A cyclooxygenase-2 inhibitor impairs ligament healing in the rat.

Celecoxib was the first of a new class of nonsteroidal antiinflammatory drugs, the cyclooxygenase-2 (COX-2) specific inhibitors, marketed as having the same antiinflammatory efficacy as other nonsteroidal antiinflammatory drugs without their increased risk of gastrointestinal ulceration. Among the widest uses of nonsteroidal antiinflammatory drugs is in the treatment of acute soft tissue injuries. Although the benefits of celecoxib have been shown when used for rheumatoid arthritis and osteoarthritis, we are unaware of any studies concerning its effect on soft tissues. We used the surgically incised medial collateral ligament of male Sprague-Dawley rats as an experimental model for acute ligament injuries to investigate the effects of celecoxib on ligament healing. Fifty rats underwent surgical transection of the right medial collateral ligament. Postoperatively, half were given celecoxib for the first 6 days of recovery, the other half were not. The animals were sacrificed 14 days after the operation, and both the injured and uninjured medial collateral ligaments were mechanically tested to failure in tension. Celecoxib-treated/injured ligaments were found to have a 32% lower load to failure than untreated/injured ligaments. The results of this study do not support use of cyclooxygenase-2 specific inhibitors in the treatment of ligament injuries.

The effect of NKISK on tendon in an in vivo model.

The mechanism through which ligaments and tendons change length during growth and contracture is unclear. It has been hypothesized that there is a reversible "interfibrillar bond" that, when broken, allows the sliding of collagen fibrils past one another during length changes. The pentapeptide NKISK has been reported to inhibit the binding of decorin to fibronectin. This study was designed to evaluate the effect of NKISK in an in vivo model. Male Sprague-Dawley rats were divided into three groups (n = 9, 9 and 14, respectively). The left patellar tendon was injected with 1.0 ml of NKISK (Group 1 = 1.0 mM, Groups 2 and 3 = 5.0 mM). The contralateral/control limb was injected with carrier. Group 1 was sacrificed after three, Group 2 after four and Group 3 after seven daily injections. The patellar tendon lengths were measured in all groups with comparisons made to the contralateral control limb. NKISK injection resulted in a significant increase in length in Group 2 (3.14% +/- 2.04, P = 0.002) and in Group 3 (6.12% +/- 3.84, P < 0.001). Biomechanical testing of Group 3 showed no differences in maximum load, ultimate strength, structural stiffness, or elastic modulus of the treated tendons but did demonstrate a statistically significant decrease in the displacement and strain at maximum load in the NKISK-treated tendons. This study demonstrates that inhibition of decorin/fibronectin binding by NKISK results in tendon lengthening in an in vivo setting as noted by a progressive increase in the length of the patellar tendon.

The pentapeptide NKISK affects collagen fibril interactions in a vertebrate tissue.

The pentapeptide NKISK has been reported to inhibit the binding of decorin, a proteoglycan on the surface of collagen fibrils, to fibronectin, a tissue adhesion molecule. Because of our interest in fibril-fibril binding as it relates to changes in length of ligament or tendon (during growth or contracture), we investigated the potential of this peptide to dissociate fibrils. The peptide permitted the release of intact fibrils into suspension for examination under the electron microscope (which has not previously been possible in mature vertebrate tissues).

Reduction of posterior hip dislocations in the lateral position using traction-countertraction: safer for the surgeon?

Closed reduction of a hip dislocation is a physically demanding task for the orthopaedic surgeon. The most commonly used methods for reduction of the hip involve vigorous axial traction on the lower extremity with the patient in the supine position, using an assistant who attempts to hold the pelvis down. The surgeon generally stands over the patient to pull up on the bent knee, which puts the surgeon at risk for a low back injury and, if done while the patient remains on a stretcher, can put the surgeon at risk for a fall from a height. Reduction in the prone position is advocated by some, but caring for the sedated patient in the prone position can be difficult and the patient's pelvis tends to roll off the edge of the stretcher, preventing the achievement of hip flexion, which is desirable in achieving reduction. We describe a traction-countertraction technique that appears to be significantly less dangerous for the surgeon. In this technique the hip is reduced with the patient remaining on the stretcher in the lateral position. In addition, fluoroscopy can be carried out during the reduction maneuver, and the images can be quite helpful in adjusting the direction of manipulative forces.

Comparison of tricortical screw fixation versus a modified suture construct for fixation of ankle syndesmosis injury: a biomechanical study.

OBJECTIVE: To assess the viability of using a modified flexible suture implant instead of a tricortical screw for fixation of ankle syndesmosis failures. DESIGN: Randomized biomechanical study. SETTING: Orthopaedic Research Laboratories at the University of North Carolina at Chapel Hill. INTERVENTION: Formalin-preserved cadaveric legs were used in pairs. Two holes, 2.5 millimeters in diameter and 7.0 to 10.0 millimeters apart horizontally, were drilled through the fibula and tibia 2.0 centimeters above the tibial plafond. Two strands of Number 5 suture were passed through the holes and tied. Similarly, a 3.5-millimeter tricortical screw was placed on the opposite leg of each pair at 2.0 centimeters. The ankles were tested to failure. This process was repeated at 5.0 centimeters above the tibial plafond. MAIN OUTCOME MEASUREMENTS: Maximum load and displacement at failure of the suture construct at 2.0 centimeters and at 5.0 centimeters were compared with a tricortical screw at 2.0 centimeters and at 5.0 centimeters. RESULTS: There was no significant difference in strength or displacement between the flexible suture implant and the tricortical screw at either 2.0 centimeters or 5.0 centimeters. The fixations at 5.0 centimeters had significantly increased holding strength over fixations at 2.0 centimeters, and the fixations had significantly greater displacement at 2.0 centimeters than at 5.0 centimeters. CONCLUSION: This study confirms that flexible syndesmosis repair is a viable option for internal fixation of ankle mortise instability due to syndesmosis rupture.

High pressure pulsatile lavage irrigation of intraarticular fractures: effects on fracture healing.

OBJECTIVES: To evaluate the effects of pulsatile lavage and bulb syringe irrigation on fracture healing in vivo. DESIGN: Randomized prospective trial in an animal model. SETTING: Medical school orthopaedic department. SUBJECTS: Thirty New Zealand white rabbits. INTERVENTION: The control group (C) underwent osteotomy of the medial femoral condyle, stabilization, and closure. The bulb syringe and pulsatile lavage groups underwent the same procedure as group C, with the addition of irrigation with one liter of normal saline via a bulb syringe (B) or a pulsatile lavage system (P). Animals were administered two fluorescent bone stains: xylenol orange at the time of operation, and calcein green one week postoperatively. Animals were euthanized two weeks postoperatively and femurs were retrieved for histological analysis. MAIN OUTCOME MEASURES: Union was determined by examination of microradiographs under light microscopy. The viability of bone along the fracture site was determined by evaluation of xylenol orange and calcein green staining under fluorescent microscopy. The density of new bone formed in the osteotomy site was assessed by computerized digitization of standardized regions of the proximal and distal osteotomy. RESULTS: Xylenol orange bands were present a mean of 66 +/- 8 percent (mean +/- standard error of the mean), 65 +/- 6 percent, and 44 +/- 5 percent of the distance along the osteotomy in groups C, B, and P, respectively (p < 0.001). Calcein green bands were present throughout the osteotomy site in all specimens. Calcified new bone was present in 62 +/- 4 percent, 58 +/- 7 percent, and 41 +/- 9 percent of the area measured in groups C, B, and P, respectively (p = 0.07). Twenty percent of the osteotomies in groups C and B did not unite, compared with 30 percent in group P (p > 0.5). CONCLUSIONS: Pulsatile lavage irrigation of fresh intraarticular fractures in rabbits has a detrimental effect on early new bone formation; this effect, however, is no longer apparent two weeks following irrigation. While this study evaluated the effects of pulsatile lavage irrigation in noncontaminated fractures without extensive soft tissue injury, the detrimental effects observed on early new bone formation may translate to an increased risk of nonunion in the setting of a contaminated open fracture with extensive soft tissue injury. Based on the results of this investigation, the selective use of pulsatile lavage irrigation appears warranted. In the absence of gross wound contamination, irrigation with a bulb syringe appears less likely to impair fracture healing than does pulsatile lavage irrigation. Expansion of the model used in this study to include bacterial contamination and soft tissue crushing may further elucidate the effects of pulsatile lavage irrigation on fracture healing.

Collagen fiber sliding during ligament growth and contracture.

It is hypothesized that the sliding of collagen fibers past one another plays an important role in changes of ligament length during growth or contracture. To explore this possibility, we used the fluorescent dye dichlorotriazinyl fluorescein to stain collagen fibers perpendicular to their orientation in a rat medial collateral ligament model. Growth, contracture, and control models (with rats weighing 50-75 g in the first and 500-600 g in the latter two groups) were studied. In the contracture model, the medial collateral ligament was transected distally. Marking sutures were used to verify the presence of growth or contracture in each medial collateral ligament. Fluorescence photomicrography after 2 weeks demonstrated stained collagen fibers protruding from either side of the original mark as one would expect, in either growth or contracture, if the fibers slid past one another and away from their initial location during changes in length. By measuring the initial and final widths of the growth and contracture model marks and correlating them to controls that had minimal growth (rats grow throughout their life) and were free of contracture, we have provided evidence that collagen sliding plays a significant role in changes in ligament length.

Effect of ciprofloxacin on the proliferation of osteoblast-like MG-63 human osteosarcoma cells in vitro.

Locally applied antibiotic therapy is gaining popularity for the treatment of infections associated with open fractures and posttraumatic osteomyelitis. With use of local techniques, ciprofloxacin levels as high as 1,300 microg/ml, or over 200 times the bone levels achieved with intravenous administration, have been reported. To study the possible effects of ciprofloxacin on bone, osteoblast-like cells from the MG-63 human osteosarcoma cell line were studied. The cells were grown in antibiotic-free media and exposed to concentrations of ciprofloxacin at 0, 10, 100, 200, and 1,000 microg/ml to establish an initial dose-response curve. Media containing the appropriate dose of ciprofloxacin were changed every 24 hours. Cell number and [3H]thymidine incorporation per cell were determined at 0, 24, and 72 hours. A second dose-response curve was performed at concentrations of 0, 10, 20, 40, and 80 microg/ml. Three experiments, each with four observations, were performed. The results of this study demonstrated that ciprofloxacin caused significant decreases (p < 0.05) in cell number at 40 microg/ml at 24 hours and 20 microg/ml at 72 hours. [3H]thymidine incorporation per cell decreased significantly at levels of 80 microg/ml at 24 hours and 20 microg/ml at 72 hours. The authors conclude that reported local levels of ciprofloxacin seen in vivo inhibit the proliferation of human osteoblast-like cells in vitro.

Technical notes on a radiolucent distractor for indirect reduction and intramedullary nailing.

For many years, the fracture table has served as the gold standard for the application of the distraction forces necessary to indirectly reduce fractures during internal fixation procedures. However, the fracture table is expensive, often is cumbersome, requires intraoperative adjustment by "nonscrubbed" personnel, can be difficult to use in the care of multiply traumatized patients, and often is unsuitable for the morbidly obese patient. This technical note describes the application of distraction with a sterile device that is used "in the surgical field" and applies distraction from a K-wire (or Steinman pin) tensioner to either another K-wire tensioner or a "perineal post." The multiply traumatized patient who is placed on a radiolucent table for thoracoabdominal procedures can undergo intramedullary nailing using this device without requiring transfer to a fracture table (or alternatively without requiring that surgical team members apply manual distraction during the nailing procedure). Such a device also can be used to apply distraction for tibial nailing, for indirect reduction and plating, and for hip and ankle arthroscopy.

Current treatment of tibial plateau fractures.

Treatment of tibial plateau fractures is evolving, and two treatment methods have emerged. One is the use of small incisions and percutaneous stabilization of depression fractures; another is the use of thin wire external fixation for bicondylar fractures. Preoperative planning is aided by classifying fractures as depressed, split, or bicondylar. Depressed fractures can often be treated with insertion of subchondral screws and supporting bone graft under fluoroscopic or arthroscopic guidance. Split fractures are treated with an open approach and application of a buttress plate. Bicondylar fractures require both medial and lateral support to prevent collapse and subsequent varus or valgus deformity. Current treatment of these fractures favors reassembling the articular surface and using thin wire external fixators to align the reconstructed articular block with the diaphysis. Avoiding extensive dissection of comminuted metaphyseal fragments can speed healing, so dissection is generally limited to the region near the tibial articular surface.

Isolation of intact collagen fibrils from healing ligament.

The inability to isolate intact collagen fibrils has limited the study of their growth and structure. Although intact fibrils have been isolated from echinoderms and from embryonic chick tissues, no method has previously succeeded in isolating intact collagen fibrils from a postfoetal vertebrate tissue. Having previously observed that gentamicin weakens rat tail tendon, we hypothesized that gentamicin may weaken interfibrillar bonds and that intact collagen fibrils might be isolated from tissue treated with gentamicin. In this study medial collateral knee ligaments of Sprague Dawley rats were transected and then harvested 24, 48 or 96 h postoperatively. These specimens were placed in gentamicin or phosphate-buffered saline for 72 h, vortexed for 1 h, incubated in gentamicin for an additional 24 h, and vortexed again for 1 h. Negatively stained specimens were examined with a transmission electron microscope. The phosphate-buffered saline specimens yielded only broken fibrils. The gentamicin specimens yielded both broken and intact fibrils. The latter and tapering ends and consisted of molecules orientated such that their amino termini pointed toward the tip and their carboxy termini pointed toward a short central region where the molecular polarity reversed.

Effect of cefazolin and vancomycin on osteoblasts in vitro.

The effect of cefazolin and vancomycin on osteoblast-like cells was studied. Cells from the MG-63 human osteosarcoma cell line were grown in antibiotic free media and exposed to concentrations of cefazolin and vancomycin at order of magnitude intervals between 0 and 10,000 microg/ml. For cefazolin, a second interval was performed between 100 and 1000 microg/ml to define toxic levels more accurately. Cell number and 3H-thymidine incorporation at 0, 24, and 72 hours were determined. The results of this study show that local levels of vancomycin of 1000 microg/ml and less have little or no effect on osteoblast replication, and concentrations of 10,000 microg/ml cause cell death. Concentrations of cefazolin of 100 microg/ml and less have little or no effect on osteoblast replication, 200 microg/ml significantly decrease cell replication, and 10,000 microg/ml cause cell death. The authors conclude that vancomycin is less toxic than is cefazolin to osteoblasts at higher concentrations and may be a better antibiotic for local administration in the treatment of similarly sensitive bacterial infections.

Influence of dosage and timing of application of platelet-derived growth factor on early healing of the rat medial collateral ligament.

In previous studies, platelet-derived growth factor has demonstrated beneficial in vivo effects on wound healing. We report the results of two studies of platelet-derived growth factor in the rat medial collateral ligament injury model. Experimental injury sites were implanted with platelet-derived growth factor, whereas contralateral controls received only collagen. Twelve days postoperatively, the femur-medial collateral ligament-tibia complex was tested mechanically. Our first study found a marked drop in the effectiveness of platelet-derived growth factor when it was administered more than 24 hours after injury. Dose-response testing showed maximum increases in strength (90%) with 5.0 micrograms of platelet-derived growth factor, but the 1.0 microgram group showed similar strength increases, indicating a probable plateau effect in the response. These results indicate that platelet-derived growth factor has promise for healing ligaments but that it must be administered in appropriate doses soon after injury.

Internal fixation of proximal humeral fractures.

Fractures of the proximal humerus are common, especially in elderly individuals, and are usually classified according to Neer into fractures having one, two, three, or four parts with or without an associated dislocation or an injury splitting the humeral head. This article is intended to assist the surgeon in selecting and using techniques for internal fixation of these fractures. The use of open reduction and internal fixation using plates and screws has become less popular because of the extensive dissection required and the tendency for the plate to impinge. Use of multiple percutaneous pins to fix the humeral head to the shaft (surgical neck) and heavy sutures or wires to reattach the tuberosities is often preferable.

Bone toxicity of locally applied aminoglycosides.

The effect of tobramycin on osteoblasts was studied. Osteoblast-like cells from the MG-63 human osteosarcoma cell line were grown in antibiotic-free media and exposed to concentrations of tobramycin: first at order of magnitude intervals between 0 and 10,000 micrograms/ml, and then at closer intervals between 100 and 1,000 micrograms/ml to more accurately define toxic levels. Cell number and 3H-thymidine incorporation at 0, 24 and 72 h were determined. Similarly, primary cultures of rat osteoblasts were exposed to the same concentrations of tobramycin to confirm the validity of the MG-63 cell line as a model for nontransformed cells. The results of this study demonstrate that local levels of tobramycin of < or = 200 micrograms/ml have little or no effect on osteoblast replication. Concentrations of 400 micrograms/ml significantly decreased cell replication, and concentrations of 10,000 micrograms/ml caused cell death. Results obtained with primary rat osteoblast cultures were similar to those obtained from the MG-63 cultures at the tested tobramycin concentrations.

The effect of combinations of growth factors on ligament healing.

Platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor Type 1 have demonstrated chemotactic and mitogenic properties in vitro that could benefit healing ligaments. These growth factors also have demonstrated in vivo effects when used in skin wound-healing models. In a previous study, bFGF and IGF-1, used alone, failed to improve healing. The authors wished to test the hypothesis that platelet-derived growth factor alone or combinations of platelet-derived growth factor plus insulin-like growth factor Type 1, platelet-derived growth factor plus basic fibroblast growth factor, or basic fibroblast growth factor plus insulin-like growth factor Type 1 would increase the healing efficiency of ligaments because of their effects on different parts of the cell replication cycle and their abilities to induce chemotaxis. Ligaments receiving platelet-derived growth factor alone were 73% +/- 55% stronger than their contralateral internal controls (p < 0.0025). Stiffness increased 94% +/- 63% over controls (p < 0.0025), and breaking energy was 101% +/- 104% > controls (p < 0.1). Ligaments treated with a combination of platelet-derived growth factor plus insulin-like growth factor Type 1 and platelet-derived growth factor plus basic fibroblast growth factor also had increases in rupture force, stiffness, and breaking energy over internal controls. Ligaments treated with a combination of basic fibroblast growth factor plus insulin-like growth factor Type 1 also appeared to have some improved healing; the results, however, did not prove to be statistically significant. Synergistic effects of growth factor combinations were not evident.

The effects of nerve injury on ligament healing in a rat model.

The presence of an intact nerve supply is important in the regeneration of injured tissue in some animals. It has not been determined whether an intact nerve supply is important in ligamentous healing. The authors hypothesize that the nerve supply of a ligament might have a significant effect on its healing. The purpose of this paper was to determine whether injury to the nerve supply of the medial collateral ligament in a rat model results in poor ligament healing (which would suggest that intact nerve supply enhances ligament repair). Clinically, such a finding would demonstrate the importance of avoiding injury to nerve-ligament systems in reparative ligament surgery. Twenty three rats underwent complete bilateral dissection of the major nerves supplying the medial collateral ligament, and each ligament was transected at the level of the tibial tuberosity. The major nerve supplies of the experimental ligaments were destroyed by segmental excision, either distally at the medial articular nerves or proximally at the saphenous nerve, while the control ligament's nerve supplies were left intact. The rats were euthanized at 12 days, and each medial collateral ligament was tested biomechanically using a hydraulic materials testing machine. This time point was chosen because the rat ligament transection site heals rapidly, causing the ligament to avulse from its tibial insertion instead of rupturing at the transection site at later time points. This rat medial collateral ligament injury model has shown statistically significant differences in healing at this time point in numerous experiments evaluating the effects of other variables on ligament healing.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of different levels of direct current on early ligament healing in a rat model.

Electrical stimulation has been shown to enhance the repair of biological tissues such as bone and tendon. The objective of this study was to determine whether low level direct current enhances the early healing of injured medial collateral ligaments. Eighty-seven rats were divided into three groups on the basis of the level of current delivered. All underwent transection of the medial collateral ligament bilaterally. The experimental medial collateral ligaments received current (which varied by group), while the contralateral medial collateral ligaments (the controls), with identical electrodes, received no current. After 12 days, each ligament was tested biomechanically with use of a hydraulic materials testing machine. Group 1 (8.6 +/- 5.9 microA) showed statistically significant improvements in maximum rupture force, energy absorbed, stiffness, and laxity. The groups that had received lower levels of current did not show significant improvements. In this study, stimulation of 1-20 microA was the most effective level of direct current for the enhancement of early healing of the medial collateral ligament.

Incidence, management, and outcome of femoral shaft fracture: a statewide population-based analysis of 2805 adult patients in a rural state.

UNLABELLED: Early surgical management of femoral shaft fracture (FSF) is considered the standard but patients are still treated nonsurgically. The purpose of this study was to analyze the results of management of FSF in a large population based data base. METHODS: Data were obtained from a statewide hospital discharge data base for 1989-1992. Adults having a FSF were stratified by ISS (ISS < 15 vs. ISS > or = 15) and management (nonsurgical, surgery within 1 day, surgery at 2-4 days, or surgery at > 4 days). Mortality rates and mean length of hospital stay were compared among groups. RESULTS: 2805 patients had FSFs: 69% were managed surgically and 31% nonsurgically. Mortality was higher for nonsurgical therapy in both ISS groups. In the surgically treated groups, length of hospitalization increased as delay to surgery increased. In patients with an ISS > or = 15, repair at 2-4 days was associated with the lowest mortality and shortest hospitalization, while a trend to higher mortality and longer hospitalization was noted with repair within 1 day. CONCLUSION: 31% of patients were treated nonsurgically with higher associated mortality. These results support "early" surgical fixation, which can shorten hospital stay without increasing mortality regardless of overall injury severity. The trend toward higher mortality in severely injured patients operated on within 1 day of admission suggests that this group warrants further study and individualized management.