bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractSeveral 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

AbstractTo 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

AbstractWe 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

AbstractThe 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

AbstractThe 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

AbstractA 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

AbstractThe 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

AbstractThe 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

AbstractAcute 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

AbstractThe 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

AbstractResistance 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

AbstractThe 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

AbstractThe 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

AbstractSevere 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.