Kalia K. Sadasivan

Biomechanical Study of Atlantoaxial Arthrodesis: Transarticular Screw Fixation Versus Modified Brooks Posterior Wiring

OBJECTIVE The purpose of the present study was to compare the biomechanical stability of C1 and C2 vertebrae after treatment of ligamentous instability by either modified Brooks posterior wiring (MB) or transarticular screw (TAS) techniques. We hypothesized that the TAS technique would be more stable because of direct fixation through the facet joints. STUDY DESIGN We studied the in vitro stability (arthrodesis) of TAS fixation of C1 and C2 versus that of MB. TAS fixation involves placing screws across the facets from posteriorly at C2 to the anterior surface of C1, plus a bone graft and posterior wiring of C1 and C2. METHODS Cervical spines from nine individuals with an average age of sixty-two years (range 51 to 71 years) were harvested from cadavers (six male, three female). C1 and the segment from C2 to C5 were potted to allow motion only at the C1-C2 articulation. The specimens were destabilized by cutting the transverse ligament on both sides of the odontoid and the tectorial membrane between C1 and C2. The MB and TAS techniques were performed by methods similar to those described in the literature. The stiffness of the C1-C2 articulation of each specimen was tested under rotation, lateral bending, flexion, and anterior translation in random order. Intact and destabilized specimens fixed with either MB or TAS were tested in sequence. RESULTS Significantly higher stiffness values in the elastic zone were obtained with the TAS technique than with the MB technique for all modes of testing (p < 0.002, t test). Values for the neutral zone (the region where minimal loads produce displacement) were not significantly different between the MB and TAS techniques (p > 0.1, t test). CONCLUSION We conclude that stability is significantly enhanced by use of the TAS construct for treatment of ligamentous instability at the atlantoaxial joint for all motions tested in the present study.

Mechanical Stability of Thoracolumbar Pedicle Screw Fixation : The Effect of Crosslinks

Study Design. Pedicle screw fixation for unstable thoracolumbar spine injuries is relatively new. The ef fect of one or two crosslinks on rotational and lateral bending stiffness was studied. Objective. To determine the rotational and bending stiffness values of thoracolumbar fractures fixed by the AOs internal fixation system with zero, one, or two crosslinks. Methods. Eight embalmed thoracolumbar spine segments (T12‐L2) were instrumented at T12 and L2 with a pedicle screw‐rod system. Rotational stiffness was determined for 10 cycles to 2.5°, 3.5°, and 5° of rotation, with and without one or two crosslinks, and lateral bending stiffness for 10 cycles to 0.25, 0.40, and 0.50 inch. The results showed a clear trend toward increased stiffness with crosslinks. Results. The stiffness values of the two‐crosslink construct at 2.5° and 3.5° of rotation were significantly higher than those of the zero‐crosslink system. Also, the bending stiffness of the two‐crosslink construct was significantly higher than that of no‐crosslink system at all of the displacements. Conclusions. Rotational stiffness values of the two‐crosslink construct were significantly higher than those of the zero‐crosslink system, at 2.5° and 3.5° of rotation. Lateral bending stiffness of the two‐crosslink system was higher than that of the zero‐crosslink system at all levels of displacement.

Design and implementation of a system-based course in musculoskeletal medicine for medical students.

BACKGROUND The amount of time devoted to musculoskeletal medicine in the typical undergraduate curriculum is disproportionately low compared with the frequency of musculoskeletal complaints that occur in a general practice. Consequently, whether because of the quantity or quality of the education, the competence level of graduating physicians regarding musculoskeletal problems is inadequate. Our purposes were to design a self-contained, system-based course in musculoskeletal medicine for medical students in the preclinical years and to measure the level of competence achieved by a class of first-year medical students who took the course. METHODS The course was formulated by faculty from the departments of orthopaedic surgery, anatomy, and rheumatology and included elements of both objectives-based and problem-centered curricular models. The clinical lectures were preceded by pertinent anatomy lectures and dissections to provide a context for the clinical information. The lectures on basic science were designed to rationalize and explicate clinical practices. Small-group activities were incorporated to permit engagement of the students in critical thinking and problem-solving. A general musculoskeletal physical examination was taught in two two-hour-long small-group sessions with the orthopaedic residents serving as instructors. Cognitive competency was evaluated with use of comprehensive anatomy laboratory and written examinations, the latter of which included a validated basic competency examination in musculoskeletal medicine. Process-based skills were evaluated in the small-group meetings and in a timed, mock patient encounter in which each students ability to perform the general musculoskeletal physical examination was assessed. RESULTS The course lasted six weeks and consisted of forty-four lecture hours, seventeen hours of small-group meetings, and twenty-eight hours of anatomy laboratory. The average student score on the basic competency examination was 77.8%, compared with 59.6% for a historical comparison group (p < 0.05). Each student demonstrated the ability to adequately perform a general musculoskeletal physical examination in twenty minutes. The survey of student opinion after the course indicated a high level of student satisfaction. CONCLUSIONS The main features of the course were: (1) an emphasis on both cognitive and process-based knowledge; (2) more contact hours and broader content than in previously described courses in musculoskeletal medicine; (3) the use of small groups to focus on problem-solving and physical examination competencies; (4) basic-science content directly related to clinical goals. These features might be used at other institutions that employ a system-based curriculum for the preclinical years to help improve competence in musculoskeletal medicine.

Effect of soft-tissue trauma on the early periosteal response of bone to injury

OBJECTIVE To determine whether the periosteal response to skeletal trauma is impaired when muscle is also injured, thereby providing a possible explanation for why fractures with extensive soft-tissue damage may take longer to heal. METHODS A bone defect was made in the tibia of male Fisher rats, and the proliferative response, osteoblast concentration, and callus formation that occurred within 7 days were measured in the presence and absence of simultaneously administered model soft-tissue injury (removal of 10% of the anterior tibialis muscle from a region within 2 to 3 mm of the bone defect). Measurements were made by using autoradiography, quantitative histology, and morphometry. RESULTS Addition of the muscle injury increased proliferation in the cambium and in the fibrous periosteum on day 1, but had no effect thereafter; proliferation of fibroblasts in the loose connective tissue above the periosteum was not affected. Addition of the muscle injury resulted in increased osteoblast levels 2 to 5 days after injury but had no effect on the amount of callus produced. CONCLUSION The inflammatory milieu created by the muscle injury unexpectedly resulted in an increased periosteal response to skeletal trauma, suggesting that inflammatory mediators generated in response to wounding of soft tissues are unlikely to account for delayed fracture healing. These findings may indicate that surgical trauma associated with internal fixation by using plates and screws may not be as deleterious to the fracture-healing response as previously thought.

Regulation of osteoblast levels during bone healing

OBJECTIVE To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1beta (IL-1beta) in regulating osteoblast concentration. STUDY DESIGN Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1beta administered continuously for three days. METHODS A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1beta was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1beta significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1beta treatment. CONCLUSION The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1beta mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.

Electromagnetic Fields Can Affect Osteogenesis by Increasing the Rate of Differentiation

Electromagnetic fields of various kinds can alter osteogenesis in animals with osteotomies and patients with nonunions, but the underlying cellular mechanisms are unknown. The aims of this study were to determine whether I gauss at 60 Hz affected periosteal proliferation and differentiation in either the normal rat tibia or 1 to 14 days after a surgically induced defect. In the injured rats, using histologic study, autoradiography, and morphometry, it was found that exposure for 1 or 3 days had no effect on proliferation but that it produced an increase in osteoblasts 3 days after the injury. Proliferation and differentiation were unaffected by exposure in the absence of injury. The results suggest that the primary effect of the fields was to promote differentiation but not proliferation. Because fields can stimulate proliferation of osteoblastlike cells in vitro, the results of this study may indicate the presence of an in vivo factor that antagonizes the tendency of fields to increase mitotic activity.

Neutrophil Mediated Microvascular Injury in Acute, Experimental Compartment Syndrome

The purpose of this study was to determine the contribution of neutrophils and tissue xanthine oxidase to the skeletal muscle microvascular dysfunction in an ex vivo model of acute compartment syndrome. Adult dogs were rendered neutropenic or depleted of tissue xanthine oxidase before gracilis muscle isolation. Compared with continuously perfused, nonischemic muscles, acute, experimental compartment syndrome resulted in a dramatic increase in microvascular permeability, muscle neutrophil content, and muscle vascular resistance. Neutropenia prevented, whereas xanthine oxidase depletion had no effect on, the microvascular dysfunction and muscle neutrophil infiltration elicited by experimental compartment syndrome. These results suggest that neutrophils contribute to the microvascular dysfunction and blood flow distribution abnormalities elicited by acute, experimental compartment syndrome.

Assessment of immunologic mechanisms for flare reactions to Synvisc.

Intraarticular injection of Synvisc® for treatment of knee pain sometimes results in an acute local reaction (flare). We tested the hypothesis that the flare was a Type-1 hypersensitivity reaction as manifested by the presence of Synvisc® antibodies in the synovial fluid and serum and by an increase in the concentration of the mast-cell enzyme tryptase in the synovial fluid. Our second objective was to determine whether the ratio of CD4+ to CD8+ lymphocytes in the synovial fluid was increased, as would be expected in a Type-4 hypersensitivity reaction. The study population was a prospective, consecutive series of 16 patients who had a flare, and 20 control patients. We found no differences in product-specific antibodies in the synovial fluid or serum between patients with flares and patients without flares. The mean tryptase level in the synovial fluid of patients with flares, 3.8 ± 0.8 μg/L, was not different from the corresponding level in the control patients. The CD4+/CD8+ ratio in the synovial fluid was more than eight times greater in patients with flares. Flares that sometimes occur after treatment with Synvisc® are probably not Type-1 (antibody-mediated) hypersensitivity reactions, but may be Type-4 (cell-mediated) hypersensitivity reactions.

Bone injury response : An animal model for testing theories of regulation

Therapeutic treatment of bone disease and attempts to accelerate normal healing require knowledge of the soluble factors that control bone repair and the specific effects that they produce. To facilitate study of this regulatory system, an animal model involving creation of a hole in the cortex of the rat tibia was developed. Proliferation, differentiation, and callus formation at the injury site were measured more precisely than in previous animal models by means of autoradiographic, histologic, histochemical, and morphometric methods. Several novel features of bone healing were observed, including the following: (1) synthesis of bone matrix in the defect occurred only after a cambial compartment was established by regeneration of the fibrous periosteum and (2) at least 3 kinds of osteoblasts could be distinguished depending on when and where they deposited calcifiable matrix. The model is well suited to evaluating the use of interventional startegies that involve chemical or electrical agents because the cellular parameters of interest can be measured precisely.

Increased intercellular communication through gap junctions may contribute to progression of osteoarthritis

Our aim was to support the hypothesis of a specific association between gap junctions in synovial tissue and the presence of osteoarthritis, as evidenced by differences between osteoarthritis and non-osteoarthritis synovia in the number of gap junctions, the amount of gap-junction protein, and the amount of enzymatic activity produced through a pathway mediated by gap-junction intercellular communication. An average of 4.41 gap junctions were found per 100 cells counted in the osteoarthritis synovia, compared with 1.00 in the controls. The amount of the gap-junction protein connexin 43 in synovial lining cells was approximately 50% greater in patients with osteoarthritis. Synovial lining cells from patients with osteoarthritis produced matrix metalloproteinases constitutively and, at higher levels, in response to stimulation by interleukin-1β. In both cases, intercellular communication through gap junctions was shown to be critical to the ability of the cells to secrete matrix metalloproteinases. Overall, the results indicated that gap junctions between synovial lining cells were altered significantly in patients with osteoarthritis, as a consequence of the disease process or as part of the causal chain. In either case, gap junctions seem to be a rational therapeutic target.