bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional recovery following neurorrhaphy of the rat sciatic nerve by epineurial repair compared with tubulization
Authors: Meyer R. Scott , Abrams Reid A. , Botte Michael J. , Davey Joseph P. , Bodine‐Fowler Sue C.
Published: February 2005

Recovery of motor function is often poor following transection injuries to peripheral nerves. The purpose of this study was to measure and compare functional recovery of the sciatic nerve in the rat following transection and neurorrhaphy with the use of a nerve guide tube and with traditional end‐to‐end epineurial repair. Muscle recovery was also evaluated following a crush injury, a model of an axonotmetic lesion. Recovery was assessed at 8, 16, and 32 weeks after injury by measuring the isometric contractile properties of the soleus muscle and at 8 and 16 weeks by measuring the conduction properties of the sciatic nerve. The mean conduction velocity of the sciatic nerve in the crush group and both transection groups was significantly slower than that of controls at both 8 and 16 weeks. Following a transection injury, the soleus became, significantly faster muscle as measured by time to peak twitch tension. By 32 weeks, the maximum isometric tension of the soleus muscle recovered to 90% that of the control group following a crush injury and to less than 70% following a trensection injury and repair. Recovery was better in the epineurial repair group than in the tube repair group at 8 weeks, but no difference was found between the groups at 16 or 32 weeks. These, results demonstrate that nerve guide tubes are a potential alternative to epineurial repair. The poor motor recovery following repair of transection injuries may be related to poor specificity of reinnervation.
Method of histomorphometric assessment of glycosaminoglycans in articular cartilage
Authors: Shimizu Choji , Coutts Richard D. , Healey Robert M. , Kubo Toshikazu , Hirasawa Yasusuke , Amiel David
Published: February 2005

A method of image analysis has been developed for use in the semiquantitative histomorphometric assessment of glycosaminoglycans in articular cartilage stained with safranin O. The reliability of the methodology is reported along with its application to the assessment of articular cartilage in a model of osteoarthritis, i.e., transection of the anterior cruciate ligament in rabbits. With this system, specimens of normal and osteoarthritic articular cartilage were assessed histomorphometrically for the following parameters: total cartilage area, percentage of safranin O stained area, mean gray scale (average stain intensity), and gray scale index (the relative total amount of glycosaminoglycans). Reproducibility was established for 12 specimens of normal cartilage and found to have a SD of less than 8% of the mean for each parameter that was measured. Image analysis of osteoarthritic cartilage revealed each of the parameters, except for average stain intensity, to be significantly lower than that in control cartilage.
Changes in the expression of type‐X collagen in the fibrocartilage of rat Achilles tendon attachment during development
Authors: Fujioka Hiroyuki , Wang Gwo‐Jaw , Mizuno Kosaku , Balian Gary , Hurwitz Shepard R.
Published: February 2005

This study histologically and immunohistochemically demonstrated developmental changes in cell morphology and expression of type‐X collagen in the attachment of the Achilles tendon to the calcaneus in the rat. Although the site of attachment in the mature rat showed a well organized, direct insertion that was composed of tendon, fibrocartilage, calcified fibrocartilage, and bone, this four‐zone structure was not observed in the immature 1‐week‐old rat. Formation of fibrocartilage was observed at 2 weeks, together with the hypertrophy of chondrocytes and the appearance of the secondary center of ossification. Type‐X collagen was not detected either in chondrocytes in the attachment area at 1 week or in hypertrophic chondrocytes at the attachment at 2 weeks. In the 3‐week‐old rat, the secondary center of ossification extended to the area of attachment and type‐X, collagen was detected both in cartilage spicules within the secondary center of ossification and in cells found at the attachment adjacent to the secondary center of ossification. A four‐zone structure had been established by 6 weeks and remained through 20 weeks. After 6 weeks, type‐X collagen was identified both in the attachment of the tendon and beneath the calcaneal fibrocartilage. Type‐X collagen is produced by cells in transitional zones between calcified and noncalcified tissue, such as the interface between articular cartilage and subchondral bone. In these areas, the expression of this protein persists through maturity and is not transient.
Sequential dynamics of monocyte chemotactic protein‐1 expression in herniated nucleus pulposus resorption
Authors: Haro Hirotaka , Komori Hiromichi , Okawa Atsushi , Murakami Shunichi , Muneta Takeshi , Shinomiya Kenichi
Published: February 2005

We previously demonstrated that the granulation tissues of herniated nucleus pulposus are composed of a marked infiltration of macrophages that strongly express monocyte chemotactic protein‐1. Monocyte chemotactic protein‐1 is a chemotactic cytokine that contributes to the activation and recruitment of macrophages. Relatively little is known about its role in the resorption process of herniated nucleus pulposus. To clarify the sequential dynamics of expression of monocyte chemotactic protein‐1 in the granulation tissues of herniated nucleus pulposus, we introduced a rat autologous transplantation model of nuclear materials onto its lumbar dura mater and performed immunohistological analysis and competitive polymerase chain reaction assay using the grafted samples. Immunohistological analysis demonstrated that the majority of infiltrating mononuclear cells expressed monocyte chemotactic protein‐1. Monocyte chemotactic protein‐1 mRNA was expressed in the first 3 weeks after the procedure and was significantly and maximally upregulated at 1 week. To determine whether human recombinant monocyte chemotactic protein‐1 facilitates the resorption process of herniated nucleus pulposus, we introduced another model of autologous transplantation, wherein the nuclear materials were grafted to the abdominal subcutaneous tissues and recombinant monocyte chemotactic protein‐1 was subsequently applied to these materials. When monocyte chemotactic protein‐1 was injected into the murine nucleus pulposus tissues, they reduced in size more rapidly than in the control group. These findings suggest that monocyte chemotactic protein‐1 plays an important role in the recruitment of macrophages in the early phase of the resorption process of herniated nucleus pulposus and that its application may physiologically facilitate the resorption process of the nucleus pulposus.
Orthotopic ossification of the spinal ligaments of zucker fatty rats: A possible animal model for ossification of the human posterior longitudinal ligament
Authors: Okano Toshihiro , Ishidou Yasuhiro , Kato Mitsuyasu , Imamura Takeshi , Yonemori Koji , Origuchi Nobuo , Matsunaga Shunji , Yoshida Hiroki , ten Dijke Peter , Sakou Takashi
Published: February 2005

Ossification of the posterior longitudinal ligament is a human genetic disease in which pathological ectopic ossification of the spinal ligaments develops. This leads to myelopathy or radiculopathy due to compression of the spinal cord. In this study, we investigated the histological features of orthotopic ossification of the spinal ligaments of senile Zucker fatty rats. A remarkably high incidence of orthotopic ossification was observed mainly in the thoracic spinal ligaments as compared with controls. The histopathological findings were similar to those for ossification of the human posterior longitudinal ligament. Bone morphogenetic proteins and activins, which exert their effects by way of specific type‐I and type‐II serine/threonine kinase receptors, play important roles in the formation of bone and cartilage. In the spinal ligaments of Zucker fatty rats, bone morphogenetic protein receptors and activin receptors were immunohistochemically detected around the ossified foci in a manner similar to that previously shown for the ossified tissue from patients who had ossification of the posterior longitudinal ligament. Thus, bone morphogenetic proteins and activin receptors might play important roles in orthotopic ossification of the spinal ligaments of Zucker fatty rats as well as in ossification of the posterior longitudinal ligament of humans. In addition, bone morphogenetic protein‐receptor‐IA was expressed in the nonossified ligament, suggesting that the spinal ligaments of the rats may have a predisposition to orthotopic ossification. In the controls, no expression of bone morphogenetic protein receptors or of activin receptors was observed. In conclusion, there is a great degree of similarity between orthotopic ossification of the spinal ligaments of Zucker fatty rats and ossification of the posterior longitudinal ligament of humans. Thus, the rats provide a useful animal model for the study of ossification of the human posterior longitudinal ligament.
Evaluation of bovine‐derived bone protein with a natural coral carrier as a bone‐graft substitute in a canine segmental defect model
Authors: Sciadini Marcus F. , Dawson John M. , Johnson Kenneth D. , Sciadini M. F.
Published: February 2005

The efficacy of a bone‐graft substitute (bovine‐derived bone protein in a carrier of natural coral) in the healing of a segmental defect of a weight‐bearing long bone was evaluated. Twenty dogs, divided into two groups, underwent bilateral radial osteotomies with creation of a 2.5 cm defect. On one side of each dog, the defect was filled with autogenous cancellous bone graft. Contralateral defects received, in a blinded randomized fashion, cylindrical implants consisting of natural coral (calcium carbonate) or calcium carbonate enhanced with a standard dose of bovine‐derived bone protein (3.0 mg/implant; 0.68 mg bone protein/cm3). The limbs were stabilized with external fixators, and all animals underwent monthly radiographs. They were killed at 12 (group 1) or 24 (group 2) weeks, and regenerated bone was Studied by biomechanical testing and histology. Radiographic union developed in all 20 radii with autogenous cancellous bone grafts and in all 10 of the radii with the composite implants. None of the radii with implants of calcium carbonate alone showed radiographic evidence of union. This represented a statistically significant difference between implant types. In addition, calcium carbonate implants both with and without bone protein demonstrated radiographic evidence of near total resorption of the radiodense carrier by 12 weeks. This resorption facilitated radiographic evaluation of healing. Mean values for. biomechanical parameters of radii with the composite implants exceeded those for the contralateral controls at 12 and 24 weeks; the difference was statistically significant at 12 weeks. Histology revealed scant residual calcium carbonate carrier at either time in the defects with calcium carbonate implants; however, a moderate amount was present in defects with the composite implants. In these specimens, the residual carrier was completely surrounded by newly formed bone that may have insulated the calcium carbonate from further degradation. The present study used a carrier of granular calcium carbonate reconstituted with bovine type‐I collagen to deliver an osteoinductive protein to the defect site. This carrier is of nonhuman origin (eliminating the risk of disease transmission or antigenicity) and resorbs rapidly. In this model, bovine‐derived bone protein in a natural coral carrier performed consistently better than the gold standard autogenous cancellous bone graft in terms of the amount of bone formation and strength of the healed defect. This may have implications for removal of hardware or resumption of weight‐bearing in certain clinical situations. These data also indicate that coralline calcium carbonate alone. represents a poor option as a bone‐graft substitute in this critical‐sized segmental defect model.
Zoledronate (CGP 42'446), a bisphosphonate, protects against metaphyseal intracortical defects in experimental inflammatory arthritis
Authors: Pysklywec Michael W. , Moran Erica L. , Bogoch Earl R.
Published: February 2005

This study investigated zoledronate (CGP 42′446), a bisphosphonate, as a potential prophylactic and therapeutic agent against intracortical defects in metaphyseal bone in an experimental model of inflammatory arthritis. Inflammatory arthritis was induced in the right tibiofemoral joint of rabbits by the repeated injection of carrageenan. Three groups of animals were treated with the bisphosphonate daily, beginning at different points after the induction of arthritis. Cross sections of the right distal femoral metaphysis were prepared, and intracortical defects were examined by computerized image analysis. The percentage of total bone area with defects (the ratio of void area to total bone area) was greatly increased in the arthritic group compared with that in the normal group (p <0.001). In all groups treated with the bisphosphonate, there was a significantly lower percentage of total bone area with defects compared with that in the arthritic group (p <0.001). Treatment was likewise effective in reducing the zonal (anterior and posterior) predilection for the formation of defects observed in arthritis. Although inflammatory arthritis has a substantial effect in producing intracortical defects in metaphyseal bone, a bisphosphonate, zoledronate, was considerably effective in preventing these changes from occurring.
Roentgen stereophotogrammetric analysis of metal‐backed hemispherical cups without attached markers
Authors: Valstar E. R. , Spoor C. W. , Nelissen R. G. H. H. , Rozing P. M.
Published: February 2005

A method for the detection of micromotion of a metal‐backed hemispherical acctabular cup is presented and tested. Unlike in conventional roentgen stereophotogrammetric analysis, the cup does not have to be marked with tantalum markers: the micromotion is calculated from the contours of the hemispherical part and the base circle of the cup. In this way two rotations (tilt and anteversion) and the translations along the three cardinal axes are obtained. In a phantom study, the maximum error in the position of the cup's centre was 0.04 mm. The mean error in the orientation of the cup was 0.41 with a 95% confidence interval of 0.28‐0.54°. The in vivo accuracy was tested by repeated measurement of 21 radiographs from seven patients. The upper bound of the 95% tolerance interval for the translations along the transversal, longitudinal, and sagittal axes was 0.09. 0.07. and 0.34 mm. respectively: for the rotation, this upper bound was 0.39°. These results show that the new method, in which the position and orientation of a metal‐backed hemispherical cup is calculated from its projected contours, is a simple and accurate alternative to attaching markers to the cup.
Cellular immune responses to orthopaedic implant materials following cemented total joint replacement
Authors: Wooley Paul H. , Petersen Steve , Song Zheng , Nasser Sam
Published: February 2005

In vitro cellular immune responses to metallic and polymeric implant materials in particulate form were measured preoperatively in 185 patients. The patients were candidates for either primary total joint replacement (n = 65) or revision arthroplasty (n = 120). Proliferative cellular responses to polymethylmethacrylate‐ particles in patients with osteoarthritis at revision surgery for aseptic loosening were significantly higher than the responses of patients with osteoarthritis at either primary surgery or surgical revision for mechanical failure of the prosthesis or, sepsis. The responses to particles of cobalt‐chromium alloy at revision surgery were also higher than the responses at primary surgery. The responses were reevaluated in 32 patients after a minimum of 10 months following surgery to correlate individual changes in the biological responses with clinical progress. Reevaluation at early follow‐up of patients who had undergone primary surgery revealed significantly elevated proliferative responses and in vitro cytokine production in response to poly‐methylmethacrylate and cobalt‐chromium alloy particles compared with their preoperative responses. In contrast, the response at follow‐up to polymethylmethacrylate was significantly reduced in patients who had undergone revision surgery, and this reduction corresponded with a marked improvement in pain, joint motion, and function following revision surgery. These data suggest that specific cellular responses to polymethylmethacrylate or cobalt‐chromium alloy particles, or both, may be associated with loose or painful prostheses.
Functional evaluation of hip abductor muscles with use of magnetic resonance imaging
Authors: Kumagai Masaru , Shiba Naoto , Higuchi Fujio , Nishimura Hiroshi , Inoue Akio
Published: February 2005

The hip abductor muscles are considered important for gait and biomechanics of the hip joint; however, their specific function has not been defined precisely. The intensity of magnetic resonance imaging signals in skeletal muscle has been reported to increase immediately after exercise. Making use of this phenomenon, we evaluated the hip abductor muscles. Magnetic resonance imaging was performed after isometric exercise of the hip abductor in three positions (20° of abduction, neutral, and 20° of adduction). The abduction force of the hip was measured with a dynamometer, and electromyographic measurements were made simultaneously for the same hip positions. Additionally, magnetic resonance imaging was performed after one‐legged stance. As the hip was more adducted, the signal intensity increased on the scans. The values for muscle force, as evaluated with the dynamometer and integratedoelectromyography, also supported the results. The increase in signal intensity of the gluteus minimus at 20° of abduction and after one‐legged stance was significantly greater than that of the gluteus medius (p <0.0001 and p <0.0001, respectively). The results of this study indicate that the gluteus minimus muscle, along with the gluteus medius, plays an important role in hip abduction, gait, and stabilization of the pelvis.
Effects of in situ freezing and stress‐shielding on the ultrastructure of rabbit patellar tendons
Authors: Tsuchida Takamasa , Yasuda Kazunori , Kaneda Kiyoshi , Hayashi Kozaburo , Yamamoto Noritaka , Miyakawa Kiyoshi , Tanaka Kunio
Published: February 2005

The effects of in situ freezing and the combination of in situ freezing and stress‐shielding on the microstructure and ultrastructure of the patellar tendon were studied with use of 20 mature rabbits. The patellar tendon was frozen in situ with liquid nitrogen to kill fibroblasts and then was completely released from stress by chronically pulling a stainless‐steel wire installed between the patella and the tibial tubercle, Microstructurally, the freezing treatment induced separation of collagen fiber bundles and fibroblast necrosis at 3 weeks, although the separation disappeared at 6 weeks. Ultrastructurally, small collagen fibrils with a diameter of less than 90 nm were predominant; at 6 weeks, the area occupied by collagen fibrils had decreased. In the frozen‐shielded tendon, numerous large spaces were observed in the matrix at 3 weeks. This treatment increased the number of fibrils with a diameter greater than 360 nm and decreased the number of collagen fibrils per unit of area and the area occupied by collagen fibrils at 3 weeks. This study demonstrated that in situ freezing and the combination of in situ freezing and stress‐shielding leads to a smaller volume of collagen fibrils per unit of cross section of the patellar tendon by mechanisms that remain to be defined.
In vivo gene transfer and overexpression of focal adhesion kinase (pp125 FAK) mediated by recombinant adenovirus‐induced tendon adhesion formation and epitenon cell change
Authors: Lou Jueren , Kubota Hideaki , Hotokezaka Shunsuke , Ludwig Fredrick J. , Manske Paul R.
Published: February 2005

Adhesion formation is a frequent complication of tendon injury repair; however, little is known bout its mechanism. The intracellular focal adhesion kinase (FAK)‐related signaling pathway may be one of the mechanisms involved in the induction of tendon adhesions. The replication deficient adenovirus containing the FAK gene (pp125 FAK) was constructed and named Adv‐Fak. By in vitro transductions with the recombinant virus, overexpression of the FAK protein was documented in transduced cultured primary tendon cells. By in vivo direct injection of Adv‐FAK into the space between the tendon and tendon sheath of White Leghorn chickens, FAK gene transfer with overexpression of the FAK protein was detected by immunohistological staining. The morphology of these stained cells changed from the normal flat shape to cuboid. The group with overexpressed adenovirus‐mediated FAK had significant adhesion formation, as seen by increased work of flexion (118.197 ± 29.616), compared with the group with overexpressed adenovirus‐mediated β‐galactosidase (67.507 ± 36.066) (p <0.0393) and the group with adenovirus‐mediated FAK antisense gene transfer (60.357 ± 48.562) (p <0.0211). Histological examination of the samples from tendons with Adv‐FAK showed fibers between the tendon and tendon sheath; there were no fibers in the cavities of samples of injured tendons infected with Adv‐βgal. Moreover, at the application site of the former tendons, a thick fiber layer without epitenon cells was built up on the outer surface, whereas a thin fiber layer with clear epitenon cells was observed in the tendons to which Adv‐βgal was applied. Our results show that overexpression of FAK can induce tendon adhesion formation in vitrvo. This indicates that FAK and the FAK‐related signaling pathway may be involved in the process of tendon adhesion formation. Understanding the details of this process may help to prevent tendon adhesion and improve healing.
In vivo measurements show tensile axial strain in the proximal lateral aspect of the human femur
Authors: Aamodt A. , Lund‐Larsen J. , Eine J. , Andersen E. , Benum P. , Husby O. Schnell
Published: February 2005

Two conflicting theories exist concerning the stress pattern for the proximal lateral aspect of the human femur. According to the classic theory of Pauwels, a bending moment on the femur leads to compression medially and to tension laterally. The alternative theory is that muscle forces contribute to a moment‐free loading of the femur, with both the medial and lateral cortices subjected to compression. To examine these theories, we measured the strain at the external surface of the proximal lateral aspect of the femur of two female patients undergoing surgery for “snapping hip syndrome.” During the surgical procedure, a strain‐gauge rosette was bonded to the lateral aspect of the femur and the cortical strains were monitored while the patient performed a series of activities. In both patients, principle tensile strain increased significantly during one‐legged stance, walking, and stair climbing as compared with that during two‐legged stance. During each loading situation, the principal tensile strain was aligned within 22° to the longitudinal femoral axis. Dynamic strain measurements consistently revealed tensile axial strain at the lateral aspect of the femur during each activity. The present studv supports the classic bending theory of Pauwels and demonstrates that the proximal lateral aspect of the femur is subjected to tension during the stance phase of gait.
Evidence for the upregulation of osteogenic protein‐1 mRNA expression in musculoskeletal neoplasms
Authors: Weber Kristy L. , Bolander Mark E. , Rock Michael G. , Pritchard Douglas , Sarkar Gobinda
Published: February 2005

Little is known about bone and cartilage tumors at the molecular level; thus, the identification of genes associated with these tumors may be useful as markers and therapeutic targets. To address this issue and to test the hypothesis that abnormal expression of one or more growth factors in the transforming growth factor‐β superfamily is associated with musculoskeletal neoplasia, degenerate primers based on the conserved sequences in these genes were made for screening tumor samples by reverse transcription‐polymerase chain reaction. First, these primers were used to obtain a comparative profile between a low‐grade chondrosarcoma and its dedifferentiated high‐grade counterpart in the same patient. This experiment identified an amplified DNA product in the high‐grade sample that was identical to osteogenic protein‐1/bone morphogenetic protein‐7. Osteogenic protein‐1 mRNA expression was 17‐fold greater in this high‐grade sample than in the low‐grade one. Osteogenic protein‐1 was highly expressed (three of three) in human osteosarcoma cell lines but was not expressed (zero of four) in normal osteoblast samples. Screening for gene expression of osteogenic protein‐1 in 57 osteosarcomas and chondrosarcomas indicated that 44% (range: 38–52%) of them were positive for osteogenic protein‐1 mRNA. Screening of breast and prostate tumors revealed a similar association with osteogenic protein‐1 mRNA expression.
Skeletal anomalies in the adriamycin‐exposed prenatal rat: A model for VATER association
Authors: Kotsios Christine , Merei Jamal , Hutson John M. , Graham H. Kerr
Published: February 2005

Vertebral and radial anomalies are prominent features of VATER vertebral defects, anorectal anomaly, tacheoesophageal fistula with esophageal atresia, and radial dysplasia association. It has been shown that exposure of the rat fetus to adriamycin produces a spectrum of anomalies, including esophageal atresia and other features of VATER association. We aimed to document the skeletal defects found in rats exposed to teratogenic doses of adriamycin in utero. Vertebral, rib. and limb anomalies were found in 54, 54, and 35% of these examined fetuses, respectively. The range of bone lesions seen in this animal model was similar to the range of lesions seen in infants born with VATER association.
Increased content of type‐VI collagen epitopes in human ostearthritic cartilage: Quantitation by inhibition ELISA
Authors: Swoboda Bernd , Pullig Oliver , Kirsch Thorsten , Kladny Bernd , Steinhäuser Bernhard , Weseloh Gerd
Published: February 2005

Type‐VI collagen is an integral part of the extracellular cartilage matrix. However, the exact amounts of type‐VI collagen in normal and osteoarthritic human cartilage still are not known. In this study, we describe an inhibition enzyme‐linked immunosorbent assay that was developed to quantitate type‐VI collagen epitopes found in guanidinium chloride extracts from normal and osteoarthritic human cartilage. In 31 cartilage samples from various localizations of healthy adult human knees, type‐VI collagen epitopes accounted for approximately 0.40% of the total collagen content. Interestingly, type‐VI collagen epitopes increased about 4‐fold in osteoarthritic cartilage. A statistically significant increase of type‐VI collagen epitopes was found during early stages of the disease, with only a superficial roughening of the cartilage surface and a loss of proteoglycans. Thus, these findings indicate that type‐VI collagen is a minor component of normal human articular cartilage and that the amount of type‐VI collagen epitopes increases significantly during early stages of osteoarthritis.
Generation of nitric oxide by lapine meniscal cells and its effect on matrix metabolism: Stimulation of collagen production by arginine
Authors: Cao M. , Stefanovic‐Racic M. , Georgescu H. I. , Miller L. A. , Evans C. H.
Published: February 2005

Slices of lapine meniscus produced large amounts of nitric oxide after stimulation with interleukin‐1, tumor necrosis factor α, or a mixture of lapine synovial cytokines known as chondrocyte‐activating factors. Monolayer cultures of meniscal cells produced from the proteolysis of meniscal tissue contained a mixed population of chondrocytic and fibroblastic cells. These cultures also produced large amounts of nitric oxide in response to cytokines. Monolayer cultures of meniscal cells produced by the explant method, in contrast, were uniformly fibroblastic and did not produce nitric oxide in response to cytokines. We conclude that menisci contain two populations of cells, one fibroblastic and the other chondrocytic. The chondrocytic cells are responsible for generating most of the nitric oxide in response to cytokines. Endogenously generated nitric oxide suppressed the synthesis of collagen and proteoglycan by menisci but protected proteoglycan from the catabolic effects of interleukin‐1. The inhibitory effect of nitric oxide on collagen synthesis occurred without greatly altering the abundance of mRNAs encoding the various collagen α chains. During further investigation, arginine was unexpectedly found to stimulate the synthesis of collagen and, to a lesser degree, of noncollagenous proteins but not of proteoglycans. Fragments of meniscus, but not meniscal cells in monolayer culture, increased their production of matrix metalloproteinases. lactate, and, especially, prostaglandin E2 in response to interleukin‐1. Inhibition of nitric oxide production with NG‐monomethyl‐L‐arginine enhanced production of matrix metalloproteinases but had little effect on the synthesis of lactate or prostaglandin E2.
Effect of combined axial compressive and anterior tibial loads on in situ forces in the anterior cruciate ligament: A porcine study
Authors: Li Guoan , Rudy Theodore W. , Allen Christina , Sakane Masataka , Woo Savio L‐Y.
Published: February 2005

This study investigated the impact of a combination of axial compressive and anterior‐posterior tibial loads on the in situ forces in the anterior cruciate ligament. An axial compressive load is believed to contribute to increased stability of the knee joint; however, its effect on in situ forces in the anterior cruciate ligament has not been clearly defined, to our knowledge. It was hypothesized that the application of an axial compressive load, when combined with an anterior tibial load, would result in larger in situ forces in the anterior cruciate ligament than those caused by an isolated anterior tibial load. With use of a porcine knee model, the results confirmed this hypothesis; the addition of a 200 N axial compressive load to a 100 N anterior tibial load increased knee stability by reducing anterior‐posterior tibial translation and internal‐external tibial rotation and also caused a significant increase in in situ forces in the anterior cruciate ligament (p < 0.05). Specifically, there was a 34% increase in the in situ force at 30° of flexion, a 68% increase at 60° of flexion, and an 84% increase at 90° of flexion compared with those for an isolated anterior tibial load of 100 N. Additionally, there was a statistically significant increase of the in situ forces in the anterior cruciate ligament at 60 and 90° as compared with those at 30°. These results suggest that axial compressive loads on the knee may play a role in injury of the anterior cruciate ligament when the knee is flexed.
Endothelin‐1 is upregulated during skeletal muscle ischemia and reperfusion
Authors: Hvaal K. , Øie E. , Attramadal H. , Halvorsen V. , Svindland A. , Nordsletten L. , Skjeldal S.
Published: February 2005

The aim of the present study was to test the hypothesis that the vasoconstrictive peptide endothelin‐l is upregulated in ischemia and reperfusion in skeletal muscle. Sixty‐eight Wistar rats were included in the series: 12 served as controls that did not undergo the procedure, 16 underwent sham operations, and 40 were subjected to a modified tourniquet ischemia for 3 hours and 20 minutes. Of the 40 rats, 16 were killed at the end of the ischemic period, 16 underwent reperfusion for 2 hours, and eight underwent reperfusion for 72 hours. Areas of necrosis were measured by morphometry in hematoxylin and eosin‐stained cross sections of the anterior tibial muscles that had been reperfused for 72 hours. Sections from the controls, the muscles that had not been reperfused and the reperfused muscles were immunostained for endothelin‐1. Serum endothelin‐1 levels in blood samples from the aorta were determined with a commercial enzyme immunoassay kit. The anterior tibial muscle was harvested for preproendothelin‐1 mRNA analysis with RNase protection assay. The hematoxylin and eosin‐stained sections showed extensive necrosis with an acellular core of no reperfusion. The muscular core demonstrated weak immunostaining for endothelin‐1 in all sections, a subfascial narrow brim of fibers showed enhanced immunoreactivity at the end of ischemia, and all fibers outside the core stained by 2 hours after the start of reperfusion. After 72 hours of reperfusion. the fibers outside the core stained positive in a checkerboard‐like pattern. There were no differences in serum endothelin‐1 levels between the groups. Preproendothelin‐1 mRNA analysis with RNase protection assay showed 2‐fold upregulation at the end of ischemia and 4‐fold upregulalion'after 2 hours of reperfusion (p = 0.001). This study supports the hypothesis that both ischemia and reperfusion upregulate endothelin‐1 in skeletal muscle.
Biomechanical analysis of limited intercarpal fusion for the treatment of Kienböck's disease: A three‐dimensional theoretical study
Authors: Iwasaki Norimasa , Genda Eiichi , Barrance Peter J. , Minami Akio , Kaneda Kiyoshi , Chao Edmund Y. S.
Published: February 2005

Although several types of intercarpal fusion have been advocated for the treatment of Kienböck's disease, the clinical outcome of each procedure is still inconclusive. The joint load and ligament tension based on a three‐dimensional model were measured to determine which intercarpal fusion procedures unload the lunate and whether they alter the force transmission through the entire wrist joint. Ten theoretical models of wrists were used to simulate three different operative procedures: capitate‐hamate fusion, scapho‐trapezial‐trapezoidal fusion, and scaphocapitate fusion. A discrete element analysis technique was used to perform these investigations. The joint force and ligament tension of normal wrists and of simulated operative procedures were calculated according to the deformation of each spring element, simulating the articular cartilage and the carpal ligaments. Scaphocapitate and scapho‐trapezial‐trapezoidal fusions significantly decreased the joint force at the radiolunate joint and the lunocapitate joint compared with the intact wrist. In contrast, these fusions significantly increased this value at the radioscaphoid joint in comparison with the intact wrist. In the midcarpal joint, scaphocapitate fusion also increased the joint force at the scapho‐trapezial‐trapezoidal joints and at the triquetral‐hamate joint, whereas scapho‐trapezial‐trapezoidal fusion increased it at the scaphocapitate joint. Capitate‐hamate fusion yielded no significant changes of the joint forces through the entire wrist joint. In the analysis of ligament tension, scaphocapitate and scapho‐trapezial‐trapezoidal fusions significantly decreased the tension only in the dorsal scapholunate ligament. These findings demonstrate that scaphocapitate and scapho‐trapezial‐trapezoidal fusions are effective in decompressing the lunate. By contrast, capitate‐hamate fusion is ineffective in reducing lunate compression. Although scaphocapitate and scapho‐trapezial‐trapezoidal fusions are recommended for the treatment of Kienböck's disease, clinicians should consider that the increase of force transmission through the radioscaphoid and the midcarpal joints may lead to early degenerative changes after these procedures have been performed.
Damage type and strain mode associations in human compact bone bending fatigue
Authors: Boyce Todd M. , Fyhrie David P. , Glotkowski Mark C. , Radin Eric L. , Schaffler Mitchell B.
Published: February 2005

When compact bone is subjected to fatigue loading, it develops matrix microdamage, which reduces the tissue's ability to resist fracture. The relative influence of different strain modes on damage and strength in compact bone has not been characterized, to our knowledge. In this study, the nonuniform strain field produced by four‐point bending was used to introduce fatigue damage into tibial bending beam specimens from men 40‐49 years old. The specimens were then bulk‐stained with basic fuchsin to mark damage surfaces and were examined histologically and with confocal microscopy to describe damage morphologies and position relative to tension and compression‐strained regions of the specimen. Histomorphometric methods were used to quantify the amounts of different types of bone microdamage. Three major types were observed. In regions subjected to tensile strains, the bone had focal regions of diffusely increased basic fuchsin staining (i.e., diffuse microdamage). Confocal microscopy of these regions showed them to be composed of extensive networks of fine, ultrastructural‐level cracks. In compressive strain regions, the tissue developed linear microcracks in interstitial areas similar to those originally described by Frost. Fine, tearing‐type (wispyappearing) cracks were observed near and in the plane of the neutral axis. The paths of these fine cracks were not influenced by microstructural boundaries. Other minor damage morphologies (sector‐stained osteons, delamination of regions of lamellae, and intraosteonal cracking) were observed, but their distribution was unrelated to local strain field. Thus, in fatigue of human compact bone, the principal mechanisms of matrix failure (i.e., linear microcrack, diffuse damage foci, and tearing‐type damage) are strongly dependent on local strain type.
Analysis of the kinematics of different hip simulators used to study wear of candidate materials for the articulation of total hip arthroplasties
Authors: Ramamurti Balaji S. , Estok Daniel M. , Jasty Murali , Harris William H.
Published: February 2005

We developed an analytical technique to determine the paths traced by specific points on the femoral head against the acetabulum in the human hip joint during gait. The purpose of the study was to apply this technique to the mechanical hip simulators chosen to conduct wear tests on polymeric acetabular liners used in total hip replacements. These simulators differ from one another in the type of motion produced, apart from other variables such as type of lubricant and head position. Due to the variation in the kinematics between the machines, the paths traced by the points on the femoral head against the acetabular liner ranged from simple linear traces to figure‐8 loops and quasi‐elliptical paths during a single simulator cycle. The distances traveled by these points during the same period also varied appreciably among the different hip simulator designs. These results are important when combined with other studies that have shown that kinematics can play an important role in the outcome of in vitro wear experiments. The kinematic differences quantified in this study can partially explain the substantial differences in wear data reported from different simulator designs and also underscore the usefulness of the technique described in this study in judging the results from different hip simulator experiments.
Fiber‐based anterior cruciate ligament model for biomechanical simulations
Authors: Martelli S. , Joukhadar A. , Zaffagnini S. , Marcacci M. , Lavallee S. , Champleboux G.
Published: February 2005

Although accurate predictions of the behavior and function of the anterior cruciate ligament would aid in diagnosis and operative treatment, no agreement exists on the best way to model the ligament with a reliable description of its mechanical and geometric features. We propose a new model of the anterior cruciate ligament based on multiple viscoelastic curvilinear fibers. This model was used for quasi‐static simulations of the passive motion of eight porcine knees, after registration of the passive trajectories and digitization of the surface of the ligament in flexion. Simulations of anterior cruciate ligament deformations during passive motion predicted a fiber strain of less than 20%, low insertion forces, and isometric anterior fibers. The model explains actions of the ligament fibers, as reported in the literature, better than classic models based on linear fibers and consistent with the mechanical properties of the anterior cruciate ligament.
Can an isometer predict the tensile behavior of a double‐looped hamstring graft during anterior cruciate ligament reconstruction?
Authors: Wallace Michael P. , Hull M. L. , Howell Stephen M.
Published: February 2005

An isometer, a highly compliant spring‐scale device for measuring suture displacement, has been used intraoperatively by surgeons to select the optimal placement of the femoral tunnel for an anterior cruciate ligament graft. The isometer measures the displacement of a suture centered in a tibial tunnel and attached to an intraarticular location on the femur before the femoral tunnel is drilled. Because the placement of the femoral tunnel strongly impacts the tensile behavior of an anterior cruciate ligament graft and because surgeons have used the amount of suture displacement to guide the placement of the femoral tunnel, the objective of this study was to determine the ability of an isometer to predict graft tension. In 14 patient undergoing reconstructive surgery of the anterior cruciate ligament, an isometer was used to measure suture displacement during passive knee motion for a provisional femoral tunnel location. An electrogoniometer recorded the flexion angle of the knee. The femoral tunnel was drilled. A double‐looped semitendinosus and gracilis autograft was inserted around a post in the femoral tunnel, and the tension in the four limbs of the graft exiting the tibial tunnel was measured during passive knee motion. Graft‐tension versus knee‐flexion‐angle curves revealed that each knee exhibited one of two distinct curve shapes: L‐shaped, characterized by the maximum tension occurring at full extension and a nearly flat profile from 35 to 90° of flexion, or U‐shaped, with elevated tensions at 80–90° of flexion (p < 0.001) reaching at least half of the tension in full extension. Because the shapes of the suture‐displacement versus flexion‐angle curves were more consistently L‐shaped, the intraoperative measurement of suture displacement was not a useful predictor of either the increase in tension in the graft with flexion or the maximum tension in the graft.
Experimental testing of a DEXA‐derived curved beam model of the proximal femur
Authors: Beck Thomas J. , Mourtada Firas A. , Ruff Christopher B. , Scott William W. , Kao George
Published: February 2005

This study was designed to test whether, using curved beam theory, a structural model of the proximal femur derived from two‐dimensional dual energy x‐ray absorptiometry could be used to predict femoral strength in an experimental simulation of a fall on the greater trochanter. A set of 22 fresh cadaveric femoral specimens were scanned with use of two‐dimensional dual energy x‐ray absorptiometry and then were tested to failure in a materials testing system, under three‐point loading, with the ground impact vector, aligned within the plane and along the bisector of the femoral neck‐shaft angle. Failure locations generally corresponded to stress peak locations predicted by the curved beam model. Predicted failure loads correlated well with measured failure loads for femoral neck fractures (r = 0.89; percent SE of estimate = 23%) and somewhat less well for intertrochanteric fractures (r = 0.83; percent SE of estimate = 29%). Overall predictions for failure load calculated from the maximum stress peak value over both locations corresponded to measured failure loads with an r value of 0.91 (percent SE of estimate = 21%). This kind of structural approach to the analysis of data for hip bone mass has the potential to provide mechanistic interpretations of the statistical associations frequently shown between conventional bone mineral measures and either hip fracture risk in vivo or bone strength in vitro.
Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair
Authors: Young Randell G. , Butler David L. , Weber Wade , Caplan Arnold I. , Gordon Stephen L. , Fink David J.
Published: February 2005

This investigation tested the hypothesis that delivering mesenchymal stem cell‐seeded implants to a tendon gap model results in significantly improved repair biomechanics. Cultured, autologous, marrowderived mesenchymal stem cells were suspended in a collagen gel delivery vehicle; the cell‐gel composite was subsequently contracted onto a pretensioned suture. The resulting tissue prosthesis was then implanted into a 1‐cm‐long gap defect in the rabbit Achilles tendon. Identical procedures were performed on the contralateral tendon, but only the suture material was implanted. The tendon‐implant constructs were evaluated 4, 8, and 12 weeks later by biomechanical and histological criteria. Significantly greater load‐related structural and material properties were seen at all time intervals in the mesenchymal stem cell‐treated tendons than in the contralateral, treated control repairs (p < 0.05), which contained suture alone with natural cell recruitment. The values were typically twice those for the control tissues at each time interval. Load‐related material properties for the treated tissues also increased significantly over time (p < 0.05). The treated tissues had a significantly larger cross‐sectional area (p < 0.05), and their collagen fibers appeared to be better aligned than those in the matched controls. The results indicate that delivering mesenchymal stem cell‐contracted, organized collagen implants to large tendon defects can significantly improve the biomechanics, structure, and probably the function of the tendon after injury.
Method to assess in vivo knee stability longitudinally in an animal model of ligament injury
Authors: Maitland Murray E. , Leonard Tim , Frank Cyril B. , Shrive Nigel G. , Herzog Walter
Published: February 2005

The purpose of this study was to develop a method to prospectively quantify passive knee stability in an animal model of joint injury over time. Knee stability is defined here as the amount of translation or rotation of the tibia relative to the femur for a given application of force or moment, respectively. Five animals that had undergone transection of the anterior cruciate ligament and three control animals that had undergone a sham operation were anaesthetized and positioned in a stereotaxic frame. Motion of the tibia relative to the femur was quantified with use of reflective markers secured to modified bone pins and a three‐dimensional motion analysis system. External forces and moments in the transverse plane of the tibia were measured with use of force transducers based on a strain‐gauge design. Longitudinal measurements of knee stability were made before either sham surgery (control animals) or transection of the ligament (experimental animals), immediately after surgery, and at 2 and 4 months after transection. The results showed that the animals tolerated the procedures well and that systematic measurements could be obtained. The method described here has the practical advantage over cross‐sectional experimental designs in that the number of subjects can be decreased while maintaining statistical power and has the further conceptual advantage that individual changes can be accounted for over time.