Prophylactic and therapeutic fixation of weight-bearing long bones with metastatic cancer.

BACKGROUND: We retrospectively studied the duration of operations and the hospitalizations for impending and manifest fractures of weight-bearing long bones with metastatic disease, which has rarely been done. METHODS: The duration of operative fixation and the hospital stay in patients with an impending (n = 7) or actual (n = 15) fracture in a weight-bearing long bone with metastatic tumor were assessed, including symptomatic response, posttreatment mobility, and survival rate. RESULTS: Most patients had significant relief of pain. More than half of patients with impending fracture and 80% with actual fracture were ambulatory after therapy; 3-year survival rates were 29% and 13%, respectively. Corresponding mean durations for the operations were 175 minutes and 185 minutes, respectively; mean durations of hospitalization were 22 days and 16 days, respectively. CONCLUSION: Surgical fixation of fractures in weight-bearing long bones with metastatic cancer does not require excessive operative time as compared with that of impending fractures, does not extend hospitalization, and has an acceptable risk-reward ratio.

Gap junctions in human synovial cells and tissue.

Our objective was to establish the existence of intercellular communication through gap junctions in synovial lining cells and in primary and passaged cultures of human synovial cells. Communication between cells was assessed using the nystatin perforated-patch method, fluorescent dye transfer, immunochemistry, transmission electron microscopy, and immunoblotting. Functional gap junctions were observed in primary and passaged cultures and were based on measurements of the transient current response to a step voltage. The average resistance between cells in small aggregates was 300 +/- 150 MOmega. Gap junctions were also observed between synovial lining cells in tissue explants; the size of the cell network in synovial tissue was estimated to be greater than 40 cells. Intercellular communication between cultured cells and between synovial lining cells was confirmed by dye injection. Punctate fluorescent regions were seen along intercellular contacts between cultured cells and in synovial membranes in cells and tissue immunostained for connexin43. The presence of the protein was verified in immunoblots. Regular 2-nm intermembrane gap separations characteristic of gap junctions were seen in transmission electron micrographs of synovial biopsies. The results showed that formation of gap-junction channels capable of mediating ionic and molecular communication was a regular feature of synovial cells, both in tissue and in cultured cells. The gap junctions contained connexin43 protein and perhaps other proteins. The physiological purpose of gap junctions in synovial cells is unknown, but it is reasonable to anticipate that intercellular communication serves some presently unrecognized function.

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.

Programmed cell death in post-traumatic bone callus.

Some osteoblasts in the expanded population of periosteal cells that occurs following bone injury are removed from the callus by apoptosis. Our objective was to study whether the consequences of activation of the death program could include feedback control of the healing response. Transforming growth factor beta and interleukin-1beta were delivered together continuously to a standardized tibial defect in rats for 3 days using implanted micro-osmotic pumps. The bones were recovered at 1, 2, 3, 5, 7, 10 and 14 days after injury (n = 6 in each treated and control group) and concentrations of proliferating cells, osteoblasts and apoptotic bodies were determined. The injury-induced apoptotic component of the healing response was shifted in time due to the combined cytokines, compared with vehicle only, with the result that the peak in the concentration of apoptotic bodies occurred 2-3 days earlier in the treated animals. Neither osteoprogenitor proliferation nor osteoblast concentration was affected by addition of the cytokines. The results suggested that activation of apoptosis during injury repair was not necessarily a passive consequence of the cellular response to injury. Programmed cell death could therefore have an active role in modulating bone repair.

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.

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.

Effect of femoral fracture and intramedullary fixation on lung capillary leak.

BACKGROUND: Pulmonary injury is an important complication in the trauma patient with long-bone fractures. The purpose of this study was to determine the effect of femoral fracture or fracture and intramedullary fixation on lung capillary leak. The contribution of leukocytes to lung injury in this model was also determined. METHODS: The pulmonary capillary filtration coefficient was determined in lungs of rats after femur fracture or fracture and reamed or unreamed intramedullary fixation. Pulmonary arterial vascular resistance and lung neutrophil content were also determined. RESULTS: Fracture alone did not cause lung injury, whereas fracture and intramedullary fixation elicited lung capillary leak. Fracture alone and intramedullary fixation increased pulmonary vascular resistance, whereas unreamed intramedullary fixation caused lung leukosequestration. CONCLUSION: Femoral fracture alone does not cause an increase in pulmonary microvascular permeability. Femoral fracture and intramedullary fixation causes lung capillary leak, which is not increased by reaming the femoral canal.

Intracellular signaling mechanisms of interleukin-1beta in synovial fibroblasts.

The possibility that membrane depolarization of synovial fibroblasts caused by interleukin-1beta (IL-1beta) was mediated by protein kinase C (PKC) and Ca2+ influx was studied using inhibitor and activator analysis. The effect of IL-1beta was blocked by bisindolylmaleimide I, an inhibitor of PKC, and by the Ca2+ channel blockers nifedipine and verapamil. In other experiments, PKC was activated using phorbol 12-myristate 13-acetate, and Ca2+ influx was increased by means of a Ca2+ ionophore. Simultaneous application of phorbol ester and Ca2+ ionophore in the absence of IL-1beta mimicked the depolarization caused by IL-1beta. The results were consistent with the hypothesis that, under the conditions studied, activation of PKC and Ca2+ influx are necessary and sufficient processes in the transduction of IL-1beta by synovial cells leading to membrane depolarization. The essential role of protein phosphorylation and Ca2+ influx in the early electrophysiological response of synovial fibroblasts to IL-1beta was therefore established. The role of IL-1beta-induced depolarization in regulating protein expression by the cells remains to be determined, but the results reported here, taken together with observations that protein phosphorylation and Ca2+ influx also mediate the effect of IL-1beta on protease production (1, 2), suggest that electrophysiological changes are actually part of the pathway for expression of proteases in response to IL-1beta.

Interleukin-1 beta switches electrophysiological states of synovial fibroblasts.

The role of electro-physiological events in signal transduction of interleukin-1 beta (IL-1 beta) was investigated in rabbit synovial fibroblasts using the perforated-patch method. Aggregated synovial fibroblasts using the perforated-patch method. Aggregated synovial fibroblasts occurred in two different electrophysiological states having membrane potentials (Vm) of -63 +/- 4 (n = 71) and -27 +/- 10 mV (n = 55) (high and low Vm, respectively). IL-1 beta affected the cells with high Vm; it switched the state of the cell from high to low Vm. This effect was strongly dependent on the external potential applied to the cell membrane. Low Vm (-30 mV) alone without IL-1 beta did not switch the state of the cells. Thus a synergistic effect involving the cytokine and cell Vm in switching the electrophysiological state of the cell was shown, indicating that electrophysiological changes are involved in signal transduction. Gap junctions between aggregated cells were necessary for the cells to have a high Vm and to respond to IL-1 beta. Gap junction resistance between adjacent cells was estimated as 300 +/- 100 M omega. Our findings suggest that the electrophysiological behavior of synovial fibroblasts is tightly connected to a signaling or intracellular mediator system that is triggered by IL-1 beta.

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 effect 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 AO's 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 degrees, 3.5 degrees, and 5 degrees 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 degrees and 3.5 degrees 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 degrees and 3.5 degrees of rotation. Lateral bending stiffness of the two-crosslink system was higher than that of the zero-crosslink system at all levels of displacement.

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.

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.

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 strategies that involve chemical or electrical agents because the cellular parameters of interest can be measured precisely.

Open dislocation of the knee.

Traumatic open dislocation of the knee is an infrequent, severe injury associated with extensive ligamentous damage and a high incidence of vascular and neurologic involvement. Eighteen patients with 19 open knee dislocations were treated at the affiliated hospitals of the University of Pennsylvania and Louisiana State University Medical Center during an 18-year period. Final results included three above-knee amputations, one knee fusion, and one total knee arthroplasty. The 14 knees salvaged had only fair to poor function according to the Hospital for Special Surgery Knee Injury Score at an average follow-up of 36 months after the injury (average score = 29, range - 17 to 37). Nine patients (47%) had concomitant neurologic or vascular injury, and eight patients (42%) had wound healing difficulties. Five complete disruptions of the popliteal artery or posterior tibial artery underwent emergent revascularization, successful in three of the extremities, with the remaining two extremities requiring above-knee amputations. These massive injuries are often limb-threatening despite prompt surgical intervention and early antibiotic therapy. There is a very high incidence of infection and neurologic injury with a guarded prognosis for limb survival and satisfactory function.

The natural history of cervical spondylotic myelopathy.

This is a retrospective study of twenty-two patients with cervical spondylotic myelopathy who were admitted to the hospital for surgical treatment of their neurological condition. The purpose of the study was to evaluate the presenting symptoms, factors affecting the diagnosis and the course of the disease prior to surgical intervention. The earliest consistent symptom in all of our patients was a gait abnormality. The course of the disease was one of progressive deterioration. Spontaneous regression did not occur in any of the cases. The vagueness of the initial complaints led to considerable delay in the diagnosis (average of 6.3 years). Magnetic Resonance Imaging (MRI) was the most useful test in confirming the diagnosis.

Anatomic variations of the blood supply of the soleus muscle.

A total of 36 cadaver and fresh amputation specimens were studied by dissection. Two vascular patterns were identified--a segmental posterior tibial artery (Type 1) and a proximally dominant posterior tibial artery (Type 2). Type 1 was seen in 77.8% of cases, and Type 2 in 22.2%. Injection studies in five fresh specimens demonstrated numerous cross-connections between the two halves of the muscle. A distally based hemisoleus flap should not be performed when a Type 2 vascular pattern is encountered. Also, vascular cross-connections between the two halves of the soleus muscle should be preserved, when possible.

Tibial plateau fractures: standardized evaluation of operative results.

Twenty patients with fractures of the tibial plateau were treated operatively by a single surgeon experienced in the techniques advocated by the Association for the Study of Internal Fixation (AO/ASIF). Patients were reviewed an average of 27.4 months postoperatively. Results are reported and evaluated according to standardized criteria recommended in the literature. In addition, subjective and objective evaluation parameters were integrated into a 100-point knee rating score. Thirteen patients had good or excellent results. Poor results were attributed to the severity of the fractures, associated soft tissue injuries, and postoperative complications. Results of patients treated in a similar manner and reported in the literature are reviewed. The recent emphasis on operative treatment of displaced tibial plateau fractures requires detailed uniform reporting and evaluation of results to allow comparison between series and to improve outcome.

Analysis of mechanical factors affecting fixation of olecranon fractures.

Fractures of the most distal part of the olecranon process differ from more proximal fractures because a plane of instability exists between the humerus and the radial head. Thus, the fixation of these fractures must resist the deforming forces of the forearm flexor muscles. The investigators fixed 10 paired cadaver ulnae with either the tension-band wire technique or a one-third tubular plate, and tested the specimens to simulate the effect of the biceps and brachialis muscles. The average maximum fixation stiffness for specimens fixed with the one-third tubular plate was found to be 163 N/mm compared with 53 N/mm for the tension-band wire group. This study indicates that for fractures of the distal part of the olecranon, fixation with screws and a one-third tubular plate affords better resistance to the forces applied by the brachialis and the biceps brachii than the tension-band wire technique.

The fate of intraarticular loose bodies of meniscus origin in canine species.

A potential risk of arthroscopic meniscectomy is the retention of debris of meniscus origin in the knee joint. This prospective study analyzes the fate of loose bodies of meniscus origin placed into the canine knee joint. At 12 weeks, 16.7% of the free fragments were completely degraded, 16.7% were absorbed by the synovium, and 66.6% were loose, located between synovial folds. At 12 weeks, 93.3% of the fragments had disappeared, and the remaining fragments had decreased 70% in length and 50% in width. A focus of calcification was present in one fragment at 12 weeks. By three weeks, all loose bodies had a pseudocapsule composed of cells with intense fibroblastic activity, occasional mitoses, and a loss of connective tissue matrix at the periphery. A mononuclear leucocytic response was present in the synovium at 12 weeks in four of the five dogs. Free fragments of meniscus origin are most commonly degraded completely by 12 weeks. Enzymatic digestion, mechanical abrasion, and synovial phagocytosis are processes that may contribute to this phenomenon.