The object of this study was to compare growth factor and cytokine profiles in canine autologous conditioned serum (ACS) to canine plasma. Blood collected from 16 medium to large breed dogs was used to produce ACS (Orthokine® vet irap 10 syringes) and citrated plasma (control). Canine-specific ELISA assays were run per manufacturers’ instructions for interleukin (IL)-10, IL-4, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-β1, IL-1β, and interleukin-1 receptor antagonist (IL-1ra). Serum, in addition to plasma and ACS, was collected from an additional 6 dogs for TNF-α, IL-1β, and IL-1ra analysis (total of 22 dogs). Data were analyzed for differences in cytokine concentrations between ACS, plasma, and serum using the Wilcoxon signed-rank test with significance set at P<.05.There was a large variability in growth factor and cytokine concentrations between individual dogs in both plasma and ACS. There were no significant differences in IL-10, TNF-α, IGF-1, FGF-2, and TGF-β1 concentrations between ACS, plasma, or serum. ACS concentrations of IL-1β (median, range; 46.3 pg/mL, 0-828.8) and IL-4 (0.0 pg/mL, 0-244.1) were significantly increased compared to plasma (36.6 pg/mL, 0-657.1 and 0.0 pg/mL, 0-0, respectively). IL-1ra concentrations in ACS (median, range; 3458.9 pg/mL, 1,243.1-12,089.0) were significantly higher than plasma (692.3 pg/mL, 422.5- 1,475.6), as was the IL-1ra:IL-1β ratio (39.9 and 7.2, respectively). / Master of Science

Twelve normal mixed-breed dogs were selected and assigned to acetabular rotation or sham-operated groups. Rotation group dogs had pelvic osteotomies followed by application of an ilial bone plate, causing rotation of the acetabulum to reduce dorsal coverage of the femoral head. Sham group dogs received identical osteotomies but were plated in normal orientation. All dogs had force plate and subjective lameness evaluations pre-operatively and post-operatively. Pelvic radiographs were evaluated pre-operatively and at four-week intervals post-operatively. The dogs were killed at the conclusion of the study, and samples were taken for evaluation. Analysis of vertical ground reaction forces indicated a significant difference between treatment groups, however no difference was noted based on subjective scores. No difference was observed between groups based on radiographic estimations of degenerative changes or Norberg angle, however the coverage of the femoral head was less in rotated dogs. Mild inflammatory changes were discernible in the joint capsule of some dogs in both groups. A trend toward more severe change was present in the left hip of the treatment group, but statistically significant difference was noted only when comparing the right and left legs of the acetabular rotation group. Although evidence of osteoarthritis was noted histologically, only minor differences were detected in the dogs by other means. Because of the minimal changes noted over the duration of the study, we conclude that the model does result in histopathologic change consistent with osteoarthritis, but that force plate analysis, radiographic evaluation, and clinical lameness evaluation are insensitive measures of this change. / Master of Science

Thesis (Ph. D.)--University of Missouri--Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 104-110). Also available on the Internet.

The purpose of this study was to describe the therapeutic interventions used for people with limited function of the hand due to osteoarthrtis or rheumatoid arthritis. The study was accomplished through a literature studie. Data were collected through a search of databases considering the criteras for inclusion or exclusion that were established by the authors before the search. Twelve articles were included in the study and analysed through a qualitative content analysis. Fivedifferent categories of occupational interventions were revealed through the analysis. The categories are orthotics, heat and cold treatment, information and education, strength and range of motion exercises and training in activity of daily life. The result of the analysis continued with an interpretation of OTIPM to furher iluminate the occupational focus of activity. A minority of the occupational interventions used as treatment of clients with a limited function of the hand due to osteoarthrits or rheumatoid arthritis correspond to the focus of activity described in OTIPM. / Validerat; 20110607 (anonymous)

Introduction: Arthroscopic partial resection of degenerative meniscal injuries has previously been frequently performed but has been questioned in recent years. However, contradictory data exist. Aim: We aimed to asses patient- reported outcome in patients over 40 years of age after arthroscopic surgery due to degenerative meniscal injury. We further aimed to compare women and men due to diagnosis and to examine the number of patients that have needed knee arthroplasty during the follow-up period. Methods: Patients &gt; 40 years of age who underwent arthroscopic surgery of the knee in the years of 2011-2013 were studied using validated questionnaire KOOS (Knee Injury and Osteoarthritis Outcome Score) along with a self-constructed questionnaire. Results: In all subjects, the highest median score was seen in all daily living (Women:93, Men: 96) and knee pain (Women: 86, Men: 92). The lowest score was seen in sports and recreation (Women: 55, Men: 65). Men had an overall higher KOOS-score in every subscale compared to women (p&gt;0.05). No significant difference was seen between women and men divided by diagnosis (p&gt;0.05). 72% women and 80% men experienced improved knee function today compared to before surgery. 22% women and 14% men experienced deterioration in knee function. 6% women and men experienced unaltered knee function. 24 patients (9.5%) had got a knee arthroplasty. Conclusions: This study showed that most middle-age patients experienced increased knee function and high satisfaction rate after partial meniscectomy when suffering from degenerative meniscal injury.

Introduction: Gait biomechanics are associated with knee osteoarthritis (OA) structural progression, but no studies have included: i) all three lower extremity joints, ii) non-frontal plane factors, iii) temporal loading patterns, and iv) progression from structural and symptomatic perspectives. This dissertation addressed gaps in our understanding of lower limb biomechanics and their implication for determining whether we have identified and are targeting the most effective biomechanical variables in the development and evaluation of conservative interventions to slow knee OA structural and symptom progression (progression to TKA). Methods: 54 patients with knee OA underwent baseline gait analysis. Three-dimensional hip, knee, and ankle angles and moments were calculated. Waveform characteristics were determined using Principal Component Analysis (PCA), and knee adduction moment (KAM) peak and impulse were calculated. At follow-up 5-8 years later, 26 patients reported undergoing total knee arthroplasty (TKA). Unpaired Student’s t-tests detected differences in baseline demographic and gait characteristics between TKA and no-TKA groups. Receiver operating curve analysis determined discriminative abilities of these differences. Stepwise discrimination analysis determined which multivariate combination best classified the TKA group. Logistic regression analysis determined the predictive ability of the multivariate model. Results: There were no baseline differences in clinical and spatiotemporal gait characteristics, but the TKA group showed significant gait biomechanical differences, including higher KAM magnitude (KAMPC1), less difference between early and mid-stance KAM (KAMPC2), higher KAM peak and impulse, reduced early stance knee flexion and late stance knee extension moments (KFMPC2), and reduced stance dorsiflexion moments (AFMPC4). The multivariate discriminant function with the highest classification rate (74.1%) combined KAMPC1, KFMPC2, and AFMPC4, with sensitivity of 84.6 and specificity of 71.4. A one-unit increase in the model score increased risk of progression to TKA six-fold. Conclusion: Higher KAMPC1 scores suggest higher overall loading during gait. Lower KFMPC2 and AFMPC4 scores suggest inability to unload the knee and therefore sustained loading. Interventions reducing overall load and altering patterns of loading (i.e. increase unloading) may reduce risk of progression to TKA. Future research should determine how components of the discriminant model can be altered conservatively, and what impact alterations have on the risk of progression to TKA.

Osteoarthritis (OA) of the knee affects between 5.4% and 38% of older adults and this prevalence is increasing as the population ages and becomes more obese. As health costs rise, it is important to have accurate and cost-effective methods to assess knee OA and the risk for OA. One risk factor for progression of knee OA is lower extremity (LE) frontal-plane malalignment. The first goal of this thesis was to assess the suitability of knee radiographs and LE photographs for the estimation of frontal-plane LE alignment. In the first study, several versions of the femoral shaft-tibial shaft (FS-TS) angle, assessed from knee radiographs, were compared to the hip-knee-ankle (HKA) angle, assessed from full-length radiographs. We concluded that the FS-TS angle is not a recommended substitute for the HKA angle, because the association between the two measures differs depending on alignment, OA severity and the method of determining the FS-TS angle. In the second study, the hip-knee-ankle angle determined from a pelvis-to-ankle photograph (HKA-P) was assessed for its ability to estimate the HKA angle. The HKA-P angle was reliable and highly correlated to the HKA. It therefore shows promise as an accurate and cost-effective assessment tool for the estimation of LE alignment. Commonly-used grading scales for the severity of knee OA seen on a radiograph emphasize just one feature of OA; therefore the second goal of this thesis was to assess the psychometric properties of the unicompartmental osteoarthritis grade (UCOAG), a composite scale which grades several features of OA in the tibiofemoral (TF) compartment. In the third and fourth studies, the reliability, validity and sensitivity to change of the UCOAG scale was assessed and compared to two commonly-used scales (Kellgren-Lawrence and Osteoarthritis Research Society International joint space narrowing). The UCOAG scale showed moderate to excellent reliability. All three scales demonstrated comparable validity and sensitivity to change. The UCOAG is therefore recommended for the assessment of OA severity and change over time. This research provides evidence for the use of accurate and cost-effective measures to assess LE alignment using photographs, and TF OA severity using radiographs, for clinical assessment and research purposes. / Thesis (Ph.D, Rehabilitation Science) -- Queen's University, 2013-09-26 13:21:06.097

Anteromedial Gonarthrosis (AMG) is a distinct phenotype of knee osteoarthritis (OA), with a specific pattern of disease on the tibia. There is full thickness cartilage loss anteromedially, progressing to an area of damaged cartilage, and then to an area of macroscopically and histologically normal cartilage posteriorly. This reproducible pattern of disease can be considered to be a spatial model of OA progression and provides an alternative and less biologically varied set of specimens than the commonly used multiple joint compartments in which to quantify disease-related changes. The aim of this thesis was to explore in detail spatial and quantitative differences in cell, matrix and molecular features between areas of cartilage in AMG. A real time PCR study was undertaken comparing damaged and undamaged cartilage in AMG. Previous work from our research group had shown increased type I collagen content of undamaged cartilage in AMG. This gene expression study corroborated this finding by demonstrating increased COL1A1 expression in undamaged cartilage, compared to damaged cartilage. MMP1, MMP3, MMP13 and ADAMTS4 were also shown to have increased expression in undamaged cartilage. Since these changes arise in tissue before any macroscopic damage is apparent, these may indicate early changes of the cartilage matrix in AMG. In order to confirm that these changes are directly related to the damage process and not only to normal regional variations, Above Knee Amputations were collected from patients with peripheral vascular disease but no overt OA and a template of the AMG joint surface created to allow for matched regional sampling. Studies into their histology, immunoassays and qPCR were performed in order to compare results with those from AMG specimens. Histology demonstrated low scores throughout but allowed for a division into lower (macroscopically and histologically normal) and higher grade (surface wear/possible early signs of OA) groups. Immunoassays showed elevated type I collagen in high grade but not low grade groups in the posterior cartilage. No differences in mRNA expression were detected using qPCR suggesting that changes seen in AMG specimens were specific to the OA disease process. Because the causes of cell death in OA are not fully understood an immunohistochemical study into apoptosis was performed. TUNEL staining demonstrated higher levels of apoptosis, the more damaged the cartilage. The presence of Active Caspase 3, Cytochrome C, Active Bax and Bim with the same distributions demonstrated apoptosis occurring via the intrinsic or mitochondrial pathway. The high levels of 3-Nitrotyosine in more damaged cartilage implicated reactive oxygen species in apoptotic mechanisms. A microarray study was conducted comparing regions of damaged and undamaged cartilage in AMG. 389 genes were found to be significantly differentially expressed between regions. Several pathways rich in gene expression changes were highlighted including cellular development, inflammatory response and skeletal disorders. Results suggest complex changes in the signaling microenvironment of AMG and identify areas for future study. In summary, this thesis has highlighted several quantitative molecular and cellular differences between regions of cartilage in AMG, demonstrating its usefulness as a tight disease model. Gene expression differences corroborate changes previously seen by immunohistochemistry; microarray has shown the wider picture of gene expression changes. Apoptosis has been shown to occur via the intrinsic pathway and involve reactive oxygen species, highlighting this damage pathway as an important driver of cell loss. Most importantly this thesis has identified the apparently normal region in AMG specimens as a region undergoing considerable molecular changes and as a potential early disease model. The dysregulation of collagen I distribution seen in AMG and slightly worn AKA specimens is very interesting and suggests a possible early response to loading alterations caused by joint wear and opening the way for future experiments. The identification of wear patterns in AKA specimens specifically mapping to the zone of maximal damage in AMG confirms the site of initial injury and progression over time proposed in this model. These AKA specimens with no overt OA should therefore be used in future studies to assess emerging biomarkers of disease progression.

Background: Inverse-probability-of-treatment-weighted estimation (IPTW) of marginal structural models was proposed to adjust for time-varying confounders that are influenced by prior treatment use. It is unknown whether pharmacoepidemiologic studies that applied IPTW conformed to the recommendations proposed by methodological studies. In addition, no previous study has compared the performance of different analytic strategies adopted in IPTW analyses. Objectives: This project aims 1) to review the reporting practice of pharmacoepidemiologic studies that applied IPTW, 2) to compare the validity and precision of several approaches to constructing weight, 3) to use IPTW to estimate the effectiveness of glucosamine and chondroitin in treating osteoarthritis. Methods: We systematically retrieved pharmacoepidemiologic studies that were published in 2012 and applied IPTW to estimate the effect of a time-varying treatment. Under a variety of simulated scenarios, we assessed the performance of four analytic approaches what were commonly used in studies conducting IPTW analyses. Finally, using data from Osteoarthritis Initiative, we applied IPTW to estimate the long-term effectiveness of glucosamine and chondroitin on treating knee osteoarthritis. Results: The practice of reporting use of IPTW in pharmacoepidemiologic studies was suboptimal. The majority of reviewed studies did not report that the positivity assumption was assessed, and several studies used unstablized weights or did not report that the stabilized weights were used. With data simulation, we found that intention-to-treat analyses underestimated the actual treatment effect when there was non-null treatment effect and treatment non-adherence. This underestimation was linearly correlated with adherence levels. As-treated analyses that took into account the complex mechanism of treatment use generated approximately unbiased estimates without sacrificing the estimate precision when the treatment effect was non-null. Finally, after adjustment for potential confounders with marginal structural models, we found no clinically meaningful benefits of glucosamine/chondroitin in relieving knee pain, stiffness and physical function or slowing joint space narrowing. Conclusions: It may be prudent to develop best practices of reporting the use of IPTW. Studies performing intention-to-treat analyses should report the levels of adherence after treatment initiation, and studies performing as-treated analyses should take into the complex mechanism of treatment use in weight construction.

Title: The influence of pharmacological substances from the SYSADOA group on knee osteoarthritis. Objectives: The aim of this work is to determine the effect of three - month usage of pharmacological substances from the SYSADOA group on the subjective perception of the difficulties associated with the knee osteoarthritis and on the reological changes in the joint. Methods: In collaboration with rehabilitation and orthopedic centres 18 probands with knee osteoarthritis in the second degree were obtained. These probands were divided into two groups - the experimetal group (including those who have taken Proenzi 3 plus) and the control group (including those who have taken placebo). With all the pacients the input clinical examination and the medical history were done. Probands had been using these preparations for twelve weeks. After this time, the changes in the subjective perception using the WOMAC test and reological changes in the joint were evaluated, using a special knee rheometer. Results: The results of objectively measured parameters clearly proved that the Proenzi 3 plus has a positive effect on the rheological properties of the knee osteoarthritis. The experimental group had a statistically significant improvement in both of these parameters, as opposed to the control group. Concerning...