be avoided, particularly specimens with low bulk density or high porosity.