No description available.

This thesis is an investigation of the access provided to the vertebral canal in dogs by the hemilaminectomy and mini-hemilaminectomy surgical techniques using computed tomography (CT), and the completeness of evacuating extruded material in dogs with intervertebral disc (IVD) extrusion using magnetic resonance imaging (MRI). Hemilaminectomy and mini-hemilaminectomy were performed on opposite sides of the spine at T11-T12, T13-L1, and L2-L3 in 10 cadavers. Measurements of the vertebral canal height, defect height, and any dorsal and ventral remnants of the vertebral arch were obtained by CT. A covariate analysis was used to compare measurements with the surgical technique, surgical site, and side of the vertebral column. Defect height was greater with hemilaminectomy due to a smaller dorsal lamina remnant. There was no statistical difference in the height of the ventral remnant, or with surgical site. Nineteen prospectively recruited dogs with suspected IVD extrusion were randomly assigned to hemilaminectomy (10 dogs) or mini-hemilaminectomy (9 dogs) groups. Intervertebral disc extrusion was identified pre-operatively with MRI and later confirmed surgically, and immediate post-operative MRI was performed at the surgical site. The volume of extruded IVD material pre- and post-operative was calculated from transverse T2 images. Although residual IVD material was present in post-operative images from all dogs in the hemilaminectomy group and only 4 in the mini-hemilaminectomy group, there was no statistically significant difference between the proportionate volumes of material removed by either technique. The median residual volume with hemilaminectomy was 13.6% (confidence interval: 7.8 – 23.6%), and with mini-hemilaminectomy was 7.7% (4.3 – 13.8%). The results of this study confirm that the difference in the defect height between techniques is related to the removal of the articular processes creating a larger defect along the dorsal vertebral canal, while no difference in access to the ventral canal was observed. No effect of vertebral site was detected suggesting neither procedure provides an advantage over the other due to location of the lesion along the thoracolumbar spine. Residual extruded IVD material occurs with both techniques; while no statistical difference was noted, a larger population should be examined. / Ontario Veterinary College Pet Trust

Abstract Low back pain (LBP) is a truly enervating condition, presenting with considerable negative socioeconomic and health impacts on many levels. Although LBP may be attributed to many factors, there is increasing evidence that disc degeneration (DD) of the lumbar spine is a strong contributing factor, especially among young individuals. Understanding the aetiopathogenesis of DD has changed over the past few decades as numerous studies have indicated that inherited factors are largely responsible for the development of DD. Despite the many genetic associations in DD that have been reported, these associations have proven difficult to validate. The genetic component of DD is still unexplained for the most part. Previous studies have focused on adults, who have been exposed to environmental risk factors of DD, which may mask genetic associations. Thus, investigations among young individuals are well justified. The purpose of this study was to validate the associations between DD defined by magnetic resonance imaging (MRI) and genetic polymorphisms in two study populations of Finnish and Danish young individuals. New polymorphisms that have not been associated with DD were also included in the study. Associations with progression of DD were also investigated among Danish individuals. Furthermore, this study aimed to clarify the level of evidence of previously identified associations. Among Finnish individuals, polymorphisms in IL6, SKT and CILP were associated with moderate DD, but the association in CILP was significant only in women. Among Danish individuals, polymorphisms in IL6 and IL1A were associated with early DD and progression of DD. The genetic associations among the Danish teenagers were gender-specific as they were mainly observed in girls. Among both populations, the individuals with DD were significantly taller than individuals without DD. In the systematic analysis of previous reports, polymorphisms in GDF5, THBS2, MMP9, COL11A1, SKT and ASPN were found to have a moderate level of association evidence. The results mostly support earlier findings in adults. However, unexpected differences between genders were observed. In conclusion, this study increased the knowledge of genetics in DD but more investigations are needed to draw any solid conclusions. / Tiivistelmä Alaselkäkipu on yksi merkittävimmistä toimintakykyyn vaikuttavista sairauksista. Alaselkäkivun riskitekijöitä tunnetaan useita, mutta näyttö siitä, että selän välilevyrappeuma on yksi tärkeimmistä riskitekijöistä, erityisesti nuorilla henkilöillä, lisääntyy jatkuvasti. Aiemmat tutkimukset ovat osoittaneet, että perintötekijöillä on merkittävä osuus välilevyjen rappeutumisessa. Useiden geenien on raportoitu vaikuttavan välilevyrappeumaan. Positiivisten tulosten toistaminen on kuitenkin osoittautunut vaikeaksi, ja kokonaiskuva on vielä suurelta osin epäselvä. Aikaisemmat tutkimukset aiheesta ovat keskittyneet aikuisiin, joilla nuoria pidempi altistus ympäristötekijöille saattaa peittää geneettisten tekijöiden yhteyttä. Tämän tutkimuksen tavoitteena oli varmentaa yhteyksiä magneettikuvauksella (MRI) määritetyn välilevyrappeuman ja geneettisten monimuotoisuuskohtien (polymorfioiden) välillä käyttäen yhtä suomalaisista ja yhtä tanskalaisista nuorista koostuvaa aineistoa. Työssä analysoitiin myös polymorfioita, joita ei ole aiemmin yhdistetty välilevyrappeumaan. Yhteyttä polymorfioiden ja välilevyrappeuman etenemisen välillä tutkittiin tanskalaisessa aineistossa. Lisäksi tutkimuksen tavoitteena oli selvittää aiemmin tunnistettujen geneettisten yhteyksien näytön aste. Suomalaisten nuorten aineistossa polymorfiat IL6-, SKT- ja CILP-geeneissä olivat yhteydessä kohtalaista astetta olevaan välilevyrappeumaan. Tanskalaisten nuorten aineistossa polymorfiat IL6- ja IL1A-geeneissä olivat yhteydessä varhaiseen välilevyrappeumaan ja sen etenemiseen. Tanskalaisten nuorten aineistossa nämä yhteydet olivat sukupuolesta riippuvaisia, koska yhteyksiä havaittiin pääasiassa tytöillä. Suomalaisten nuoren aineistossa yhteys CILP-geenissä havaittiin ainoastaan nuorilla naisilla. Kummassakin tutkimusaineistossa nuoret, joilla oli välilevyrappeuma, olivat pidempiä, kuin nuoret, joilla ei ollut välilevyrappeumaa. Aikaisempien tutkimusten systemaattinen analyysi osoitti, että tunnistetun geneettisen yhteyden näytön aste on kohtalainen GDF5-, THBS2-, MMP9-, COL11A1-, SKT- ja ASPN-geenien polymorfioissa. Tutkimusten tulokset ovat pääosin samansuuntaisia aiempien tutkimuksien kanssa, mutta nyt nähty eroavaisuus sukupuolten välillä on uusi havainto. Kokonaisuudessaan tämä väitöstutkimus kasvattaa ymmärtämystä välilevyrappeumasta, mutta lisätutkimuksia aiheesta tarvitaan.

No description available.

Abstract Background: The process that involves the migration of the nucleus pulposus from the innermost annular layers and culminates with the final extrusion of the nucleus has been limited to a few studies. This investigation was directed towards a better understanding of the herniation process. The architecture of the annulus fibrosus and the mechanism of progressive disc herniation were analyzed, using a controlled porcine model. Microscopic and histochemical techniques were employed. <br /><br /> Methodology: Two studies were performed. In the first stage, the macroscopic and microscopic structures of twelve cervical intervertebral discs were compared with young human disc data from studies reported in the literature. Important structural features were studied such as annulus fibrosus thickness, number of lamellae, lamellae thickness, orientation of the lamellae fibers and blood supply. In the second study, sixteen fresh-frozen functional spine units were submitted to repetitive flexion?extension motions combined with a low compressive load in a servo-hydraulic dynamic testing system. Discograms, dissections and histochemical techniques were applied to characterize the cumulative damage. The experiment produced eight complete herniations, four partial herniations and four specimens without any microscopic detectable annular damage. <br /><br /> Results and Discussion: The structure of the cervical porcine disc resembles the lumbar human disc. Some differences are evident. The size of the annulus is smaller, the thickness of the lamellae is narrower and the number of layers is fewer in the pig. It is hypothesized that the flexion-extension motion combined with a low-level load produced an increased hydraulic pressure in the inner wall of the posterior annulus. This pressure and repetitive motion first produced a small cleft, spreading the collagen bundles inside the first layer. The nuclear material was "pumped" through the small cleft to the first layer filling the layer creating a fluid-filled pocket between the collagen fibers. Once the "pocket" acquired enough pressure a new cleft was produced in the weakest part of the layer allowing the nuclear material to create a new "pocket" in the second layer. This was the first stage of damage and disc herniation production. This mechanism was repeated until the nucleus traveled along the annulus reaching the posterior longitudinal ligament. At this point a complete extrusion herniation was produced. <br /><br /> Conclusion: The porcine model appears to be suitable as a model to understand the mechanism of disc herniation when the spine is subjected to flexion-extension motions combined with a low-level load. The first cumulative injury appears to be a cleft between the lamellae bundles produced by the nuclear hydraulic pressure. A cumulative load/cumulative injury model approach was used to create the damage that was quantified in the study.

Breakdown of the disc extracellular matrix is thought to arise from increased activity of matrix metalloproteinases (MMPs). Aggrecan, one of the major disc matrix macromolecules, is degraded through action of MMPs and aggrecanases and its concentration falls early in the degeneration process. Loss of the constituent glycosaminoglycans (GAGs), which are osmotically active, leads to a decrease in osmotic pressure and subsequently to a fall in tissue hydration. Apart from the major biomechanical consequences, fall in extracellular osmolarity is known to influence cell function. Apart from aggrecan, other macromolecules such as fibronectin are also broken down by MMPs. Fibronectin fragments (Fnfs) have been identified in degenerate discs. Such Fnfs have been found to stimulate production and activity of MMPs in articular cartilage but little is known about the effect of these fragments on disc cells. The aim of the work was thus to determine whether Fnf stimulated expression of MMPs and hence induced aggrecan breakdown and loss in the disc and whether extracellular osmolarity influenced this potential response. NP cells or explants were harvested from adult bovine caudal discs. They were cultured in DMEM culture medium over a range of osmolarities with or without Fnf treatment. Profiles of gene expression of MMPs and their inhibitors and effect of changes in osmolarity on expression of selected MMPs were determined. The effect of Fnf on responses of cells and tissue explants from the central region of the disc, the nucleus pulposus (NP) and the role of changes in extracellular osmolarity in relation to GAG loss and expression of selected MMPs was then examined both at the protein level and by gene profiling using a microarray. My results showed that expression of MMPs by disc cells is regulated by extracellular osmolarity rather than the 30 kD Fnf, with the level of some MMPs secreted by disc cells and involved in degradation of disc matrix rising as osmolarity falls. These results could explain in part the finding that MMP expression increases with degree of disc degeneration i.e. with loss of aggrecan and fall in extracellular osmolarity. These also suggested that a fall in osmolarity could induce a degenerative cascade with proteolytic digestion of aggrecan leading to a fall in osmolarity and hence a further increase in proteinase expression and matrix degradation.

Intervertebral disc (IVD) degeneration is strongly associated with back pain, and affects approximately 60% of the population by age 70. Furthermore, it has been suggested that this degeneration may play an important role in the initiation or perpetuation of vertebral fractures. Given that the IVD is a primary load-bearing structure in the spine, the change of intradiscal pressure (IDP) over time that accompanies disc degeneration provides a functional measure of the disease pathology. Studies show that both an overall decrease in IDP magnitude and changes in the spatial distribution of IDP are found with increasing levels of degeneration. Thus, the overall goal of this study was to determine the correlation between the spatial distributions of IDP, as measured along both mid-sagittal and mid-coronal paths, and a clinically feasible assessment of disc health. Disc degeneration was assessed non-invasively using quantitative computed tomography (QCT). A custom, electro-mechanical device was designed, manufactured and assembled to measure IDP distributions. The results indicated that the spatial distribution of IDP was most homogenous for the nucleus pulposus (NP) region regardless of load type and disc health grade. Mean IDP tended to be lowest in severely degenerated discs, consistent with earlier findings that axial loads in spinal columns with degenerated IVDs shift from the disc to the neural arch in both flexural and erect postures.

Physical activity impacts health and disease in multiple body tissues including the intervertebral discs. Fluid flow within the disc is an indicator of disc health that can be observed using diffusion weighted magnetic resonance imaging. We monitored activity levels of 26 participants, age 35 to 55 yrs, using Actigraph accelerometers for four days to evaluate vigorous-intensity activity, moderate to vigorous-intensity activity, and sedentary time. Participants underwent structural and diffusion weighted magnetic resonance imaging to evaluate intervertebral disc health and fluid flow. They also underwent bone density scans, carotid artery ultrasounds, a treadmill test, and a physical exam for pain, range of motion, and instability. These measures were used to correlate MRI indicators of intervertebral disc health with participant activity. Participants with any vigorous-intensity physical activity compared with no vigorous-intensity activity had significantly greater L5/S1 apparent diffusion coefficient values (p = 0.002), corresponding to higher freedom of diffusive movement for cellular nutrients and metabolic waste. Sagittal T2 values in the L5/S1 were also higher (p = 0.004), corresponding to higher water content in the discs. Higher apparent diffusion coefficients were also found in participants with more than 30 minutes compared with less than 30 minutes of daily moderate to vigorous physical activity (p = 0.03), and in participants with less than 67% awake time as sedentary time compared with more than 67% sedentary time (p = 0.03). Increased dynamic loading through physical activity and decreased static loading from sedentary time benefit intervertebral disc health. Physical activity, particularly vigorous activity, is beneficial in helping maintain intervertebral disc health.

Back pain is one of the most common physical conditions in the United States, for which approximately 15% of the population will visit a doctor every year. The most common type of back pain is low back pain (LBP) and millions of dollars are spent every year healthcare are a due to LBP. Although poorly understood, low back pain has been associated to interveterbral disc (IVD) degeneration. The IVD is an important structure that helps maintaining normal skeletal support. It is composed of three different tissues called the annulus fibrosus (AF), and the nucleus pulposus (NP), attached to a cartilage endplate (CEP) at its top and bottom surfaces. The AF tissue is composed of chondrocyte-like cells, while the NP tissue is composed of notochordal cells at a young age, which are replaced by mature NP cells later in life. Common signs of degeneration are the inability to maintain extracellular matrix integrity and calcification of the cartilage endplate. Extracellular matrix synthesis and cartilage endplate calcification are closely related to production of adenosine triphosphate (ATP) or energy metabolism of the cells. AF and NP tissues are known to be structurally and compositionally different; therefore it is believed that their metabolic pathways are also distinct. The objective of this study was to determine the differences between AF and NP cells, specifically in their energy metabolism with and without dynamic loading.

Low back pain is one of the major health concerns in the US. It affects up to 80% of the population at some time during their lives. It not only causes discomfort to patients and affects their physical ability but also has a huge economic impact on society. Although the cause of low back pain is still poorly understood, it is implicated that degeneration of the intervertebral disc is the primary factor. Currently, researchers are trying to use tissue engineering approaches to develop new treatments capable of removing the degenerated disk and replacing it with a biological substitute. However, to create such a biological substitute, we need to first understand the structure-function relationship of the tissue. Only when we understand the function of the tissue, can we begin creating biological substitutes. While culturing a biological substitute, we also need methods to determine how the substitute responds to its environment. At present, there are many different types of bioreactors developed for cartilaginous tissues. However, there is a lack of a system that can detect the chemical, electrical and mechanical response noninvasively with control feedback in real-time. It is hard to provide the optimal culture environment to the substitute without knowing its response in real-time. The objective of this dissertation is to develop new methods to investigate the transport property, oxygen consumption rate and mechano-electrochemical and mechanical properties of the tissue. Because cells are responsible for the tissue health, it is necessary to understand how they can obtain nutrients under different environments, e.g. under different loading condition. In addition, with the use of a bioreactor with the capability of detecting the real-time response combined with a feedback control system, we can provide the most favorable conditions for tissue or biological substitutes to grow. The new measurement methods developed in this dissertation can contribute to further understanding the function of the tissue. The methods outlined in this dissertation can also provide new tools for future tissue engineering applications. Moreover, the findings in this dissertation can provide information for developing a more comprehensive theoretical model to elucidate the etiology of disc degeneration.