bluuebunny/crossref_metadata_2025 huggingface dataset:
The functional recovery of peripheral nerves following defined acute crush injuries
Authors: Chen Long‐En , Seaber Anthony V. , Glisson Richard R. , Davies Helen , Murrell George A. C. , Anthony Douglas C. , Urbaniak James R.
Published: February 2005

This study evaluates the effect of crushing load on functional recovery of the sciatic nerve. Male Sprague‐Dawley rats were divided into five groups: sham operation, resected sciatic nerve, and 100 g (13 mm Hg/mm2), 500 g (50 mm Hg/mm2), and 15,000 g (1,000 mm Hg/mm2) of sciatic crush load (groups 1–5). In groups 3–5, a 5‐mm segment of sciatic nerve was crushed for 10 min using a specially designed crushing device. Motor functional recovery was assessed from hind‐limb walking tracks by calculating a sciatic functional index. There was no detectable functional deficit in the group receiving sham operations, while the resected sciatic nerve group exhibited complete dysfunction for the full duration of the experiment. All groups subjected to crush exhibited an initial deficit that gradually recovered to normal by day 14 (100‐g crush), day 39 (500‐g crush), and day 53 (15,000‐g crush). Histological changes were also related to the initial crushing load and the length of the recovery period. Results indicate that the crushing device described is able to administer an adjustable, defined crush injury to the rat sciatic nerve, and that the functional deficit resulting from such an injury can be easily monitored with a sciatic functional index. The rate of recovery of crushed nerves was directly related to the initial load. All crushed nerves recovered in this experiment, even after the application of a 15,000‐g load for 10 min.
A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus
Authors: Melrose J. , Ghosh P. , Taylor T. K. F. , Hall A. , Osti O. L. , Vernon‐Roberts B. , Fraser R. D.
Published: February 2005

A 5 × 5‐mm anterolateral incision was made in the annulus fibrosus (AF) of lumbar discs of 16 sheep; four animals of similar age not operated on were used as controls. The experimental animals were sacrificed 2, 4, 6, 8, 12, and 18 months postoperatively (PO), and the incised and adjacent lumbar discs were collected. Discs were dissected into four zones: AF (zones 1 and 2) and nucleus pulposus (NP) (zones 3 and 4) corresponding to the half of the AF in which the cut was made and its opposite half, and the complementary halves of the NP. Each zone was analyzed for moisture, proteoglycan (PG), collagen, and noncollagenous protein (NCP) content. The PG extractability, aggregation, and hydrodynamic size were also examined. The NP of injured discs showed a significant loss of PGs and collagen 8 months PO, but NCP levels increased. In the incised discs, PG aggregation initially declined but recovered to within control values 6–8 months PO. The NP of discs adjacent to the incised disc also showed time‐dependent changes in matrix components that included loss of collagen and PG; however, the AF matrix remained essentially uneffected. Double immunodiffusion studies indicated that a sizeable proportion of the NCPs present in the injured discs (but not the adjacent lumbar discs) were derived from serum.
Trunk muscle cocontraction: The effects of moment direction and moment magnitude
Authors: Lavender S. A. , Tsuang Y. H. , Andersson G. B. J. , Hafezi A. , Shin C. C.
Published: February 2005

This study investigated the cocontraction of eight trunk muscles during the application of asymmetric loads to the torso. External moments of 10, 20, 30, 40, and 50 Nm were applied to the torso via a harness system. The direction of the applied moment was varied by 30° increments to the subjects' right side between the sagittally symmetric orientations front and rear. Electromyographic (EMG) data from the left and right latissimus dorsi, erector spinae, external oblique, and rectus abdominus were collected from 10 subjects. The normalized EMG data were tested using multivariate and univariate analyses of variance procedures. These analyses showed significant interactions between the moment magnitude and the moment direction for seven of the eight muscles. Most of the interactions could be characterized as due to changes in muscle recruitment with changes in the direction of the external moment. Analysis of the relative activation levels, which were computed for each combination of moment magnitude and direction, indicated large changes in muscle recruitment due to asymmetry, but only small adjustments in the relative activation levels due to increased moment magnitude.
Cross talk in surface electromyograms of human hamstring muscles
Authors: Koh Timothy J. , Grabiner Mark D.
Published: February 2005

Signals generated from muscles other than the muscle(s) of interest (cross talk) can confound the interpretation of surface electromyograms (EMGs). In this study, the amount of cross talk in surface EMGs of human hamstring muscles was estimated using a protocol in which the quadriceps femoris was electrically stimulated via the femoral nerve. EMGs were recorded from the vastus lateralis and the medial and lateral hamstring muscle groups. The amplitude of the EMG response of the vastus lateralis to electrical stimulation was adjusted to match that of its maximum voluntary effort (MVE) under isometric conditions. Subsequent power density spectrum analysis showed that the median frequencies of the signals generated by electrical stimulation and MVE were not significantly different. In conventional bipolar recordings, cross talk in lateral hamstring EMGs averaged 17.1% MVE and in medial hamstring EMGs 11.3% MVE (average‐rectified values). The double differential technique significantly reduced cross talk to 7.6% MVE for the lateral hamstrings, and to 4.2% MVE for the medial hamstrings. The double differential technique appears to be more selective than the bipolar technique when recording EMGs from muscles with highly active neighbors and thus should be used in such situations. Software simulations of the double differential technique also appear to be more selective than the bipolar technique and may be used when the number of amplifiers available is limited.
A comparison of cortical strain after cemented and press‐fit proximal and distal femoral replacement
Authors: Hua J. , Walker P. S.
Published: February 2005

Proximal and distal femoral replacements with intramedullary stems are usually cemented in place but frequently show severe bone remodeling changes in the long term, which can contribute to a loosening process. The remodeling is likely to be associated with stress and strain distribution. This study compared the strain patterns, particularly the maximum principal strains, between cemented and press‐fit components in five cadaveric femurs by using a photoelastic coating technique. The specimens were loaded with 2,000 N in the sequences of intact femur and press‐fit and cemented stems. On the medial side of the bone for proximal femoral replacements, the strain values for the press‐fit stems on the proximal, middle, and distal regions were 73 ± 11%, 78 ± 15%, and 80 ± 15% of normal, respectively, but for the cemented stems they were 53 ± 15%, 57 ± 19%, and 60 ± 20%. The differences were statistically significant (p < 0.05). On the lateral side, the overall strain values for the press‐fit stem were higher than those for the cemented stem, but the differences were not statistically significant (p > 0.05). On the medial side of the distal femoral replacement, the strain values for the press‐fit stems in the proximal and middle regions were significantly closer to normal than for the cemented stems. Because the press‐fit femoral stems (both the proximal and distal replacement) transferred closer to normal strains than the cemented stems, less adverse bone remodeling may be expected, which could be reflected in increased longevity.
Subchondral damage after acute transarticular loading: An in vitro model of joint injury
Authors: Vener Michael J. , Thompson Roby C. , Lewis Jr. Jack L. , Oegema Theodore R.
Published: February 2005

Intact canine metacarpophalangeal and metatarsophalangeal joints were subjected to a variety of loads in vitro. Intraarticular fracture occurred in 19 joints loaded to an average force of 2.4 ± 0.4 kN with a corresponding loading rate of 88 ± 23 kN/s. The remaining 29 joints were without gross evidence of fracture with an average load and loading rate of 1.7 ± 0.9 kN and 64 ± 32 kN/s, respectively. In the fractured specimens, damage to the zone of calcified cartilage and subchondral bone was much more extensive than was initially evident by gross inspection when assessed by scanning electron microscopy. Cracks with associated step‐off displacement at the zone of calcified cartilage were found distant to the gross fractures. These findings were confirmed histologically. In addition, cracks localized to the zone of calcified cartilage were commonly identified histologically in specimens loaded in the range of 1.9–2.8 kN, but were not grossly fractured. The contact area determined with pressure‐sensitive film increased with increasing load up to the point of fracture. The average pressure generated at the articular cartilage surface at the time of fracture in this model is ≥40 MPa, and the fracture occurred at the contact site. Our findings suggest that failure in acute transarticular loading begins in the zone of calcified cartilage and subsequently involves the subchondral bone and overlying cartilage. This type of injury may contribute to the development of osteoarthritis after intraarticular fracture, or at high loads that do not result in gross fracture.
Identification of integrin cell‐substratum adhesion receptors on cultured rat bone cells
Authors: Brighton Carl T. , Albelda Steven M.
Published: February 2005

The interactions of bone cells with their extracellular matrix is of major importance in bone development, repair, and disease. We examined the ability of rat calvarial bone cells to adhere to various matrix proteins and to define the role of integrin cell‐substrate adhesion receptors in these interactions. Isolated newborn rat calvarial bone cells prelabeled with3H‐thymidine and plated on plastic wells that had been precoated with serial dilutions of various substrates showed typical dose‐response adherence curves to fibronectin, fibrinogen, laminin, vitronectin, and collagen I and IV. Cell adherence to poly‐D‐lysine, a nonspecific cell adherent, was high at all substrate concentrations >0.0001 μg/ml. A polyclonal anti‐rat integrin antibody blocked cell adhesion to all substrates tested except poly‐D‐lysine. Isolated rat calvarial bone cells were surface labeled with125I, extracted, and immunoprecipitated with polyclonal antibodies made against the rat integrin complex and peptides derived from the cytoplasmic domains of the α2, α3, and α5subunits. Analysis by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (nonreduced) identified four bands representing a mixture of integrins including the α1β1laminin/collagen receptor, the α5β1fibronectin receptor, and the αvβ3(or possibly αvβ5) vitronectin receptor. These experiments show that bone cells adhere to a wide variety of extracellular matrix proteins via specific integrins. Increased knowledge about the regulation of these receptors and the mechanisms by which they transmit information to the cell will be important for a more complete understanding of bone physiology and pathophysiology.
Cast immobilization and tibial diaphyseal blood flow: An initial study
Authors: Triffitt Paul D. , Cieslak Catharine A. , Gregg Paul J.
Published: February 2005

The effect of cast immobilization on blood flow to the tibial diaphysis was studied by the microsphere method, both before and after casting of one hindlimb of adult New Zealand White rabbits. Preliminary studies were undertaken to investigate the possibility of the reduction of tibial flow by the microspheres used for the control measurements of blood flow. There were no significant differences in the flows to the tibial diaphysis or skeletal muscle between the immobilized and control limbs after either 1 or 2 weeks. This similarity between control and experimental limbs indicates that immobilization had no major effect on tibial blood flow over and above the systemic effects of the procedure.
Acute effect of traction, compression, and hip joint tamponade on blood flow of the femoral head: An experimental model
Authors: Naito Masatoshi , Owen Jeffrey H. , Schoenecker Perry L. , Sugioka Yoichi
Published: February 2005

Blood flow rates of the canine femoral head were experimentally determined during traction, compression, and hip joint tamponade using the hydrogen washout technique. In puppies, blood flow rate of the femoral head was significantly decreased with either traction or compression applied at one half body weight. Either maneuver, when combined with hip joint tamponade, reduced blood flow rate of the femoral head an average of more than 70% as compared with the initial control rate. In adult dogs, combinations of either traction or compression, at one‐half body weight, with hip joint tamponade did not significantly decrease blood flow rate of the femoral head as compared with control values. Perfusion defect of blue silicone could be observed only in puppies around the hip during combinations of traction or compression with hip joint tamponade and involved the posterior superior capital branches of the medial circumflex artery and the arteries in the ligamentum teres. These experimental data may have important implications for the pathogenesis of iatrogenic avascular necrosis in the treatment of congenitally dislocated hip, Legg‐Perthes disease, and avascular necrosis following nondisplaced femoral neck fracture.
A theory of fatigue damage accumulation and repair in cortical bone
Authors: Martin Bruce
Published: February 2005

An analysis is presented of the balance between the accumulation and repair of fatigue damage in osteonal bone. Fatigue damage is defined in terms of cracks seen histologically when precautions are taken to avoid preparation artifact. The rate of occurrence of such damage is assumed to be proportional to the product of applied peak‐to‐peak stress, raised to a power, and the loading frequency. The rate of damage repair is assumed to be proportional to the activation rate for osteonal remodeling, and to the mean cross‐sectional area of the resulting osteons. An additional factor is introduced to account for the possibility that damage provokes nearby remodeling. The theory is used to compare data from previous experiments of two types: fatigue‐to‐failure, and studies in which histologically observable cracks are made more numerous by repetitive loading. The analysis shows that there is a measure of agreement between the results of the two kinds of experiments, but the current data are too limited, and the results are too dependent on the mode of loading, to adequately test the theory. However, the analysis provides a framework for designing experiments to more efficiently clarify the relationships between fatigue failure, cracks seen in histologic sections, and the rate at which such cracks are repaired by osteonal remodeling.
Migration of porous coated acetabular prostheses fixed with screws: Roentgen stereophotogrammetric analysis
Authors: Kärrholm Johan , Snorrason Finnur
Published: February 2005

The fixation of screw‐fixed, porous‐coated acetabular prostheses was studied during 2 years in 21 patients (22 hips) using repeated roentgen stereophotogrammetric measurements. Migration of the center of the prostheses and/or tilting were recorded in five cups after 6 months. Two years after operation, migration was recorded in three, migration and rotation in six, and only rotation in three cups. Bone quality, prosthetic position, and immediate postoperative radiographic appearance of the prosthesis‐bone interface did not correlate with the occurrence of migration. Narrow radiolucent zones had developed in half of the patients after 2 years and was associated with proximal migration. Micromovements of screw‐fixed, press‐fit cups seem to start later compared with previously presented results from cemented acetabular prosthesis.
In vitro hyperextension injuries in the human cadaveric cervical spine
Authors: Shea M. , Wittenberg R. H. , Edwards W. T. , White A. A. , Hayes W. C.
Published: February 2005

To investigate the relationship between the type of hyperextension injuries and the conditions producing them, nine cervical specimens (occiput to T1) were loaded to failure in tension at a fixed extension angle of 30°. Under these loading conditions, specimens failed at average tensile loads and extension moments of 499 ± 148 (SD) N and 4.0 ± 3.1 Nm, respectively. Failure occurred at an average tensile displacement of 18.8 ± 7.7 mm. The anterior longitudinal ligament reptured and the intervertebral disc failed in at least one level in all specimens. In four specimens, the disc failed at an additional level, leaving the anterior longitudinal ligament intact at that site. With one exception, all injuries occurred in the lower cervical spine (C5‐C6 and C6‐C7), the region most often injured in vivo. The location of the injuries was associated with the degree of degeneration of the facet joints and the discs. The discs of the lower cervical spine were significantly more degenerated than those at the C2‐C3 level. In addition, the degree of disc degeneration in the noninjured discs was significantly less than in the injured discs. These data help quantify the threshold of injury and the patterns of tissue damage resulting from hyperextension loading of the cervical spine.
Physiological cross‐sectional area of human leg muscles based on magnetic resonance imaging
Authors: Fukunaga T. , Roy R. R. , Shellock F. G. , Hodgson J. A. , Day M. K. , Lee P. L. , Kwong‐Fu H. , Edgerton V. R.
Published: February 2005

Magnetic resonance imaging techniques were used to determine the physiological cross‐sectional areas (PCSAs) of the major muscles or muscle groups of the lower leg. For 12 healthy subjects, the boundaries of each muscle or muscle group were digitized from images taken at 1‐cm intervals along the length of the leg. Muscle volumes were calculated from the summation of each anatomical CSA (ACSA) and the distance between each section. Muscle length was determined as the distance between the most proximal and distal images in which the muscle was visible. The PCSA of each muscle was calculated as muscle volume times the cosine of the angle of fiber pinnation divided by fiber length, where published fiber length:muscle length ratios were used to estimate fiber lengths. The mean volumes of the major plantarflexors were 489, 245, and 140 cm3 for the soleus and medial (MG) and lateral (LG) heads of the gastrocnemius. The mean PCSA of the soleus was 230 cm2, about three and eight times larger than the MG (68 cm2) and LG (28 cm2), respectively. These PCSA values were eight (soleus), four (MG), and three (LG) times larger than their respective maximum ACSA. The major dorsiflexor, the tibialis anterior (TA), had a muscle volume of 143 cm2, a PCSA of 19 cm2, and an ACSA of 9 cm2. With the exception of the soleus, the mean fiber length of all subjects was closely related to muscle volume across muscles. The soleus fibers were unusually short relative to the muscle volume, thus potentiating its force potential. Using the relationship between PCSA and fiber length to represent the maximum force‐velocity potential of a muscle and assuming a similar moment arm, the soleus, MG, and LG would be expected to produce ±71, 22, and 7% of the force and 54, 30, and 16% of the power of the major plantarflexors. These data illustrate some of the major limitations in the use of ACSA measurements to predict the functional properties of a muscle.
Evaluation of a local microsphere injection method for measurement of blood flow in the rabbit lower extremity
Authors: Maki Yutaka , Breidenbach Warren C. , Firrell John C.
Published: February 2005

The precision of a modified microsphere technique to measure blood flow in the hind limb of the rabbit was determined. Regional (local) injections made via a catheter in the aorta and blood withdrawn through a catheter in the hind limb enabled deposition of a high concentration of microspheres in the tissues while minimizing the number of microspheres needed for accurate measurement. 95Niobium and 141cerium‐labeled 16 μm diameter microspheres were used. Blood flow was measured in 15 locations of muscle and skin for simultaneous injections into the aorta and left ventricle (group A), simultaneous injections of a mixture into the left ventricle (group B), and ventricular injections given 1 h apart (group C). No significant differences in mean blood flow measurements were found. Correlation coefficients between local and ventricular injections ranged from 0.89–0.99 and between 0.994 and 0.999 for two simultaneous ventricular injections. The variability over time was greater, with correlations between the first and second injections ranging from 0.13–0.939. Precision of the local technique compared with the ventricular technique can be kept within 30% with five or six animals. The advantage of this technique over ventricular injections is in the measurement of blood flow in small tissue samples when the number of microspheres deposited from ventricular injections is insufficient.
The relationship between inert gas wash‐out and radioactive tracer microspheres in measurement of bone blood flow: Effect of decreased arterial supply and venous congestion on bone blood flow in an animal model
Authors: Kiær Thomas , Dahl Benny , Lausten Gunnar Schwarz
Published: February 2005

Several methods have been employed in the study of bone perfusion. We used a method of determining inert gas wash‐out by mass spectrometry in the study of blood flow rates in pigs. The method was validated by comparison of the result obtained with inert gas wash‐out to that with measurement by microspheres. Furthermore, the effect of decreased inlet flow and venous congestion on the bone perfusion data was tested. The undisturbed bone blood flow was not significantly different when measured with wash‐out of inert gas (7 ± 0.7 ml/min/100 g) or with microspheres (9 ± 2.9 ml/min/100 g), and the methods were correlated. Perfusion was reduced significantly, to 20% of the original value, after arterial occlusion. The changes in wash‐out curves and accumulation of radioactive tracer provided substantial evidence for impaired intraosseous circulation following venous obstruction also. In conclusion, the study showed that this method of determining inert gas wash‐out is feasible for studies of local perfusion rates in bone. The flow rates obtained by wash‐out correlated well with the results of microsphere studies. In this animal model, both methods detected a fivefold reduction in flow rate after clamping of the arterial inflow. Obstruction of the venous outflow also impaired blood flow and lowered the cellular supply.
Calcification inhibitors in human ligamentum flavum
Authors: Maruta Kimiko , Ichimura Kazunori , Matsui Hisao , Yamagami Tohru , Sano Akimi , Tsuji Haruo
Published: February 2005

To examine the presence of substances which inhibit calcification in human ligamentum flavum, the inhibitory effect of an Na2HPO4 extract of the flavum was determined in terms of the in vitro calcium uptake of the ligamentum flavum matrix. Additionally, grafts of extracted and non‐extracted dry ligamentum flavum matrices were transplanted into the dorsal muscles of rats, and calcification in the grafts was examined radiologically and histochemically. In order to determine if component cells of human ligamentum flavum produce calcification inhibitors, ligamentum flavum cells were cultured, and the crystal inhibitor activity of the culture medium was measured by a seed test which used hydroxyapatite as the nucleus of precipitation. The calcification reaction system demonstrated that the ligamentum flavum extract contains an inhibitory factor for calcium uptake by the ligamentum flavum matrix. The seed test revealed that human ligamentum flavum cells produce calcification inhibitor activity.
Intraosseous infusion of prostaglandin E2 in the caprine tibia
Authors: Welch R. D. , Johnston C. E. , Waldron M. J. , Poteet B.
Published: February 2005

We evaluated the effects of intraosseously administered prostaglandin E2 (PGE2) within the proximal metaphysis of the goat (caprine) tibia under intraosseous normotensive and hypertensive conditions. PGE2 was administered at 0.5 or 1.0 mg (1 ml vol) twice daily for 10 days via an Osteoport which had been surgically implanted within the proximal tibial metaphysis. Intraosseous hypertension was produced when venous outflow obstruction (VOO) was created by ligation of the popliteal vein, which drained the proximal tibia, and occlusion of the diaphyseal medullary space distally with bone cement. After VOO, the intraosseous pressure measured at the metaphysis increased significantly (p < 0.05) from a baseline mean of 14.9 ± 4.2 mm Hg to 28.6 ± 5.3 mm Hg. Serum radioimmunoassays indicated that VOO prolonged the venous drainage of PGE2 from the tibia after an infusion. Static histomorphometric analysis indicated a marked dose‐dependent increase in new bone formation in all PGE2 groups at 30 days after the PGE2 infusion. Significant (p < 0.05) formation of new bone occurred, primarily at the subperiosteal and endocortical surfaces, and moderately increased the marrow cavity of cancellous new bone as compared with the VOO‐only group and the controls. Bone remodeling indices were also increased by PGE2. The PGE2 infusion, combined with VOO, produced significantly more new bone formation than the PGE2 infusion alone. Intensive marrow fibrosis was associated with the active bone remodeling.
Differentiating and antitumor activities of 1α,25‐dihydroxyvitamin D3 in vitro and 1α‐hydroxyvitamin D3 in vivo on human osteosarcoma
Authors: Tsuchiya Hiroyuki , Morishita Hajime , Tomita Katsuro , Ueda Yoshimichi , Tanaka Motohiro
Published: February 2005

The differentiating and antitumor activities of 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) in vitro and 1α‐hydroxyvitamin D3 (1α(OH)D3) in vivo were studied with a human osteosarcoma cell line (OST strain). Antitumor activity was estimated with the use of 3‐(4,5‐dimethylthiazol)‐2, 5‐diphenyltetrazolium bromide (MTT) assay, colony‐forming assay, and athymic mouse assay. The intracellular alkaline phosphatase (ALP) activity of tumor cells and production of bone Gla protein (BGP) in culture media were measured to mark osteoblastic differentiation. In addition, the combination of 1α,25(OH)2D3 and cis‐dichlorodiammineplatinum(II) (CDDP) was tested by the colony‐forming assay and the measurement of ALP activity and BGP production for differentiating and antitumor effects. The assays revealed that 1α,25(OH)2D3 exerted a dose‐related, growth‐inhibitory influence. In the colony‐forming assay, the 1α,25(OH)2D3‐treated colonies were smaller than the untreated colonies. The ALP activity and the BGP production also increased in relation to dose. In the assay in athymic mice, the relative weight of tumors treated with 1α(OH)D3 at 2.5 nmol/kg was significantly smaller than that of the controls, and no side effects were observed in the 1α(OH)D3‐treated mice. Marked tumor chondrogenesis was observed in human osteosarcoma treated with 1α(OH)D3 in athymic mice. The combination of 1α,25(OH)2D3 at 10−8 M and CDDP at 2 μg/ml significantly enhanced both the differentiation and the growth inhibition in vitro. Our study apparently is the first demonstration that vitamin D3 metabolites have an antitumor and differentiating effect on human osteosarcoma cells in vitro and in athymic mice. Vitamin D3 should be examined further to discover whether it could be a useful drug in hormonal treatment for human osteosarcomas.
Early postoperative fixation of tibial components: An in vivo roentgen stereophotogrammetric analysis
Authors: Ryd Leif , Toksvig‐Larsen Sören
Published: February 2005

The fixation of cemented and noncemented tibial components in 19 total knee arthroplasties was examined 3 to 10 weeks postoperatively with roentgen stereophotogrammetric analysis. Physiologic external forces were applied either in outward‐inward rotation or as eccentric posterior loading generated by squatting. In one case there was no motion, while in the remaining 18 cases relative interface motion of up to 1 3 mm was found. In some cases, the largest motion was found during inward‐outward rotatory stress, while in others, the largest motion was found during squatting. Posterior tilt was weakly correlated with posterior displacement of the femoral component on the tibia during squatting (r2 = 0.323, p < 0.05). For the noncemented cases, the initial fixation to bone was probably insufficient, and ingrowth of bone would not have been achieved. For the cemented cases, motion of the implant was reduced. Given the short postoperative time and the probable absence of any substantial fibrous tissue membrane, we suggest that the observed motion represented elastic deformation of the bone.
Functional assessment of joint use in experimental inflammatory murine arthritis
Authors: Williams James M. , Zurawski Jill , Mikecz Katalin , Glant Tibor T.
Published: February 2005

A select group of cartilage proteoglycans (fetal human, porcine, and canine articular cartilages and human osteophytes, all depleted of chondroitin sulfate) produces progressive polyarthritis and spondylitis in BALB/c mice. The development of the disease in this murine strain is dependent on the expression of both cell‐mediated and humoral immunities to host mouse cartilage proteoglycan. Autoantibodies have been detected in sera of arthritic animals from the fifth to sixth week after immunization, and their appearance precedes the development of the first clinical symptoms by a few days in animals with passively transferred arthritis. In this preliminary experiment, we describe several functional tests and gait analyses in normal mice, in acutely and chronically arthritic mice, and in randomly selected mice with proteoglycan‐induced and collagen‐induced arthritis. The procedures revealed that changes in joint use and gait could predate by weeks the appearance of the first clinical symptoms (joint swelling, redness, and joint stiffness) of arthritis in mice. Moreover, abnormalities measured by functional tests, such as strength of grip and maintenance of posture on sandpaper, wood, or vinyl surfaces at three different tilt angles (30, 45, and 60°), and gait analysis preceded the appearance of autoantibodies in sera of immunized animals; this indicates that such measurements could provide a noninvasive and simple method to assess joint function accurately during the development of arthritis.
Effect of substance p on mechanosensitive units of tissues around and in the lumbar facet joint
Authors: Yamashita Toshihiko , Cavanaugh John M. , Özaktay A. Cüneyt , Avramov Avram I. , Getchell Thomas V. , King Albert I.
Published: February 2005

The purpose of this study was to examine how substance P affects the mechanosensitive afferent units identified in the tissues around and in the lumbar facet joint of the rabbit. Substance P was applied to the receptive fields of the units by microinjection, and the afferent activity of the units was recorded from dorsal root filaments. Changes in afferent discharge rates and von Frey thresholds were measured sequentially after the application of substance P. Most of the units (83.3%) had an increase in the ongoing discharge rates after the application of substance P: 54.2% of the units had immediate excitation and 29.2% had delayed excitation. One‐third of the units had a decreased von Frey threshold after the application of substance P. Substance P had an excitatory effect on 81.8% of the units with a threshold of >5.0 g and a conduction velocity of ≤30 m/s, which may serve as nociceptors, and on 84.6% of the units with a threshold of ≤2.0 g, which may serve as proprioceptors. These results suggest that substance P has an excitatory effect on both nociceptive and proprioceptive units in the tissues around and in the lumbar facet joint.
Compressive properties of the cartilaginous end‐plate of the baboon lumbar spine
Authors: Setton Lori A. , Zhu Wenbo , Weidenbaum Mark , Ratcliffe Anthony , Mow Van C.
Published: February 2005

The viscoelastic behavior of the cartilaginous end‐plate of the baboon (Papio anubis) was studied in an experiment on compressive creep. Data were analyzed with the biphasic poroviscoelastic constitutive theory to assess the relative contributions of flow‐dependent and flow‐independent viscoelastic mechanisms to the observed creep behavior. Material coefficients describing the equilibrium compressive behavior (HA) and both flow‐independent (c, τ1, and τ2) and flow‐dependent (K) viscoelastic effects were determined for the end‐plate by the curve‐fitting of the theoretical solution to the experimental creep data. Biochemical analyses were performed to test for potential relationships between material properties and composition which may give rise to the viscoelastic behavior of the end‐plate. The results indicate that the cartilaginous end‐plate has a hydraulic permeability of 14.3 × 10−14 m4/N‐s, which is associated with rapid transport and pressurization of the interstitial fluid in response to loading and an increased emphasis on flow‐independent viscoelastic effects. Biochemical analyses for water, sulfated glycosaminoglycan content, and hydroxyproline indicate that end‐plate of the baboon is compositionally similar of the cartilaginous end‐plate in humans. Interpretation of the mechanical and compositional data suggests that fluid pressurization in the cartilaginous end‐plate may be important in the maintenance of a uniform stress distribution across the boundary between vertebral body and intervertebral disc.
Bioerodible polyanhydrides for antibiotic drug delivery: In vivo osteomyelitis treatment in a rat model system
Authors: Laurencin C. T. , Gerhart T. , Witschger P. , Satcher R. , Domb A. , Rosenberg A. E. , Hanff P. , Edsberg L. , Hayes W. , Langer R.
Published: February 2005

Acute and chronic osteomyelitis can be difficult to treat by conventional means. Current methods of treatment involve the use of systemic antibiotics, the local implantation of non‐degradable drug carriers, and surgical débridement. Each method has specific drawbacks. We report on the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis. We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non‐degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin. Polyanhydride copolymers of bis‐carboxyphenoxypropane and sebacic acid P loaded with gentamicin sulfate and PMMA/gentamicin matrices were implanted in the long bones of Sprague‐Dawley rats infected with a strain of Staphylococcus aureus. After 3 weeks of implantation, the polymeric delivery devices were removed and quantitative cultures were used to determine bacterial levels in bone. The polyanhydride/gentamicin matrices demonstrated significant degradation over the 3 week implantation period. Levels of bacteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p ≤ 0.01) of animals with a polyanhydride polymer implant alone (p ≤ 0.01), and of animals with a PMMA/gentamicin implant (p =0.03). Bioerodible polyanhydrides show promise as a new treatment modality for infections in bone.
Effects of severe diabetes and insulin on the femoral neck of the immature rat
Authors: Hou Jack C.‐H. , Zernicke Ronald F. , Barnard R. James
Published: February 2005

The interactive effects of severe diabetes and insulin therapy on the geometrical, biomechanical, and histomorphological characteristics of the femoral neck were studies in rats that had streptozotocin‐induced, insulin‐dependent (Type‐I) diabetes. Thirty‐six female Sprague‐Dawley rats (8 weeks of age) were assigned randomly to one of three groups: 12 to control (C), 12 to severe diabetes mellitus (SDM), and 12 to severe diabetes with insulin treatment (SDI). At the conclusion of 10 weeks, the femoral necks were loaded to failure via cantilever‐bending tests, and the geometrical, structural, and material properties of the femoral neck were measured and correlated with fracture‐surface cross sections. Decalcified cross sections of the femoral necks were analyzed histomorphometrically to determine the porosity, the bone‐cell counts, and the bone spicule/marrow space ratio. Rats with severe insulin‐dependent diabetes had significantly lower total body mass than did control rats, as well as significantly less femur mass, femur length, total‐bone cross‐sectional area, and cortical‐shell cross‐sectional area. Insulin therapy ameliorated some, but not all, of the detrimental effects of diabetes on femoral neck geometry. Compared with control and SDI rats, SDM rats had lower values for femoral neck structural properties, although differences in structural properties may have been related to retarded growth as well as to diabetes. SDM rats had a significantly lower bone spicule/marrow space ratio and number of osteoclasts than did either the control or SDI rats and had significantly greater porosity in the femoral neck cortex than did control rats. Decrements in femoral neck material properties — which were independent of differences in body size — were significantly and linearly correlated with severity of diabetes (as measured by blood glucose level).
Expression of the multidrug resistance gene in osteosarcoma: A pilot study
Authors: Wunder Jay S. , Bell Robert S. , Wold Lester , Andrulis Irene L.
Published: February 2005

Resistance to combination chemotherapy remains a challenge in the treatment of osteosarcoma yet has not been studied extensively in this tumour. One mechanism of multiple drug resistance is increased expression of the multidrug resistance gene (mdr1). The level of mdr1 messenger RNA (mRNA) expression has been found to correlate with the degree of drug resistance in a number of tumour cell lines in vitro, which suggests that it also may be useful as a predictor of similar resistance in vivo. Using a highly sensitive assay based on the polymerase chain reaction to measure the amount of mdr1 mRNA, we detected various levels of mdr1 expression in 18 osteosarcoma specimens from 15 patients with resectable nonmetastatic osteosarcoma. At follow‐up at a minimum of 30 months later, a trend toward a worse outcome was observed in patients with tumours exhibiting high levels of mdr1 expression. The results of this pilot study suggest that a larger scale prospective investigation of the effect of mdr1 gene expression on outcome in osteosarcoma is warranted.
Targeting of microdiscs in white cells to tibial abscesses in rabbits
Authors: Bhamra Manjit , Tyrrell Mark R. , Hulme Alison L. , Dye Julian F. , Dudley Hugh A. F.
Published: February 2005

The ability to deliver drugs to specific foci of infection is a sought‐after goal. One solution is to use microparticles as drug carriers. This approach is limited by detection of microparticles by the reticuloendothelial system (RES). In order to reduce RES uptake of such particles, we investigated the possibility of “hiding” microparticles within white cells prior to targeting them to experimental tibial abscesses. We used radioactive silicone microdiscs, supplied by the Royal Signals & Radar Establishment. Twelve rabbits with abscesses in the right tibia were used: six control animals received radioactive opsonised microdiscs intravenously, and six animals received the same dose of microdiscs following incubation of the microdiscs with white cells. Each animal's liver, spleen, lungs, and both tibiae were removed, weighed, and homogenised. Radioactivity counts were obtained from each tissue, and the ratio of counts per gram of tissue for the right/left tibiae was calculated for the two groups of animals. The ratio of counts in the control group was 1.66 (±0.57 SD), and the mean ratio of counts from the rabbits who had microdiscs incubated with white cells was 3.32 (±0.52 SD). This difference was statistically significant at p = 0.02 (Mann‐Whitney U test).
Diffusion of small solutes in cartilage as measured by nuclear magnetic resonance (NMR) spectroscopy and imaging
Authors: Burstein Deborah , Gray Martha L. , Hartman Audrey L. , Gipe Robert , Foy Brent D.
Published: February 2005

The ability of water and solutes to move through the cartilage matrix is important to the normal function of cartilage and is presumed to be altered in degenerative diseases of cartilage such as osteoarthritis and rheumatoid arthritis. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) techniques were used to measure a self diffusion coefficient (D) for small solutes in samples of explanted cartilage for diffusion times ranging from 13 ms to 2s. With a diffusion time of 13 ms, the intratissue diffusivity of several small solutes (water, Na+, Li+, and CF3CO2−) was found consistently to be about 60% of the diffusivity of the same species in free solution. Equilibration of the samples at low pH (which titrates the charge groups so that the net matrix charge of −300 mM at pH 8 becomes approximately −50 mM at pH 2) did not affect the diffusivity of water or Na+. These data, and the similarity between the D in cartilage relative to free solution for water, anions, and cations, are consistent with the view that charge is not an important determinant of the intratissue diffusivity of small solutes in cartilage. With 35% compression, the diffusivity of water and Li+ dropped by 19 and 39%, respectively. In contrast, the diffusivity of water increased by 20% after treatment with trypsin (to remove the proteoglycans and noncollagenous proteins). These data and the lack of an effect of charge on diffusivity are consistent with D being dependent on the composition and density of the solid tissue matrix. A series of diffusion‐weighted proton images demonstrated that D could be measured on a localized basis and that changes in D associated with an enzymatically depleted matrix could be clearly observed. Finally, evidence of restriction to diffusion within the tissue was found with studies in which D was measured as a function of diffusion time. The measured D for water in cartilage decreased with diffusion times ranging from 25 ms to 2 s, at which point the measured D was roughly 40% of the diffusivity in free solution. Although changes in matrix density by compression or digestion with trypsin led to a decrease or increase, respectively, in the measured D, the functional change in measured diffusivity with diffusion time remained essentially unchanged. In a different type of study, in which bulk transport could be observed over long periods of time, cartilage was submerged in 99% D2O and MRI studies were performed to demonstrate the bulk movement of water out of the cartilage matrix. These studies yielded a diffusivity estimated to be approximately 40% of the diffusivity of water in solution, which is in agreement with the value obtained for the diffusivity at a diffusion time of 2 s. These NMR measurements of diffusion can be totally noninvasive; thus, the results reported here can be extended to in vivo situations.
Adaptive bone remodeling around bonded noncemented total hip arthroplasty: A comparison between animal experiments and computer simulation
Authors: Weinans H. , Huiskes R. , Van Rietbergen B. , Sumner D. R. , Turner T. M. , Galante J. O.
Published: February 2005

Severe loss of bone related to stress‐shielding is one problem threatening the long‐term integrity of noncemented total hip arthroplasty. It is widely accepted that this phenomenon is caused by adaptive bone remodeling according to Wolff's law. Recently, quantitative bone‐remodeling theories have been proposed, suitable for use in computer‐simulation models in combination with finite‐element codes, which can be applied to simulate the long‐term effect of the remodeling process. In the present paper, the results of such a computer simulation are compared with those in an animal experiment. A three‐dimensional finite‐element model was constructed from an animal experimental configuration concerning the implantation of a fully coated femoral hip prosthesis in dogs. The simulation results of the adaptive bone‐remodeling process (geometric adaptations at the periosteal surface and density adaptations within the cancellous bone) were compared with cross‐sectional measurements of the canine femurs after 2 years of follow‐up. The detailed comparison showed that long‐term changes in the morphology of bone around femoral components of total hip replacements can be fully explained with the present quantitative adaptive bone‐remodeling theory.
Amplification of c‐myc oncogene and absence of c‐Ha‐ras point mutation in human bone sarcoma
Authors: Barrios Carlos , Castresana Javier S. , Ruiz Juan , Kreicbergs Andris
Published: February 2005

The genomic organization of four oncogenes, c‐myc, c‐myb, c‐Ha‐ras, and v‐fms, was analyzed in 21 patients with malignant bone tumors. Amplification of the c‐myc proto‐oncogene without rearrangement was the sole abnormality detected in four tumors: two chondrosarcomas, one osteosarcoma, and one lymphoma of bone. DNA hybridizations with c‐myb, c‐Ha‐ras, and v‐fms probes disclosed no structural gene abnormalities. Point mutations at the 12th codon of the c‐Ha‐ras gene were investigated with the polymerase chain reaction technique; no alterations were detected. The observed amplification of the c‐myc there was not related to histologic type, grade, surgical stage, or ploidy level of the tumors. The results indicated that c‐myc amplification, presumed to be involved in the development of malignancy in a variety of solid tumors, is encountered sporadically in malignant bone tumors; however, this occurs without relation to common histopathologic features. The clinical significance of oncogene amplification in bone sarcoma remains to be established.
Effects of transforming growth factor beta on cells derived from bone and callus of patients with osteogenesis imperfecta
Authors: Mörike Martin , Windsheimer Elke , Brenner Rolf , Nerlich Andreas , Bushart Gregor , Teller Walter , Vetter Ulrich
Published: February 2005

We studied the influence of transforming growth factor beta (TGF‐β) on cultured bone cells derived from two patients with osteogenesis imperfecta (OI) and from human controls. Additionally, cells from a hyperplastic callus that had developed spontaneously at the femur of the patient in Case 1 and cells from a normal fracture callus were included in the study. TGF‐β increased the synthesis of total protein and collagen of all cells without changing the pattern of interstitial collagens. Proliferation was stimulated by TGF‐β in the OI bone cells from Case 1, in cells from the central part of the hyperplastic callus, and in cells from the fracture callus. In Case 2, proliferation of bone cells was decreased by low concentrations of TGF‐β. Alkaline phosphatase (AP) activity was enhanced by TGF‐β in normal human bone cells, not affected in bone cells from the patient in Case 2 or in cells from the central part of the hyperplastic callus, and inhibited in bone cells and cells from the peripheral part of the hyperplastic callus of Case 1 and in cells from the fracture callus. We conclude that TGF‐β has common and specific effects on cultured human cells derived from different types of skeletal tissues. Simultaneous stimulation of collagen synthesis and AP activity by TGF‐β was restricted to normal human bone cells and might reflect their mature state of osteoblastic differentiation. Cells derived from bone of both patients with OI, from the hyperplastic callus, and from the fracture callus showed a different response pattern to TGF‐β. The difference in response to TGF‐β of bone cells from the two patients with OI might be related to the development of a hyperplastic callus in one of them (Case 1). This study indicates that the effects of TGF‐β on cells isolated from human skeletal tissues depend on their metabolic state and their stage of maturation and might be correlated with the formation of a hyperplastic callus in OI.