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- Al-Ani, Amer, et al.
(författare)
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Low bone mineral density and fat free mass in young and middle-aged patients with a femoral neck fracture
- 2015
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 45:8, s. 800-806
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundReduced bone mineral density (BMD) together with muscle wasting and dysfunction, that is sarcopenia, emerges as a risk factor for hip fracture. The aim of this study was to examine body composition and BMD and their relationship with trauma mechanisms in young and middle-aged patients with femoral neck fracture.Materials and methodsAltogether, 185 patients with femoral neck fracture aged 20–69 were included. BMD, body composition and fat-free mass index (FFMI) were determined by dual-X-ray absorptiometry (DXA), and trauma mechanisms were registered.ResultsNinety per cent of the whole study population had a femoral neck BMD below the mean for age. In the young patients (< 50 years), 27% had a Z-score of BMD ≤ −2 SD. More than half of the middle-aged patients (50–69 years) had osteopenia, that is T-score −1 to −2·5, and 35% had osteoporosis, that is T-score < −2·5, at the femoral neck. Patients with low-energy trauma, sport injury or high-energy trauma had a median standardised BMD of 0·702, 0·740 vs. 0·803 g/cm2 (P = 0·03), and a median FFMI of 15·9, 17·7 vs. 17·5 kg/m2 (P < 0·001), respectively. FFMI < 10th percentile of an age- and gender-matched reference population was observed in one-third.ConclusionsA majority had low BMD at the femoral neck, and one-third had reduced FFMI (i.e. sarcopenia). Patients with fracture following low-energy trauma had significantly lower femoral neck BMD and FFMI than patients with other trauma mechanisms. DXA examination of both BMD and body composition could be of value especially in those with low-energy trauma.
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| 4. |
- Ekström, Elin, et al.
(författare)
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WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells
- 2014
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Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion. Methods: Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data. Results: We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM. Conclusions: These data indicate that WNT5A has a broader function on tumor progression and metastatic spread than previously known; by inducing exosome-release of immunomodulatory and pro-angiogenic factors that enhance the immunosuppressive and angiogenic capacity of the tumors thus rendering them more aggressive and more prone to metastasize.
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| 5. |
- Ekström, Lars, 1959, et al.
(författare)
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In vivo porcine intradiscal pressure as a function of external loading
- 2004
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Ingår i: J Spinal Disord Tech. - 1536-0652. ; 17:4, s. 312-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Spinal loading during daily activity as it relates to the ability of the intervertebral disc to sustain its integrity has been a major issue in spinal research. The purpose of this investigation was to establish the relationship between the intervertebral disc pressure in the nucleus and the load applied to the motion segment in an in vivo porcine model. METHODS: Nine domestic pigs were used in this study. A miniaturized servohydraulic testing machine was affixed to the lumbar spine via four intrapedicular screws, which were inserted bilaterally into the L2 and L3 vertebrae. A pressure needle was inserted through the lateral part of the L2-L3 disc annulus and into the nucleus pulposus. Force, deformation, and intradiscal pressure data were collected during a loading scheme that consisted of applying a set of constant loads in increasing order, that is, 50, 100, 150, 200, and 250 N. Each load was applied for 30 seconds followed by 30-second restitution. RESULTS: Intradiscal nucleus pressure was found to correlate to the applied load in all cases. Linear regression analyses resulted in the following equation: intradiscal pressure (MPa) = 0.08 + 1.25E(-3)(load, N), r(2) = 0.81, n = 8. Intradiscal pressure was also highly linearly dependent on the stress. The intrinsic intradiscal pressure was found to be 81 +/- 5 kPa. The results also indicated that the pressure within the disc exhibited a creep behavior. CONCLUSION: In conclusion, pressure in the nucleus of the porcine intervertebral disc was linearly related to the applied load and stress.
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| 6. |
- Ekström, Lars, 1959, et al.
(författare)
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Intervertebral disc response to cyclic loading--an animal model.
- 1996
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Ingår i: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine. - 0954-4119. ; 210:4, s. 249-58
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Tidskriftsartikel (refereegranskat)abstract
- The viscoelastic response of a lumbar motion segment loaded in cyclic compression was studied in an in vivo porcine model (N = 7). Using surgical techniques, a miniaturized servohydraulic exciter was attached to the L2-L3 motion segment via pedicle fixation. A dynamic loading scheme was implemented, which consisted of one hour of sinusoidal vibration at 5 Hz, 50 N peak load, followed by one hour of restitution at zero load and one hour of sinusoidal vibration at 5 Hz, 100 N peak load. The force and displacement responses of the motion segment were sampled at 25 Hz. The experimental data were used for evaluating the parameters of two viscoelastic models: a standard linear solid model (three-parameter) and a linear Burger's fluid model (four-parameter). In this study, the creep behaviour under sinusoidal vibration at 5 Hz closely resembled the creep behaviour under static loading observed in previous studies. Expanding the three-parameter solid model into a four-parameter fluid model made it possible to separate out a progressive linear displacement term. This deformation was not fully recovered during restitution and is therefore an indication of a specific effect caused by the cyclic loading. High variability was observed in the parameters determined from the 50 N experimental data, particularly for the elastic modulus E1. However, at the 100 N load level, significant differences between the models were found. Both models accurately predicted the creep response under the first 800 s of 100 N loading, as displayed by mean absolute errors for the calculated deformation data from the experimental data of 1.26 and 0.97 percent for the solid and fluid models respectively. The linear Burger's fluid model, however, yielded superior predictions particularly for the initial elastic response.
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| 8. |
- Hodges, Paul, et al.
(författare)
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Intervertebral stiffness of the spine is increased by evoked contraction of transversus abdominis and the diaphragm : in vivo porcine studies.
- 2003
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Ingår i: Spine. - 1528-1159. ; 28:23, s. 2594-601
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: In vivo porcine study of intervertebral kinematics. OBJECTIVES: This study investigated the effect of transversus abdominis and diaphragm activity, and increased intra-abdominal pressure on intervertebral kinematics in porcine lumbar spines. BACKGROUND: Studies of trunk muscle recruitment in humans suggest that diaphragm and transversus abdominis activity, and the associated intra-abdominal pressure contribute to the control of intervertebral motion. However, this has not been tested in vivo. METHODS: Relative intervertebral motion of the L3 and L4 vertebrae and the stiffness at L4 were measured in response to displacements of the L4 vertebra imposed via a device fixed to the L4 vertebral body. In separate trials, diaphragm and transversus abdominis activity was evoked by stimulation of the phrenic nerves and via electrodes threaded through the abdominal wall. RESULTS: When intra-abdominal pressure was increased by diaphragm or transversus abdominis stimulation, the relative intervertebral displacement of the L3 and L4 vertebrae was reduced and the stiffness of L4 was increased for caudal displacements. There was no change in either parameter for rostral displacements. In separate trials, the diaphragm crurae and the fascial attachments of transversus abdominis were cut, but intra-abdominal pressure was increased. In these trials, the reduction in intervertebral motion was similar to trials with intact attachments for caudal motion, but was increased for rostral trials. CONCLUSIONS: The results of these studies indicate that elevated intra-abdominal pressure, and contraction of diaphragm and transversus abdominis provide a mechanical contribution to the control of spinal intervertebral stiffness. Furthermore, the effect is modified by the muscular attachments to the spine.
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| 9. |
- Holm, Sten, 1948, et al.
(författare)
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Experimental disc degeneration due to endplate injury
- 2004
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Ingår i: J Spinal Disord Tech. - 1536-0652. ; 17:1, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to create an experimental model of disc degeneration that closely mimicked human disc degeneration. In six domestic pigs, an L4 cranial endplate perforation into the nucleus pulposus was made. Three months postoperatively, compressive testing was performed on the L2-L4 motion segments, and intradiscal pressure was measured in the intervening discs. Histochemical and morphologic examinations were made on the excised degenerated and adjacent discs. A significant reduction in water content was observed in the outer anterior annulus of the degenerated disc. In the nucleus, the proteoglycan content was significantly reduced, as well as the cellularity, although not significantly. The nucleus lost its gel-like structure and was discolored, and there was delamination of annular layers. Intradiscal pressure in the nucleus was significantly lower in the degenerated disc. In conclusion, experimental degeneration of the intervertebral disc induced by endplate penetration resembled human disc degeneration, as exemplified by biochemical and structural changes.
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| 10. |
- Holm, Sten, 1948, et al.
(författare)
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Intradiscal pressure in the degenerated porcine intervertebral disc
- 2007
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Ingår i: Vet Comp Orthop Traumatol. - 0932-0814. ; 20:1, s. 29-33
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Tidskriftsartikel (refereegranskat)abstract
- Measuring intradiscal pressure is one way of mechanically assessing the discs degenerative state. In this study, the load-bearing capacity of degenerated and their adjacent lumbar intervertebral discs was evaluated using two different injury models. Seventeen adolescent pigs were divided into two groups, an annulus injury group and an endplate injury group. The annulus injury group was subjected to a stab incision in the L3-L4 disc, whereas the endplate injury group received a cranial endplate perforation of the L4 vertebral body. Both groups were biomechanically evaluated three months later using a miniaturized servohydraulic testing machine across L2-L4 and with two pressure needles inserted into the nucleus pulposus of the L2-L3 and L3-L4 discs. Linear relationships between the intradiscal pressure and the applied load were determined within the load range studied. When comparing the ratio of the injured to the adjacent disc pressure, the endplate injury was lower (mean value 0.31) than the annulus injury (mean value 0.51). The pressures in the discs adjacent to the degenerated level were found to be slightly higher. This increase can be expected due to a redistribution in mobility demands in segments adjacent to those with increased stiffness, i.e. degenerated intervertebral discs.
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