bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteoglycan alterations following immobilization and remobilization in the articular cartilage of young canine knee (stifle) joint
Authors: Säämänen Anna‐Marja , Tammi Markku , Jurvelin Jukka , Kiviranta Ilkka , Helminen Heikki J.
Published: February 2005

The distribution of proteoglycans (PGs) at 11 sites on the knee (stifle joint) cartilage of young female beagle dogs was studied following cast immobilization for 11 weeks in 90° flexion and after a subsequent remobilization for 15 weeks. Immobilization induced a reduction in PG uronic acid at all sites (mean of −38%), but the greatest depletion ( −64%) occured at the anterior and posterior extremes of the femoral condyles, i.e., at locations where the immobilized cartilage lost contact to the opposing cartilage. Following remobilization, the content of uronic acid remained lower than in the agematched controls (−18% on average), particularly at the minimum contact sites most affected by immobilization (−33%). The chondroitin‐6‐sulfate to chondroitin‐4‐sulfate ratio was reduced by immobilization in most locations (average of −14%) and returned to control values after remobilization. There was no consistent change in the percentage of aggregating PGs observed in Sephacryl S‐100 gel filtration after immobilization or remobilization. However, following remobilization, the aggregating PGs showed an enhanced proportion of the slower mobility band in agarose gel electrophoresis, indicative of a larger monomer size. In the contralateral, load‐bearing knee joint, both the uronic acid content and PG monomer type distribution were identical to those observed in the experimental joint, suggesting that the state reached after the remobilization period was due to factor(s) influencing both side. The results suggest that contact forces between articulating surfaces are required to maintain normal PG content and that the control mechanism works locally at each cartilage site. Restriction of joint mobility and loading in young animals is concluded to cause persistent changes in cartilage matrix. Furthermore, the use of the contralateral joint as the sole control in this kind of studies, although experimentally convenient, seems not to be appropriate.
Immunohistochemical and biochemical demonstration of calcium‐dependent cysteine proteinase (calpain) in calcifying cartilage of rats
Authors: Shimizu Katsuji , Hamamoto Takashi , Hamakubo Takao , Lee Woon Joo , Suzuki Kiichi , Nakagawa Yasuaki , Murachi Takashi , Yamamuro Takao
Published: February 2005

Calpain is a Ca2+‐dependent cysteine proteinase that has neutral pH optima. There are two classes of calpains that differ in their optimal calcium ion concentration for enzymatic activity. Calpain I requires a low concentration of Ca2+ for activation, and calpain II requires a much higher Ca2+ concentration. This report describes the immunohistochemical and biochemical demonstration of calpain II in calcifying cartilage in rats and also the degradation of the cartilage proteoglycan subunit by calpain II. Immunoperoxidase (peroxidase‐antiperoxidase) staining of the frozen sections of the knee joint from 3‐day‐old and 6‐day‐old Wistar rats, using polyclonal antibodies against the respective heavy subunits of calpains I and II, showed positive staining only with the anti‐calpain II antibody in the hypertrophic chondrocytes and surrounding cartilaginous matrix of the growth cartilage. Diethylaminoethyl‐cellulose chromatography of the cartilaginous extract from 3‐day‐old rats showed a peak of caseinolytic activity attributable to calpain as well as an inhibitory peak of calpastatin, a specific inhibitor protein of calpains. Immunoblotting using the anti‐calpain II antibody of the calpain peak demonstrated identity with the heavy subunit of calpain II (80 kDa). Proteoglycan‐degrading activity of calpain was assessed using porcine kidney calpain II and the porcine articular cartilage proteoglycan subunit. After incubation in the presence of Ca2+, degradation of proteoglycan was demonstrated by the change of the elution position on Sepharose‐2B chromatography. It is possible that calpain functions as one of the proteoglycan‐degrading proteolytic enzymes of growth cartilage. Intracellular localization of calpain in hypertrophic chondrocytes also suggests a role in the hypertrophic process of the chondrocyte in growth cartilage.
Biomechanical evaluation of a biodegradable composite as an adjunct to internal fixation of proximal femur fractures
Authors: Witschger Pierre M. , Gerhart Tobin N. , Goldman Janet B. , Edsberg Laura E. , Hayes Wilson C.
Published: February 2005

Internal fixation of comminuted unstable fractures of the severely osteoporotic proximal femur is sometimes supplemented with polymethyl‐methacrylate (PMMA). We here report an in vitro biomechanical evaluation of a biodegradable particulate composite that might be used for similar purposes. The composite includes a matrix phase consisting of a hydrolyzable prepolymer [polypropylene fumarate (PPF)] cross‐linked with methacrylate monomer, and a particulate phase consisting of tricalcium phosphate and calcium carbonate. We implanted dynamic hip screws in 22 cadaveric proximal femora and measured the yield load for an oblique force applied to the femoral head. The hip screws were then reinforced with either PMMA or the PPF composite and tested again. On the basis of analysis of variance, the average increases in yield load for PMMA and PPF reinforcement of 1, 750 and 1,130 N were statistically significant (p < 0.00005), suggesting that both materials enhance congruence between implant and bone and thereby increase the projected load‐bearing area of the implant. The increase in yield force with PMMA was slightly higher than the increase with PPF (p < 0.05), but both values after reinforcement were close (3,790 ± 561 N for PMMA vs. 3,240 ± 669 N for PPF). If we can demonstrate that appropriate rates of degradation, bony ingrowth, and static and fatigue properties can be achieved in vivo with this system, our data suggest that this PPF composite may have potential as an adjunct to the internal fixation of unstable fractures of the osteoporotic hip.
Variables affecting disc size in the lumbar spine of rabbits: Anesthesia, paralysis, and disc injury
Authors: Neufeld J. Hulse , Machado T. , Margolin L.
Published: February 2005

Methods have been developed that permit repetitive radiographic measurement of the lumbar intervertebral disc space in a rostral‐caudal direction (width) in the anesthetized laboratory rabbit. Using isolated control discs and injured discs in which narrowing has been induced for chronic and acute periods, the widths of the lumbar intervertebral disc spaces determined radiographically correlate with widths determined histologically (p < 0.000, r = 0.75). Both an increase (widening) and a decrease (narrowing) in disc width were observed using radiography after different experimental treatments. Anesthesia and lower‐body paralysis (an experimentally induced inability to bear weight on and to perceive a pinch stimulus in hind limbs) caused widening of the discs: anesthesia causing a general widening throughout the lumbar spine and lower‐body paralysis causing a specific widening low in the lumbar spine. Both disc injection and piercing the disc with needles to recover nucleus pulposus material caused narrowing of the discs. Acridine‐orange injection induced a narrowing accompanied by osteophytosis. Experimentally induced narrowing at L4–5 (the result of injury to the disc) resulted in narrowing also at L2–3. These findings are consistent with the hypothesis that in vivo disc‐width size in the young rabbit depends on both the quantity of nucleus pulposus material and the force‐generating activities of the adjacent spinal muscles, and that disc injury at one level stimulates narrowing at other levels.
Three‐dimensional kinematics of glenohumeral elevation
Authors: An K.‐N. , Browne A. O. , Korinek S. , Tanaka S. , Morrey B. F.
Published: February 2005

To help resolve longstanding uncertainties about kinematics of the shoulder, we studied three‐dimensiona glenohumeral joint motion during arm elevation. A magnetic tracking system was used to monitor the threedimensional orientation of the humerus with respect to the scapula. Appropriate coordinate transformations were then performed for the calculation of glenohumeral joint rotation based on the defined Eulerian angle. The effects of the plane of elevation and the humeral rotation on the magnitude of arm elevation were documented. The maximum humeral elevation at the glenohumeral joint took place in a plane anterior to the scapular plane. Maximum elevation in all planes anterior to the scapular plane required external axial rotation of the humerus. Conversely, internal axial rotation was necessary for maximum elevation posterior to the scapular plane. Quantifying the obligatory axial rotation explains the relationship of internal and external rotation with maximum elevation.
A quantitative analysis of matrix alignment in ligament scars: A comparison of movement versus immobilization in an immature rabbit model
Authors: Frank C. , MacFarlane B. , Edwards P. , Rangayyan R. , Liu Z‐Q. , Walsh S. , Bray R.
Published: February 2005

This investigation quantified the alignment of fibrillar matrix in normal rabbit medial collateral ligaments (MCLs) and in healing MCLs from animals treated with or without knee immobilization. Twenty‐four immature female rabbits were given complete midsubstance injuries to their right MCLs. Fifteen of them had that knee pin immobilized in flexion, while the remaining nine were allowed unrestricted cage activity. Animals were sacrificed in groups of three at intervals of 3, 6, or 14 weeks after injury, and both healing MCLs and unoperated contralateral controls were fixed in situ for subsequent removal, freeze‐fracture, and preparation for scanning electron microscopy (SEM). A random sampling of SEM photographs followed by atuomated, statistically validated image processing was used to quantify alignment of matrix in all samples. Results showed that nonimmobilized MCL scars in this model do remodel over 14 weeks of healing, returning to normal alignment values in that time. Surprisingly, MCL scars in immobilized knees were even better, with mean matrix alignments falling statistically within normal MCL limits at all healing intervals studied. If not due to an unknown sampling or fixation artifact, these results suggest that gross knee flexion and extension is not a prerequisite for scar matrix alignment in this immature model of ligament healing.
Comparison of the stability of press‐fit hip prosthesis femoral stems using a synthetic model femur
Authors: McKellop H. , Ebramzadeh E. , Niederer P. G. , Sarmiento A.
Published: February 2005

The motion of three different press‐fit hip prosthesis femoral components was compared with that of a cemented stem and an Austin Moore noncemented hemiarthroplasty. Synthetic composite femurs were used as an experimental model to reduce the variations in shape and quality typical among cadaver femurs. Motion was measured under axial and rotational loading approximating a walking load. On the initial application of load, axial subsidence was as much as several millimeters for the noncemented stems. Considerable tightering occurred during the 5,000 walking cycles, such that the motion of the noncemented stems in some directions eventually was as small as that of the cemented stem, on the order of tens of microns.
Immunology of peripheral nerves and response to trauma
Authors: Trumble Thomas , Stanislaw James
Published: February 2005

Research in limb reconstruction using peripheral nerve tissue has been hampered by tissue rejection. In order to provide more information on the immunology of peripheral nerves, 35 specimens (26 from seven cadavers and nine from surgical biopsies) were analyzed for the presence of human leukocyte antigens (HLA), which are a key component of major histocompatibility complex class II (MHC Class II) antigens. MHC Class II antigens were noted in all human nerve specimens, and the percentage of areas of positive staining by immunohistochemistry was significantly higher (3.82% ± 1.01%) than that of negative controls (.05% ± 0.02%) (p < 0.01). The negative controls consisted of serial sections that were stained in the same manner except that the primary antibody was deleted. There was no significant difference in the presence of MHC Class II antigens between sensory and mixed motor nerves or among the different HLA groups (HLA‐DR, HLA‐DP, HLA‐DQ). A mouse model was used to evaluate the effect of trauma on the presence of MHC Class II antigens. Three weeks after transsection of the sciatic nerve there was a statistically significant increase (p < 0.05) in the presence of MHC Class II antigens in the distal portion of the nerve (4.49% ± 0.78%) as compared with samples from animals that had had exposure of the nerve without transsection (1.44% ± 0.21%) or in nerves from animals that had had no surgery (1.02% ± 0.21%). The presence of MHC Class II antigens could require more complex cross‐matching for tissue transplantation. Nerve grafts that have undergone Wallerian degeneration may actually be more prone to rejection than are other peripheral nerve tissue transplants.
Absorption of lidocaine following topical application in microvascular procedures on rabbits
Authors: Hou Sheng‐Mou , Liu Tang‐Kue , Yu Hsiu‐Ying
Published: February 2005

Fifty rabbits were used to investigate the absorption of lidocaine following its topical application to blood vessels. The lidocaine level in the blood was determined by gas chromatography and the enzyme immunoassay. Animals were divided into five groups according to anatomic site (femoral vs iliac) and according to whether vessels were intact or anastomosed. In the last group (E), a water‐tight sleeve was placed on the anastomosed femoral artery so that the lidocaine contacted only a small segment of the artery. In each group, 0.4 and 1 ml of 10% lidocaine were used. Our results revealed that absorption of lidocaine from topical usage was rapid. The absorption peak occurred within 5–15 min. The serum concentration of lidocaine was significantly higher in groups with intact vessels than in those with anastomosed ones. The peak level of lidocaine in the serum occurred sooner in the iliac area than in the femoral area. Absorption in group E was very low due to only a small segment of the artery being immersed with lidocaine. The main absorption site of lidocaine was not through the vessel but through the perivascular area. Toxicity may develop clinically if a high concentration of lidocaine is applied on a vessel during microsurgery.
Trunk positioning accuracy in the frontal and sagittal planes
Authors: McGlashen K. , Ashton‐Miller J. A. , Green M. , Schultz A. B.
Published: February 2005

The accuracy with which the head and spine could be positioned in the frontal and sagittal planes relative to the pelvis was measured and compared in ten healthy adult males. Subjects were tested with eyes closed, while standing with their pelvis externally restrained. The positions of markers, attached to the back of the head and over each of the T1, T6, T11, and L3 spinous processes, were measured to the nearest mm using strain‐gaged flexible beam transducers. Subjects were tested for their accuracy in sensing return of the trunk to an initial neutral position under different test conditions. Results showed that positioning was 16–45% more accurate in the frontal than in the sagittal plane, although the difference did not reach statistical significance. T1 could be centered to within 7 and 10 mm in the frontal and sagittal planes, respectively. No significant differences were found between active and passive positioning accuracies. Presence of an external trunk moment did not significantly affect trunk positioning accuracy, although it systematically caused overshoot of the neutral position. Lastly, lateral trunk shifts exceeding 12 mm may be classified as abnormal in young adults.
Comparison of cortical bone and serum concentrations of clindamycin achievable by direct local infusion and intravenous administration
Authors: Budsberg Steven C. , Gallo James M. , Starliper Clifford E. , Shotts Emmett B. , Brown John
Published: February 2005

Tibial cortical bone and serum concentrations of clindamycin were compared using two drug delivery methods in dogs. An implantable drug pump, used to continuously infuse clindamycin directly into the cortical bone, was compared with clindamycin administered i.v. Dosage for the direct continuous infusion was 4 mg/kg/day, and 44 mg/kg/day for the i.v. bolus regimen. Serum concentrations of clindamycin were significantly higher during i.v. bolus administration when compared with those achieved during pump infusion (p < 0.05). However, tibial cortical bone concentrations were significantly higher during pump infusion than were those achieved by i.v. bolus. When examining serum and bone clindamycin concentrations over 21 days of direct local infusion, there was no significant difference in concentrations between sampling days within each tissue (p > 0.05). Furthermore, there were significantly greater concentrations of clindamycin in the cortical bone than in the serum at each sampling period (p < 0.05). Results indicate that delivery of clindamycin to canine bone by implantable drug pump achieve significantly higher bone concentrations than i.v. bolus administration of the drug at higher dosages. Direct infusion also can sustain high concentrations in cortical bone without increasing systemic concentrations of clindamycin.
Studies on the autocrine activation of a synovial cell line
Authors: Baratz M. E. , Georgescu H. I. , Evans C. H.
Published: February 2005

The lapine synovial cell line HIG‐82 secretes factors that activate cultures of articular chondrocytes. We showed that these “chrondrocyte‐activating factors” (CAF) also activate quiescent cultures of HIG‐82 cells in an autocrine fashion. After exposure to partially purified preparations of CAF, HIG‐82 cells increased their synthesis of prostaglandin E2 (PGE2) and the neutral proteinases collagenase, gelatinase, and stromelysin. CAF also induced their own synthesis. Both PGE2 synthesis and endogenous production of CAF started to increase between 1 and 3 h after treatment of cells with exogenous CAF, but the neutral proteolytic activity of the conditioned medium took ∼ 12 h to increase. Induction of neutral proteinases by CAF was inversely related to the degree of cell confluency. Whereas their induction by phorbol myristate acetate (PMA) was independent of this parameter. Both CAF and PMA provoked morphologic changes in subconfluent cultures of HIG‐82 cells. Although the intracellular concentration of free Ca2+ increased rapidly in response to CAF, the results of experiments with calcium channel blockers and ionophores failed to support a role for Ca2+ fluxes in induction of neutral proteinases. In similar types of experiments, no evidence could be found to implicate fluxes in cyclic AMP or cyclic GMP in the induction of collagenase, gelatinase, or stromelysin. Because PMA is such a strong inducer of these enzymes, protein kinase C may be involved in signal transduction, but further work is needed to determine whether this is so.
Proteoglycan alterations during developing experimental osteoarthritis in a novel hip joint model
Authors: Inerot Sven , Heinegård Dick , Olsson Sten‐Erik , Telhag Hans , Audell Lars
Published: February 2005

Degenerative hip joint disease was induced in dogs by extraarticular surgery that created a condition that mimics hip dysplasia. Decreased acetabular coverage of the femoral head gave altered mechanical load, with ensuing cartilage degeneration. For comparison, degenerative knee joint disease was induced in other dogs by transection of the anterior cruciate ligament of the knee. The femoral head articular cartilage showed macroscopic signs of degeneration within a month. No macroscopical changes of synovitis were present. Chemical analysis of cartilage samples showed loss of proteoglycans. Guanidine hydrochloride extracts of the cartilage contained proteoglycan fragments that could be separated by equilibrium density gradient centrifugation in cesium chloride. The data indicate that proteoglycans are fragmented by proteolytic cleavage and lost from the cartilage. The proteoglycans remaining in the tissue are smaller and have lost the ability to aggregate with hyaluronic acid. Similarly, in experimental knee joint osteoarthritis, the proteoglycan content of the cartilage decreased. The structural changes of those proteoglycans remaining were of a different nature, with no changes in proteoglycan size or aggregation properties, possibly indicating that both degradation and repair took place in the knee articular cartilage and/or that fragments were rapidly lost from the tissue. This may follow from different surgical procedures, only the one used for the hip joint being extra‐articular, or from the different anatomy and physiology of the hip joint and the knee joint.
Elimination of exogenously injected sodium‐hyaluronate from rabbit flexor tendon sheaths
Authors: Hagberg Lars , Tengblad Anders , Gerdin Bengt
Published: February 2005

To obtain information about the elimination of Na hyaluronate (NaHe) deposited in flexor tendon sheaths in rabbits, two flexor tendon sheaths from each hind limb were operatively exposed in 15 animals and each filled with one of four different NaHe preparations, namely: 10 mg/ml, MW 2.6 × 106; 10 mg/ml, MW 6.3 × 106; 19 mg/ml, MW 3.0 × 106; and 19 mg/ml, MW 6.5 × 106. One, 3, and 7 days after surgery, the NaHe concentration was measured in frozen specimens from the tendon sheaths. One day after surgery, NaHe concentration in the tendon sheath fluid was close to 10 mg/ml in all groups. Three and 7 days after surgery it was higher in tendon sheaths in which NaHe preparations with a high (19 mg/ml) rather than with a low concentration (10 mg/ml) had been deposited. At 3 days, NaHe concentration was also higher in sheaths that had received a preparation with a high MW (6.5 × 106) than those with a lower MW (2.6 or 3.0 × 106). The findings suggest that within the first 24 h, a dilution of concentrated NaHe preparations takes place, probably as a result of their hyperoncotic properties. After 24 h, there was a slower decline in NaHe concentration when more concentrated solutions (19 mg/ml) and solutions with high MWs (6.5 × 106) were administered. Development of pharmaceutical NaHe preparations with slow elimination from tendon sheaths should reasonably be focused on a solution with a high MW and high concentration.
Bone graft translation of four upper cervical spine fixation techniques in a cadaveric model
Authors: Crisco Joseph J. , Panjabi Manohar M. , Oda Takenori , Grob Dieter , Dvorak Jiri
Published: February 2005

The goal of spinal fixation is to promote bony fusion by restricting motion at the site of the bone graft. Therefore, in order to evaluate the efficiency of various cervical fixation techniques, we determined the translations at the posterior arch of C1 for four C1—C2 posterior techniques: Gallie, Brooks, Magerl, and Halifax. Our model was the cadaveric specimen, with extensive soft tissue injury: transection of the alar, transverse, and capsular ligaments. Under three‐dimensional physiological loading, we recorded the motion of C1 relative to C2, and calculated the translations at the surface of the graft in three dimensions, 10 specimens being tested intact, injured, and instrumented with each of the techniques. We assumed that translational laxity or neutral zone was the critical motion parameter and evaluated it, quantified herein as the neutral zone, at seven points at the graft site. The three‐dimensional neutral zone translations were analyzed by their axial and shear components. We found that there was no significant difference with the fixation techniques in the average axial translation (Brooks: 1.1 mm; Magerl: 1.3 mm; Gallie: 1.5 mm; and Halifax: 0.5 mm). In shear, the Magerl averaged 1 mm, which was significantly less than the Gallie (2.1 mm). The Brooks (1.6 mm) and Halifax (1 mm) were not different from each other, Magerl, or Gallie. We propose that evaluation by translational laxity (neutral zone) at the graft site is a noteworthy concept in biomechanical analysis.
Proliferation and macromolecular synthesis by rat calvarial bone cells grown in various oxygen tensions
Authors: Brighton Carl T. , Schaffer Jonathan L. , Shapiro David B. , Tang Johnson J. S. , Clark Charles C.
Published: February 2005

Perinatal rat calvarial bone cells were isolated by sequential collagenase digestion and grown in oxygen tensions ranging from 1 to 60% O2. Cell proliferation as determined by automated cell counting and DNA content was greatest in the lower oxygen tensions (≥ 9% O2), whereas alkaline phosphatase activity and [35S]sulfate and [14C]proline incorporation were greatest in the higher oxygen tensions (≥ 13% O2). It is concluded that lower oxygen concentrations favor bone cell proliferation, whereas higher oxygen concentrations favor macromolecular synthesis. These findings, when related to the known pO2 of the fracture callus, suggest the following sequence of events: first, at the time of fracture an ingrowth of osteoprogenitor cells, capillary buds, and primitive mesenchymal cells occurs in the fracture site, a region of low pO2; second, a great increase in cellular proliferation accompanied by an initiation of macromolecular synthesis follows; finally, as the pO2 levels begin to increase, cellular proliferation decelerates, accompanied by an increase in macromolecular synthesis.
Postfracture irradiation effects on the biomechanical and histologic parameters of fracture healing
Authors: Brown Robert K. , Pelker Richard R. , Friedlaender Gary E. , Peschel Richard E. , Panjabi Manohar M.
Published: February 2005

The effects of single‐dose local irradiation on the biomechanical properties of closed femoral fractures were studied in 75 mature Sprague‐Dawley rats. Ten days after fracture, the rats were irradiated with 900 rads at 250 kV to the entire fractured femur. At 2, 3, 4, 8, and 16 weeks after fracture, both fractured and contralateral intact femurs were recovered and evaluated biomechanically by testing to failure in torsion. Results were compared with those from a similar study involving fractures irradiated 3 days after fracture as well as nonirradiated control fractures. Fracture healing progressed faster when irradiation was delayed 10 days than when delayed 3 days, and control fractures healed more rapidly than after either delay. In the 10‐day delay group, fractures showed greater strength than did those in the 3‐day delay group at 8 weeks, but the strength of irradiated fractures in both groups was similarly depressed at 16 weeks, with a maximum torque well below that of control fractures. These results suggest that delaying radiation exposure of a fracture may mitigate short‐term deleterious effects on fracture repair, but that long‐term results may be similar to those associated with expeditious irradiation.
Electromagnetic stimulation of bone repair: A histomorphometric study
Authors: Canè Valerio , Botti Paolo , Farneti Daniele , Soana Silvana
Published: February 2005

The effect of pulsing electromagnetic fields (PEMFs) on bone repair was studied in principal metacarpal bones of eight adult male horses: Six horses were treated with PEMFs, and two horses were untreated. In treated horses, Helmholtz coils were applied during a 60‐day period to the left metacarpal bones, bored with eight holes of equal diameter and depth, from the middiaphysis toward the distal metaphysis. Eight equal holes bored in the right metacarpal, surrounded by unactivated Helmholtz coils, were taken as controls. The two untreated horses were taken as additional control. The results of computer‐assisted histomorphometric analysis indicate that (a) in diaphyseal levels, the amount of bone formed during 60 days is significantly greater (p < 0.01) in PEMF‐treated holes than in contralateral ones and those in control horses; (b) in metaphyseal levels, PEMF‐treated holes are sometimes more closed, sometimes less, as compared with contralateral holes and those in control horses; in any case the statistical analysis indicates that the symmetry in the rate of hole repair, found between the two antimeres of control horses, is not appreciable at metaphyseal levels also; (c) there was no statistically significant difference between untreated holes in PEMF‐treated horses and holes in control horses, neither at diaphyseal nor at metaphyseal levels. These preliminary findings indicate that PEMFs at low frequency influence the process of bone repair on both diaphysis and metaphysis, and seem to improve the process of bone repair in skeletal regions normally having a lower osteogenetic activity, i.e., in diaphyses as against metaphyses.
Effects of free and bound insulin‐like growth factors on proteoglycan metabolism in articular cartilage explants
Authors: Tesch Gregory H. , Handley Christopher J. , Cornell Hugh J. , Herington Adrian C.
Published: February 2005

This article describes the effects of bound forms of insulin‐like growth factors (IGFs) on proteoglycan metabolism by bovine articular cartilage in explant culture. When these growth factors were added to articular cartilage explants complexed with their native serum binding proteins (BPs), both IGF‐I‐BP complex and IGF‐II‐BP complex stimulated proteoglycan synthesis to different degrees over a 3‐day period. When added to the medium of cultures of articular cartilage over 5 days, IGF‐II‐BP complex induced high rates of synthesis and low rates of catabolism of proteoglycans, giving rise to tissue levels of proteoglycan similar to those observed in fresh tissue. When articular cartilage was maintained in culture with the same concentration of IGF‐I‐BP complex, tissue levels of proteoglycans fell over the culture period because of lower rates of proteoglycan synthesis. Analysis of the proteoglycans synthesized by articular cartilage in the presence of free or bound IGF‐I or IGF‐II showed that these growth factors stimulated the rate of synthesis of the large proteoglycan species present in cartilage but did not affect the synthesis of the small proteoglycans.
Morphological basis for back pain: The demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum
Authors: Ashton I. K. , Ashton B. A. , Gibson S. J. , Polak J. M. , Jaffray D. C. , Eisenstein S. M.
Published: February 2005

The innervation of lumbar facet capsule and ligamentum flavum was investigated using antisera to a general neuronal marker protein gene product (PGP) 9.5 and to peptide markers of sensory nerves (calcitonin generelated peptide [CGRP] and substance P) and autonomic nerves (vasoactive intestinal polypeptide [VIP] and C‐flanking peptide of neuropeptide Y [CPON]). In the facet capsule (n = 14), PGP 9.5 and CGRP‐immunoreactive nerves occurred in 12 and five specimens, respectively, both around blood vessels and as free fibers in the stroma. Free fibers immunoreactive for substance P or VIP were noted in three and five specimens, whereas in nine specimens there were CPON‐immunoreactive nerves located perivascularly. There was no immunoreactivity in the ligamentum flavum. This study provides further evidence that the facet capsule but not the ligamentum flavum has substantial innervation by sensory and autonomic nerve fibers and has a structural basis for pain perception.
Ultrastructural morphometry of anterior cruciate and medial collateral ligaments: An experimental study in rabbits
Authors: Hart R. A. , Woo S. L‐Y. , Newton P. O.
Published: February 2005

This study presents morphometric analyses of collagen subfascicle area fraction and collagen fibril diameter distributions for the anterior cruciate (ACL) and medial collateral (MCL) knee ligaments from transmission electron micrographs of ligament cross sections of five mature, female New Zealand White rabbits. Statistically significant differences in subfascicular area fractions were found between the ACL and MCL (0.89 ± 0.02, 0.97 ± 0.01, respectively; p < 0.001). Mean fibril diameters for the ACL and MCL were also significantly different (0.059 ± 0.005, 0.085 ± 0.011 μm, respectively; p < 0.025). Fibril eccentricity (a measure of parallel alignment of collagen fibrils within the ligaments, defined as the ratio of minor to major axes of elliptical fibril outlines) was 0.89 ± 0.03 and 0.85 ± 0.08, respectively, for the ACL and MCL; these data were not significantly different (p > 0.1). The relative amount of variation in the pooled fibril diameter data due to variation between animals, ligaments, locations within ligaments, and among fibrils at individual locations are reported. The variation of fibril diameter distributions between the ACL and MCL was substantially greater than the variation between different locations within each ligament cross section as well as between different animals. The structural differences reported may help explain known differences in the biomechanical properties of the ACL and MCL.
Combined effect of acute denervation and ischemia on the microcirculation of skeletal muscle
Authors: Chen Long‐En , Seaber Anthony V. , Urbaniak James R.
Published: February 2005

Using direct in vivo videomicroscopy and a fluorescein dye technique, reperfusion injury after 3 h of ischemia was studied in the acutely denervated cremaster muscle of the rat. Compared with normally innervated controls, ischemia‐induced reperfusion injury was more severe in the denervated group and included a delay of blood flow recovery, vortex formation, edema, hemorrhage, and vessel spasm. Vessel size was reduced at the arteriole and small artery level, and there was a decrease of reactive hyperemia. The injury mechanism may be related to a loss of active vasomotion and vascular response to vasoactive substances after denervation. The results suggest that shortening the ischemia time of denervated tissues may reduce ischemia‐induced reperfusion injury. Similarly, given the same ischemia time, improved tissue reperfusion may be expected if the nerve supply is maintained.
Angular deformities and forearm function
Authors: Sarmiento Augusto , Ebramzadeh Edward , Brys David , Tarr Richard
Published: February 2005

Angular deformities were created in cadaver forearms at proximal, middle, and distal third levels of the radius and ulna separately, and at middle and distal third levels of both bones, to determine the corresponding limitations of pronation and supination. The ranges of pronation and supination were recorded using a rotational motion measurement apparatus instrumented with a 360° goniometer. These experimental results were compared to data obtained from clinical and radiographic examination of 105 patients with similar residual deformities following treatment of fractures by nonsurgical means, to evaluate the accuracy of the experimental model and to determine if loss of rotational motion could be predicted based on radiographic findings. With cadaver forearms, on the average, angulation of 10° of the radius or ulna in coronal or sagittal planes limited pronation and supination by <24°, whereas angulation of 10° of both the radius and the ulna limited pronation and supination by <18%. Comparison of experimental results with clinical findings showed that, despite the errors involved in measuring forearm deformities in patients using biplanar radiographs, the experimental results predicted the clinical loss of pronation and supination to within 17% for the fractures of the radius, and within 8% accuracy for the fractures of the ulna.
The effect of hypothermic ischemia on the α‐adrenergic mechanisms of the canine tibia vascular bed
Authors: Davis T. R. C. , Wood M. B. , Vanhoutte P. M.
Published: February 2005

The effect of hypothermic ischemia on α‐1 and ‐2 adrenergic receptor mediated vasoconstriction has been studied in an in vitro perfused canine tibia preparation. Bones were perfused at a constant rate with aerated (95% O2, 5% CO2) modified Krebs Ringer solution and the effect of bolus injections of norepinephrine (0.025–6.4 nmol) on the perfusion pressure was studied. For all bones the first dose‐response curve was produced under control conditions. In one group the second dose‐response curve was generated during a constant infusion of prazosin (α‐1 adrenergic antagonist); in another it was produced during a constant infusion of rauwolscine (α‐2 adrenergic antagonist); in the control group it was generated under control conditions. The results demonstrate that, after 48 h of hypothermic ischemia, α‐1 adrenergic‐mediated vasoconstriction was significantly attenuated (p < 0.001). However, α‐2 adrenergic‐mediated vasoconstriction was unaffected by increasing periods of hypothermic ischemia.
Pattern analysis of electromyographic linear envelopes exhibited by subjects with uninjured and injured knees during free and fast speed walking
Authors: Shiavi Richard , Zhang Li‐Qun , Limbird Thomas , Edmondstone Mary Ann
Published: February 2005

We wished to determine whether anterior cruciate ligament (ACL) injury caused changes in patterns of activity of individual or groups of muscles that control the knee joint. The electromyographic (EMG) patterns of six muscles in 26 individuals with uninjured knees and 20 individuals with ruptured ACL were studied during free and fast speed walking. A previously developed clustering technique was used for analysis. This technique involves making the Fourier transform of the average linear envelope (LE) of each muscle for each subject and using the amplitude and phases angles of the lower frequency harmonics as features to describe a pattern. These features are then grouped to subdivide the population of EMG patterns into different types. The results of analyses on single muscles showed that there exists a typical or “normal” pattern for each muscle which most uninjured and some injured subjects exhibit as well as several atypical patterns which mostly injured subjects exhibit, and that the atypical patterns are much more evident a fast walking speed. The characteristic of atypical patterns with respect to normal include time shifts in the peak of major phases of activity, the absence of a second phase of activity, and the existence of additional phases of activity. Synergy analysis showed that if one muscle has an atypical pattern, then several do; i.e., ACL injury induces major changes in the control strategy of the knee. The implications are that for rehabilitation programs one must focus on the training and strengthening of more than one muscle, and that for reconstructive procedures the changes in mechanics of the joint can possibly induce a significant change in its control strategy.
Influence of continuous infusion of interleukin‐1α on the core protein and the core protein fragments of the small proteoglycan decorin in cartilage
Authors: Witsch‐Prehm P. , Karbowski A. , Ober B. , Kresse H.
Published: February 2005

Decorin, a collagen‐binding small proteoglycan, is considered to have a specific function in the organization or stability of the collagen network. Therefore, alteration of its molecular properties may be of pathophysiological relevance during the development of cartilage damage. It is shown here that normal cartilage from rabbit knee‐joint contains glycosaminoglycan chain‐bearing core protein fragments of 39, 23, and 18 kDa, each one amounting to ∼5–6% of the intact decorin core protein. Continuous infusion of human recombinant interleukin‐1α for 14 days (200 ng/day) into a knee‐joint led in condylar cartilage to a reduction in the amount of intact core protein from 2 μg/mg wet tissue to about 1.1 μg/mg. The increase in its quantity found after infusion of heat‐inactivated interleukin‐1 was not statistically significant. The concentration of all three core protein fragments became reduced to a similar extent as the intact core protein under the influence of the cytokine, and additional fragments were not found. Surprisingly, there was a much smaller response to interleukin‐1‐treatment in patellar cartilage.
Cortical bone microperfusion: Response to ischemia and changes in major arterial blood flow
Authors: Swiontkowski Marc F. , Senft David
Published: February 2005

In order to investigate the effects of short‐term ischemia on cortical bone microperfusion, an isolated porcine tibia diaphyseal preparation based on intact nutrient vessels was developed. Laser Doppler flowmetry (LDF) was utilized to assess continuously the cortical microcirculation and the response to short‐term ischemia. The femoral artery was isolated and clamped to develop the condition of bone ischemia. On release of the clamp, reactive hyperemia was documented in all animals. Using a roller pump connected to a segment of femoral artery, the same preparation was utilized to investigate the effect of a changing femoral artery flow on the cortical microcirculation. A positive correlation between LDF output and change in arterial inflow (r = 0.64) was defined. This model has the potential for studying the effect of ischemia on bone cell viability.
Endothelial control of long bone vascular resistance
Authors: Davis T. R. C. , Wood M. B.
Published: February 2005

This in viro study investigates whether intraosseous endothelial cells can regulate long bone blood flow by secretion of vasodilator prostaglandin and EDRF (endothelium‐derived relaxing factor). Canine tibia were perfused through the nutrient artery at a constant flow rate, and the increases in perfusion pressure caused by standard doses of norepinephirine were recorded first under control conditions and then during acetylcholine infusion. Acetyl‐ choline attenuated the norepinephrine pressure responses (−62±3%). This attenuatintg effect of acetylcholine was partially abolished by inhibition of pros‐taglandin synthesis (−20±6%) and completely abolished by inhibition of EDRF synthesis (+73±43%) or combined inhibition of prostaglandin and EDRF synthesis (+134±30%). These results are statistically significant (p < 0.0001) and suggest that both EDRF and vasodilator prostaglandin are synthesized by intraosseous endothelial cells, and can modify long bone vascular resistance. Thus, as in other organs, intraosseous endothelial cells may provide bone with an autoregulatory control mechanism and enable it to respond to a diverse group of vasodilator stimuli.
Intramuscular wire electromyography of the subscapularis
Authors: Kadaba M. P. , Cole A. , Wootten M. E. , McCann P. , Reid M. , Mulford G. , April E. , Bigliani L.
Published: February 2005

The action of the subscapularis muscle is an important component in maintaining shoulder stability. Because of its relative inaccessibility, there have been few electromyographic (EMG) studies of its normal patterns of activity. The subscapularis is innervated by two or more distinct nerves, and therefore the upper and lower parts of the muscle may have different functional roles depending on the position of the humerus. The purpose of this study was to develop safe, reproducible insertion paths to the upper and lower parts of the subscapularis. Six subjects with no previous history of shoulder injury were evaluated. The paths of insertion were designed based on previous anatomical studies as well as dissections. Two pairs of intramuscular wire electrodes were inserted: one directed toward the upper subscapularis and one toward the lower subscapularis. Electrode locations were confirmed using posteroanterior and lateral radiographs and through electrical stimulation. EMG data were recorded during isometric internal rotation exercises with the humerus in 0 or 90° abduction. Significant differences were observed in the EMG activity recorded from the two pairs of electrodes. The EMG activity of the upper subscapularis either remained the same or decreased in going from 0 to 90° abduction, while that of the lower subscapularis increased. The observed differential response confirmed that the electrodes were in different parts of the subscapularis. These preliminary results suggest that in future EMG studies, the subscapularis should be considered as at least two independent muscle units.
Efficacy of autograft and freeze‐dried allograft to enhance fixation of porous coated implants in the presence of interface gaps
Authors: Kienapfel H. , Sumner D. R. , Turner T. M. , Urban R. M. , Galante J. O.
Published: February 2005

Autogenous cancellous bone and freeze‐dried allogeneic cancellous bone were tested in a total of 41 adult male mongrel dogs. In each humerus, an implant with a commercially pure titanium fiber metal porous coating was placed in an overreamed cavity so that a uniform 3‐mm gap was present between the implant and host cancellous bone. Graft material was placed in the gap of one humerus while the gap of the other humerus was left empty and served as a paired negative control. Histologically, both autograft and allograft appeared to aid repair of the defect, but quantitatively only autograft enhanced new bone formation within the defect. Treatment with autograft significantly increased the amount of bone ingrowth within the implants by nearly three‐fold at 4 weeks and eight‐fold at 8 weeks. The enhancing effect was recognizable as early as 2 weeks. The strength of fixation was increased by nearly seven‐fold at 4 weeks and two‐fold at 8 weeks in the autograft group, but this was only statistically significant at 4 weeks. Treatment with allograft did not enhance bone ingrowth at any time period, but had a small positive effect on strength of fixation at 4 weeks.
The effect of intramedullary polymethylmethacrylate on healing of intercalary cortical allografts in a canine model
Authors: Straw R. C. , Powers B. E. , Withrow S. J. , Cooper M. F. , Turner A. S.
Published: February 2005

The purpose of this study was to evaluate the effect of intramedullary polymethylmethacrylate (PMMA) bone cement on the healing of intercalry allografts. Thirteen adult beagles had bilateral intercalary femoral allografts implanted. The medullary canal of one randomly assigned allograft in each dog was filled with PMMA. Healing was followed clinically and femora were evaluated radiographically, biomechanically, histologically, and histomorphometrically 9 months after surgery. There was an increased percent of eroded surface at the endosteal area of the center region of grafts containing PMMA and there was an increased percent osteoblast surface in this area in grafts not containing PMMA. There was an increased percent eroded surface at the periosteal area in the center region in grafts not containing PMMA and there was an increased percent osteoblast surface at the periosteal area in the graft adjacent to the host junction in grafts containing PMMA. There was no significant difference between PMMA‐treated and untreated allografts in any other parameters measured. The results from this study suggest that, although the pattern of incorporation is altered, intramedullary PMMA does not appear to effect allograft healing adversely.