Cell transplantation in lumbar spine disc degeneration disease.

Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that received cells demonstrated a significant difference as a group in the fluid content of their treated disc when compared to control. Autologous disc-derived cell transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration. Adipose tissue provides an alternative source of regenerative cells with little donor site morbidity. These regenerative cells are able to differentiate into a nucleus pulposus-like phenotype when exposed to environmental factors similar to disc, and offer the inherent advantage of availability without the need for transporting, culturing, and expanding the cells. In an effort to develop a clinical option for cell placement and assess the response of the cells to the post-surgical milieu, adipose-derived cells were collected, concentrated, and transplanted under fluoroscopic guidance directly into a surgically damaged disc using our dog model. This study provides evidence that cells harvested from adipose tissue might offer a reliable source of regenerative potential capable of bio-restitution.

Coaxial portals for posterior ankle arthroscopy: An anatomic study with clinical correlation on 29 patients.

PURPOSE: The authors performed a cadaveric study on 10 ankles and retrospectively reviewed 29 arthroscopic synovectomies to determine the trajectory, minimal safe distances, and complications using a new approach for posterior ankle arthroscopy. TYPE OF STUDY: Anatomic study and case series. MATERIALS AND METHODS: A posterolateral portal was established immediately posterior to the peroneal tendon sheath. While staying within the posterior ankle capsule, an inside-out technique was then used to establish the posteromedial portal directly behind the medial malleolus adjacent to the posterior tibial tendon. The cadaveric ankles were frozen, sectioned, and photographed to measure the proximity of neurovascular structures to these coaxial portals. From 1988 to 1994, arthroscopic synovectomy was performed on 23 patients (29 ankles) with hemophilia using these modified portals. RESULTS: Results of the anatomic study showed that the posterior tibial nerve and posterior tibial artery were located a mean distance of 5.7 mm (SEM, 0.6 mm) and 6.4 mm (SEM, 0.7 mm) from the edge of the cannula, respectively. Neither penetration nor contact of nerve or vessel was observed at either posterior portal. In the 29 clinical cases, posterior capsular synovectomy was achieved arthroscopically with no detectable complications at an average 45-month follow-up. CONCLUSIONS: Our anatomic data show that the coaxial portals described here are essentially equidistant to the neurovascular structures compared with conventional portals. Our clinical results suggest that his technique for posteromedial and posterolateral portals is safe, effective, and reproducible.

Does long-term compressive loading on the intervertebral disc cause degeneration?

STUDY DESIGN: Coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs of dogs for up to 53 weeks. OBJECTIVE: To test the hypothesis that compressive forces applied to the intervertebral disc for a long period of time cause disc degeneration in vivo in a dog model. SUMMARY OF BACKGROUND DATA: It is a commonly held belief that high forces applied to the intervertebral disc, and to joints in general, play a role in causing degeneration. METHODS: Coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs (L3/L4) of 12 dogs. After up to a year, the dogs were killed, and their lumbar spines were removed and radiographed. The L3/L4 disc and the controls (T13/L1 and L4/L5) were excised and examined for visible signs of degeneration. The discs then were assessed using immunohistochemical analysis and enzyme-linked immunosorbent assay. Disc chondrocytes also were assayed for apoptosis. RESULTS: No obvious signs of degeneration in the discs (L3/L4) that had been under compression for up to a year could be observed. There was no disc bulging, anular fissures, or disc space narrowing. Some changes were observed at the microscopic level, although no thickening of the endplate was apparent. The enzyme-linked immunosorbent assay analysis provided significant data for all three regions of the disc (nucleus, inner anulus, and outer anulus). When comparing the compressed disc (L3/L4) with either of the control discs (T13/L1 and L4/L5), in the compressed disc: 1) the nucleus contained less proteoglycan and more collagen I and II; 2) the inner anulus contained less proteoglycan and collagen I; and 3) the outer anulus contained more proteoglycan and less collagen I. The collagen II differences for the inner and outer anulus were not significant. CONCLUSION: Compression applied to the lumbar intervertebral discs of dogs for up to a year does not produce degeneration in any visible form. It does produce microscopic changes and numerical changes, however, in the amounts of proteoglycan and collagen in the nucleus, inner anulus, and outer anulus. The present results add no credence to the commonly held belief that high compressive forces play a causative role in disc degeneration.

Morphologic and radiographic characterization of fibular dimelia.

Fibular dimelia accompanied by complete tibial agenesis is a rare developmental anomaly that has been reported in the anatomic and clinical literature as both a dimelia and a diplopodia. Previous reports have offered variable descriptions of structural aberration and possible modes of altered embryologic development. We present a clinical and radiographic history of the progressive development of this anomaly, and a detailed postsurgical dissection and histopathologic examination. The specific mirroring of the separate components in this case has not been previously reported, and suggests that a reestablishment of limb polarity may have occurred during embryogenesis. Our detailed morphologic investigation strongly suggests a central role for the mesenchymal precursor from which chondro-osseous morphology subsequently emerges, and the relevance to establishing muscular attachments.

Mechanical comparison of plates used in the treatment of unstable subtrochanteric femur fractures.

OBJECTIVES: To determine the stiffness and strength characteristics of certain plate-composite femur models designed to simulate unstable subtrochanteric femur fractures (OTA 31-A2.3). DESIGN: Fifteen identical composite femora were osteotomized to produce like models of an unstable subtrochanteric femur fracture. The femora were fixed with either the Synthes 95 degree angled condylar blade plate, a 95 degree dynamic condylar screw plate (DCS), or a 135 degree dynamic compression hip screw (DHS). MAIN OUTCOME MEASUREMENTS: A materials testing machine was used to apply compression to the femoral head through an adapter plate. Stiffness values were calculated from the load-deformation curves obtained. RESULTS: The DHS-femur model was the stiffest (586 newtons/ millimeter), followed by the 95 degree DCS (404 newtons/millimeter) and the 95 degree condylar blade plate (260 newtons/ millimeter). The DHS also had the highest ultimate load-to-failure (4,877 newtons), followed by the 95 degree DCS (3,107 newtons) and the 95 degree condylar blade plate (2,272 newtons). All of these differences were statistically significant (p < 0.00001 ). CONCLUSIONS: Our findings suggest that the Synthes 95 degree DCS has greater stiffness and strength than the Synthes 95 degree condylar blade plate when tested in this model of an unstable subtrochanteric femur fracture. This model may not be completely appropriate for testing the 135 degree DHS because the hard plastic "cortex" of the model prevented cut-out of the screw.

The effect of compressive force applied to the intervertebral disc in vivo. A study of proteoglycans and collagen.

STUDY DESIGN: Coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs of dogs for up to 27 weeks. OBJECTIVE: To test the hypothesis that a high compressive force applied over a period of time affects the production of proteoglycans and collagen by the intervertebral disc cells. SUMMARY OF BACKGROUND DATA: It is a commonly held belief that high forces applied to the intervertebral disc, and to joints in general, play a role in causing degeneration. METHODS: Pairs of stainless steel coil springs were stretched and attached to produce a compressive force across the lumbar intervertebral discs (L1-L2 and L3-L4) of 16 dogs. Dogs were killed between 13 and 27 weeks after the springs were attached. The discs (L1-L2 and L3-L4) were excised and assessed using immunohistochemical analyses and enzyme-linked immunosorbent assay; T13-L1 and L4-L5 were used as controls. RESULTS: The main result relates to a group effect in the six dogs, assessed using enzyme-linked immunosorbent assay, that were generally at the highest values of force for the greatest number of weeks. For the nucleus, but not the anulus, Spearman rank correlations revealed a strong correlation between increases in force and force-weeks (force multiplied by number of weeks) and increases in collagen type I accompanied by decreases in proteoglycans, chondroitin sulfate, and collagen type II for both experimental discs (L1-L2 and L3-L4), as compared with corresponding values in the controls (T13-L1 and L4-L5). In other words, as either the force or the force-weeks increased, the effect on the nucleus became greater. CONCLUSION: A high compressive force applied to the disc over a period of time initiates changes in proteoglycans and collagen.

Biomechanical study of lumbar pedicle screws: does convergence affect axial pullout strength?

We tested the hypothesis that two pedicle screws placed in convergence offer more resistance to axial pullout than do two pedicle screws placed in parallel. Eight fresh cadaveric lumbar spines, L2-L5, were harvested. Individual vertebra were then paired for testing. Into each L2 and L3 vertebra, a pair of pedicle screws were inserted. The screws were placed parallel (i.e., at 0 degrees convergence) in L2 and at 30 degrees convergence in L3, in the first pair. In the second pair of L2 and L3, this order was reversed. Alternating the convergence angle was carried out on each successive pair of L2 and L3. A section of standard longitudinal rod was attached to each pedicle screw by using top-loading three-point shear clamp fixation with tangential lock screws. Transverse connectors were attached superiorly and inferiorly to the longitudinal rods. As in L2 and L3, each L4 and L5 received a pair of screws placed at either 0 or 30 degrees convergence, with the angle of convergence alternated on each successive pair. Each pair of screws in each vertebra was tested in axial pullout at 1 mm/s. Fourteen pairs of vertebra were tested and two findings emerged: paired pedicle screws at 30 degrees of convergence offered more resistance to axial pullout (28.6% on average) and sustained higher loads at the clinical threshold of loosening (101% on average) than paired pedicle screws placed in parallel. Thus there seems to be an advantage to screws placed in 30 degrees of convergence as compared with screws in parallel.

Pathologic morphology of the dislocated proximal femur in children with cerebral palsy.

We describe the gross and microscopic anatomic changes in the hip that result from the deforming forces in children with neuromuscular imbalance. Twelve dislocated proximal femora that had been resected from children with spastic diplegia or tetraplegia were evaluated with respect to their gross, microscopic, and radiographic structure. The epiphyses were wedge shaped with deformation of the femoral head apparent in all cases. In addition to a severe loss of articular cartilage, a furrowed erosion of epiphyseal bone suggested a sustained, blunt, band-like force across the surface of the hip where it opposed the acetabular labrum. The underlying physis of the capital femur was irregular with aberrant histologic structure, whereas that of the lesser trochanter was hypertrophic and angulated in a superior and anterior direction. A significant degree of valgus was not noticeable in most specimens. In summary, the spastic adductor and iliopsoas, responsible for the changes in the lesser trochanter, work in conjunction with the hip flexor and internal rotator muscles to subluxate the proximal femur. In the process, the superior rim of the acetabulum and capsule causes focal deformation of the superolateral femoral head, creating a fulcrum upon which the hip then progressively subluxates. The indentation locks the femoral head at the lateral acetabular margin, preventing complete dislocation, but leading to bone pain consequent to cartilage erosion.

Postnatal development of the human sternum.

Postnatal development and maturation of the human sternum are highly variable. Endochondral ossification centers (sternebrae) form within each cartilaginous segment of the sternum, with each center enveloped by a spherical growth plate. Within a cartilaginous center there may be either one or two ossification centers, those with two centers retaining and reflecting features of their bilateral embryonic origin. Malaligned bifid centers are clearly associated with rib articulation asymmetry as well. Expansion of individual ossification centers progresses within the peripheral cartilaginous domains of the sternum. With respect to the rostrocaudal axis, sternebrae form between the costosternal articulations. Consistent with the biology of endochondral transition, cartilage canals are evident throughout unossified regions of the hyaline matrix. Expanding ossification of adjacent sternebrae results in depletion of the common area of cartilage between the two sternebrae, and eventually in physiologic epiphysiodesis. Fusion of the mesosternebrae reciprocates the initial pattern of sternebral ossification site appearance, proceeding in a caudal-to-cranial direction. Union of adjacent sternebrae, initiated through a central osseous bridge, progresses through anterior, lateral, cephalocaudal, and posterior domains to achieve synostosis. Accessory and bifid centers of ossification within the same intercostal space coalesce prior to adjoining adjacent sternebrae. Manubriosternal fusion is rare due to the presence of a fibrocartilaginous joint restricting ossification. The xiphoid process remains connected to the most caudal mesosternum via a common zone of hyaline cartilage that ossifies by middle to late adulthood. A single pattern of development does not appear fundamental to successful growth of the sternum, as morphological variants were common.

Guidelines to decortication in posterolateral spine fusion.

Despite the development of innovative approaches and the general success that has been achieved with spinal fusion, the rate of nonunion in some studies has been reported as high as 35%. Decortication has been shown to promote the fusion process and provides not only a rich source of vascular supply from the underlying cancellous bone, but also access to pluripotent stem cells within the marrow. Although the blood supply to the lumbar spine has been described, little attention has been paid to relevant areas of the spine most affected by decortication during the posterolateral fusion process. To assess these areas of the spine and attribute some potential importance to spinal fusion outcome, a perfusion study was designed to delineate the vascular anatomy involved in a decortication procedure. Cadaver spines were perfused with a radiopaque contrast material, fixed, decalcified, and cleared en bloc by the method of Spalteholz. Transverse, sagittal, and coronal slabs were made and the vascular supply was documented. The dominant intraosseous architecture of the vertebra reflected a cancellous bone structure, characterized by marrow and a sinusoidal blood distribution within a trabecular matrix. A contrasting architecture could be differentiated in the pars interarticularis that was more consistent with dense, cortical bone. Matrix from this region typified haversian lamellar bone and exhibited parallel osteons that contained a central vascular component. The relevance of this variance could have multiple implications, given the differences between cortical and cancellous bone in function, formation, healing, and remodeling. In posterolateral intertransverse process arthrodesis, the transverse processes and lateral facets are good areas to be decorticated, whereas the pars interarticularis is less attractive.

The primary care physician's role in evaluating the pediatric amputee.

The clinician must have an understanding of the spectrum of potential problems that can occur in the pediatric patient with a limb deficiency. These various complications-osseous, nonosseous, infection, phantom limb phenomenon and pain, pre-existing conditions, and psychosocial-are discussed.

Contiguous discitis and osteomyelitis in children.

Magnetic resonance imaging of 16 patients with contiguous discitis and osteomyelitis provided a specific diagnosis and defined the anatomic extent of vertebral and soft-tissue involvement. Altered signal changes were evident in the disc, adjacent vertebra in the end plate and metaphyseal equivalent regions, and the anterior prevertebral tissues. Significant posterior spread and disc herniation were not evident. Fourteen patients had lumbar involvement; two had cervical involvement. The patients were followed-up for an average of 4 years 5 months. Scoliosis has developed in one patient, and four continue to have a loss of lumbar lordosis. By comparing serial roentgenograms, the mean decrease of disc-space height after the acute episode was 43% (range, 51-61%). There was no restitution of normal disc-space height at the latest follow-up roentgenogram in any of the patients. A 14% (average) narrowing of the vertebral foramina was evident in seven cases. In one patient, a fusion progressively developed 7 years after the acute episode (before full skeletal maturity). However, several patients appear to be progressing toward fusion of adjacent vertebra. A study of histologic specimens elucidated vascular anatomy of the immature vertebra that further explain the disease characteristics.

Impingement after total hip arthroplasty related to prosthetic component selection and range of motion.

This study was designed to define the relationship between different combinations of prosthetic head diameters, neck lengths, and acetabular containment angles, and range of motion before component impingement. Three cadaveric pelves with attached lower limbs were mounted in their correct anatomic position. Acetabular and modular femoral stems were inserted into each of the six hips. For each combination of femoral head diameter, neck length, and acetabular liner overhang, the range of motion to impingement was measured in flexion, extension, abduction, adduction, external rotation, internal rotation, and internal rotation with 90 degrees hip flexion. These experiments suggest that the maximum range of motion before impingement can be attained by increasing the prosthetic head diameter and avoiding longer neck lengths with skirts. Acetabular liners with greater overhang decrease motion in all planes except flexion when the overhang is positioned posteriorly.

Ilizarov treatment of congenital pseudarthroses of the tibia.

Eleven children with congenital pseudarthrosis of the tibia were treated with the Ilizarov device. This was successful in nine of 11 patients with an average of 322 days in the fixator and 1.6 additional surgeries. Two patients eventually had amputations. These results demonstrate this to be an effective tool for this complex condition, but amputation should be considered if union is not achievable with this method and other procedures have previously been attempted.

Metallic dissolution of a civil war bullet embedded in a sternum.

The contemporary trend of converting departments of anatomy into departments of cell biology has brought with it the task of examining archive collections and storage facilities to figure out how to best utilize the available space. During one such inspection at the University of Louisville School of Medicine, a human sternum containing a dull metal projectile was uncovered. The projectile was easy to characterize as a bullet that had been deeply embedded in the bone. Less clear, however, were the circumstances detailing how the bullet had become lodged in the sternum, or how long the sternum might have been in storage at the University of Louisville. Radiographs of the sternum revealed a halo of surrounding density that dissipated in intensity from the margins of the bullet. Our initial hypothesis was that lead had been leached from the bullet into the bone matrix. To better assess what in fact contributed to this density, the sternum and the bullet were analyzed by energy-dispersive spectroscopy (EDS) to determine their elemental composition. That the bullet was composed of lead and aluminum was not surprising, but the extent to which the presence and dissolution of the bullet had affected the composition of the bony sternum was not entirely expected. The contribution of metal ions from the bullet to the inorganic matrix of bone was most notable for aluminum but nearly negligible for lead. This finding confirmed that bone affinity for metals is dependent upon the metal and supports previous reports that have suggested that lead is released from bone as soluble blood product during bony remodeling, whereas aluminum results in a significant elevation of bone density.

Effects of radiation therapy on reconstruction of mandibular defects with a titanium reconstruction plate.

Titanium fixation plates are commonly used in reconstruction of mandibular defects resulting from tumor resections in head and neck surgery. The effects of radiation therapy on the interface of bone, plate, and soft tissue were examined in this in vivo study. Four conditioned beagles had 1-cm segmental mandibular defects that were reconstructed with titanium plates. Two of the four also had placement of vascularized bone grafts. Healing was evaluated with or without postoperative radiotherapy. After collection of tissues using histologic methods and analysis with energy-dispersive spectroscopy, we found that the effects of radiation on bone-plate and bone-screw interfaces is minimal. Although radiation decreased the bone density and the rate of bone repair at the bone-screw interface, this did not appear to affect stability of the plate repair or the viability of bone tissue.

The histopathology of injury to the accessory malleolar ossification center.

The evaluation of a traumatic lower limb amputation specimen revealed an incomplete fracture between the main and accessory malleolar ossification centers. This was not associated with extensive subperiosteal or intraarticular bleeding. This pattern of injury, without any displacement or completion to an unstable fracture, should be considered in a patient with specific tenderness over a malleolus after a twisting injury or direct blow to the ankle.

Osseous overgrowth after amputation in adolescents and children.

We retrospectively studied the incidence of primary surgical revision for stump overgrowth in a population of childhood and adolescent amputees. The anatomic location and the etiology of amputation are critical to the occurrence of overgrowth needing revision. Metaphyseal-level amputations are the most likely to develop overgrowth requiring revision (50%), whereas diaphyseal amputations are slightly less likely (45%). Joint disarticulations never develop overgrowth. Traumatic amputations are the most frequent mode of injury requiring revision of overgrowth (43%), followed by congenital or intrauterine amputations (30%) and elective amputations (20%). Radiographic classification of the osseous overgrowth helps define its severity and degree of ossific progression. Surgical revisions are usually performed when overgrowth reaches a grade 3 classification. The majority of skeletally immature diaphyseal- or metaphyseal-level amputees, including those with certain preexisting orthopaedic conditions, retain the ability to develop osseous overgrowth at the apex of the stump skeleton.

Postnatal development of the thoracic spine.

STUDY DESIGN: Forty-two thoracic spines ranging from neonate to 15 years of age were studied. OBJECTIVES: Postnatal development of the thoracic vertebrae and their component elements were cataloged. SUMMARY OF BACKGROUND DATA: This study was part of an ongoing series concerning the progressive morphologic development of the human postnatal skeleton. METHODS: The spines were studied morphologically and radiologically. RESULTS: Fusion of the thoracic spine neurocentral synchondroses occurs in a cranial to caudal direction in humans by 6 to 7 years of age. The transverse processes exhibit a progressive posterior and inferior angulation with age and moving down the thoracic spine. The facet joints angulate accordingly. The spinous processes elongate and increasingly angulate with age, especially in the mid-thoracic region. The relative contribution of the posterior elements, compared with the centrum, to the growth of the vertebral body progressively decreases moving down thoracic spine. CONCLUSION: This study demonstrated areas of anatomic change that undoubtedly play a role in normal and abnormal spine development.