Early versus late femoral fracture stabilization in multiply injured pediatric patients with closed head injury.

The purpose of this study was to analyze retrospectively pediatric femur fracture patients with concomitant head injury to determine whether time to fracture fixation affects central nervous system, orthopaedic, or additional complications. Twenty-five patients with a Head Abbreviated Injury Scale score of > or =3 and a femoral shaft fracture were reviewed. Patients were divided by time to treatment for their femur fracture. Average stay was 10.5 days for the early group and 18.5 days for the late group, the only statistically significant finding. Orthopaedic and central nervous system complications were similar between the two groups. Sixteen additional complications were found in the late group versus three for the early group. Femur fractures in the head-injured pediatric patient can be adequately addressed with early or late fixation with similar long-term outcomes. Early femur fracture fixation may decrease the length of hospital stay and the number of nonorthopaedic, nonneurologic complications.

Growth factors improve muscle healing in vivo.

Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries.

Use of growth factors to improve muscle healing after strain injury.

Muscle injuries represent a large number of professional and recreational sports injuries. Muscle strains habitually occur after an eccentric contraction, which often leads to an injury located in the myotendinous junction. Treatment varies widely, depending on the severity of the trauma, but has remained limited mostly to rest, ice, compression, elevation, antiinflammatory drugs, and mobilization. The authors' research group aims to develop new biologic approaches to improve muscle healing after injuries, including muscle strains. To achieve this goal, the authors investigated several parameters that will lead to the development of new strategies to enhance muscle healing. The authors first evaluated natural muscle healing after strain injuries and showed that muscle regeneration occurs in the early phase of healing but becomes impaired with time by the development of tissue fibrosis. Several growth factors capable of improving muscle regeneration were investigated; basic fibroblast growth factor, insulin-like growth factor, and nerve growth factors were identified as substances capable of enhancing muscle regeneration and improving muscle force in the strained injured muscle. The current study should aid in the development of strategies to promote efficient muscle healing and complete recovery after strain injury.

Direct-, fibroblast- and myoblast-mediated gene transfer to the anterior cruciate ligament.

The anterior cruciate ligament (ACL) has poor capabilities of healing. Maturation or "ligamentization" of the ACL following autograft or allograft reconstruction has been found slow and remains under investigation. In vitro and in vivo studies have shown that platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), and epidermal growth factor (EGF) have the potential to improve ligament healing. Gene therapy approaches may represent a new alternative in delivering these specific growth factors to the ACL. The aim of this study was to investigate the feasibility of three different gene therapy approaches (direct-, fibroblast-, and myoblast-mediated gene transfer) to the ACL. Rabbit myoblasts and ACL-fibroblasts were transduced with 5 x 10(7) recombinant adenoviral particles carrying the LacZ reporter gene (MOI = 50). Myoblasts and fibroblasts (1 x 10(6)) were each injected into the right ACL of 10 adult rabbits; direct injection of 5 x 10(7) adenoviral particles was performed in 10 other rabbits. The left side was used as sham. The beta-galactosidase production was revealed using the LacZ histochemical technique. The transduced fibroblasts and myoblasts were found in the ligament tissue and in the synovial tissue surrounding the ACL at 4, 7, 14, and 21 days postinjection. The myoblasts fused and formed myotubes in the ligament. The direct approach also allowed the transfer of the marker gene in the ligament at 4, 7, 21, and 42 days postinjection. X-gal staining revealed no expression of beta-galactosidase in the sham ligament. The presence of cells expressing the marker gene in the ACL opens up the possibility of delivering proteins (i.e., PDGF, TGF-beta, and EGF) capable of improving ACL healing and graft maturation. Furthermore, engineered myoblasts may mediate and accelerate the intraligament neovascularization. This new technology based on gene therapy and tissue engineering may allow a persistent expression of selected growth factors to enhance ACL healing following injury.

Use of muscle cells to mediate gene transfer to the bone defect.

Segmental bone defects and nonunions are relatively common problems facing all orthopaedic surgeons. Osteogenic proteins, i.e., BMP-2, can promote bone healing in segmental bone defects. However, a large quantity of the human recombinant protein is needed to enhance the bone healing potential. Cell mediated gene therapy in the bone defect can allow a sustained expression of the osteogenic proteins and further enhance bone healing. Muscle cells can be easily isolated and cultivated, and they are known to be an efficient gene delivery vehicle to muscle and nonmuscle tissues. Furthermore, they are capable of transforming into osteoblasts when stimulated by BMP-2. Thus, the utilization of muscle cells as the gene delivery vehicle to a bone defect would be an important step in establishing a less invasive treatment for non-unions and segmental bone defects. Muscle cells were transduced when the adenoviral-lacZ vector and injected into the bone defect and the muscles surrounding the defect. Expression of the marker gene was visualized 7 days after the injection, both macroscopically and microscopically, using lacZ histochemistry. The lacZ expressing cells in the defect tissue were also stained for desmin, a muscle specific marker, indicating the presence of muscle cells that have fused into myofibers in this nonmuscle bone defect area. With successful myoblast mediated gene delivery into the segmental bone defect, future experiments would focus on delivering viral vectors expressing osteogenic proteins to eventually improve bone healing postinjury.

Suturing versus immobilization of a muscle laceration. A morphological and functional study in a mouse model.

Muscle laceration remains a difficult problem for orthopaedic surgeons. Despite many studies related to the muscle's ability to regenerate after muscle degeneration, very few reports are available regarding structural and functional recovery after skeletal muscle laceration. We developed an animal model of muscle laceration in mice, where the gastrocnemius muscles were reproducibly transected. We compared the effect of a surgical repair versus a short period of immobilization (5 days) on the muscle healing. The natural course of muscle recovery was monitored at several points after injury using histologic, immunohistochemical, and functional testing. In the injured muscle, we observed a high number of regenerating myofibers and development of fibrotic scar tissue. Suturing the lacerated muscle immediately after injury promoted better healing of the injured muscle and prevented the development of deep scar tissue in the lacerated muscle; conversely, immobilization resulted in slower muscle regeneration and the development of a large area of scar tissue. Tetanus strength 1 month after injury was 81% of control muscles for the sutured muscles, 35% for the lacerated muscles with no treatment, and 18% for the immobilized muscles. Based on this study, suturing a muscle laceration with a modified Kessler stitch results in the best morphologic and functional healing.

Development of approaches to improve the healing following muscle contusion.

Muscle injuries are a challenging problem in traumatology, and the most frequent occurrence in sports medicine. Muscle contusions are among the most common muscle injuries. Although this injury is capable of healing, an incomplete functional recovery often occurs, depending on the severity of the blunt trauma. We have developed an animal model of muscle contusion in mice (high energy blunt trauma) and characterized the muscle's ability to heal following this injury using histology and immunohistochemistry to determine the level of muscle regeneration and the development of scar tissue. We have observed a massive muscle regeneration occurring in the first 2 wk postinjury that is subsequently followed by the development of muscle fibrosis. Based on these observations, we propose that the enhancement of muscle growth and regeneration, as well as the prevention of fibrotic development, could be used as approach(es) to improve the healing of muscle injuries. In fact, we have identified three growth factors (bFGF, IGF-1, and NGF) capable of enhancing myoblast proliferation and differentiation in vitro and improving the healing of the injured muscle in vivo. Furthermore, the ability of adenovirus to mediate direct and ex vivo gene transfer of beta-galactosidase into the injured site opens possibilities of delivering an efficient and persistent expression of these growth factors in the injured muscle. These studies should help in the development of strategies to promote efficient muscle healing with complete functional recovery following muscle contusion.

Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery to dystrophic muscles.

Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle disease characterized by a lack of dystrophin expression. Myoblast transplantation and gene therapy have the potential of restoring dystrophin, thus decreasing the muscle weakness associated with this disease. In this study we present data on the myoblast mediated ex vivo gene transfer of full-length dystrophin to mdx (dystrophin deficient) mouse muscle as a model for autologous myoblast transfer. Both isogenic primary mdx myoblasts and an immortalized mdx cell line were transduced with an adenoviral vector that has all viral coding sequences deleted and encodes beta-galactosidase and full-length dystrophin. Subsequently, these transduced myoblasts were injected into dystrophic mdx muscle, where the injected cells restored dystrophin, as well as dystrophin-associated proteins. A greater amount of dystrophin replacement occurred in mdx muscle following transplantation of mdx myoblasts isolated from a transgenic mouse overexpressing dystrophin suggesting that engineering autologous myoblasts to express high amounts of dystrophin might be beneficial. The ex vivo approach possesses attributes that make it useful for gene transfer to skeletal muscle including: (1) creating a reservoir of myoblasts capable of regenerating and restoring dystrophin to dystrophic muscle; and (2) achieving a higher level of gene transfer to dystrophic muscle compared with adenovirus-mediated direct gene delivery. However, as observed in direct gene transfer studies, the ex vivo approach also triggers a cellular immune response which limits the duration of trans-gene expression.

Proposed curriculum model for resident education in pediatric orthopaedic surgery.

A curriculum developed for pediatric orthopaedic residency training is described. The curriculum is practice based, emphasizing those components thought to be necessary for orthopaedic practice. Highly technical or esoteric topics are deemphasized, because they are not relevant to practice capabilities at the end of residency training. The curriculum is designed to serve as a guide for educational direction in pediatric orthopaedic residency training, and not as a description of competency. Resource materials are being developed to provide the educator with relevant clinical material, objectives, and bibliography. The advantages of a practice based curriculum warrant further development of this model for other orthopaedic subspecialties.

Limb lengthening promotes muscle growth.

Studies of limb lengthening have demonstrated successful bone formation in the distraction gap. Failure of the muscle units to lengthen leads to many complications that significantly limit the success of this approach; it is, therefore, of paramount importance to characterize the behavior of the muscle during limb lengthening. In this study, tibiae of adult rabbits were lengthened for 10 days at a rate of 1 mm/day. The proliferative ability of the lengthened muscle was characterized using bromodeoxyuridine, a thymidine analogue that is incorporated during cell division, and desmin, a muscle-specific marker. We observed a large number of proliferating cells, specifically in the lengthened muscle, that were co-localized with many desmin-positive cells. The presence of bromodeoxyuridine nuclei inside desmin-positive muscle fibers suggests that limb lengthening promotes muscle growth by triggering myoblast proliferation and fusion into the lengthened muscle. Our findings are consistent with those of other studies in the reviewed literature that also suggest that limb lengthening promotes muscle growth.

Myoblast-mediated gene transfer to the joint.

Several genetic and acquired pathologic conditions of the musculoskeletal system, such as arthritis and damage to ligament, cartilage, and meniscus, may be amenable to gene therapy. Even though ex vivo gene transfer with synovial cells has been shown to deliver genes encoding for anti-arthritic proteins into the rabbit knee joint, its success has been limited by a transient transgene expression. In this study, data were investigated regarding the use of muscle cells as an alternative gene-delivery vehicle to the joint in newborn rabbit and adult severe combined immunodeficiency mice. We demonstrated that myoblasts were transduced more efficiently than synovial cells with use of the same adenoviral preparation in vitro. After intra-articular injection, the engineered muscle cells adhered to several structures in the joint, including the ligament, capsule, and synovium. In addition, myoblasts fused to form many post-mitotic myotubes and myofibers at different locations of the joint of the newborn rabbit 5 days after the injection. In the knee of the adult mouse, myoblasts fused and expressed the reporter gene for at least 35 days after the injection. The presence of post-mitotic myofibers in the knee joint raises the possibility of long-term expression of the secreted protein. Currently, numerous tissues in the joint (ligament, meniscus, and cartilage) have poor intrinsic healing capacity and frequently need surgical corrections. A stable gene-delivery vehicle to the joint producing proteins that ameliorate these different musculoskeletal conditions may change the clinical implications of these pathologies.

Intersegmental spinal flexibility with lumbosacral instrumentation. An in vitro biomechanical investigation.

Flexibility of the porcine lumbosacral spine was measured after application of six different types of surgical instrumentation, and in a control state. Fifteen adult pig spines were tested with flexion, extension, lateral bending, and axial rotation torques applied to the upper end with the pelvis fixed. Instrumentation was applied across two lumbar segments and the lumbosacral level (L5-6, L6-7, and L7-S1). Stereophotogrammetry was used to track markers applied to each vertebra. Intersegmental motion was measured as three angles and as the relative linear translation of adjacent transverse processes and spinous processes. Results showed that all instrumentation systems reduced intersegmental motion compared with the control state, except for minimal reduction at L5-6 by Harrington instrumentation in all loading directions, especially axial rotation. The pedicle screw systems were always the most rigid. After applying instrumentation, there were differences in the motion occurring at different anatomic levels, most commonly with the least motion occurring in the middle of the instrumented segment (L6-7). When intervertebral motion was expressed as the linear motion between adjacent spinous and transverse processes, the usual site of posterolateral fusion, it was 0.6 to 1.8 mm per degree of angular motion at the transverse processes and 1.3 to 2.1 mm per degree at spinous processes.

Rib cage asymmetry in idiopathic scoliosis.

Seventy-one patients attending a scoliosis clinic and 10 control subjects were studied by a stereoradiographic three-dimensional reconstruction of the spine and rib cage. The symmetry of each rib pair (at each anatomic level) was described by measurements of rib arc length, chord length, enclosed area, maximum curvature, and frontal and lateral angulations. Patients were divided into four groups: 19 with a single right thoracic curve, 15 with a single left lumbar or thoracolumbar curve, 22 with double curves, and 15 with a curve with less than 10 degrees Cobb angle. In the control group and the group with minimal scoliosis, there was no statistically significant rib asymmetry. Among the patients with scoliosis, 11 of 19 patients with right single thoracic curves had rib arc lengths greater on the right side at the curve apex, and nine of 15 patients with left lumbar scoliosis had longer ribs on the left side in the corresponding region of the thoracic spine. Eleven of 22 patients with double curves had symmetrical rib lengths (within +/- 3%), the other 11 had ribs longer on the left. These proportions should not have occurred by chance (p less than 0.001). The mean rib length difference in patients with single thoracic curves was 1.39% (right longer than left), in single lumbar curves it was 3.57% (left longer than right), and in double curves 3.18% (left longer than right). These differences between the groups of patients and control subjects were statistically significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Concordance of back surface asymmetry and spine shape in idiopathic scoliosis.

In order to determine why topographic methods have shown a poor correlation with radiographically measured scoliosis in clinical studies, the accuracy of detection of the presence, side, apex, and magnitude of a scoliosis curve was determined topographically (by moiré fringe photography and by projected raster photography) in 104 patients attending a scoliosis clinic. The presence or absence of thoracic curves was correctly shown by the topograms in 77% of cases, and in the lower region (lumbar and thoracolumbar curves) in 79% of cases. For correctly identified curves, the greatest back surface rotation was, on average, 1.0 vertebral levels below the skeletal curve apex in the thoracic region and 0.5 levels below the apex in the lower region. The moiré fringe with the greatest asymmetry occurred on average at 1.5 and 1.8 vertebral levels above the spinal apex in upper and lower regions, respectively. The magnitude of the Cobb angle was determined to within +/- 5 degrees in 24% of cases by moiré measurements, and in 27% by the raster technique. The side of the scoliosis was incorrectly diagnosed by topography in ten patients with minimal or 'nonstandard' vertebral rotation. It was concluded that the presence, level, and side of a scoliosis curvature is well demonstrated by back surface topography in patients with 'standard' rotation, but the magnitude of the scoliosis cannot be determined from topograms sufficiently accurately for most clinical purposes.

Pediatric orthopedic surgery during the residency--too much, too little?

Questionnaires sent to chairpersons of orthopedic surgery residency programs and to private practitioners were analyzed to determine how training in children's orthopedics is accomplished, to define which procedures should be taught to residents, and to describe what the private practitioner perceives as appropriate education in children's orthopedics. The amount of time spent on children's orthopedics is adequate by present standards. For most procedures, the residency directors and private practitioners were in agreement concerning what was appropriate to teach. Education during the residency continues to be the most important resource used by the practicing orthopedic surgeon in pediatric problems.