Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 37-41).

This study aimed to characterize the in-situ mechanical property and morphology of individual collagen fibril in osteoarthritic (OA) cartilage using indentation-type atomic force microscopy (IT-AFM). The specimens with intact articular cartilage (AC), mild to severe degenerated OA cartilage were collected with informed consent from the postmenopausal women who underwent hip or knee arthroplasty. The fresh specimens were cryo-sectioned by layers with 50m thick for each from the articular surface to calcified cartilage, and then processed for AFM imaging and nanoindentation test. For each layer, a total of twenty collagen fibrils were randomly selected for testing. AFM tips with the nominal radius less than 10 nm were employed for probing the individual collagen fibril, and the obtained cantilever deflection signal and displacement were recorded for calculating its elastic modulus. Besides AFM nanoindentation, AFM and scanning electron microscopy (SEM) images, haematoxylin & eosin (H&E) staining and micro-indentation were performed on AC to study the changes of ultrastructure and composition between intact AC and OA cartilage. Results showed that an intact AC exhibited a gradation in elastic modulus of collagen fibrils from surface region (2.65±0.31GPa) to bottom region (3.70±0.44GPa). It was noted in the initial stage of OA cartilage that the coefficient of variation for mechanical properties of collagen fibers, ranging from 25~48%, significantly increased as compared with intact one (12%). The thickened and stiffened collagen fibrils initially occurred at either surface region (3.11±0.91GPa) or bottom region (5.64±1.10GPa) with OA progression. Besides thickens, alteration of D-periodic banding patterns of collagen fibrils was observed. It was echoed by fibrotic changes of surface region and tidemark irregularities. On the contrast, the micromechanical properties of cartilage decreased while AC suffered from OA. This result revealed the different approachs of nano and micro-mechanical properties changes in AC. In summary, the alteration of mechanical properties of collagen fibrils started from calcified cartilage as well as articular surface during OA onset, and the low compliance of thickened collagen fibrils deteriorated along disease progression. This study also reveals that the outstanding ability by AFM, in investigating the structure and mechanical properties of collagen fibrils and AC in nanometer scale, is impressive and this nanotechnological instrument is worth to be expected in further development for clinical use. / published_or_final_version / Mechanical Engineering / Master / Master of Philosophy

Osteoarthritis (OA) affects nearly 27 million people alone and is the leading cause of chronic disability in the US. Current treatment methods target pain relief for OA via non-steroidal anti-inflammatory drugs (NSAIDs) since there are currently no clinically approved disease modifying osteoarthritis drugs (DMOADs) demonstrating efficacy. Despite multiple pre-clinical DMOAD experiments being conducted, the screening rate for drugs is severely limited by the lack of sensitivity of outcome measures and the time consuming process to achieve them. Our lab has previously developed and validated a technique to evaluate articular cartilage changes with micro-CT. The objective of this thesis was to examine two distinct treatment strategies for OA in a rat joint degeneration model using equilibrium partitioning of an ionic contrast agent based micro-CT (EPIC-µCT). We hypothesized that these novel therapeutics will assist in preventing degradation of cartilage after injury and will be measurable by EPIC-µCT. First, we characterized two of the commonly used rat joint degeneration models - monosodium iodoacetate injection (MIA) and transection of medial meniscus (MMT) in rats using EPIC-µCT. The MMT model was then used to test the effects of a matrix metalloproteinase inhibitor (MMPi) using EPIC-µCT to detect changes in articular cartilage. Finally, micronized dehydrated human amnion/chorion membrane (dHACM) was delivered intra-articularly in the MMT model and evaluated as a disease modifying OA drug.

Trunk lean over the stance limb during gait has been linked to a reduction in the knee adduction moment, which is associated with joint loading. Differences were examined in knee adduction moments and frontal plane trunk lean during gait between subjects with knee osteoarthritis and a control group of healthy adults. Additionally, subject variability in human motion data presents a challenge to researchers when trying to detect differences between subject groups. The individual differences in neutral posture between subjects is a source of variation in joint angles. A method was developed using principal component analysis (PCA) to objectively reduce this inter subject variability. Gait analysis was performed on 80 subjects (40 osteoarthritis). Models were developed to define lateral thoracic tilt, as well as pelvic tilt. The trunk and pelvis frontal plane angles were used to describe trunk lean and pelvic tilt. Angles were calculated across the stance phase of gait. We analyzed the data, (i) by extracting discrete parameters (mean and peak) waveform values, and (ii) using principal component analysis (PCA) to extract shape and magnitude differences between the waveforms. Osteoarthritis (OA) subjects had a higher knee adduction moment than the control group (α=0.05). Although the discrete parameters for trunk lean did not show differences between groups, PCA did detect characteristic waveform differences between the control and osteoarthritis groups. The data show that subjects display similar waveform shapes, however waveforms vary in magnitude, suggesting a variation in posture between subjects. The results from the PCA reveal that the first PC, which captures the most variation in the data, represents this variation in magnitude. The second PC describes a significant difference in range of motion between the subject groups. Subjects with knee OA were found to have a different range of motion of their pelvis and trunk than control subjects. These changes are consistent with a strategy to lower the knee adduction moment. As an alternative to conventional subjective methods, PCA should be employed to reduce inter subject variability in order to ensure objective analysis in human motion waveform data. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2009-08-14 14:43:53.127

No description available.

Osteoarthritis is characterized by pain and inflammation in joints, typically weight-bearing joints such as the knee. An early warning sign of osteoarthritis is the loss of proteoglycan molecules in the cartilage matrix. A surrogate method for measuring proteoglycan loss is detection of sodium ions, which ionically bond to negatively charged glycosaminoglycan side chains. Sodium MRI has the potential to non-invasively measure proteoglycan content, and hence act as a diagnostic tool for osteoarthritis. However, as sodium MRI suffers from low sodium concentrations in vivo and reduced MR sensitivity compared to standard proton MRI, techniques are required which optimize signal. This thesis examines the hardware, software, and acquisition techniques required in order to achieve high resolution, excellent quality sodium MR images of the human knee in vivo, which has potential applications in early diagnosis as well as pharmacological treatment evaluations of osteoarthritis.

Doctor of Philosophy / The aim of the studies reported in this project was to examine factors associated with the prevention and management of trapeziometacarpal osteoarthritis, both in musculoskeletal physiotherapists and the general patient population. Two studies were undertaken to investigate factors associated with the aggravation of thumb pain in musculoskeletal physiotherapists. Study 1 was a survey of the prevalence of thumb pain, and allowed determination of the most aggravating spinal manipulative therapy technique. It identified that 83% of respondents complained of an aggravation of thumb pain due to the performance of spinal manipulative therapy techniques, with 85-87% of the painful respondents complaining of thumb pain aggravated by unilateral and central PA glides. Study 2 was conducted to determine whether the alignment of the joints of the thumb during performance of these glides was associated with thumb pain. This observational study of 129 musculoskeletal physiotherapists performing a PA glide identified that aligning the metacarpophalangeal and interphalangeal joints in extension was associated with a lower prevalence of work-related thumb pain. Therefore, it is suggested that musculoskeletal physiotherapists be taught to perform these techniques with the joints of their thumb in extension in an effort to reduce the development of work-related thumb pain. Furthermore, it is suggested that those who are unable to maintain this alignment voluntarily be provided with a thermoplastic thumb splint to maintain the extended alignment. Two studies were undertaken to investigate the conservative and surgical management of patients with trapeziometacarpal osteoarthritis. Study 3 was a randomised controlled trial conducted to compare the efficacy of a new thumb strap splint and an abduction exercise regimen against the standard approach to conservative management of trapeziometacarpal osteoarthritis, namely a short opponens splint and pinch exercise regimen. While there was no additional benefit of one approach over the other, all participants improved in the outcomes of pain, strength and hand function over the six-week period of intervention. Nevertheless, some people find that symptom relief from conservative intervention is inadequate and short-lived, requesting surgery for the treatment of disabling and persistent pain from trapeziometacarpal osteoarthritis. Study 4 was a systematic review, conducted to determine evidence of efficacy of one surgical procedure over another. This review identified six randomised controlled trials of surgery for trapeziometacarpal osteoarthritis. While there was evidence of no difference in the reduction in weakness between the procedures, there was insufficient evidence to confirm that there was no difference in the outcomes of pain, contracture, hand function, or patient global assessment. Furthermore, there was sufficient evidence to conclude that trapeziectomy had significantly fewer adverse effects, and trapeziectomy with ligament reconstruction and tendon interposition (LRTI) had significantly more, when compared with the other procedures analysed in this review. It is suggested that the decision as to which intervention is most appropriate for a given patient be based upon the individual patient’s requirements, the extent of disease, and the demands placed upon the joint by domestic duties, work, leisure and recreational activities. The studies presented in this project assist in formulating preventative and management strategies for people with trapeziometacarpal osteoarthritis.

Thesis (MHSc--Health Science) -- AUT University, 2007. / Primary supervisor : Professor Peter McNair. Includes bibliographical references. Also held in print (xi, 147 leaves : col. ill. ; 30 cm.) in North Shore Campus Theses Collection (T 617.582 BRE)

Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 2003. / "January 2003" Errata slip inserted inside front cover. Includes bibliographical references (leaves 282-313).

Thesis (Ph. D.)--Colorado State University, 2004. / Includes bibliographical references.