bluuebunny/crossref_metadata_2025 huggingface dataset:
Method for assessment of vascular reactivity in bone: In vitro studies on resistance arteries isolated from porcine cancellous bone
Authors: Lundgaard Annette , Aalkjær Christian , Mulvany Michael J. , Holm‐Nielsen Peter , Hansen Ebbe Stender
Published: February 2005

Knowledge about vascular regulation in bone is central to the understanding of both normal and pathological bone physiology. This article describes a new method for direct assessment of the reactivity of bone blood vessels. Resistance arteries (diameter approximately 250 μm) were isolated from epiphyseal cancellous bone (porcine femoral condyle). Arterial segments (2 mm long) were mounted as ring preparations on a myograph, and isometric force development was measured continuously. Fifty‐nine vessels from 31 pigs were investigated. The active force development was maximal at 0.9 × L100 in nine of 12 investigated arteries (L100 corresponds to the circumference the vessel would have if relaxed and exposed to a luminal pressure of 100 mm Hg [13.3 kPa]). In all subsequent experiments, the vessels were stretched to 0.9 × L100. Noradrenaline (2 × 10−8 to 10−5 M) induced a concentration‐dependent vasoconstriction; mean maximal tension development was 3.69 N/m. This force development would enable the arteries to contract against a pressure of more than 22 kPa (165 mm Hg), indicating preserved function of the media smooth muscle. Response to acetylcholine (10−7 to 10−5 M) was observed in only two of 12 arteries. Bradykinin (10−11 to 10−6 M) induced a concentration‐dependent and reproducible relaxation in all vessels; the relaxation was endothelium‐dependent, since no effect of bradykinin was detected after mechanical removal of the endothelium, Sodium nitroprusside (10−4 M) induced a reproducible and endothelium‐independent vasorelaxation. The results demonstrate preserved function of both smooth muscle and endothelium in this preparation. The model allows pharmacological investigations of bone arteries under well defined conditions and enables studies on focal bone lesions and human bone tissue.
Kinematics of the glenohumeral joint: Influences of muscle forces, ligamentous constraints, and articular geometry
Authors: Karduna Andrew R. , Williams Gerald R. , Iannotti Joseph P. , Williams John L.
Published: February 2005

Despite recent interest in the study of shoulder kinematics, there is considerable controversy in the literature regarding translations at the glenohumeral joint. The purpose of this study was to investigate the key factors that control shoulder motions, thus leading to a better understanding of joint function. Translation and rotation patterns were studied in fresh‐frozen glenohumeral joints of human cadavers with a six‐degrees‐of‐freedom magnetic tracking device. Shoulders were positioned from maximal internal to external rotation at several arm positions (various elevations and planes of motion). In order to determine the effect of muscle forces, joints were positioned both actively and passively. Additionally, articular surface geometry and ligament origin‐insertion wrap lengths were measured to assess their influences on joint kinematics. When joints were positioned passively, large translations were observed at the extremes of motion. With active positioning, muscle forces tended to limit humeral head translations, principally by restricting rotational ranges of motion. However, when data from the passive model were reanalyzed by considering only the rotational ranges of motion seen actively, no significant differences in translation were found between the two models. Joint conformity was found to have a significant influence on translations during active positioning but not during passive positioning. Glenohumeral ligament wrap lengths, however, correlated with translations when joints were positioned passively but not when positioned actively. Findings from this study emphasize the importance of muscle forces in keeping the humeral head centered in the glenoid. Although large translations are possible, they can be achieved only with increases in rotational ranges of motion associated with the removal of muscle force. Additionally, joint conformity appears to play a role in controlling translations during active motions, whereas capsular constraints become more important during passive motions.
Genetic analysis of structural elastic fiber and collagen genes in familial adolescent idiopathic scoliosis
Authors: Miller N. H. , Sponseller P. , Mims B. , Child A. , Milewicz D. M. , Blanton S. H.
Published: February 2005

Adolescent idiopathic scoliosis is a genetic disorder of unknown etiology. Scoliosis is a clinical feature of inherited connective‐tissue disorders including Marfan syndrome. Mutations within the gene of FBN1 (fibrillin 15), a component of the extracellular matrix, are now linked to Marfan syndrome and similar clinical phenotypes. This study investigated the potential association of structural genes encoding for extracellular matrix components of FBN1, elastin, and one of the polypeptides of type‐I collagen (COL1A2) with familial adolescent idiopathic scoliosis. Eleven pedigrees, including 96 individuals, were identified in which adolescent idiopathic scoliosis segregated in an apparent autosomal dominant pattern. Fifty‐two individuals were determined to be affected with scoliosis. Genomic DNA was analyzed by genetic linkage utilizing four intragenic markers for the structural genes FBN1, elastin, and COL1A2. Collectively, our results exclude the structural genes of FBN1. elstin, and COL1A2 as candidate genes within these families. However, when viewed individually, specific markers cannot be excluded within all of the families. This information complements previously reported data that fibrillin production and matrix incorporation from scoliotic fibroblasts in vitro are normal in more than 80% of patients studied.
Braided polypropylene augmentation device in reconstructive surgery of the anterior cruciate ligament: Long‐term clinical performance of 594 patients and short‐term arthroscopic results, failure analysis by scanning electron microscopy, and synovial histomorphology
Authors: Kdolsky R. K. , Gibbons D. F. , Kwasny O. , Schabus R. , Plenk H.
Published: February 2005

Long‐term clinical results and short‐term arthroscopic and microscopic findings from two agumented roconstruction procedures for the reptured anterior cruciate ligament are reported. The braided polypropylene ligament augmentation device (Kennedy model) was used with temporary double‐end fixation in 279 patients to augment the attachment of the anterior cruciate ligament after acute proximal rupture and in 315 patients to augment a bone‐tendon‐bone autograft, mainly after chronic instability. Check arthroscopy was performed and the metal fixation hardware was removed after a mean of 11 months. Of the 569 patients evaluated, 101 partial or total breakages of the ligament augmentation device were found. Together with nine breakages detected late in the follow‐up period, 110 (19.3%) failures were found. Most of these failures were accompanied by effusion that was immediately alleviated when the failed device was removed. No generalized synovitis was visible. Scanning electron microscopic analysis of 24 retrieved failed ligament augmentation devices showed fatigue to be the principal failure mode, together with local abrasion at the fracture. synovial biopsies were taken during arthroscopy in 84 patients with and without ligament augmentation device‐failure who had given informed consent, and histological evaluation revealed that in 21 patients, chronic but no acute synovial inflammation was found, and wear particles could be identified in foreign body cells in 17. Statistically, the presence of chronic synovitis was predicted neither by wear particles and foreign body cells nor by abrasion or fatigue failure of the ligament augmentation device. Irrespective of the failures, for which ligament augmentation device removal is recommended, in the final Orthopaedische Arbeitsgemeinschaft Knie evaluation (after a mean of 6.2 year). excellent and good clinical results were found in 83.6% of all 594 patients.
Intrinsic healing capacity and tearing process of torn supraspinatus tendons: In situ hybridization study of α1(I) procollagen mRNA
Authors: Hamada Kazutoshi , Tomonaga Akihito , Gotoh Masafumi , Yamakawa Hideyuki , Fukuda Hiroaki
Published: February 2005

To determine the healing potential and healing process of torn supraspinatus tendons, in situ hybridization was used to localize cells containing α1 type‐I procollagen mRNA. Biopsy specimens of torn supraspinatus tendons from 19 patients with complete‐thickness tears and 13 patients with incomplete‐thickness tears were obtained during surgery. Four macroscopically normal supraspinatus tendons were obtained to serve as normal controls. Specimens were fixed in 10% buffered formalin and embedded in paraffin. A 22‐mer oligonucleotide probe was labeled with digoxigenin and used as an in situ marker. The labeled cells were mainly composed of tenocytes and undifferentiated mesenchymal cells. In complete‐thickness tears, the labeled cells at the proximal tendon stumps in the specimens that were obtained less than 4 months after trauma were significantly more abundant than in the specimens obtained 4 months or more after trauma. However, the number of labeled cells was maintained at the torn portion even in long‐standing incomplete‐thickness tears. The labeled cells at the margins of concomitant intratendinous extensions of the tears were detected even in the long‐standing tears. The intratendinous extensions exhibited more labeled cell than were bursal‐side or joint‐side layers of the tendon substance in the incomplete‐thickness tears (p < 0.05). The torn supraspinatus tendon may possess an intrinsic healing capability in the intermediate and late phases of tendon healing. Incomplete‐thickness tears and concomitant intratendinous extensions can continue to rupture after the initial injury.
Effects of polyethylene on macrophages
Authors: Horowitz Stephen M. , Gonzales Joel B.
Published: February 2005

A system was developed to expose macrophages to polyethylene in vitro. Exposure of macrophages to these particles in isolation led to the release of tumor necrosis factor alpha and prostaglandin E2. Exposure of macrophages in co‐culture with osteoblasts to polyethylene particles increased the release of prostaglandin E2 and also led to the release of interleukin‐6. Incubation of radiolabelled calvariae with conditioned medium from macrophages exposed to polyethylene particles alone or to particles in co‐culture with osteoblasts led to bone resorption reflected by release of 45Ca. Incubation with pamidronate was effective in inhibiting resorption stimulated by conditioned medium from macrophages exposed to these particles alone or in co‐culture with osteoblasts. This demonstrates that pamidronate, or other bisphosphonates, may be effective in inhibiting bone resorption at the implant/bone interface in association with the macrophage ressponse to particulate polyethylene. Further investigation into the possible use of pamidronate or other bisphosphonates in the treatment of aseptic loosening is warranted.
Degradation rate of ultra‐high molecular weight polyethylene
Authors: Kurtz S. M. , Rimanc C. M. , Bartel D. L.
Published: February 2005

Ultra‐high molecular weight polyethylene components for total joint replacement chemically degrade before and after implantation, and the degradation is associated with an increase in density. The goal of this study was to determine the average rate of density change in these components following sterilization by gamma radiation in air as a function of shelf age and implantation time. Using the density gradient column method, density profiles were obtained through the thickness from loaded and unloded regions of 10 retrieved Insall‐Burstein/Posterior‐Stabilized II tibial components and one operating‐room inventory component for which the initial density profile and patient history (if applicable) were known. The average density of the components increased at a constant rate of 0.000186 g/cc/month during the first 50 months after sterilization (r2 = 0.54) but was not significantly affected by loading (p > 0.05). The quantitative degradation rates may be useful to help verify kinetic models to predict bulk degradative changes on the basis of microstructural and chemical processes. This research also suggests the hypothesis that degradation of ultra‐high molecular weight polyethylene can be modeled in terms of changes in bulk or average properties.
Effects of stem length on mechanics of the femoral hip component after cemented revision
Authors: Mann Kenneth A. , Ayers David C. , Damron Timothy A.
Published: February 2005

Bone loss in the proximal femur at the time of revision hip arthroplasty for a failed primary cemented femoral component can substantially reduce the stability of the revision stem, Use of an extended‐length femoral component has been suggested to aid in achieving long‐term fixation; however, the optimal stem length is unknown, A three‐dimensional finite element model of a charnley‐type revision femoral component in a sclerotic shell of cortical bone devoid of cancellous bone was developed, and five different stem lengths ranting from 140 to 273 mm were used. The interface between the sclerotic bone and cement mantle consisted of fibrous tissue. Distal to the sclerotic bone, bonding was allowed between the cement and bone. Relative motion between the cement and bone was reduced substantially when the stem extended beyond the original defect. Maximum principal stresses in the proximal cement mantle decreased from 7.7 to 5.5 MPa, but cement stresses near the distal tip increased from 7.9 to 10.7 MPa when the stem just bridged the defect. Further increases in stem length reduced the distal cement stresses. Increases beyond two femoral diameters had a minor effect on changes in relative motion, cement mantle stresses, and stresses across the cement‐bone interface. The results suggest that a femoral component that extends beyond the area of cancellous bone defect by two femoral diameters will be most effective in minimizing stresses and motion that could be associated with clinical loosening of the cemented revision. A shorter stem that just bridges the cancellous bone defect left from the primary procedure may not provide adequate distal fixation due to high cement‐bone shear stresses.
Nitric oxide and G proteins mediate the response of bovine articular chondrocytes to fluid‐induced shear
Authors: Das P. , Schurman D. J. , Smith R. Lane
Published: February 2005

Mechanical loading alters the metabolism of articular cartilage, possibly due to effects of shear stress on chondrocytes. In cultured chondrocytes, glycosaminoglycan synthesis increases in response to fluidinduced shear. This study tested the hypothesis that shear stress increases nitric oxide production in chondrocytes, and nitric oxide then influences glycosaminoglycan metabolism. Inhibitors of nitric oxide synthase, G proteins, phospholipase C, potassium channels, and calcium channels were also analyzed for effects on nitric oxide release and glycosaminoglycan synthesis. Fluid‐induced shear was applied to primary high‐density monolayer cultures of adult bovine articular chondrocytes using a cone viscometer. Nitric oxide release in chondrocytes increased in response to the duration and the magnitude of the fluid‐induced shear. Shearinduced nitric oxide production was reduced in the presence of nitric oxide synthase inhibitors but was unaffected by pertussis toxin, neomycin, tetraethyl ammonium chloride, or verapamil. The increase in glycosaminoglycan synthesis in response to shear stress was blocked by nitric oxide synthase inhibitors, pertussis toxin, and neomycin but not by tetraethyl ammonium chloride or verapamil. The phospholipase C inhibitor, neomycin, also decreased glycosaminoglycan synthesis in the absence of flow‐induced shear. As studied here, shear stress increased nitric oxide production by chondrocytes, and the shear‐induced change in matrix macromolecule metabolism was influenced by nitric oxide synthesis, G protein activation, and phospholipase C activation.
Tissue characterization of symptomatic and asymptomatic disc herniations by quantitative magnetic resonance imaging
Authors: Boos Norbert , Dreier Daniel , Hilfiker Esther , Schade Volker , Kreis Roland , Hora Josef , Aebi Max , Boesch Chris
Published: February 2005

The purpose of this investigation was to determine differences in tissue composition of symptomatic and asymptomatic disc herniations as reflected in T1 and T2 relaxation times (quantitative magnetic resonance investigation of the lumber spine. The longitudinal and transverse magnetic rlaxation times (T1 and T2, respectively) were calculated from a set of 20 images obtained with five single‐slice/multi‐echo sequences at different repetition time values on a commercial whole‐body system (1.5 T). Twenty‐two symptomatic and asymptomatic disc herniations could be matched according to age, gender, disc level, and the extent of herniation (protrusion or extrusion) and were compared with regard to T1 and T2 relaxation times. Symptomatic disc herniations exhibited significantly (pT1 < 0.04 and pT2 < 0.003) shorter T1(ΔT1:–182.1 milliseconds, −15%) and T2(ΔT2: −11.0 milliseconds, −21%) relaxation times than matched asymptomatic herniations. Symptomatic disc herniations also exhibited more advanced disc degeneration as graded by Pearce's criteria (p < 0.01). These results suggest that symptomatic and morphologically matched asymptomatic disc herniations differ with regard to disc matrix composition.
Hydrostatic pressur influences mRNA exprssion of trnsforming growth factor‐β1 and heat shock protein 70 in chondrocyte‐like cell line
Authors: Takahashi Kenji , Kubo Toshikazu , Kobayashi Kappei , Imanishi Jiro , Tkigawa Masaharu , Arai Yuji , Hirasawa Yasusuke
Published: February 2005

The present study investigated the influence of hydrostatic prssure on the exprssion of cytokines and heat shock protein 70 in a chondrocyte‐like cell line. Chondrocyte‐like cells (HCS‐2/8) were exposed to hydrostatic pressur by a special pressure apparatus. Total RNA for cytokines (interleukin‐1β, basic fibroblast growth factor, insulin‐like growth factor‐I, and transforming growth factor‐β1) and for heat shock protein 70 was extracted and was analyzed by a polymerase chain reaction method and Northern blotting. An assay for incorporation of [35S]sulfate was performed to assess proteoglycan synthesis. The expression of transforming growth factor‐β1 mRNA was enhanced after exposure to 5 Mpa of hydrostatic prssure and was reduced after 50 Mpa, whereas the expression of heat shock protein 70 was enhanced following exposure to 50 Mpa of hydrostatic pressure. The incorporation of [35S]sulfate into the cultured cells increased following exposure to 1‐5 Mpa of hydrostatic pressure and decreased following 10‐50 Mpa of pressure. These results suggest that hydrostatic pressure at physiologic levels enhances the expression of transforkming growth factor‐β mRNA in addition to increasing proteoglycan synthesis in chondrocytes and that excessively high hydrostatic pressure reduces the expression of transforming growth factor‐β1 mRNA and increases the expression of heat shock protein 79 mRNA while decreasing proteoglycan synthesis.
Treatment of experimental osteomyelitis by surgical debridement and the implantation of bioerodable, polyanhydride‐gentamicin beads
Authors: Nelson Carl L. , Hickmon Sandra G. , Skinner Robert A.
Published: February 2005

Osteomyelitis was induced in the radius in 77 rabbits and confirmed by histological examination and culture. At 4 weeks, the wounds were debrided and the animals were treated with (a) fatty acid dimersebacic acid beads (a bioerodable composite) impregnated with 20% or (b) 10% gentamicin sulfate, (c) placebo beads and intramuscular gentamicin sulfate. (d) placebo beads alone, or (e) debridement only. After 4 weeks, eradication of infection was determined by histological examination and culture. Osteomyelitis was eradicated in 93% of the animals treated with the beads and 20% gentamicin, in 67% of those treated with the beads arid 10% gentamicin, in 25% of those treated with placebo beads and intramuscular gentamicin, in 7% of those treated with placebo beads alone, and in 12.5% of those treated with debridement only (p values from <0.001 to 0.02). Fatty acid dimer‐sehacie acid beads with gentamicin were then implanted in noninfected rabbits, and gentamicin sulfate concentrations in bone, serum, urine, and wound exudate were measured. Gentamicin sulfate was detectable in bone for as long as 8 weeks after implantation. Levels as high as 4,746 g/ml were present in the wound exudate for the first 7 days. Levels in the serum peaked at 1.03 μg/ml. Urine levels peaked at 135 μg/ml.
Evaluation of the effect of joint constraints on the in situ force distribution in the anterior cruciate ligament
Authors: Livesay Glen A. , Rudy Theodore W. , Woo Savio L‐Y. , Runco Thomas J. , Sakane Masataka , Li Guoan , Fu Freddie H.
Published: February 2005

The function of the anterior cruciate ligament was investigated for different conditions of kinematic constraint placed on the intact knee using a six‐degree‐of‐freedom robotic manipulator combined with a universal force‐moment sensor. To do this, the in situ forces and force distribution within the porcine anterior cruciate ligament during anterior tibial loading up to 100 N were compared at 30, 60, and 90° of flexion under: (a) unconstrained, five‐degree‐of‐freedom knee motion, and (b) constrained, one‐degree‐of‐freedom motion (i.e., anterior translations only). The robotic/universal force‐moment sensor testing system was used to both apply the specified external loading to the in tact joint and measure the resulting kinematics. After tests of the intact knee were completed, all soft tissues except the anterior cruciate ligament were removed, and these motions were reproduced such that the in situ force and force distribution could be determined. No significant differences in the magnitude of in situ forces in the anterior cruciate ligament were found between the unconstrained and constrained testing conditions. In contrast, the direction of in situ force changed significantly; the force vector in the unconstrained case was more parallel with the direction of the applied tibial load. In addition, the distribution of in situ force between the anteromedial and posterolateral bundles of the ligament was nearly equal for all flexion angles for the unconstrained case, whereas the anteromedial bundle carried higher forces than the posterolateral bundle at both 60 and 90° of flexion for the constrained case. This demonstrates that the constraint conditions placed on the joint have a significant effect on the apparent role of the anterior cruciate ligament. Specifically, constraining joint motion to one degree of freedom significantly alters both the direction and distribution of the in situ force in the ligament from that observed for unconstrained joint motion (five degrees of freedom). Furthermore, the changes observed in the distribution of force between the anteromedial and posterolateral bundles for different constraint conditions may help elucidate mechanisms of injury by providing new insight into the response of the anterior cruciate ligament to different types of external knee loading.
Effect of freeze‐drying or γ‐irradiation on remodeling of tendon allograft in a rat model
Authors: Toritsuka Yukiyoshi , Shino Konsei , Horibe Shuji , Nakamura Norimasa , Matsumoto Norinao , Ochi Takahiro
Published: February 2005

Freezing or freeze‐drying and γ‐irradiation are techniques currently used for processing tendon allografts. However, it is still unknown how these processing methods affect graft remodeling. In this study, we used a rat patellar tendon transplantation model to investigate the effect of various processing methods on remodeling by quantifying loss of collagen labeled with a radioactive isotope. The grafts were divided into the following four groups according to the processing method: fresh‐frozen, freeze‐dried, fresh‐frozen and γ‐irradiated, or freeze‐dried and γ‐irradiated. The percentage of donor collagen, calculated from hydroxyproline content and radioactivity level, was used as an indicator of graft remodeling. At 2 weeks, the level of donor collagen in the fresh‐frozen group was 62%; in the freeze‐dried group, 59%; in the fresh‐frozen and irradiated group, 57%; and in the freeze‐dried and irradiated group, 44%. At 4 weeks, the percentage of donor collagen remaining in grafts decreased to 38% in the fresh‐frozen group, 19% in the freeze‐dried group, 27% in the fresh‐frozen and irradiated group, and 12% in the freeze‐dried and irradiated group. Finally, at 12 weeks, the levels were 19% in the fresh‐frozen group, 20% in the freeze‐dried group, 15% in the fresh‐frozen and irradiated group, and 6% in the freeze‐dried and irradiated group. The percentages of donor collagen in the freeze‐dried and the fresh‐frozen and irradiated groups were significantly lower than that in the fresh‐frozen group at 4 weeks. The values for the freeze‐dried and irradiated group were significantly lower than those for the fresh‐frozen and irradiated group at 4 and 12 weeks. These data suggest that freeze‐drying, freeze‐drying followed by γ‐irradiation, and fresh‐freezing followed by γ‐irradiation temporarily accelerate graft remodeling.
Uncinate processes and Luschka joints influence the biomechanics of the cervical spine: Quantification using a finite element model of the C5‐C6 segment
Authors: Clausen John D. , Goel Vijay K. , Traynelis Vincent C. , Scifert Jeffrey
Published: February 2005

A fully three‐dimensional finite element model of a C5‐C6 motion segment of the human spine was developed and validated for the purpose of investigating the biomechanical significance of uncinate processes and Luschka joints. The original intact cervical model was modified to create two additional models. The first simulated the absence of Luschka joints by replacing the fissures with continuous annulus fibrosus and leaving the uncinate processes intact. The second model simulated a surgical resection of the uncinate processes, while leaving the Luschka joints intact. The results of these two models were compared with the intact model, which served as a baseline; thus, the relative contributions of these two structures to cervical motion were established With use of our model, it was possible for the first time, to provide quantitative data concerning the source of coupled motions in the lower cervical spine. In principle, the results from this model support the hypothesis of Penning and Wilmink. Our resultsindicate that the facet joints and Luschka joints are the major contributors to coupled motion in the lower cervical spine and that the uncinate processes effectively reduce motion coupling and primary cervical motion (motion in the same direction as load application), especially in response to axial rotation and lateral bending loads. Luschka joints appear to increase primary cervical motion, showing an effect on cervical motion opposite to that of the uncinate processes. Surgeons should be aware of the increase in motion accompanied by resection of the uncinate processes.
Reproducibility of the kinematics and kinetics of the lower extremity during normal stair‐climbing
Authors: Yu Bing , Kienbacher Thomas , Growney Eric S. , Johnson Marjorie E. , An Kai‐Nan
Published: February 2005

The purpose of this study was to examine the intrasubject reproducibility of the kinematic and kinetic measures of the lower extremity during normal stair‐climbing. Three‐dimensional video and force‐plate data were collected for three trials per subject during each of three conditions: ascending, descending, and level walking. Three‐dimensional angles and moments of the ankle, knee, and hip joints were calculated. The coefficient of multiple correlation was used to determine the intrasubject reproducibility of joint angles and resultant moments. Analysis of variance with repeated measures was conducted to compare the magnitudes of the coefficients between different steps, different joints, and different joint functions. The results showed that (a) generally, the kinematic and kinetic measures of normal subjects climbing stairs were reproducible; (b) the kinetic measures during the transition steps from level walking to ascending and from descending to level walking were significantly less reproducible than those during the other steps; (c) the data from the sagittal plane, were more reproducible than those from the other two planes; and (d) the kinetic measures were more reproducible than the kinematic measures, especially for abduction‐adduction and internal‐external rotation.
Structure and function of embryonic growth plate in the absence of functioning skeletal muscle
Authors: Germiller John A. , Goldstein Steven A.
Published: February 2005

Normal growth and development of the skeleton require the presence of viable, actively contracting skeletal muscle throughout the fetal period. A chick embryo model of midgestation chemical paralysis and secondary muscle atrophy was used to test the hypothesis that functioning muscle stimulates the growth of long bones by influencing the proliferation, differentiation, and hypertrophy of chondrocytes in cartilage of the epiphysis and growth plate. Paralysis did not alter the overall developmental stage of the long bone or the organization of the growth plate. Compared with controls, however, uptake of bromodeoxyuridine in the paralyzed chick was reduced by 27‐55% in the chondroepiphysis and uppermost zone of the tibial growth plate, indicating reduced proliferation of chondrocytes. A specific reduction in the size of the proliferative zone and a reduced number of proliferating cells were also observed. By contrast, in the second, post‐proliferative zone of the growth plate, the height of the zone was unchanged and its area was only slightly reduced compared with controls. Finally, median hypertrophic cell profile area, a measure of cell size, was not significantly affected by paralysis, although frequency analysis revealed modest numerical reductions in the population of the largest hypertrophic chondrocytes in the paralyzed group. These data suggest that the role of functioning fetal muscle in maintaining proper skeletal growth may be mediated primarily through specific stimulation of the recruitment or proliferation of immature chondrocytes, or of both.
Characterization of a rabbit model of staphylococcal osteomyelitis
Authors: Smeltzer Mark S. , Thomas J. Roby , Hickraon Sandra G. , Skinner Robert A. , Nelson Carl L. , Griffith David , Parr Thomas R. , Evans Richard P.
Published: February 2005

We previously described a rabbit osteomyelitis model that involved the direct introductiof Staphylococcus aureus into devascularized bone. To further evaluate the model, we performed expeirijj aimed at correlating the microbiological, radiographic, and histologic parameters involved in the development of experimental osteomyelitis. Using the strain UAMS‐1, we achieved an infection rate of 75% with an inoculum as small as 2 × 103 colony‐forming unit's. However, development of significant radiographieja'TOifaife logic signs of disease required an inoculum of at least 2 × 104 colony‐forming units. Radiographic singns were minimal 1 week after infection and progressed steadily to a maximum 3 weeks after infection.‐, In contrasthistologic signs of disease were observed within 1 week and remained essentially unchanged throughout the4‐week evaluation period. Unlike the results obtained with UAMS‐1, rabbits infected with the heavily encapsulated Staphylococcus aureus, strain Smith diffuse exhibited little evidence of disease even whdrf'‐inreicl with 2 × 106 colony‐forming units. The reduced virulence of strain Smith diffuse was surprising given its greatly enhanced, Virulence (relative to UAMS‐1) in a murine peritonitis model of staphylococcal disease. These results suggest that UAMS‐1 expresses virulence factors that are important in the pathogeritesis of osteomyelitis and that some or all of these virulence factors are either absent or are not expressed jrisfraffl Smith diffuse. Most importantly, the results suggest that our model may be appropriate for the identificationf and characterization of these virulence factors.
Immunolocalization of cytokines and their receptors in adhesive capsulitis of the shoulder
Authors: Rodeo Scott A. , Hannafin Jo A. , Tom James , Warren Russell F. , Wickiewicz Thomas L.
Published: February 2005

The purpose of this study was to test the hypothesis that specific cytokines are involved in the initiation and evolution of the fibrotic process in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder arthroscopy from 19 patients with adhesive capsulitis, 14 patients with nonspecific synovitis and no fibrosis or clinical evidence of adhesive capsulitis, and seven patients undergoing surgery for another pathology who had a normal capsule and synovium. Immunohistochemical localization with monoclonal antibodies to transforming growth factor‐β and its receptor, platelet‐derived growth factor and its receptor, basic fibroblast growth factor, interleukin‐1β, tumor necrosis factor‐α, and hepatocyte growth factor was performed using standard immunoperoxidase techniques. The frequency of cytokine staining was correlated with the clinical diagnosis Synovial cells, fibroblasts, T‐cells, and B‐cells were identified with specific antibodies, and newly synthesized matrix was examined for type‐I and type‐III collagen by immunohistochemical staining. The predominant cell types present were synovial cells and fibroblasts. Staining for type‐III collagen in adhesive capsulitis tissues indicated new deposition of collagen in the capsule. There was staining for transforming growth factor‐β and its receptor, platelet‐derived growth factor and its receptor, interleukin‐1β, and tumor necrosis factor‐α in adhesive capsulitis and nonspecific synovitis tissues, compared with minimal staining in normal capsule. Staining was more frequent in snovial cells than in capsular cells. The frequency of cell and matrix staining for transforming growth factor‐β, platelet‐derived growth factor, and hepatocyte growth factor was greater in adhesive capsulitis tissues than in those from patients with nonspecific synovitis. No difference in the frequency of staining between primary (idiopathic) and secondary adhesive capsulitis was found. The results of this study indicate that adhesive/capsulitis involves both synovial hyperplasia and capsular fibrosis. Cytokines such as transforming growth factor‐β and platelet‐derived growth factor may be involved in the inflammatory and fibrotic processes in adhesive capsulitis. Matrix‐bound transforming growth factor‐β may act as a persistent stimulus, resulting in capsular fibrosis. Understanding the basic pathophysiology of adhesive capsulitis is an important step in the development of clinically useful antifibrotic agents that may serve as novel treatments for patients with this condition.
Nitric oxide and proteoglycan turnover in rabbit articular cartilage
Authors: Stefanovic‐Racic M. , Möllers M. O. , Miller L. A. , Evans C. H.
Published: February 2005

Articular chondrocytes are known to synthesize large amounts of nitric oxide in response to exposure to interleukin‐1, but the role of this radical in proteoglycan turnover remains controversial. In this study, we used two different inhibitors of nitric oxide synthase, NG‐methyl‐L‐arginine and thiocitrulline, to study the effects of nitric oxide on the synthesis and breakdown of proteoglycan in rabbit articular cartilage. Synthes of nitric oxide by cartilage slices in response to treatment with interleukin‐1 and a partially purified mixture of synovial cytokines known as chondrocyte‐activating factors peaked during the first 2 days of culture and then fell to low levels, despite daily replenishment with fresh medium and cytokines to the cultures. The production of nitric oxide was completely inhibited by NG‐methyl‐L‐arginine and thiocitrulline. Interleukin‐1 and the chondrocyte‐activating factors inhibited proteoglycan synthesis and accelerated proteoglycan breat down in the slices of cartilage. Both nitric oxide synthase inhibitors substantially counteracted the suppression of prdteoglycan synthesis but exacerbated proteoglycan catabolism occurring in response to interleukin‐1 and the chondrocyte‐activating factors. The accelerated eatabolism was associated with increased levels of matrix metalloproteinases in the conditioned medium. This dual effect of nitric oxide complicates decision making with regard to the possible clinical applications of nitric oxide agonists or antagonists in diseases of cartilage.
Regulation of the expression of the type‐II collagen gene in periosteum‐derived cells by three members of the transforming growth factor–β superfamily
Authors: Ballock R. Tracy , Heydemann Ahlke , Izumi Toshihiro , Reddi A. Hari
Published: February 2005

Although transforming growth factors‐β and bone morphogenetic proteins are both capable of inducing bone formation in vivo, the target cells of their osteoinductive actions may be different. To evaluate periosteal cells as potential targets of the actions of transforming growth factor–β and bone morphogenetic protein, we investigated the ability of three members of the transforming growth factor–β superfamily to modulate expression of the gene encoding the α1(II) chain of type‐ll collagen in periosteum‐derived cells in Vitro. The results demonstrate that transforming growth factor–β mRNA is expressed by periosteum‐derived cells and that exogenous transforming growth factor–β1 acts to upregulate expression of the gene encoding collagen α1(II). This effect was observed as early as 12 hours after administration of transforming growth factor–β1 but was not observed in response to bone morphogenetic proteins 3 or 4. No synergy was demonstrated between transforming growth factor–β1 and bone morphogenetic protein‐3 in the ability to upregulate expression of the collagen α1(II) gene. These results support the hypothesis that committed periosteal mesenchymal cells are cellular targets of the action of transforming growth factor–β.
Correspondence between theoretical models and dual energy X‐ray absorptiometry measurements of femoral cross‐sectional growth during adolescence
Authors: van der Meulen Marjolein C. H. , Marcus Robert , Bachrach Laura K. , Carter Dennis R.
Published: February 2005

We have developed an analytical model of long bone cross‐sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x‐ray absorptiometry. Measurements of mid‐diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9–26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross‐sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.
Robertsonian translocations in Paget's disease of bone
Authors: Mills Barbara G. , Oizumi Jun , Kudo Emily , Rude Robert
Published: February 2005

The karyotypes of 14 patients with Paget's disease of bone were studied. The patients were recruited from our bone metabolism clinic where they received specific therapy for their skeletal disease. Eight of the 14 patients had chromosomal translocations localized to the D and G groups. None of the patients were related to one another, nor had any had the same lifelong environment. Thus, 57% of a sample of active patients with Paget's disease had Robertsonian translocations. By comparison, an age and sex‐matched group of eight controls and 13 patients with osteoporosis who had been treated with bisphosphonates demonstrated no Robertsonian translocations. The prevalence of Robertsonian translocations in 14,000 newborns was reported to be 0.1%. These data suggest that a factor from the environment introduced during the lifetime of the patient could be present and could, in addition to genetic factors, affect gene replication during the development of Paget's disease.
Regional and temporal changes in the acoustic properties of fracture callus in secondary bone healing
Authors: Harten Robert D. , Lee Francis Y. , Zimmerman Mark C. , Hurowitz Eli , Arakal Rajesh , Behrens Fred F.
Published: February 2005

Controlled fractures were created in the right femora of 17 male Sprague‐Dawley rats. The fractured limbs were harvested at 2, 4, 6, and 8 weeks after fracture, fixed, and embedded in polymethylmethacrylate. Midsagittal sections from each animal were evaluated with a scanning acoustic microscope, a device that generates an acoustic impedance map of the scanned material. The impedance of the fracture callus was measured in six regions on each specimen. These regions were chosen in an effort to distinguish between the impedance of the callus formed through intramembranous or endochondral ossification, and we found that the time course of increasing impedance differed for the fracture callus formed through the two pathways. Additionally, we found a significant difference in the mean impedance of the callus at each time period (p ≤ 0.0013 for all comparisons), which resulted in an extremely linear relationship (r2 = 0.999) between mean callus impedance and healing time. This experimental model has become a popular choice for the investigation of fracture healing. As such, an accurate determination of the mechanical properties of the fracture callus is often sought. We propose that the implementation of scanning acoustic microscopy in the study of fracture healing may determine the changes in the material properties more accurately than conventional testing methods.
Influence of size and stability of the osteotomy gap on the success of fracture healing
Authors: Claes Lutz , Augat Peter , Suger Gebhard , Wilke Hans‐Joachim
Published: February 2005

Flexible fixation of fractures with minimally invasive surgical techniques has become increasingly popular. Such techniques can lead to relatively large fracture gaps (larger than 5 mm) and considerable interfragmentary movements (0.2‐5 mm). We investigated the influence of the size of the fracture gap, interfragmentary movement, and interfragmentary strain on the quality of fracture healing. A simple diaphyseal long‐bone fracture was modeled by means of a transverse osteotomy of the right metatarsus in sheep. In 42 Sheep, the metatarsus was stabilized with a custom‐made external ring fixator that was adjustable for gap size and axial interfragmentary movement. The sheep were randomly divided into six groups with three different gap sizes (1, 2, or 6 mm) and small or large interfragmentary strain (approximately 7 or 31%). The movement of the fracture gap was monitored telemetrically by a displacement transducer attached to the fixator. After 9 weeks of healing, the explanted metatarsus was evaluated mechanically in a three‐point bending test to determine bending, stiffness and was radiographed to measure the amount of periosteal callus formation. Increased size of the gap (from 1 to 6 mm) resulted in a significant reduction in the bending stiffness of the healed bones. Larger interfragmentary movements and strains (31 compared with 7%) stimulated larger callus formation for small gaps (1‐2 mm) but not for larger gaps (approximately 6 mm). The treatment of simple diaphyseal fractures with flexible fixation can be improved by careful reduction of the fracture; this prevents large interfragmentary gaps. The experimental fracture model for the metatarsus showed that the healing process was inferior when the gap was larger than 2 mm.
Lengths of hamstrings and psoas muscles during crouch gait: Effects of femoral anteversion
Authors: Schutte Lisa M. , Hayden Scott W. , Gage James R.
Published: February 2005

Recent studies of muscle lengths measured by means of gait analysis data and musculoskeletal models have suggested that in many cases of crouch gait in patients with cerebral palsy, the hamstrings are of normal length and the psoas muscles are short. In these studies, however, muscle lengths were calculated by applying kinematic data from a child's joint to a normal adult model. Children with cerebral palsy and other disorders generally do not have normal bone architecture but instead have muscle attachment points and muscle paths altered by osseous deformities. In this study, we explored the consequences of using normal adult musculoskeletal models to calculate hamstring and psoas lengths for children with cerebral palsy. Specifically, for a group of subjects with cerebral palsy who walk with a crouch gait, we investigated the changes in muscle lengths that arise when a patient‐specific representation of clinically measured femoral anteversion was added to a model of normal musculoskeletal geometry. The calculation of psoas muscle length was found to be very sensitive to femoral anteversion, whereas the calculation of hamstrings length was found to be relatively insensitive to this osseous deformity.
In vivo forces during remodeling of a two‐segment anterior cruciate ligament graft in a goat model
Authors: Lundberg William R. , Lewis Jack L. , Smith Joel J. , Lindquist Conrad , Meglitsch Toni , Lew William D. , Poff Bradley C.
Published: February 2005

An existing goat model was used to measure in vivo graft forces during walking, to determine if the forces set at surgery change over time under the same external load and if the forces in the graft during in vivo function can be dictated by the forces set at surgery. The anterior cruciate ligament was reconstructed in 12 goats with use of a composite graft consisting of a bone‐patellar tendon‐bone autograft and a synthetic augmentation segment. The forces in the graft segments were established intraoperatively by a force‐setting technique. In five animals, the tendon segment was set to carry 90% of the total graft force, and in the seven other animals, the augmentation segment was set to carry 90% of the total force. The total graft force was the same in all animals. Graft forces due to anterior tibial loads of 67 N were measured before and after fixation and 6 weeks after surgery with the use of buckle transducers mounted extra‐articularly over the anterior tibia. They were also measured during straight, level walking at 6 weeks. The forces changed significantly from just after surgery to 6 weeks later, such that the initially set load‐sharing was eliminated by 6 weeks. At 6 weeks, a relatively smooth gait had been achieved, and the maximum total graft force in each animal during walking averaged 35 N and was of similar magnitude to forces generated by the anterior tibial loads of 67 N with the animal anesthetized. After fixation, forces in the tendon graft segments were significantly different between the group with high set forces and that with low set forces. At 6 weeks, when functional joint loads were approaching normal levels, the graft segment forces for the two groups were not significantly different. Load‐sharing between tendon and augmentation segment and load in the tendon segment at 6 weeks could not be dictated at surgery.