Nuclease-resistant ribozymes decrease stromelysin mRNA levels in rabbit synovium following exogenous delivery to the knee joint.

Catalytic RNA molecules, or ribozymes, have generated significant interest as potential therapeutic agents for controlling gene expression. Although ribozymes have been shown to work in vitro and in cellular assays, there are no reports that demonstrate the efficacy of synthetic, stabilized ribozymes delivered in vivo. We are currently utilizing the rabbit model of interleukin 1-induced arthritis to assess the localization, stability, and efficacy of exogenous antistromelysin hammerhead ribozymes. The matrix metalloproteinase stromelysin is believed to be a key mediator in arthritic diseases. It seems likely therefore that inhibiting stromelysin would be a valid therapeutic approach for arthritis. We found that following intraarticular administration ribozymes were taken up by cells in the synovial lining, were stable in the synovium, and reduced synovial interleukin 1 alpha-induced stromelysin mRNA. This effect was demonstrated with ribozymes containing various chemical modifications that impart nuclease resistance and that recognize several distinct sites on the message. Catalytically inactive ribozymes were ineffective, thus suggesting a cleavage-mediated mechanism of action. These results suggest that ribozymes may be useful in the treatment of arthritic diseases characterized by dysregulation of metalloproteinase expression.

Combined medical-engineering study of injury and damage to the knee joint in impact. Final report.

National Highway Safety Bureau, Washington, D.C.

Two knees or not two knees? Patient costs and outcomes following bilateral and unilateral total knee joint replacement surgery for OA

Aims: This study aims to address medical and non-medical direct costs and health outcomes of bilateral and unilateral total knee replacement from the patients' perspective during the first year post-surgery. Methods: Osteoarthritis patients undergoing primary unilateral total knee or bilateral total knee replacement (TKR) surgery at three Sydney hospitals were eligible. Patients completed questionnaires pre-operatively to record expenses during the previous three months and health status immediately prior to surgery. Patients then maintained detailed prospective cost diaries and completed SF-36 and WOMAC Index each three months for the first post-operative year. Results: Pre-operatively, no significant differences in health status were found between patients undergoing unilateral TKR and bilateral TKR. Both unilateral and bilateral TKR patients showed improvements in pain, stiffness and function from pre-surgery to 12 months post-surgery. Patients who had bilateral TKR spent an average of 12.3 days in acute hospital and patients who had unilateral TKR 13.6 days. Totally uncemented prostheses were used in 6% of unilateral replacements and 48% of bilateral replacements. In hospital, patients who had bilateral TKR experienced significantly more complications, mainly thromboembolic, than patients who had unilateral TKR. Regression analysis showed that for every one point increase in the pre-operative SF-36 physical score (i.e. improving physical status) out-of-pocket costs decreased by 94%. Out-of-pocket costs for female patients were 3.3 times greater than for males. Conclusion: Patients undergoing bilateral TKR and unilateral TKR had a similar length of stay in hospital and similar out-of-pocket expenditures. Bilateral replacement patients reported better physical function and general health with fewer health care visits one year post procedure. Patients requiring bilateral TKR have some additional information to aid their decision making. While their risk of peri-operative complications is higher, they have an excellent chance of good health outcomes at 12 months and are not going to be doubly 'out-of-pocket' for the experience. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effects of experimentally-induced anterior knee pain on knee joint position sense in healthy individuals

Purpose. The ability to sense the position of limb segments is a highly specialised proprioceptive function important for control of movement. Abnormal knee proprioception has been found in association with several musculoskeletal pathologies but whether nociceptive Stimulation can produce these proprioceptive changes is unclear. This study evaluated the effect of experimentally induced knee pain on knee joint position sense (JPS) in healthy individuals. Study design. Repeated measures, within-subject design. Methods. Knee JPS was tested in 16 individuals with no history of knee pathology under three experimental conditions: baseline control, a distraction task and knee pain induced by injection of hypertonic saline into the infrapatellar fat pad. Knee JPS was measured using active ipsilateral limb matching responses at 20degrees and 60degrees flexion whilst non-weightbearing (NWB) and 20degrees flexion single leg stance. During the tasks, the subjective perception of distraction and severity of pain were measured using 11-point numerical rating scales. Results. Knee JPS was not altered by acute knee pain in any of the positions tested. The distraction task resulted in poorer concentration, greater JPS absolute errors at 20degrees NWB, and greater variability in errors during the WB tests. There were no significant correlations between levels of pain and changes in JPS errors. Changes in JPS with pain and distraction were inversely related to baseline knee JPS variable error in all test positions (r = -0.56 to -0.91) but less related to baseline absolute error. Conclusion. Knee JPS is reduced by an attention-demanding task but not by experimentally induced pain. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

Effect of knee joint angle on motor unit synchronization

Activity of the vasti has been argued to vary through knee range of movement due to changes in passive support of the patellofemoral joint and the relative contribution of these muscles to knee extension. Efficient function of the knee is dependent on optimal control of the patellofemoral joint, largely through coordinated activity of the medial and lateral quadriceps. Motor unit synchronization may provide a mechanism to coordinate the activity of vastus medialis (VMO) and vastus lateralis (VL), and may be more critical in positions of reduced passive support for the patellofemoral joint (i.e., full extension). Therefore, the aim of this study was to determine whether the degree of motor unit synchronization between the vasti muscles is dependent on joint angle. Electromyographic (EMG) recordings of single motor unit action potentials (MUAPs) were made from VMO and multiunit recordings from VL during isometric contractions of the quadriceps at 0 degrees, 30 degrees, and 60 degrees of knee flexion. The degree of synchronization between motor unit firing was evaluated by identification of peaks in the rectified EMG averages of VL, triggered from MUA-Ps in VMO. The proportion of cases in which there was a significant peak in the triggered averages was calculated. There was no significant difference in the degree of synchronization between the vasti at different knee angles (p = 0.57). These data suggest that this basic coordinative mechanism between the vasti muscles is controlled consistently throughout knee range of motion, and is not augmented at specific angles where the requirement for dynamic control of stability is increased. (D 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Midterm to long-term longitudinal outcome of autologous chondrocyte implantation in the knee joint:a multilevel analysis

Background Autologous chondrocyte implantation is a cell therapeutic approach for the treatment of chondral and osteochondral defects in the knee joint. The authors previously reported on the histologic and radiologic outcome of autologous chondrocyte implantation in the short- to midterm, which yields mixed results. Purpose The objective is to report on the clinical outcome of autologous chondrocyte implantation for the knee in the midterm to long term. Study Design Cohort study; Level of evidence, 3. Methods Eighty patients who had undergone autologous chondrocyte implantation of the knee with mid- to long-term follow-up were analyzed. The mean patient age was 34.6 years (standard deviation, 9.1 years), with 63 men and 17 women. Seventy-one patients presented with a focal chondral defect, with a median defect area of 4.1 cm2 and a maximum defect area of 20 cm2. The modified Lysholm score was used as a self-reporting clinical outcome measure to determine the following: (1) What is the typical pattern over time of clinical outcome after autologous chondrocyte implantation; and (2) Which patient-related predictors for the clinical outcome pattern can be used to improve patient selection for autologous chondrocyte implantation? Results The average follow-up time was 5 years (range, 2.7–9.3). Improvement in clinical outcome was found in 65 patients (81%), while 15 patients (19%) showed a decline in outcome. The median preoperative Lysholm score of 54 increased to a median of 78 points. The most rapid improvement in Lysholm score was over the 15-month period after operation, after which the Lysholm score remained constant for up to 9 years. The authors were unable to identify any patient-specific factors (ie, age, gender, defect size, defect location, number of previous operations, preoperative Lysholm score) that could predict the change in clinical outcome in the first 15 months. Conclusion Autologous chondrocyte implantation seems to provide a durable clinical outcome in those patients demonstrating success at 15 months after operation. Comparisons between other outcome measures of autologous chondrocyte implantation should be focused on the clinical status at 15 months after surgery. The patient-reported clinical outcome at 15 months is a major predictor of the mid- to long-term success of autologous chondrocyte implantation.

The effects of foam rolling on muscular co-activation around the knee joint

The major objectives of this thesis were to determine if foam rolling had any effect on antagonist muscle activation and whether those changes would alter muscular co-activation patterns. The results from this thesis along with current literature will help clinicians to develop adequate exercise prescription for rehabilitative and pre-activity purposes. The existing literature has shown that foam rolling or roller massagers can increase range of motion (ROM), improve performance, and alter pain perception, however little research exists regarding changes in muscle activation following foam rolling. This study developed a reliable method for measuring muscle activation around the knee joint and using that method found that foam rolling the quadriceps can impair hamstrings muscle activation likely due to greater levels of perceived pain when rolling the quadriceps.

Medial and lateral hamstrings and quadriceps co-activation affects knee joint kinematics and ACL elongation : a pilot study

Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study

Objectives To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI. Methods Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (< 2 mm), grade 1 (2-4 mm) and grade 2 (> 4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter-and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed. Results 400 subjects were included (mean age 58.8 +/- 7.0 years, body mass index 29.5 +/- 4.9 kg/m(2), 46% women). For individual sites, intrareader reliability (weighted kappa) was 0.67-1.00 for reader 1 and 0.60-1.00 for reader 2. Inter-reader agreement (kappa) was 0.67-0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient (ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively). Conclusions A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.

The influence of age on weight-bearing joint reposition sense of the knee

Knee joint-position sensitivity has been shown to decline with increasing age, with much of the research reported in the literature investigating this age effect in non-weight-bearing (NWB) conditions. However, little data is available in the more functional position of weight-bearing conditions. The objective of this study was to identify the influence of age on the accuracy and nature of knee joint-position sense (JPS) in both full weight-bearing (FWB) and partial weight-bearing (PWB) conditions and to determine the effect of lower-extremity dominance on knee JPS. Sixty healthy subjects from three age groups (young: 20-35 years old, middle-aged: 40-55 years, and older: 60-75 years) were assessed. Tests were conducted on both the right and left legs to examine the ability of subjects to correctly reproduce knee angles in an active criterion-active repositioning paradigm. Knee angles were measured in degrees using an electromagnetic tracking device, Polhemus 3Space Fastrak, that detected positions of sensors placed on the test limb. Errors in FWB knee joint repositioning did not increase with age, but significant age-related increases in knee joint-repositioning error were found in PWB. It was found that elderly subjects tended to overshoot the criterion angle more often than subjects from the young and middle-aged groups. Subjects in all three age groups performed better in FWB than in PWB. Differences between the stance-dominant (STD) and skill-dominant (SKD) legs did not reach significance. Results demonstrated that for, normal pain-free individuals, there is no age-related decline in knee JPS in FWB, although an age effect does exist in PWB. This outcome challenges the current view that a generalised decline in knee joint proprioception occurs with age. In addition, lower-limb dominance is not a factor in acuity of knee JPS.

Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study.

OBJECTIVES: To determine clinical and ultrasonographic predictors of joint replacement surgery across Europe in primary osteoarthritis (OA) of the knee. METHODS: This was a 3-year prospective study of a painful OA knee cohort (from a EULAR-sponsored, multicentre study). All subjects had clinical evaluation, radiographs and ultrasonography (US) at study entry. The rate of knee replacement surgery over the 3-year follow-up period was determined using Kaplan-Meier survival data analyses. Predictive factors for joint replacement were identified by univariate log-rank test then multivariate analysis using a Cox proportional-hazards regression model. Potential baseline predictors included demographic, clinical, radiographic and US features. RESULTS: Of the 600 original patients, 531 (88.5%), mean age 67+/-10 years, mean disease duration 6.1+/-6.9 years, had follow-up data and were analysed. During follow-up (median 3 years; range 0-4 years), knee replacement was done or required for 94 patients (estimated event rate of 17.7%). In the multivariate analysis, predictors of joint replacement were as follows: Kellgren and Lawrence radiographic grade (grade &gt; or =III vs &lt;III, hazards ratio (HR) = 4.08 (95% CI 2.34 to 7.12), p&lt;0.0001); ultrasonographic knee effusion (&gt; or =4 mm vs &lt;4 mm) (HR = 2.63 (95% CI 1.70 to 4.06), p&lt;0.0001); knee pain intensity on a 0-100 mm visual analogue scale (&gt; or =60 vs &lt;60) (HR = 1.81 (95% CI 1.15 to 2.83), p=0.01) and disease duration (&gt; or =5 years vs &lt;5 years) (HR=1.63 (95% CI 1.08 to 2.47), p=0.02). Clinically detected effusion and US synovitis were not associated with joint replacement in the univariate analysis. CONCLUSION: Longitudinal evaluation of this OA cohort demonstrated significant progression to joint replacement. In addition to severity of radiographic damage and pain, US-detected effusion was a predictor of subsequent joint replacement.

Inexpensive footwear decreases joint loading in elderly women with knee osteoarthritis

Recent literature has highlighted that the flexibility of walking barefoot reduces overload in individuals with knee osteoarthritis (OA). As such, the aim of this study was to evaluate the effects of inexpensive, flexible, non-heeled footwear (Moleca (R)) as compared with a modern heeled shoes and walking barefoot on the knee adduction moment (KAM) during gait in elderly women with and without knee OA. The gait of 45 elderly women between 60 and 70 years of age was evaluated. Twenty-one had knee OR graded 2 or 3 according to Kellgren and Lawrence`s criteria, and 24 who had no OA comprised the control group (CG). The gait conditions were: barefoot, Moleca (R), and modern heeled shoes. Three-dimensional kinematics and ground reaction forces were measured to calculate KAM by inverse dynamics. For both groups, the Moleca (R) provided peak KAM and KAM impulse similar to barefoot walking. For the OA group, the Moleca (R) reduced KAM even more as compared to the barefoot condition during midstance. On the other hand, the modern heeled shoes increased this variable in both groups. Inexpensive, flexible, and non-heeled footwear provided loading on the knee joint similar to a barefoot gait and significant overload decreases in elderly women with and without knee OA, compared to modern heeled shoes. During midstance, the Moleca (R) also allowed greater reduction in the knee joint loads as compared to barefoot gait in elderly women with knee OA, with the further advantage of providing external foot protection during gait. (C) 2011 Elsevier B.V. All rights reserved.

Effects of progressive resistance strength training on knee biomechanics during single leg step-up in persons with mild knee osteoarthritis

Background: The goal of this study was to determine if increasing strength in primary knee extensors and flexors would directly affect net knee joint moments during a common functional task in persons with knee osteoarthritis. Methods: An exploratory single sample clinical trial with pre-post treatment measures was used to study volunteers with clinical diagnosis of mild knee osteoarthritis (OA) in one knee. Subjects participated in an individually supervised training program 3 times a week for eight weeks consisting of progressive resistive exercises for knee extensors and knee flexors. Pre and post training outcome assessments included: 1. Net internal knee joint moments, 2. Electromyography of primary knee extensors and flexors, and 3. Self-report measures of knee pain and function. The distribution of lower extremity joint moments as a percent of the total support moment was also investigated. Findings: Pain, symptoms, activities of daily life, quality of life, stiffness, and function scores showed significant improvement following strength training. Knee internal valgus and hip internal rotation moments showed increasing but non-statistically significant changes post-training. There were no significant differences in muscle co-contraction activation of the Quadriceps and Hamstrings. Interpretation: While exercise continues to be an important element of OA management, the results of this study suggest improvements in function, pain, and other symptoms, as a result of strength training may not be causally related to specific biomechanical changes in net joint moments. (C) 2011 Elsevier Ltd. All rights reserved.

Magnetic Resonance Imaging in Knee Osteoarthritis Research: Semiquantitative and Compositional Assessment

Semiquantitative assessment of the knee by expert magnetic resonance imaging readers is a powerful research tool for understanding the natural history of osteoarthritis (OA). Several reliable semiquantitative scoring systems have been applied to large observational cross-sectional and longitudinal epidemiologic studies and interventional clinical trials. Such evaluations have enabled understanding of the relevance of disease in structures within the knee joint to explain pain and progression of OA. Compositional imaging of cartilage has added to our ability to detect early degeneration before morphologic changes are present, which may help to prevent the permanent morphologic changes commonly seen in knee OA.

Knee angular displacement analysis in amateur ballet dancers: a pilot study

Ballet gestures are highly non-anatomical and physiological, leading to compensatory behaviors. The knee joint is most affected by this behavior, leading to an increase risk of injury. Our purpose is to describe the knee angular displacement in amateur dancers, during a demi-plié exercise, with emphasis on valgus mechanisms frequency. Methods: 192 demi-pliés collected in six amateur female dancers (mean age = 15.33 ± 1.37 years), were analyzed regarding sagittal and frontal plane angular displacement, with an electrogoniometer connected to a signal acquisition unit at 1000 Hz. Results: all subjects presented valgus peaks along the trials, despite the global varus tendency of the knee frontal plane behavior. A significant positive correlation between the frequency of valgus and practice time was noted. Discussion: A variable angular frontal displacement was observed, with some trials comprehending a high incidence of valgus peaks along the ascending or descending phase of the demi-plié exercise. Conclusion: the frontal knee angle behavior is variable. It may present fast peaks of valgus or an initial trend of varus/valgus that is different from the global varus trend. The analysis of the activity should be considered in the training. The practice time may be related to the observed behavior.