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Effects of equine recombinant interleukin-1alpha and interleukin-1beta on proteoglycan metabolism and prostaglandin E2 synthesis in equine articular cartilage explants.

OBJECTIVES: To evaluate the effects of equine recombinant interleukin-1alpha (rEqIL-1alpha) and recombinant interleukin-1beta (rEqIL-1beta) on proteoglycan metabolism and prostaglandin E2 (PGE2) synthesis by equine articular chondrocytes in explant culture. SAMPLE POPULATION: Near full-thickness articular cartilage explants (approx 50 mg) harvested from stifle joints of a 3-year-old and a 5-year-old horse. PROCEDURE: Expression constructs containing cDNA sequences encoding EqIL-1alpha and EqIL-1beta were generated, prokaryotically expressed, and the recombinant protein purified. Near full-thickness articular cartilage explants (approx 50 mg) harvested from stifle joints of a 3-year-old and a 5-year-old horse were separately randomized to receive rEqIL-1alpha or rEqIL-1beta treatments 10 to 500 ng/ml). Proteoglycan release was evaluated by 1,9-dimethylmethylene blue spectrophotometric analysis of explant media glycosaminoglycan (GAG) concentration and release of 35S-sulfate-labeled GAG to explant media. Proteoglycan synthesis was assessed by quantification of 35S-sulfate incorporation into proteoglycan. Explant media PGE2 concentrations were evaluated using a PGE2-specific enzyme-linked immunoassay. Data were collected at 48-hour intervals and normalized by DNA content. RESULTS: Proteoglycan release was induced by rEqIL-1alpha and rEqIL-1beta at concentrations > or =0.1 ng/ml, with 38 to 76% and 88 to 98% of total GAG released by 4 and 6 days, respectively. Inhibition of proteoglycan synthesis (42 to 64%) was observed at IL-1 concentrations > or = 0.1 ng/ml at 2 and 4 days. Increased PGE2 concentrations were observed at IL-1 concentrations > or = 0.1 ng/ml at 2 and 4 days. CONCLUSIONS AND CLINICAL RELEVANCE: The rEqIL-1 induced potent concentration-dependent derangement of equine chondrocyte metabolism in vitro. These findings suggest this model may be suitable for the in vitro study of the pathogenesis and treatment of joint disease in horses.

Animals↗

Quantification of radiological damage in inflammatory arthritis: rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

Quantification of radiological damage in inflammatory arthritis is important. It has proven its value in clinical trials, but its use in clinical practice is becoming more important as well. Scoring methods for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are available. These differ in the joints and features assessed. This results in differences in the scoring range, but also in the method of performance. The various methods for the three diseases are detailed in this chapter. Most information is available for rheumatoid and for this disease the relationship between radiological damage and long-term outcome is summarised.

Arthritis, Psoriatic↗

Spinal implant debris-induced osteolysis.

STUDY DESIGN: Generally, implant-induced osteolysis is a manifestation of an adverse cellular response to phagocytosable particulate wear and corrosion debris. Initially termed "cement disease," particle-induced loosening was recognized by Charnley in the early 1960s. Despite the plethora of information gained over the last 40 years on the basic science of periprosthetic bone loss, much remains unanswered. The effect of unintended debris resulting from wear and corrosion (e.g., micromotion between the interconnection mechanisms in spinal implants) remains a clinical concern. The current study highlights what is known of particle-induced osteolysis and how the presence of spinal implant particulate debris deleteriously influences osseointegration of posterolateral bone graft or disrupts an established posterolateral fusion mass. Tissue explant, animal, and cell culture studies have revealed the complexity of cellular reactivity involved in aseptic particle-induced osteolysis. OBJECTIVES: The objectives of this study are twofold: 1) to highlight the dominant cellular participants in total joint arthroplasty particle induced osteolysis, which are purportedly the macrophage, osteoblast, fibroblast, and osteoclast and several of the dominant chemical mediators have been identified as well, which include prostaglandin E2, tumor necrosis factor-alpha, interleukin-1, and interleukin-6; and 2) to demonstrate the potential deleterious effects of spinal implant debris using animal models and analysis of soft tissue surrounding spinal implants in symptomatic patients. METHODS: There are a growing number of proinflammatory and anti-inflammatory cytokines, prostenoids, and enzymes that have been shown to play important roles in the pathology of particle-induced osteolysis. Reports that aseptic granulomatous inflammation typical of that associated with corrosion debris appear to correlate with the complexity of the implant. Titanium particulate material was used to induce effects in 34 New Zealand White rabbits where analysis included serological quantification of systemic cytokines. Postmortem microradiographic, immunocytochemical, and histopathologic assessment of the intertransverse fusion mass quantified the extent of osteolysis, local proinflammatory cytokines, osteoclasts and inflammatory infiltrates. Clinical analysis of 12 patients more than 0.4 years after spinal implants (mean 4.03, range 0.4 to 11 years) presented with late operative site pain. RESULTS: Currently the etiology of this inflammation around spinal implants resembles particle-induced osteolysis around joint arthroplasties where there typically is a self-perpetuating fibroinflammatory zone adjacent to the implant, where macrophage exhaustion, reactive oxygen intermediates, and pro-inflammatory cytokines affect a host of local cell types and induce a widening zone of soft tissue damage and inflammation. Animal model analysis indicated increased levels of local inflammatory cytokines typically associated with osteolysis-tumor necrosis factor-alpha. Osteoclast cell counts and regions of osteolytic resorption lacunas were higher in the titanium-treated versus autograft-alone groups (P < 0.05), and the extent of cellular apoptosis was markedly higher in the titanium-treated sites at both time intervals. Electron microscopy indicated definitive evidence of phagocytized titanium particles and foci of local, chronic inflammatory changes in the titanium-treated sites. CLINICAL CASES: 11 of 12 clinical cases demonstrated elevated tumor necrosis factor-alpha levels and an increased osteoclastic response in the vicinity of wear debris caused by dry frictional wear particles of titanium or stainless steel. Resection of the wear debris and surrounding fibroinflammatory zone resolved clinical symptoms in all 12 cases. CONCLUSIONS: More basic science and clinical research is needed to develop novel strategies for gaining knowledge, and developing effective evaluation and treatment of patients with implant debris related osteolysis. Titanium debris simulating that produced by spinal implants introduced at the level of a spinal arthrodesis elicits an inflammatory cytokine mediated particulate-induced response through increased expression of intracellular TNF-alpha, increased osteoclastic activity and cellular apoptosis. This study highlighted the association between spinal implants particulate wear debris and increased potential for osteolysis. Aseptic osteolysis is among the primary reasons for failure of orthopedic implants. Increased awareness of this destructive process is becoming more important with the growing popularity of total disc arthroplasty and highly modular spinal implants.

Adult↗

Recent thymic output function in patients with hematological malignancy.

Thymic function is important for the generation of T-cell diversity in the periphery of both children and adults during both health and disease. Until recently, thymic function could not be monitored, as a consequence of the absence of adequate technology to differentiate recent thymic emigrants (RTEs) from naïve T cells. The generation of TCR diversity occurs in the thymus through recombination of gene segments encoding the variable parts of the TCR alpha and beta chains. During these processes, by-products of the rearrangements are generated in the form of signal joint T-cell receptor excision circles (sjTRECs). As sjTRECs are stable extrachromosomal DNA fragments, they are not replicated during mitosis and thus diluted with each round of cell division, and are therefore most frequent in naïve T cells that have recently left the thymus, their quantification is actually considered as a valuable tool to estimate thymic function. Therefore, quantitative sjTRECs content have been recently used to assess thymic output during both health and disease. In this review, we summarize recent data on the recent thymic output function feature in patients with hematological malignancy and the immune reconstitution after stem cell transplantation and we also characterize factors that may improve the thymic output function.

DNA Replication↗

Altered motor control and spasticity after spinal cord injury: subjective and objective assessment.

This study of measures of spasticity, or altered motor control, compares the clinically used Ashworth scale with a method based on surface electromyographic (sEMG) recordings called brain motor control assessment (BMCA) in a group of 97 subjects with spinal cord injury (SCI) and varying levels of motor dysfunction. In this paper, we describe how sEMG-derived scores relate to the severity of spasticity as judged clinically. When sEMG data from passive movements from the BMCA were analyzed by Ashworth category, we found that when the sEMG data were averaged for a limb, there was a significant difference between scores for those with Ashworth 0 vs. 2 and 3, and 1 vs. 2 and 3 (p<0.001), but not between 0 and 1. Analysis of the individual muscle scores improved the discrimination between Ashworth categories. Superiority of sEMG data over Ashworth category as an objective quantification of altered motor control ("spasticity") is argued.

Adult↗

Effect of submicron polyethylene particles on an osseointegrated implant: an experimental study with a rabbit patello-femoral prosthesis.

In a rabbit model of a weight bearing, articulating prosthetic joint we repeatedly injected submicron particles of Ultra-High-Molecular-Weight-Polyethylene (UHMWPE) produced in a hip simulator. The contralateral knee with the same prosthesis was injected with carrier (NaCl) without UHMWPE. Histomorphometrical studies on undecalcified cut and ground sections at 26 and 42 weeks involved quantifications of the entire bone to metal contact and the bone area around each implant. We found no statistically significant differences between test and control groups, and the UHMWPE debris did not induce any significant osteolysis, indicating that an osseointegrated implant with a sealed interface may not be affected by UHMWPE debris or progress to aseptic loosening.

Humans↗

Advanced imaging in rheumatoid arthritis: part 2: erosions.

Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder primarily affecting the synovium. We now recognise that conventional radiographic images show changes of rheumatoid arthritis late after irreversible joint damage has occured. With the advent of powerful disease-modifying drugs there is a need for early demonstration of rheumatoid arthritis and to monitor progress of the disease and response to therapy. Advanced imaging techniques such as ultrasound and MRI have focussed on the demonstration and quantification of synovitis and erosions and allow early diagnosis of RA. The technology to quantify synovitis and erosions is developing rapidly and now allows change in disease activity to be assessed. However, problems undoubtedly exist in quantification techniques and this review serves to highlight them. Much of the literature on advanced imaging in RA appears in rheumatological journals and may not be familiar to radiologists. This review article aims to increase the awareness of radiologists to this field and to encourage them to participate and contribute to the ongoing development of these modalities. Without this collaboration it is unlikely that these modalities will reach their full potential in the field of rheumatological imaging. This review is in two parts. This first part addresses synovitis imaging. The second part will look at advanced imaging of erosions in RA.

Arthritis, Rheumatoid↗

Quantitative assessment of the muscles of the rotator cuff with magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The purpose of this study was to establish a magnetic resonance (MR) imaging standard for quantification of the muscles of the rotator cuff. METHODS: Parasagittal T1-weighted turbo spin-echo images of the shoulder were obtained in 70 asymptomatic subjects (35 women, 35 men; age range: 21-70 years, mean: 45 years). Standardized cross-sectional areas (rotator cuff muscle areas divided by the area of the supraspinatus fossa) and standardized signal intensities (related to signal intensities of the teres major muscle) were measured and compared with 30 patients with different stages of rotator cuff tears and 10 patients with glenohumeral instability. In addition, a so-called tangent sign was evaluated with the hypothesis that a healthy supraspinatus muscle crosses a line (tangent) drawn through the superior borders of the scapular spine and the superior margin of the coracoid. RESULTS: Cross-sectional areas of the muscles of the rotator cuff were variable in asymptomatic subjects. Cross-sectional areas (but not signal intensities) did discriminate patients with different stages of rotator cuff tears from asymptomatic subjects. The tangent sign was negative in all asymptomatic subjects but positive in four and nine of 10 patients with medium and large rotator cuff tears, respectively. CONCLUSIONS: A method for quantification of the muscles of the rotator cuff using MR imaging is presented. Cross-sectional areas can be used for quantification of the muscles of the rotator cuff. The tangent sign is a useful MR sign for atrophy of the supraspinatus muscle.

Adult↗

Angle--angle diagrams in the assessment of locomotion.

This paper includes original research relating to kinematic information presented in the form of knee-angle/hip-angle diagrams. Cyclic loops which had been utilized in the past mainly for their visual representation have been quantified using a shape recognition technique. Quantitative analyses of angle-angle diagrams associated with 5 normal subjects were carried out. The quantification and physical interpretations of the parameters extracted from the angle-angle diagrams provided a valuable adjunct to visual assessment of the gaits.

Biomechanical Phenomena↗

Angle-angle diagrams in monitoring and quantification of gait patterns for children with cerebral palsy.

This paper proposes the use of hip-knee angle-angle diagrams as an objective method of monitoring and quantifying cerebral palsy gait. Fifteen cerebral palsy children were assessed clinically and studied in a locomotion laboratory. Six normal children in the same age range were also studied. The effects of walking speed on both normal and cerebral palsy joint-angle variables have also been investigated. All cerebral palsy angle-angle diagrams contained abnormal features. A significant relationship was found between the angle-angle results and the clinical assessments. The most important variables describing the abnormality were found to be area and perimeter of the angle-angle diagram, knee angle at initiation of stance and minimum hip angle.

Adolescent↗

Heteroassociative multiple-target tracking by fringe-adjusted joint transform correlation.

A heteroassociative joint transform correlation (JTC) technique is proposed for recognizing and tracking multiple heteroassociative or dissimilar targets from gray-level image sequences by use of the concept of fringe-adjusted JTC and a multiple-target-detection algorithm. A fringe-adjusted JTC technique is used to ensure quantification of the similarities among several input images while it satisfies the equal-correlation-peak criterion. Tracking is accomplished by retrieval of the target motion information estimated from multiple consecutive image frames. An enhanced version of the fringe-adjusted filter is incorporated into the heteroassociative multiple-target-detection process to optimize the correlation performance. The feasibility of the proposed technique is tested by computer simulation with real infrared image data.

Journal Article↗

Postural perturbations: new insights for treatment of balance disorders.

This article reviews the neural control of posture as understood through studies of automatic responses to mechanical perturbations. Recent studies of responses to postural perturbations have provided a new view of how postural stability is controlled, and this view has profound implications for physical therapy practice. We discuss the implications for rehabilitation of balance disorders and demonstrate how an understanding of the specific systems underlying postural control can help to focus and enrich our therapeutic approaches. By understanding the basic systems underlying control of balance, such as strategy selection, rapid latencies, coordinated temporal spatial patterns, force control, and context-specific adaptations, therapists can focus their treatment on each patient's specific impairments. Research on postural responses to surface translations has shown that balance is not based on a fixed set of equilibrium reflexes but on a flexible, functional motor skill that can adapt with training and experience. More research is needed to determine the extent to which quantification of automatic postural responses has practical implications for predicting falls in patients with constraints in their postural control system.

Biomechanical Phenomena↗

Use of a rotating bioreactor toward tissue engineering the temporomandibular joint disc.

This objective of this study was to determine the effects of a rotating bioreactor in temporomandibular joint (TMJ) disc tissue engineering. Porcine TMJ disc cells were seeded at a density of 20 million cells/mL onto nonwoven poly(glycolic acid) (PGA) scaffolds in spinner flasks for 1 week and then cultured either under static conditions or in a rotating bioreactor for a period of 6 weeks. A series of analyses was performed, including mechanical testing, measurement of cellularity, quantification of matrix biosynthesis with a hydroxyproline assay and enzyme-linked immunosorbent assays, and observation of matrix distribution with immunohistochemistry. Between the bioreactor and static cultures, there were marked differences in gross appearance, histological structure, and distribution of collagen types I and II. Engineered constructs from the bioreactor contracted earlier and to a greater extent, resulting in a denser matrix and cell composition. In addition, immunostaining intensity was generally uniform in static constructs, in contrast to higher intensity around the periphery of bioreactor constructs. Moreover, bioreactor constructs had higher amounts of collagen II than did static constructs. However, differences in total matrix content and compressive stiffness were generally not significant. On the basis of the results of this study there is no clear benefit from use of the rotating bioreactor, although a sequence of static culture followed by rotating bioreactor culture may prove in the future to be more beneficial than either alone.

Animals↗

Advanced imaging in rheumatoid arthritis. Part 1: synovitis.

Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disorder primarily affecting the synovium. We now recognise that conventional radiographic images show changes of rheumatoid arthritis long after irreversible joint damage has occured. With the advent of powerful disease-modifying drugs, there is a need for early demonstration of rheumatoid arthritis and a need to monitor progress of the disease and response to therapy. Advanced imaging techniques such as ultrasound and MRI have focussed on the demonstration and quantification of synovitis and erosions and allow early diagnosis of RA. The technology to quantify synovitis and erosions is developing rapidly and now allows change in disease activity to be assessed. However, problems undoubtedly exist in quantification techniques, and this review serves to highlight them. Much of the literature on advanced imaging in RA appears in rheumatological journals and may not be familiar to radiologists. This review article aims to increase the awareness of radiologists about this field and to encourage them to participate and contribute to the ongoing development of these modalities. Without this collaboration, it is unlikely that these modalities will reach their full potential in the field of rheumatological imaging. This review is in two parts. The first part addresses synovitis imaging. The second part will look at advanced imaging of erosions in RA.

Arthritis, Rheumatoid↗

Serum vascular markers and vascular imaging in assessment of rheumatoid arthritis disease activity and response to therapy.

Vascular pathology, in the form of angiogenesis, is important in the perpetuation of rheumatoid arthritis (RA) and, in the form of endothelial dysfunction, contributes to associated cardiovascular co-morbidity. Emerging evidence suggests that TNFalpha blockade may modify vascular pathology in RA. Serum concentrations of vascular endothelial growth factor (VEGF), a potent endothelial cell-specific growth factor that is up-regulated by pro-inflammatory cytokines and by hypoxia, are elevated in RA and correlate with disease activity. Serum levels of VEGF at first presentation in RA predict radiographic progression of the disease over the subsequent year. Power Doppler ultrasonography is a sensitive method for demonstrating the presence of blood flow in small vessels and the vascular signal correlates with histopathological quantification of the vascular density of synovial tissue. Recent data indicate that high-frequency ultrasound and power Doppler are sensitive tools for evaluation of disease activity and assessment of response to therapy. Power Doppler imaging may also have the potential to predict those patients most at risk of accelerated joint destruction. However, much work has yet to be done to standardize the use of these imaging technologies.

Arthritis, Rheumatoid↗

[The most common overuse injury syndromes of the upper extremity associated with work activity].

Repetitive use of upper extremities, non-physiological body posture, especially of cervical spine, shoulders, lower arms, and fists are still present in modern technological processes. Innate deformities, weakness of connective tissue, accompanying morbidity (radicular symptoms, neuropathies, superior thoracic aperture syndrome, vasopathies and neuroses) are significant pathogenic overuse syndromes. Other causes of overuse syndromes are non-ergonomic tools, musical instruments, furniture, or keyboards. Lack of training for jobs involving repetitive movements, as well as job dissatisfaction are additional aggravating factors of the overuse syndrome. Polypragmasy with drug and physical therapy, insufficient rehabilitation, and questionable medical prognosis of working capacity are challenges to public health of even in richer societies. This paper describes the most common overuse syndromes of upper extremities. The aetiology of reflex dystrophy syndrome, carpal tunnel, and myofascial painful syndrome are still insufficiently explained. The paper also presents data collected in a group of 40 metal workers exposed to significant shoulder strain. They more often reported pain in the cervical spine than the control group of workers under moderate strain (45% v. 7.5%; P < 0.01), as well as pain in the shoulders (12.5% v. 5.0%) and stiffened hand (22.5%:7.5%). Symptoms were significantly more frequent in the dominant hand. A common diagnosis in a sample of 110 musicians was a change in the shoulder joint, which was more distinct in the right shoulder (10%) than in the left (7%) and comparable in the elbows (8%). The paper proceeds with cases of advanced overuse syndrome in a textile worker and cases of dissimulation in a physician and a guitarist. The paper stresses the importance of quantification of morphological and functional changes in overuse syndromes and discusses the necessity of prevention, education, early diagnosis, pharmacological and physical therapy, and rehabilitation of overuse syndromes.

Adult↗

Indentation instrument for the measurement of cartilage stiffness under arthroscopic control.

Changes in the biomechanical properties of articular cartilage are one of the first signs of the tissue degeneration. We have developed a small size indentation instrument for the quantification of cartilage stiffness under arthroscopic control. During measurement, the indenter imposes a constant deformation on the cartilage and the maximal indenter force, by which the cartilage resists the deformation, is used as a measure for cartilage stiffness. The instrument has been tested in laboratory conditions with elastomer and cadaver knee joint cartilage samples. A linear relationship was found between indenter force and elastomer stiffness (r = 0.990, n = 14) as well as between indenter force and cartilage shear modulus obtained by a reference device (r = 0.879, n = 22). Also, the correlation between two repeated measurements at the measurement sites, used to evaluate the reproducibility, was linear (r = 0.953, n = 16). Quantitative detection of cartilage stiffness is possible with the instrument.

Arthroscopes↗

Radioactivity studies along fracture zones in areas around Galudih, East Singhbhum, Jharkhand, India.

The application of radon to delineate geological processes like faulting and deformation, groundwater flow and contamination have assumed considerable significance over the last decade due to low-level detection capabilities and long-distance time migration. Suitable modeling procedures have helped in quantification of radon emanation and migration along active and passive faults. In the present study, we have attempted to correlate the radionuclide content and the extent of fracturing. For this purpose, quartzites occurring around Galudih, Jharkhand State, India, have been investigated. The study includes fracture density measurements at selected outcrops and joint analyses to evaluate the relationship between radionuclides and mesoscopic fractures. Moreover, microstructural studies have also been performed to decipher any existing relationship between radionuclides and microscale deformation mechanisms. It has been found that the microstructural phenomena are more important than mesoscopic scale processes and the former controls the concentration of radionuclides in rocks.

Journal Article↗