Does gender influence neuromotor control of the knee and hip?

Patellofemoral pain (PFP) is a common condition that occurs more frequently in females. Anatomical, hormonal and neuromuscular factors have been proposed to contribute to the increased incidence of PFP in females, with neuromuscular factors considered to be of particular importance. This cross-sectional study aimed to evaluate differences in the neuromotor control of the knee and hip muscles between genders and to investigate whether clinical measures of hip rotation range and strength were associated with EMG measures of hip and thigh motor control. Twenty-nine (16 female and 13 male) asymptomatic participants completed a visual choice reaction-time stair stepping task. EMG activity was recorded from vastus medialis oblique, vastus lateralis, anterior and posterior gluteus medius muscles. In addition hip rotation range of motion and hip external rotation, abduction and trunk strength were assessed. There were no differences in the timing or peak of EMG activation of the vasti or gluteus medius muscle between genders during the stepping task. There were however significant associations between EMG measures of motor control of the vasti and hip strength in both females and males. These findings are suggestive of a link between hip muscle control and vasti neuromotor control.     

Deformation of articular cartilage during static loading of a knee joint – Experimental and finite element analysis

Novel conical beam CT-scanners offer high resolution imaging of knee structures with i.a. contrast media, even under weight bearing. With this new technology, we aimed to determine cartilage strains and meniscal movement in a human knee at 0, 1, 5, and 30 min of standing and compare them to the subject-specific 3D finite element (FE) model. The FE model of the volunteer?s knee, based on the geometry obtained from magnetic resonance images, was created to simulate the creep. The effects of collagen fibril network stiffness, nonfibrillar matrix modulus, permeability and fluid flow boundary conditions on the creep response in cartilage were investigated. In the experiment, 80% of the maximum strain in cartilage developed immediately, after which the cartilage continued to deform slowly until the 30 min time point. Cartilage strains and meniscus movement obtained from the FE model matched adequately with the experimentally measured values. Reducing the fibril network stiffness increased the mean strains substantially, while the creep rate was primarily influenced by an increase in the nonfibrillar matrix modulus. Changing the initial permeability and preventing fluid flow through noncontacting surfaces had a negligible effect on cartilage strains. The present results improve understanding of the mechanisms controlling articular cartilage strains and meniscal movements in a knee joint under physiological static loading. Ultimately a validated model could be used as a noninvasive diagnostic tool to locate cartilage areas at risk for degeneration.     

What is the clinical and ethical importance of incidental abnormalities found by knee MRI?

Introduction

Magnetic resonance imaging (MRI) is increasingly used to examine joints for research purposes. It may detect both suspected and unsuspected abnormalities. This raises both clinical and ethical issues, especially when incidental abnormalities are detected. The prevalence of incidental, potentially clinically significant abnormalities identified by MRI and their clinical significance in a population undergoing knee MRI in research studies are unknown.

Methods

We examined the prevalence of such lesions in healthy asymptomatic adults and those with symptomatic knee osteoarthritis (OA) undergoing knee MRI with limited sequences for the purpose of research. The MRI findings in 601 asymptomatic subjects and 132 with knee OA who underwent at least one limited knee MRI scan for cartilage volume measurement were examined by an MRI radiologist for the presence of potentially clinically significant abnormalities.

Results

These were present in 2.3% of healthy and 2.3% of OA subjects. All required further investigation to exclude non-benign disease, including four with bone marrow expansion (0.7%), requiring further investigation and management. A single potentially life-threatening lesion, a myeloma lesion, was identified in a subject with symptomatic knee OA on their second MRI scan in a longitudinal study.

Conclusion

As musculoskeletal MRI is increasingly used clinically and for research purposes, the potential for detecting unsuspected abnormalities that require further investigation should be recognized. Incorporating a system to detect these, to characterize unexpected findings, and to facilitate appropriate medical follow-up when designing studies using this technology should be considered ethical research practice.     

Can generic knee joint models improve the measurement of osteoarthritic knee kinematics during squatting activity?

Knee joint kinematics derived from multi-body optimisation (MBO) still requires evaluation. The objective of this study was to corroborate model-derived kinematics of osteoarthritic knees obtained using four generic knee joint models used in musculoskeletal modelling – spherical, hinge, degree-of-freedom coupling curves and parallel mechanism – against reference knee kinematics measured by stereo-radiography. Root mean square errors ranged from 0.7° to 23.4° for knee rotations and from 0.6 to 9.0 mm for knee displacements. Model-derived knee kinematics computed from generic knee joint models was inaccurate. Future developments and experiments should improve the reliability of osteoarthritic knee models in MBO and musculoskeletal modelling.     

Interrelationship of cartilage composition and chondrocyte mechanics after a partial meniscectomy in the rabbit knee joint – Experimental and numerical analysis

Site-specific and depth-dependent properties of cartilage were implemented within a finite element (FE) model to determine if compositional or structural changes in the tissue could explain site-specific alterations of chondrocyte deformations due to cartilage loading in rabbit knee joints 3 days after a partial meniscectomy (PM). Depth-dependent proteoglycan (PG) content, collagen content and collagen orientation in the cartilage extracellular matrix (ECM), and PG content in the pericellular matrix (PCM) were assessed with microscopic and spectroscopic methods. Patellar, femoral groove and samples from both the lateral and medial compartments of the femoral condyle and tibial plateau were extracted from healthy controls and from the partial meniscectomy group. For both groups and each knee joint site, axisymmetric FE models with measured properties were generated. Experimental cartilage loading was applied in the simulations and chondrocyte volumes were compared to the experimental values. ECM and PCM PG loss occurred within the superficial cartilage layer in the PM group at all locations, except in the lateral tibial plateau. Collagen content and orientation were not significantly altered due to the PM. The FE simulations predicted similar chondrocyte volume changes and group differences as obtained experimentally. Loss of PCM fixed charge density (FCD) decreased cell volume loss, as observed in the medial femur and medial tibia, whereas loss of ECM FCD increased cell volume loss, as seen in the patella, femoral groove and lateral femur. The model outcome, cell volume change, was also sensitive to applied tissue geometry, collagen fibril orientation and loading conditions.     

In-silico wear prediction for knee replacements—methodology and corroboration

The capability to predict in-vivo wear of knee replacements is a valuable pre-clinical analysis tool for implant designers. Traditionally, time-consuming experimental tests provided the principal means of investigating wear. Today, computational models offer an alternative. However, the validity of these models has not been demonstrated across a range of designs and test conditions, and several different formulas are in contention for estimating wear rates, limiting confidence in the predictive power of these in-silico models.This study collates and retrospectively simulates a wide range of experimental wear tests using fast rigid-body computational models with extant wear prediction algorithms, to assess the performance of current in-silico wear prediction tools.The number of tests corroborated gives a broader, more general assessment of the performance of these wear-prediction tools, and provides better estimates of the wear ‘constants’ used in computational models. High-speed rigid-body modelling allows a range of alternative algorithms to be evaluated. Whilst most cross-shear (CS)-based models perform comparably, the ‘A/A+B’ wear model appears to offer the best predictive power amongst existing wear algorithms. However, the range and variability of experimental data leaves considerable uncertainty in the results. More experimental data with reduced variability and more detailed reporting of studies will be necessary to corroborate these models with greater confidence. With simulation times reduced to only a few minutes, these models are ideally suited to large-volume ‘design of experiment’ or probabilistic studies (which are essential if pre-clinical assessment tools are to begin addressing the degree of variation observed clinically and in explanted components).     

Can a finite set of knee extension in supine position be used for a knee functional examination?

The kinematic magnetic resonance imaging technique has been developed to provide a functional examination of the knee. Technical limitations require this examination to be performed in supine position, and the knee motion is represented by an assembly of static positions at different knee angles. However, the main knee function is to support the body weight and perform continuous motion, e.g. parallel squat. Our study quantified the knee kinematics of 20 healthy subjects in different motion conditions (finite and continuous) and in different mechanical conditions (continuous unloaded and continuous loaded). We evaluated the angular and localisation difference of a finite helical axis of the knee motion for parallel squat, continuous knee extension in supine position and the finite set of knee extension in supine position. We found large inter-individual dispersion. The majority of subjects had equivalent knee kinematics between continuous knee extension and the finite set of knee extension in supine position, but not between continuous knee extension in supine position and the parallel squat. Therefore, results from a functional examination of a finite set of knee extensions in supine position do not represent the knee motion in a parallel squat. Our results suggest that functional examination of the knee from magnetic resonance imaging do not necessarily reflect the physiological kinematics of the knee. Further investigation should focus on a new magnetic resonance imaging acquisition protocol that allows image acquisition during weight bearing or includes a special device which reproduces the loaded condition.     

Is the meniscus of the knee joint a fibrocartilage?

A histological analysis of the structure of intact knee joint menisci was carried out in adult dogs. By means of specific histochemical methods for the connective tissue and cartilage, it was found that the meniscus as a whole does not have a unique structure. The anterior and posterior horns are populated by round chondroid cells encircled by abundant interstitial substance and branched wavy connective fibers; blood vessels are present. The outer third of the meniscus is constituted of cross bundles of connective fibers, fibrocytes and spindle-like areas of loose connective tissue with blood vessels. The inner avascular two thirds of the meniscus are filled with parallel circumferentially oriented fascicles of connective fibers, ovally elongated chondroid cells, and a small quantity of chondroid interstitial substance. In some menisci, in the inner two thirds of the body, there are isles of typical cartilage, which show metachromasia of the beta type and rarely of the gamma type. The occurrence and way of the manifestation of cartilage are of an individual character. The structural duality of the knee meniscus is accounted for by its functional duality manifested in offering resistance to the forces of traction and pressure, the latter ones favoring the process of evolution of tissue from connective, through chondroid, to cartilaginous.     

Characterization of caveolins from human knee joint cartilage: expression of caveolin-1, -2, and -3 in chondrocytes and association with integrin β1

Interactions between the extracellular matrix (ECM) and chondrocytes are of great importance for structure and function of cartilage. The present study was undertaken to answer the question whether caveolins take part in integrin-mediated cell–ECM interactions in the human cartilage. In samples of human knee joint cartilage, we detected the caveolin subtypes -1, -2, and -3 by immunohistochemical methods. Double-label experiments revealed a colocalization of caveolin with β1-integrin. Results of immunoprecipitation and immunoblotting assays show that β1-integrins associate with all three caveolin subtypes in human chondrocytes and indicate that they are part of the same complexes. Furthermore, immunoelectron microscopy shows the localization of β1-integrin in caveolae-like structures of the cell membrane. The data stimulate further investigations on the role of the caveolin–integrin complex for integrin-mediated signaling pathways in chondrocytes. Accepted: 17 December 1999     

Impaired varus–valgus proprioception and neuromuscular stabilization in medial knee osteoarthritis

Impaired proprioception and poor muscular stabilization in the frontal plane may lead to knee instability during functional activities, a common complaint in persons with knee osteoarthritis (KOA). Understanding these frontal plane neuromechanical properties in KOA will help elucidate the factors contributing to knee instability and aid in the development of targeted intervention strategies. The objectives of the study were to compare knee varus–valgus proprioception, isometric muscle strength, and active muscular contribution to stability between persons with medial KOA and healthy controls. We evaluated knee frontal plane neuromechanical parameters in 14 participants with medial KOA and 14 age- and gender-matched controls, using a joint driving device (JDD) with a customized motor and a 6-axis force sensor. Analysis of covariance with BMI as a covariate was used to test the differences in varus–valgus neuromechanical parameters between these two groups. The KOA group had impaired varus proprioception acuity (1.08±0.59° vs. 0.69±0.49°, p<0.05), decreased normalized varus muscle strength (1.31±0.75% vs. 1.79±0.84% body weight, p<0.05), a trend toward decreased valgus strength (1.29±0.67% vs. 1.88±0.99%, p=0.054), and impaired ability to actively stabilize the knee in the frontal plane during external perturbation (4.67±2.86 vs. 8.26±5.95 Nm/degree, p<0.05). The knee frontal plane sensorimotor control system is compromised in persons with medial KOA. Our findings suggest varus–valgus control deficits in both the afferent input (proprioceptive acuity) and muscular effectors (muscle strength and capacity to stabilize the joint).     

A double blind,randomized, placebo controlled study of the efficacy and safety of 5-Loxin<Superscript>®</Superscript>for treatment of osteoarthritis of the knee

Introduction

5-Loxin^® is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin^® in the treatment of osteoarthritis (OA) of the knee.

Methods

Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin^® daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne''s Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin^® in OA patients.

Results

Seventy patients completed the study. At the end of the study, both doses of 5-Loxin^® conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin^® as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups.

Conclusion

5-Loxin^® reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin^® may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients.

Trail Registration

(Clinical trial registration number: ISRCTN05212803.)     

Effects of spinal or general anesthesia on F₂-isoprostanes and isofurans during ischemia/reperfusion of the leg in patients undergoing knee replacement surgery

General and spinal anesthesia are used extensively in orthopedic surgery. However, these methods of anesthesia may result in different amounts of oxygen being delivered to the patient. Ischemia/reperfusion injury after release of the tourniquet initiates free radical-mediated oxidative stress. F₂-isoprostanes are reliable markers of in vivo lipid peroxidation. However, under conditions of high oxygen tension, isofurans are formed. We aimed to compare plasma isofurans and F₂-isoprostanes in spinal versus general anesthesia in patients undergoing knee-replacement surgery in a randomized, blinded study. Thirty-nine patients were randomized to spinal (SA; n = 19) or general anesthesia (GA; n = 20). Blood was collected before anesthesia, and a tourniquet was then applied to the limb during surgery. After release of the tourniquet, blood samples were collected at 30 min, 2 h, and 24 h for measurement of plasma F₂-isoprostanes and isofurans by gas chromatography–mass spectrometry. The two groups were comparable in age and body mass index. Plasma F₂-isoprostanes were significantly lower in the GA patients compared with the SA patients (p = 0.045). In contrast, the GA patients had significantly elevated plasma isofurans (p = 0.032). Increased isofurans during GA compared with SA are likely to reflect increased oxidative stress due to elevated oxygen concentrations during GA. Further studies are required to assess the implications of these findings on perioperative outcomes.     

Computation of the role of kinetics,kinematics, posterior tibial slope and muscle cocontraction on the stability of ACL-deficient knee joint at heel strike – Towards identification of copers from non-copers

Rupture of anterior cruciate ligament (ACL) undermines normal activity and function of the knee joint and places it at higher risk of re-injury and degeneration. ACL reconstruction surgery neither necessarily ensures return to pre-injury activities nor alleviates risk of long-term degeneration. Here in this computational investigation of a lower-extremity hybrid model at heel strike (HS) of gait, we search for factors that influence the stability of the joint and hence the distinct performances between post-ACL injury copers and non-copers. Due to the very unstable state of the joint under the mean gait input data, joint rotations-moments, posterior tibial slope (PTS), and cocontraction were altered within the reported data in the literature and the effects on the joint stability (anterior tibial translation (ATT) and critical muscle stiffness coefficient (q_cr)) were investigated. Results indicate that, in presence of both a small extension moment (0.1 or 0.2 Nm/kg) and a flexion rotation (∼5–8°), ACL-deficient (ACL-D) knee joint stability substantially improves to levels computed in the pre-injury intact joint. In addition, low cocontraction levels of 1–3% (in hamstrings and quads only and not in gastrocnemii) and reduced PTS (by 5°) further improve ACL-D joint stability. Therefore for a stable joint with ATT < 3 mm and q_cr < 25 similar to those in the intact knee at HS, higher flexion angles (>5°) and a small extension moment (∼0.1–0.2 Nm/kg) (i.e., higher activity in hamstrings than quads) are required. A lower posterior tibial slope (by 5°) and a small minimum cocontraction level (1–3%) in hamstrings and quads (but not in gastrocnemii) are also beneficial. These results identify mechanisms likely in play at HS in gait of copers when compared to non-copers.     

Synthesis and Cytotoxicity of О- and N-Acyl Derivatives of Azepanobetulin

Russian Journal of Bioorganic Chemistry - A five-stage synthesis of azepanobetulin from betulin with a total yield of 47% has been carried out. The acylation of azepanobetulin with anhydrides or...     

Test–retest reliability of quadriceps muscle function outcomes in patients with knee osteoarthritis

Quadriceps muscle weakness and the underlying neuromuscular deficits have been increasingly studied over the last few years in patients with knee osteoarthritis, but the applied methodologies have never been validated for this specific population. The aim of this study was to investigate test–retest reliability of several quadriceps muscle function outcomes in patients with knee osteoarthritis both before and after knee arthroplasty surgery. Ten preoperative and 20 postoperative patients participated in two identical testing sessions. A series of voluntary and/or electrically stimulated contractions of the involved quadriceps with concomitant torque and electromyographic recordings were used to characterize muscle strength, muscle activation and muscle contraction properties. Vastus lateralis morphology (thickness and fascicle pennation angle) was also assessed using ultrasonography. Overall, good reliability scores were observed for the majority of the 13 assessed variables (nine variables with intraclass correlation coefficients >0.75, 12 variables with coefficients of variation <15%). The most reliable testing protocol for patients with knee osteoarthritis would entail the assessment of (1) isometric maximal voluntary torque for evaluating muscle strength, with (2) simultaneous vastus lateralis electromyographic activity for evaluating muscle activation, (3) potentiated (resting) doublet peak torque for evaluating muscle contractility, and (4) vastus lateralis thickness for evaluating muscle size.     

Cloning and sequencing of inulinase and β-fructofuranosidase genes of a deep-sea Microbulbifer species and properties of recombinant enzymes

An inulinase-producing Microbulbifer sp. strain, JAM-3301, was isolated from a deep-sea sediment. An inulin operon that contained three open reading frames was cloned and sequenced. Two of the three genes were expressed. One product was an endo-inulinase, and the other was a β-fructofuranosidase. Both enzymes worked together to effectively degrade inulin.     

Association between ultrasound-detected synovitis and knee pain: a population-based case–control study with both cross-sectional and follow-up data

Background

An important role for synovial pathology in the initiation and progression of knee osteoarthritis has been emphasised recently. This study aimed to examine whether ultrasonography-detected synovial changes associate with knee pain (KP) in a community population.

Methods

A case–control study was conducted to compare people with early KP (n?=?298), established KP (n?=?100) or no KP (n?=?94) at baseline. Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) between groups adjusted for radiographic osteoarthritis (ROA) severity and other confounding factors. After 1 year, 255 participants with early and established KP completed the follow-up questionnaire for changes in KP. Logistic regression with adjustment was used to determine predictors of KP worsening.

Results

At baseline, effusion was associated with early KP (OR 2.64, 95% CI 1.57–4.45) and established KP (OR 5.07, 95% CI 2.74–9.38). Synovial hypertrophy was also associated with early KP (OR 5.43, 95% CI 2.12–13.92) and established KP (OR 13.27, 95% CI 4.97–35.43). The association with effusion diminished when adjusted for ROA. Power Doppler signal was uncommon (early KP 3%, established KP 2%, controls 0%). Baseline effusion predicted worsening of KP at 1 year (OR 1.95, 95% CI 1.05–3.64). However, after adjusting for ROA, the prediction was insignificant (adjusted OR 0.95, 95% CI 0.44–2.02).

Conclusions

Ultrasound effusion and synovial hypertrophy are associated with KP, but only effusion predicts KP worsening. However, the association/prediction is not independent from ROA. Power Doppler signal is uncommon in people with KP. Further study is needed to understand whether synovitis is directly involved in different types of KP.

     

Identification and Characterisation of the α and β Subunits of Succinyl CoA Ligase of Tomato

Despite the central importance of the TCA cycle in plant metabolism not all of the genes encoding its constituent enzymes have been functionally identified. In yeast, the heterodimeric protein succinyl CoA ligase is encoded for by two single-copy genes. Here we report the isolation of two tomato cDNAs coding for α- and one coding for the β-subunit of succinyl CoA ligase. These three cDNAs were used to complement the respective Saccharomyces cerevisiae mutants deficient in the α- and β-subunit, demonstrating that they encode functionally active polypeptides. The genes encoding for the subunits were expressed in all tissues, but most strongly in floral and leaf tissues, with equivalent expression of the two α-subunit genes being expressed to equivalent levels in all tissues. In all instances GFP fusion expression studies confirmed an expected mitochondrial location of the proteins encoded. Following the development of a novel assay to measure succinyl CoA ligase activity, in the direction of succinate formation, the evaluation of the maximal catalytic activities of the enzyme in a range of tissues revealed that these paralleled those of mRNA levels. We also utilized this assay to perform a preliminary characterisation of the regulatory properties of the enzyme suggesting allosteric control of this enzyme which may regulate flux through the TCA cycle in a manner consistent with its position therein.