bluuebunny/crossref_metadata_2025 huggingface dataset:
Importance of the medial meniscus in the anterior cruciate ligament‐deficient knee
Authors: Allen Christina R. , Wong Eric K. , Livesay Glen A. , Sakane Masataka , Fu Freddie H. , Woo Savio L‐Y.
Published: February 2005

The incidence of meniscal tears in the chronically anterior cruciate ligament‐deficient knee is increased, particularly in the medial menicus because it performs an important function in limiting knee motion. We evaluated the role of the medial meniscus in stabilizing the anterior cruciate ligament‐deficient knee and hypothesized that the resultant force in the meniscus is significantly elevated in the anterior cruciate ligament‐deficient knee. To test this hypothesis, we employed a robotic/universal force‐moment sensor testing system to determine the increase in the resultant force in the human medial meniscus in response to an anterior tibial load following transection of the anterior cruciate ligament. We also measured changes in the kinematics of the knee in multiple degrees of freedom following medial meniscectomy in the anterior cruciate ligament‐deficient knee. In response to a 134‐N anterior tibial load, the resultant force in the medial meniscus of the anterior cruciate ligament‐deficient knee increased significantly compared with that in the meniscus of the intact knee: it increased by a minimum of 10.1 N (52%) at full knee extension to a maximum of 50.2 N (197%) at 60° of flexion. Medial meniscectomy in the anterior cruciate ligament‐deficient knee also caused a significant increase in anterior tibial translation in response to the anterior tibial load, ranging from an increase of 2.2 mm at full knee extension to 5.8 mm at 60° of flexion. Conversely, coupled internal tibial rotation in response to the load decreased significantly, ranging from a decrease of 2.5° at 15° of knee flexion to 4.7° at 60° of flexion. Our data confirm the hypothesis that the resultant force in the medial meniscus is significantly greater in the anterior cruciate ligament‐deficient knee than in the intact knee when the knee is subjected to anterior tibial loads. This indicates that the demand on the medial meniscus in resisting anterior tibial loads is increased in the anterior cruciate ligament‐deficient knee compared with in the intact knee, suggesting a mechanism for the increased incidence of medial meniscal tears observed in chronically anterior cruciate ligament‐deficient patients. The large changes in kinematics due to medial meniscectomy in the anterior cruciate ligament‐deficient knee confirm the important role of the medial meniscus in controlling knee stability. These findings suggest that the reduction of resultant force in the meniscus may be a further motive for reconstructing the anterior cruciate ligament, with the goal of preserving meniscal integrity.
Osteogenic growth peptide normally stimulated by blood loss and marrow ablation has local and systemic effects on fracture healing in rats
Authors: Brager Michael A. , Patterson Michael J. , Connolly John F. , Nevo Zvi
Published: February 2005

Osteogenic growth peptide, a histone H4‐related, 14‐amino‐acid peptide, is an active mediator of local, as well as systemic, osteogenic activity in response to marrow ablation, trauma, and blood loss. In this study, the effect of exogenous osteogenic growth peptide on the healing of femoral fractures in rats was investigated. A fracture at the midshaft of the femur was created in 50 rats. Half of the rats were injected subcutaneously with 25 ng of osteogenic growth peptide per rat per day for the first 7 days after fracture. Radiographs were taken each week, and the diameter of the callus was measured. The femurs of four animals from each group were harvested 1, 2, 3, and 4 weeks after fracture. Two femurs from each group were sectioned for histologic examination, and two were sectioned for measurement of density and mineral content. Marrow was aspirated from the contralateral femurs to establish adhering cell cultures, which were examined for osteogenicity. At 2 weeks, a large increase in mitogenicity and osteogenicity was seen in the marrow‐derived cultures from the rats treated with osteogenic growth peptide; this increase was sustained through 4 weeks. Extraction of RNA from the contralateral marrow (systemic expression) and callus (local expression) for amplification with reverse transcription‐polymerase chain reaction revealed greater systemic expression of transforming growth factors β1, β2, and β3, fibroblast growth factor‐2, insulin‐like growth factor‐1, and aggrecan throughout the 4 weeks after fracture, whereas types IIA and IIB collagen, link protein, and fibroblast growth factor receptor‐3 had a greater local expression. The specimens treated with osteogenic growth peptide had a stronger expression of transforming growth factor‐β1, both locally and systemically. The average diameter of the callus was greater for the treated rats at all time intervals, and peak diameters were 7.58 mm at 3 weeks for the treated rats and 6.64 mm at 2 weeks and 6.63 mm at 3 weeks for the controls. Histological study revealed an earlier organization and faster healing of the treated fractures, as evidenced by the larger, earlier appearance of cartilaginous soft callus and the more rapid organizaton of bridging trabecular bone. No statistical significance was obtained when these comparisons were made between the groups. These results suggest that osteogenic growth peptide can be used to promote earlier proliferation and differentiation of osteogenic cells in marrow and bone‐repair callus, possibly through its effect on the transforming growth factor‐β family.
Changes in conduction, blood flow, histology, and neurological status following acute nerve‐stretch injury induced by femoral lengthening
Authors: Jou I‐Ming , Lai Kuo‐An , Shen Chin‐Liang , Yamano Yoshiki
Published: February 2005

The effects of an acute stretch on evoked potential, blood flow, histological change, and clinical neurological state were studied in a rat model of acute nerve stretch induced by femoral lengthening. The purposes of this study were to assess, in a model of acute limb lengthening, the safe limits of nerve stretch for nerve function, the pathogenesis of nerve dysfunction, the sensitivity of spinal somatosensory evoked potential, and one of the proposed criteria for irreversible compromise of the sciatic nerve. Thirty‐two rats were assigned to one of four groups defined by the degree of acute femoral lengthening (8, 16, 24, and 32%). Spinal somatosensory evoked potential at L5/6 following stimulation of the sciatic nerve was recorded before, immediately after, and 30 minutes after lengthening. Sciatic nerve blood flow was measured by laser Doppler flowmetry at the stretched site before and after lengthening. One week after the operation and without further lengthening, clinical neurological status was evaluated by the functional index of the sciatic nerve and histological examination was performed. At the measurement immediately after the procedure, amplitude changed significantly in all groups except for the group with 8% lengthening. In all groups, sciatic nerve blood flow also dropped significantly compared with values for the control side. Moreover, a greater percentage increase in acute lengthening corresponded with more marked changes in spinal somatosensory evoked potential and sciatic nerve blood flow. The groups that underwent acute lengthening of 24 and 32% had significant neurological deficits and histological changes and demonstrated a significant and profound (50%) drop in amplitude and blood flow. We concluded that spinal somatosensory evoked potential is very sensitive and may serve as an effective tool for the early detection of impending acute nerve‐stretch injury and that a 50% reduction in amplitude indicates irreversible damage.
Titanium particles inhibit osteoblast adhesion to fibronectin‐coated substrates
Authors: Kwon Soon Yong , Takei Hiroshi , Pioletti Dominique P. , Lin Tong , Ma Qing Jun , Akeson Wayne H. , Wood Douglas J. , Paul Sung K‐L.
Published: February 2005

To illuminate the effect of titanium particles on osteoblast function, we compared the adhesion force of neonatal rat calvarial osteoblasts on fibronection‐coated glass after incubation with titanium particles (80% had diameters of less than 5 μm). The cells were incubated with the particles for 1.5–72 hours. Using a micropipette single‐cell manipulation system, we showed that the adhesion force of the osteoblasts to fibronectin‐coated glass (1.0 μg/ml) was significantly affected by the presence of particulate debris. The adhesion force of the cells incubated with titanium particles for less than 4 hours was not significantly affected by exposure to the particles; after 4 hours, however, it was significantly reduced relative to that of controls. Aspiration of particle‐challenged osteoblasts into the micropipette demonstrated that the particles were not stripped from the cell surface and therefore confirmed that the osteoblasts had ingested them. During aspiration, the particles traveled through the cytoplasm rather than on the cell surface. When the osteoblasts were exposed to the particles and cytochalasin D, they exhibited much lower adhesion forces than did the controls or the cells exposed to titanium particles only; this indicates and important role of actin filaments in the osteoblastic response to particles. Staining for F‐actin also indicated an influence of internalized titanium particulate on cytoskeletal arrangement and cell spreading. Furthermore, with standard Northern blotting techniques, levels of mRNA for collagen type I and fibronectin were significantly reduced as early as 4 hours after exposure to particles compared with levels in controls, and this effect continued to 72 hours. These data indicate that direct exposure of osteoblasts to titanium particles, which we propose to be ingested by the osteoblasts, can significantly decrease osteoblast adhesion force; this may lead to decreased cellular activity and gene expression of fibronectin and collagen type I in the presence of titanium wear debris.
Expression of mRNA for vascular endothelial growth factor at the repair site of healing canine flexor tendon
Authors: Bidder Miri , Towler Dwight A. , Gelberman Richard H. , Boyer Martin I.
Published: February 2005

Neovascularization is an important and prominent feature of tendon healing that contributes to wound repair and potentially to adhesion formation. To define the location of cell populations that recruit and organize the angiogenic response during early healing of flexor tendon, we examined the gene expression pattern of the prototypic angiogenic factor, vascular endothelial growth factor, at and around the tenorrhaphy site in a canine mode! of flexor tendon repair. In situ hybridization with radiolabeled antisense riboprobes was used to identify tendon cell populations that contribute to the neovascularization process by expressing vascular endothelial growth factor and to relate this cell population to the previously described cell populations that participate in matrix synthesis (express type α1(I) collagen) and mitotic renewal (express histone H4). The majority of cells (∼67%) within the repair site itself express vascular endothelial growth factor mRNA: however, minimal levels accumulate within cells of the epitenon (∼10% of cells; p <0.0002). By contrast, expression of type α1(I) collagen and histone H4 does not differ significantly between the epitenon and the repair site (uniformly ∼30% of cells). Thus, a gradient of cell populations expressing vascular endothelial growth factor exists in the repairing tendon. These data suggest a potential contribution of cells with the repair site to the organization of angiogenesis during the early postoperative phase of tendon healing.
Met oncogene aberrant expression in canine osteosarcoma
Authors: Ferracini R. , Angelini P. , Cagliero E. , Linari A. , Martano M. , Wunder J. , Buracco P.
Published: February 2005

The objective of this study was to investigate the role of the MET oncogene in canine osteosarcoma. Seven large‐breed dogs affected by spontaneous skeletal osteosarcoma underwenten bloctumor excision. Total RNA was extracted from frozen tumor samples and assessed for expression of the MET oncogene by Northern blot analysis. Five of seven biopsy samples expressed high levels of the MET oncogene: its expression in the primary tumors was comparable with that previously identified in primary osteosarcomas in humans. A lung metastasis from one of the dogs expressed MET at a higher level than did its primary tumor. Spontaneously arising osteosarcoma in dogs clinically and pathologically mimics the corresponding disease in humans. We previously demonstrated that the MET oncogene was aberrantly expressed in a high percentage of human osteosarcomas. The results of the current study also provide a molecular parallel between the tumors in dogs and humans. Thisin vivomodel may be helpful in evaluating new strategies for therapy against osteosarcoma.
Ability of osteoclast formation from peripheral monocytes using anti‐fusion regulatory protein‐1/cd98/4f2 monoclonal antibodies in patients with osteoporosis
Authors: Tajima Masatoshi , Higuchi Yasumitsu , Miyamoto Noriki , Higuchi Shigeomi , Ito Morihiro , Tsurudome Masato , Sudo Akihiro , Ito Yasuhiko , Uchida Atsumasa
Published: February 2005

We investigated the difference in osteoclast formation between patients with osteoporosis and two healthy control groups by inducing it from peripheral blood monocytes with use of anti‐fusion regulatory protein‐1 monoclonal antibody. The group of patients with osteoporosis consisted of 35 women and excluded secondary osteoporosis, and the control groups consisted of 12 young healthy volunteers (control I) or 10 individuals age‐matched to the patients with osteoporosis (control II). Osteoclast formation declined with age between the two control groups, but this decline was not significant. Fusion rate and the mean number of nuclei in osteoclasts were significantly less in the patients with osteoporosis than in the young or agematched controls. It was clearly demonstrated that the ability of monocytes to fuse declines significantly in patients with osteoporosis.
Tibial plateau fracture as a measure of early estrogen‐dependent bone fragility in rats
Authors: Lotz J. C. , Kroeber M. W. , Heilmann M. , Pericherla K. , Kimmel D. , Kinney J. H. , Lane N. E.
Published: February 2005

The goals of this study were to develop a protocol to induce a compressive fracture at the tibial plateau of the rat knee in vitro and to determine if the biomechanical parameters provided a sensitive assessment of the early skeletal changes induced by estrogen deficiency. Sixty‐one rats underwent an ovariectomy (n = 36) or sham operation (n = 25) and were maintained for 50 days after the procedure. Just before death, the proximal tibia of each animal was scanned with high‐resolution x‐ray tomography. From the three‐dimensional images, the mean trabecular bone volume, thickness, and separation and the number of trabeculae were calculated. The knees were then harvested and mounted into a servohydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture. The fracture load of the ovariectomized rats was 24% less than that of the rats that had the sham operation. Similarly, the structural stiffness of the ovariectomized knees was decreased by 22%. Both of these differences were statistically significant (p < 0.01) and were explained by differences in trabecular bone volume (r = 0.56, p < 0.0001 and r = 0.42, p < 0.005, respectively). The other measures of trabecular bone structure were correlated with the volume and did not improve the prediction by the biomechanical parameters. These data demonstrate that biomechanical testing of the tibial plateau in rats can quantify the structural consequences of estrogen deficiency at an early time point before they become apparent at other bone sites, such as the lumbar spine.
Chondrocyte‐specific Enhancer Regions in the COMP Gene
Authors: Issack Paul S. , Fang Carrie , Leslie Michael P. , Di Cesare Paul E.
Published: February 2005

The molecular events governing the differentiation of mesenchymal cells into chondrocytes and the expression of cartilage marker genes are poorly understood. Cartilage oligomeric matrix protein is a non collagenous extracellular matrix protein with a relatively cartilage‐specific spatial and temporal expression pattern. To understand the mechanisms controlling chondrocyte‐specific expression of cartilage oligomeric matrix protein, we cloned 1.9 kb of the 5′ flanking promoter sequence of the murine cartilage oligomeric matrix protein gene and identified two spatially distant cartilage‐specific enhancer regions by deletion analysis. One element is situated proximally (proximal positive element: −125 to −75) and a second region is located distally (distal positive region: −1925 to −592) relative to the transcription start site. Interestingly, nucleotides within the proximal positive element are conserved between the mouse and human promoters and resemble consensus sites for the binding of members of the high mobility group class of transcription factors. Defining cartilage‐specific regulatory elements in the cartilage oligomeric matrix protein promoter may provide useful molecular probes for identifying transcription factors that control acquisition of the chondrocytic phenotype.
Cell attachment, collagen binding, and receptor analysis on bovine articular chondrocytes
Authors: Reid David L. , Aydelotte Margaret B. , Mollenhauer Jurgen
Published: February 2005

The purpose of this study was to investigate collagen receptors on primary bovine articular chondrocytes from full‐thickness and different layers of bovine articular cartilage. Cytometric studies with antibodies showed that approximately 56% of the chondrocytes from the superficial layer and 29% of the chondrocytes from the deep layer bound anti‐annexin V. A similar tendency was found for α and β1 integrin antibodies. Flow cytometric analysis initially detected annexin V on chondrocytes following isolation; the level of detection subsequently decreased by 24 hours, whereas that of α5 and β1 integrins increased. Treatment of chondrocytes with collagenase at 24 hours restored the initially high epitope recognition of annexin V, indicating masking of annexin V by newly formed collagen matrix. There was little effect on detection levels for β1 integrin. Contrary to the specific matrix receptor expression, chondrocytes from superficial and deep layers differed little in attachment to immobilized types I and II collagens. However, the attachment was more effectively inhibited with anti‐annexin V than with integrin antibodies. Competition studies with preparations of soluble collagens revealed a preferential binding of bovine type‐II collagen compared with bovine type‐I collagen. Anti‐annexin V antibodies inhibited binding of type‐II collagen more effectively than anti‐α5 or anti‐β1 integrin antibodies. Evidently, under the in vitro conditions of this study, annexin V is the quantitatively predominant type‐II collagen receptor on bovine articular chondrocytes. This opens a discussion of the possibly dualistic metabolic/mechanical annexin V‐integrin receptor elements.
Biomechanical investigations on chondromalacia of the knee after meniscal flap lesion and partial meniscal resection: An experimental model
Authors: Grifka Joachim K. , Kalteis Thomas , Broll‐Zeitvogel Eliane , Philippou Stathis , Plitz Wolfgang
Published: February 2005

Meniscal tears and resections may cause chondral lesions of the knee. To eliminate muscular control during investigation of this problem, we designed a biomechanical setup based on a knee‐joint simulator, ensuring physiological, free‐motion mobility of the joint. Fresh human knee specimens with intact cartilage were exposed to loads to 2.000 N at a frequency of 0.85 Hz during 48 hours of gait. After a preliminary test series. 18 specimens were divided into three groups: group I was tested with unchanged meniscal status, group II with arthroscopically induced mobile flap tears at the posterior horns of the menisci, and group III after partial resection of the posterior horns. Motion patterns between the groups changed after as little as a few hours due to increased translation in group III. Macroscopic and histological examination and scanning electron microscopy revealed severe chondromalacic changes after meniscal resection. We conclude that meniscal resection—however partial—may have considerable joint‐damaging potential if muscle control is lacking whereas mobile flap tears maintain stability. Our findings might explain the differences in clinical reports on cartilage status after partial meniscal resection. This study underlines the importance of muscle training when active stabilisation of the knee is reduced after partial meniscal resection.
Effect of freeze‐drying and gamma irradiation on the mechanical properties of human cancellous bone
Authors: Cornu O. , Banse X. , Docquier P. L. , Luyckx S. , Delloye Ch.
Published: February 2005

Freeze‐drying and gamma irradiation are commonly used for preservation and sterilization in bone banking. The cumulative effects of preparation and sterilization of cancellous graft material have not been adequately studied, despite the clinical importance of graft material in orthopaedic surgery. Taking benefit from the symmetry of the left and right femoral heads, the influence of lipid extraction followed by freeze‐drying of a femoral head and a final 25‐kGy gamma irradiation was determined, with the nonirradiated, nonprocessed counterpart as the control. Five hundred and fifty‐six compression tests were performed (137 pairs for the first treatment and 141 pairs for the second). Mechanical tests were performed after 30 minutes of rehydration in saline solution. Freeze‐dried femoral heads that had undergone lipid extraction experienced reductions of 18.9 and 20.2% in ultimate strength and stiffness, respectively. Unexpectedly, the work to failure did not decrease after this treatment. The addition of gamma irradiation resulted in a mean drop of 42.5% in ultimate strength. Stiffness of the processed bone was not modified by the final irradiation, with an insignificant drop of 24%, whereas work to failure was reduced by a mean of 71.8%. Freeze‐dried bone was a bit less strong and stiff than its frozen control. Its work to failure was not reduced, due to more deformation in the nonlinear domain, and it was not brittle after 30 minutes of rehydration. Final irradiation of the freeze‐dried bone weakened its mechanical resistance, namely by the loss of its capacity to absorb the energy (in a plastic way) and a subsequent greater brittleness.
Multidrug resistance‐1 gene expression does not increase during tumor progression in the MGH‐OGS murine osteosarcoma tumor model
Authors: Trammell Rita A. , Johnson Clifford B. , Barker John R. , Bell Robert S. , Allan D. Gordon
Published: February 2005

In addition to its possible role in drug resistance, expression of the multidrug resistance‐1 gene may also be associated with a more malignant phenotype and tumor progression. This study evaluated its expression during tumor progression in the MGH‐OGS transplantable murine osteosarcoma tumor model. Three variables of tumor progression were analyzed: tumor size, local recurrence, and metastasis. With a highly sensitive reverse transcription‐polymerase chain reaction method, mRNA levels of multidrug resistance‐1 were compared in primary tumors of different sizes. In addition, the levels were compared in primary, locally recurrent, and metastatic tumors isolated from individual mice. No significant difference was found in the levels of expression with increasing primary tumor size. In addition, the levels in primary, locally recurrent, and metastatic tumors were not significantly different. Our results indicate that—at least in the MGH‐OGS tumor model, which is analogous to the majority of spontaneously occurring human osteosarcomas in that it has low levels of multidrug resistance‐1/P‐glycoprotein and is sensitive to doxorubicin—there is no evidence of upregulation of multidrug resistance‐1 expression during tumor progression.
Mechanical behavior of two hamstring graft constructs for reconstruction of the anterior cruciate ligament
Authors: Höher Jürgen , Scheffler Sven U. , Withrow John D. , Livesay Glen A. , Debski Richard E. , Fu Freddie H. , Woo Savio L‐Y.
Published: February 2005

We compared the mechanical behavior of two common hamstring graft constructs that are frequently used for reconstruction of the anterior cruciate ligament—Graft A: quadrupled semitendinosus tendon fixed with titanium button/polyester tape and suture/screw post, and Graft B: a double semitendinosus and double gracilis tendon fixed with a cross pin and two screws over washers. The experimental protocol used to evaluate each graft construct included stress relaxation (with and without preconditioning), cyclic loading, and a tensile load‐to‐failure test. The amount of stress relaxation without preconditioning was 60.6% for Graft A and 53.8% for Graft B. With preconditioning, it significantly decreased (p < 0.05) to 48.7 and 42.3%. respectively. Elongation of the graft construct in response to 100 cycles of loading (20–150 N) was 1.8 and 0.6% of the original length for Grafts A and B. respectively. However, after a series of five cyclic loading tests, the residual permanent elongation for each construct was 3.8 ± 1.2 and 0.3 ± 0.2 mm, a significant difference (p < 0.05) between the two graft constructs. Further analysis found more than 90% of the permanent elongation in the proximal and distal regions of Graft A, which consisted of polyester tape tied to a titanium button (proximal) and sutures tied around a screw post (distal). The tensile load‐to‐failure tests also revealed significant differences (p < 0.05) between the two graft constructs. Linear stiffness was 32 ± 1 and 119 ± 19 Nmm and ultimate load was 415 ± 36 and 658 ± 128 N for Grafts A and B, respectively. For Graft A, the polyester tape consistently failed; for Graft B, slippage or tearing from the washers was the mode of failure. We conclude that a quadruple‐hamstring graft fixed over a cross pin proximally and with metal washers distally (Graft B) has less permanent elongation in response to cyclic loading and has structural properties superior to those of a graft construct that includes suture and tape material (Graft A). The large permanent elongation following repetitive loading of a graft construct with tape and suture material during the early postoperative period is of concern.
The pentapeptide NKISK affects collagen fibril interactions in a vertebrate tissue
Authors: Dahners Laurence E. , Lester Gayle E. , Caprise Peter
Published: February 2005

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).
Insulin‐like growth factor‐I is expressed by avian flexor tendon cells
Authors: Tsuzaki Mari , Brigman Brian E. , Yamamoto Juro , Lawrence W. Thomas , Simmons James G. , Mohapatra Nirupama K. , Lund P. Kay , Van Wyk Judson , Hannafin Jo A. , Bhargava Madhu M. , Banes Albert J.
Published: February 2005

Cells in normal tendon are in a resting G0 state, performing maintenance functions. However, traumatic injury introduces growth factors such as platelet‐derived growth factor and insulin‐like growth factor from blood as well as activates endogenous growth factors. These factors stimulate migration and proliferation of tendon cells at the wound area. Tendon cells require growth‐promoting factors to transit the cell cycle. To evaluate the contribution of endogenous growth factors in tendon, extracts of the epitenon and internal compartment of avian flexor tendon as well as medium of cultured cells from the epitenon (tendon surface cells) and internal tendon (tendon internal fibroblasts) were collected to assess their ability to stimulate DNA synthesis. Acid‐ethanol extracts of tissues and medium were chromatographed on a P‐30 molecular sieve column and assayed for mitogenic activity by quantitating [3H]thymidine incorporation into tendon cell DNA. The extract from the internal tendon compartment was more stimulatory for DNA synthesis than that from the epitenon, particularly when tested on tendon internal fibroblasts. However, conditioned medium fractions from surface epitenon cells stimulated DNA synthesis to a high degree on both tendon surface cells and tendon internal fibroblasts. Conditioned medium from tendon internal fibroblasts was also stimulatory. An anti‐insulin‐like growth factor‐I antibody ablated most of the mitogenic activity present in both tissues and conditioned medium. The levels of acid‐extractable insulin‐like growth factor‐I in tendon were determined by competitive radioimmunoassay as 1.48 ± 0.05 ng/g tissue for the epitenon and 3.83 ± 0.03 ng/g tissue for the internal compartment. Results of Western immunoblots of conditioned medium revealed insulin‐like growth factor‐I at the 7.5 kDa position. Cultured tendon surface cells and tendon internal fibroblasts as well as cells in intact flexor tendon expressed insulin‐like growth factor‐I mRNA detected by reverse transcriptase‐polymerase chain reaction. In situ hybridization histochemistry positively identified insulin‐like growth factor‐I mRNA in tendons from 52‐day‐old chickens. Platelet‐derived growth factor was not detected at the protein or message levels. Furthermore, tendon surface cells and tendon internal fibroblasts both expressed receptors for insulin‐like growth factor‐I detected by flow cytometry. These data suggest that tendon cells express insulin‐like growth factor‐I mRNA and synthesize insulin‐like growth factor‐I in both the epitenon and the internal compartment of tendon, which is present in an inactive from, most likely bound to insulin‐like growth factor‐binding proteins.
Ultrastructural findings after intraarticular application of hyaluronan in a canine model of arthropathy
Authors: Wenz W. , Breusch S. J. , Graf J. , Stratmann U.
Published: February 2005

We investigated the effect of intraarticularly applied hyaluronic acid (hyaluronan) on the cartilaginous structure of experimentally induced chondromalacia patellae in dogs. For the induction of chondromalacia, we used the Pond‐Nuki technique, which involved severance and resection of the anterior cruciate ligament, as a canine model of arthropathy in 27 foxhounds (three groups of nine animals each). In a pilot study, we evaluated the effect of resection of the anterior cruciate ligament with no therapy. Patellar specimens were retrieved at 3, 6, and 12 weeks postoperatively. Subsequently, we compared a treatment group that received intraarticular injections of hyaluronan with a placebo group that received saline solution. The groups were compared at 3, 6, and 12 weeks postoperatively. Three animals from the treatment and placebo groups received five injections of hyaluronan during one of the 4‐week intervals (weeks 3–6, 6–9, or 12–15). Specimens were retrieved 5 weeks after the last injection. In both groups, the uninvolved contralateral knee served as a control. The specimens were taken from the medial and lateral patellar poles. Histological analysis included light microscopy and transmission electron microscopy. The structural and ultrastructural changes were assessed qualitatively and were quantified with use of a modified Mankin score. Our results indicate that chondromalacia patellae may be induced with the Pond‐Nuki technique. We found a significant reduction (p < 0.01) of cartilaginous lesions in the hyaluronan group compared with the placebo group. Our results suggest that intraarticularly applied hyaluronan is effective in delaying the degenerative process of cartilage degradation. Therefore, we conclude that the use of hyaluronan may be indicated during the early stages of chondromalacia.
Effect of in vitro testing over extended periods on the low‐load mechanical behaviour of dense connective tissues
Authors: King Graham J. W. , Pillon Corrie L. , Johnson James A.
Published: February 2005

Many biomechanical studies are performed on dense connective tissues in the laboratory over a substantial time period; however, the effect of the in vitro testing environment on the cyclic load‐relaxation behaviour of these structures is not well established. This study evaluated the effect of long duration of testing on ligament viscoelastic behaviour, using the rabbit femur‐medial collateral ligament‐tibia complex as a model. Dissected rabbit knee joints were mounted on a materials testing machine, and isolated ligament complexes were cycled at a frequency of one cycle/min to a fixed displacement of 0.7 mm for an 18‐hour period. After an initial period of exponential load relaxation, the cyclic peak loads slowly decreased over the 18‐hour period. The average decrease in the cyclic peak load between 0.5 and 18.0 hours was 0.26% (of the original peak load) per hour (r2 = 0.934), or a total of 8.6 ± 4.6% over this period (p < 0.0001). Thus, lowload testing of dense connective tissues in the laboratory over extended periods significantly alters their biomechanical behaviour, and these changes should be considered in long‐term laboratory‐based studies of dense connective tissues.
Comparison of biomechanical and biochemical properties of cartilage from human knee and ankle pairs
Authors: Treppo Steven , Koepp Holger , Quan Emerson C. , Cole Ada A. , Kuettner Klaus E. , Grodzinsky Alan J.
Published: February 2005

Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale and the histological Mankin scale. Cylindrical disks of cartilage were harvested from 10 sites within the tibiofemoral and femoropatellar joint surfaces and four sites within the talocrural joint, and uniaxial confined compression measurements were performed to quantify a spectrum of physical properties including the equilibrium modulus, hydraulic permeability, dynamic stiffness, streaming potential, electrokinetic coupling coefficient, and electrical conductivity. Matched specimens from the same 14 sites were used for complementary measurements of biochemical composition and molecular interaction, including water content, hypotonic swelling behavior, and sulfated glycosaminoglycan and collagen contents. In comparison of the top 1‐mm slices of talar cartilage with the top 1‐mm of tibiofemoral cartilage, the talar cartilage appeared denser with a higher sulfated glycosaminoglycan content, lower water content, higher equilibrium modulus and dynamic stiffness, and lower hydraulic permeability. The equilibrium modulus increased with increasing sulfated glycosaminoglycans per wet weight and decreased with increasing water content for all joint surfaces. Multiple linear regression showed that greater than 80% of the variation in the equilibrium modulus could be accounted for by variations in the biochemical parameters (water content, sulfated glycosaminoglycans/wet weight, and hydroxyproline content/wet weight) for each joint surface. Nonhomogeneous depth‐dependent changes in the physical properties and biochemical composition of full‐thickness distal femoral cartilage were consistent with previous reports. Since the compressive deformation of cartilage during cyclic loading is confined to the more superficial regions, the differences in properties of the upper regions of the talar compared with tibiofemoral or femoropatellar cartilage may be important in the etiology of osteoarthritis.
Disc degeneration and bone density in monozygotic twins discordant for insulin‐dependent diabetes mellitus
Authors: Videman T. , Battié M. C. , Gibbons L. E. , Kaprio J. , Koskenvuo M. , Kannus P. , Raininko R. , Manninen H.
Published: February 2005

The effects of insulin‐dependent diabetes mellitus on bone density and connective tissue degeneration have theoretical interest and practical relevance. Several experimental studies in animals have demonstrated the harmful effects of insulin deficiency on connective tissues. However, clinical studies in humans have produced somewhat contradictory results, most likely due to difficulties controlling for general degeneration and factors associated with diabetes. In nine pairs of monozygotic twins discordant for insulin‐dependent diabetes mellitus, we compared femoral and lumbar bone mineral density (assessed by dualenergy x‐ray absorptiometry) and spinal degeneration (assessed by magnetic resonance imaging). The bone densities were, on average, 0.1–0.3% lower (p = 0.87–0.96) in diabetic patients. However, after controlling for smoking, we found that the bone density in the femoral neck was 2.5% (0.025 g/cm2) lower in diabetic individuals than in their twins (p = 0.09). The five magnetic resonance imaging parameters used to evaluate discdegeneration did not differ between diabetic patients and their twins. In conclusion, our results provide no evidence that insulin‐dependent diabetes mellitus has any major effect on bone density or disc degeneration.
Radiographic determinants of the elbow rotation axis: Experimental identification and quantitative validation
Authors: Bottlang M. , O'Rourke M. R. , Madey S. M. , Steyers C. M. , Marsh J. L. , Brown T. D.
Published: February 2005

This study identifies new radiographic indices to approximate the location of the elbow rotational axis. With use of electromagnetic motion tracking source data, the average rotational axis of the ulnohumeral articulation was calculated in seven cadaveric specimens. Quasi‐lateral radiographs of the elbow specimens were then analyzed to identify radiographic landmarks of the elbow axis in the lateral view. The spatial relationships of these landmarks with the elbow aligned on‐axis were contrasted with their relationships in eight distinct off‐axis alignments. Elbow axis orientation in the transverse plane (internal/external rotation) was identified by the location of a dense intramedullary cortical line, appearing in the projection of the distal humerus in relation to the periosteal surface of the posterior cortex of the humerus. This intramedullary line corresponds to the posteromedial cortex of the distal humerus. Correct alignment occurred when this line laid 27.1 ± 3.7% of the anteroposterior humeral diameter anterior from the periosteal surface of the posterior cortex. Axis orientation in the coronal plane (abduction/adduction) was identified by the concentric appearance of radiographic arcs formed by the capitellum, trochlear sulcus, and medial trochlear flange. Using these radiographic indices, three orthopaedic surgeons were able to fluoroscopically align the elbow along the axis of rotation with an accuracy of 3.7 ± 1.8°. These results are immediately applicable to fluoroscopic identification of the elbow axis. This technique can be used to increase the accuracy of hinge placement during application of hinged external fixation or distraction arthroplasty.
Structural properties of the subscapularis tendon
Authors: Halder A. , Zobitz M. E. , Schultz F. , An K. N.
Published: February 2005

The subscapularis muscle is an important mover and stabilizer of the glenohumeral joint. The purpose of this study was to measure regional variations in the structural properties of the subscapularis tendon in two joint positions. Subscapularis tendons from cadaveric shoulders were divided into four sections superiorly to inferiorly and tested to failure at 0 or 60° of glenohumeral abduction. Arm position had a significant influence on stiffness in the inferior and superior portions (p < 0.05). The inferior region showed a higher stiffness in the hanging‐arm position (0°) than at 60° of abduction (27.4 ± 17.7 compared with 9.5 ± 5.9 N/mm). Meanwhile, stiffness of the superior portion was higher at 60° of abduction than in the hanging‐arm position (208.7 ± 60.9 compared with 147.2 ± 32.3 N/mm). In the hanging‐arm position (0°) and at 60° of abduction, the superior and midsuperior portions failed at significantly higher loads (superior: 623.2 ± 198.6 and 478.2 ± 206.6 N at 0 and 60° of abduction, respectively; midsuperior: 706.2 ± 164.6 and 598.4 ± 268.4 N, respectively) than did the inferior portion (75.1 ± 54.2 and 30.3 ± 13.0 N, respectively). Likewise, stiffness of the superior and midsuperior portions was significantly higher than that of the inferior region in both positions. Higher stiffness and ultimate load in the superior tendon region may explain the infrequent extension of rotator cuff tears into the subscapularis tendon. Conversely, the significantly lower ultimate load and stiffness in the inferior tendon region could facilitate anterior dislocation of the humeral head when this portion stabilizes the joint in a dislocated position. Therefore, repair of torn inferior portions of the subscapularis tendon should be considered in surgery for glenohumeral instability.
Equivalence of single and incremental subfailure stretches of rabbit anterior cruciate ligament
Authors: Panjabi Manohar M. , Huang Russel C. , Cholewicki Jacek
Published: February 2005

Experimental models are often used in the laboratory to produce incomplete soft‐tissue injuries simulating those observed clinically. Single and incremental stretch protocols have been utilized. The latter has many advantages over the former. This study was designed to determine if incremental and single ligamentous stretches are biomechanically equivalent. Eleven paired fresh rabbit bone‐anterior cruciate ligamentbone preparations were used. One of each pair (single‐stretch protocol) was stretched to 88% of the average failure deformation and then stretched to failure. The other ligament (incremental‐stretch protocol) was stretched to 55, 66, 77, and 88% of the average failure deformation and then stretched to failure. All stretches were performed at 1.2 m/sec. Stress‐relaxation tests were performed before and after the 88% stretch for both stretch protocols. Relaxation curves were parameterized as forces at six time points and were also fitted to a three‐element model. Load‐deformation curves recorded during stretch to failure were characterized by eight parameters. Each incremental stretch step produced a significant increase in deformation, indicating alteration in the mechanical properties of the ligament. Both groups of ligaments, when intact, exhibited no differences in relaxation curves (p > 0.2). The 88% stretches, produced by each of the two stretch protocols, significantly altered the viscoelastic behavior of the ligaments (p < 0.002). However, after the 88% stretch, there were no differences in either viscoelastic (p > 0.1) or load‐deformation (p > 0.1) paramters of the two stretch protocols. In conclusion, the 88% subfailure stretch significantly altered the mechanical properties of ligament, and the incremental and single stretches were biomechanically equivalent.
In vivo kinematics of total knee arthroplasty: Flat compared with concave tibial joint surface
Authors: Uvehammer J. , Kärrholm J. , Brandsson S. , Herberts P. , Carlsson L. , Karlsson J. , Regnér L.
Published: February 2005

This study evaluated the influence of the geometric configuration of the tibial joint area on the kinematics of the knee. Twenty‐two patients with noninflammatory arthritis and minor preoperative deformity were studied. They each received an AMK total knee replacement with retention of the posterior cruciate ligament. Eleven patients without any knee abnormalities were used as controls. The patients were stratified to either the flat (terminology of the manufacturer: standard) or concave (terminology of the manufacturer: constrained) polyethylene insert (n = 11 in each group). Knee kinematics were assessed 1 year after the operation by having the patient ascend a platform corresponding to an extension of the knee from 50 to 70° of flexion. During this motion, two film‐exchangers simultaneously exposed six to 13 pairs of serial stereoradiographs. The concave geometric configuration of the tibial insert resulted paradoxically in increased anterior‐posterior translations compared with the flat insect but no significant change of rotations and translations in the other directions. Compared with normal knees, the most obvious abnormality was increased anterior‐posterior translations (p < 0.004). At 50° of flexion, the implants with the flat tibial polyethylene insert had displaced 2 times and the concave ones had displaced 2.5 times more posteriorly than the normal knees (p ⩽ 0.001). Less internal tibial rotation was also recorded in the flexed positions for both types of inserts compared with the normal knees (p < 0.02). Four knees in four patients, who reported symptoms of instability and abnormal knee function, showed significantly increased proximal displacement of the center of the tibial plateau in the flexed position. The findings suggest that current prosthetic designs and surgical technique do not restore normal knee kinematics and indicate that design improvements should rely on in vivo kinematic studies.