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Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobulin G compared to late phase scintigraphy with 99mTc-labelled diphosphonate.

The ability of scintigraphy with technetium 99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) to detect and quantify arthritis activity was studied in 24 patients with RA and in 10 patients with OA. The results of 99mTc-IgG scintigraphy were compared with those of scintigraphy with 99mTc-labelled hydroxymethylene-diphosphonate (HDP). The mean joint scores of 99mTc-IgG scintigraphy in RA patients with active disease were significantly higher (P < 0.001) than the mean scores in patients with inactive disease. The mean joint scores were also higher in patients with erosions compared to those in patients without erosions (P < 0.05). For 99mTc-HDP scintigraphy no significant differences were found between the mean joint scores of these patient groups. Comparison of scintigraphic results between patients with RA and OA revealed that the mean joint score of 99mTc-IgG scintigraphy was significantly (P < 0.001) higher in the patients with RA than in patients with OA, whereas for 99mTc-HDP scintigraphy this difference was not significant. These results show that 99mTc-IgG scintigraphy, when compared to 99mTc-HDP scintigraphy, is a more specific method of detecting synovitis and, also, shows differentiation between different degrees of arthritis activity in RA.

Adult↗

Quantification of progressive joint space narrowing in osteoarthritis of the hip: longitudinal analysis of the contralateral hip after total hip arthroplasty.

OBJECTIVE: The rate of progressive joint space narrowing in the contralateral hip after total hip arthroplasty (THA) for osteoarthritis (OA) and the factors which may predispose patients to more aggressive joint space narrowing remain undefined. The current study sought to evaluate the rate and pattern of, and risk factors for, progressive joint space narrowing in the contralateral hip after THA for OA. METHODS: Each patient who underwent THA for OA in 1984-1985 was followed up longitudinally, and annual anteroposterior (AP) pelvis radiographs were obtained. The radiographic joint space width (JSW) of each contralateral hip joint was quantified, and the rates of JSW narrowing were determined. Evaluation of potential risk factors for accelerated progression of joint space narrowing included age, sex, side of surgery, weight, height, body mass index (BMI), hip pain, etiology of OA, and Kellgren/Lawrence radiographic grade. RESULTS: Ninety-nine patients and 619 AP pelvis radiographs were evaluated. The median initial JSW was 3.48 mm (interquartile range 1.55). JSW declined in a linear manner at a median rate of 0.10 mm/year. The rate of decline between baseline and followup in 20 months was predictive of the overall slope. Two subpopulations were identified. Eighty-five percent of patients maintained a slow decline in JSW (< or =0.2 mm/year), and 15% exhibited an accelerated decline in JSW (>0.2 mm/year). Kellgren/ Lawrence radiographic grade > or =2 and a diagnosis of primary OA were each associated with a more rapid decline in JSW (P = 0.006 and P = 0.02, respectively). Initial JSW, age, sex, weight, height, BMI, and hip pain were not risk factors for rapid decline in JSW. CONCLUSION: Radiographic hip JSW may be reliably quantified and followed up longitudinally using standard AP radiographs. Progression of JSW narrowing in the contralateral hip after THA for OA proceeds in a linear manner over several years. A subpopulation of patients with accelerated narrowing of contralateral JSW may be identified within 20 months, and may represent a suitable population with which to assess the potential efficacy of new disease-modifying agents.

Adult↗

Quantification of first tarsometatarsal joint stiffness in hallux valgus patients.

OBJECTIVE: Comparison of the clinical mobility test of the first tarsometatarsal joint with Doppler Imaging of Vibrations measurement of the stiffness of this joint in hallux valgus patients. DESIGN: Clinical testing of first tarsometatarsal joint mobility was related to independent Doppler Imaging of Vibrations measurement of first tarsometatarsal joint stiffness. BACKGROUND: Hypermobility of the first tarsometatarsal joint has consequences for the surgical treatment of hallux valgus deformity. However, the clinical test is subjective. Doppler Imaging of Vibrations could be helpful in quantification of the stiffness of this joint. METHODS: Clinical examination of the mobility of 32 first tarsometatarsal joints in 20 hallux valgus patients was compared with Doppler Imaging of Vibrations stiffness measurements performed by an independent observer. RESULTS: There was a statistically significant relation between the clinical test and the stiffness measurement by Doppler Imaging of Vibrations. CONCLUSION: Doppler Imaging of Vibrations proves to be a method to quantify first tarsometatarsal joint stiffness and could contribute to a rational policy for the surgical treatment of hallux valgus deformity. RELEVANCE: The clinical test to establish hypermobility of the first tarsometatarsal joint is subjective. Doppler Imaging of Vibrations offers objective criteria and quantification of first tarsometatarsal joint stiffness. This provides additional information for the choice of the surgical procedure to correct hallux valgus deformity.

Biomechanical Phenomena↗

Heat distribution over normal and abnormal joints: thermal pattern and quantification.

We have identified regular thermal patterns over normal knee, ankle, and elbow joints and demonstrate how synovitis affecting these joints may be identified by alteration or loss of the thermal pattern. Sixty healthy volunteers were thermographed on a total of 190 occasions, and 614 out of 618 joints conformed to the normal thermal pattern. Eighty-five patients with synovitis of at least one of the specified joints were thermographed on a total of 339 occasions, and 322 out of 1362 thermograms were abnormal. No joint with clinical evidence of synovitis had a normal thermal pattern. As temperature-based parameters have been found to show marked diurnal variation and relative frequency distributions do not have this drawback, we suggest that quantification of synovitis by thermography should in future be based on abnormalities of thermal pattern rather than absolute skin temperature values.

Adolescent↗

Diagnostic value of quantitative sacroiliac joint scintigraphy in brucellosis

Increased bone activity in the sacroiliac joints has been shown to be a sensitive method for detecting sacroiliitis in brucellosis. Because symmetrically increased uptake usually is difficult to detect, this study was performed to improve the sensitivity by quantifying sacroiliac joint uptake. Quantification was accomplished by normalizing sacroiliac joint activity to activity in the lumbar spine and sacrum. From rectangular regions of interest over a standardized posterior pelvic view, the ratios of the sacroiliac:lumbar spine and sacroiliac:sacrum were calculated. Abnormal sacroiliac joint uptake was defined as uptake greater than the mean +2 SD of normal. This was applied to 79 patients with brucella sacroiliitis. The quantitative approach was compared with visual interpretation. Of the 16 patients in the age group of 5 to 19 years, 7 patients had visual evidence of sacroiliitis and 9 patients had positive evidence by sacroiliac-sacrum and 12 by sacroiliac-lumbar spine quantification. Of 21 patients who were 20 to 30 years old, 10 patients had positive visual evidence, whereas 17 and 20 patients had positive evidence of sacroiliitis by sacroiliac-sacrum and sacroiliac-lumbar spine, respectively. Of 42 patients who were 31 to 85 years old, 24, 32, and 36 patients had positive evidence of sacroiliitis by visual inspection, sacroiliac-sacrum, and sacroiliac-lumbar spine, respectively. Thus, the quantitative approach increased the sensitivity in diagnosing Brucella sacroiliitis in all age groups by 31.3%, 47.6%, and 28.6%, respectively, for sacroiliac-lumbar spine and by 12.5%, 33.3%, and 19%, respectively, for sacroiliac-sacrum.

Journal Article↗

Influence of physical activity-related joint stress on the risk of self-reported hip/knee osteoarthritis: a new method to quantify physical activity.

BACKGROUND: The relationship between physical activity (PA) and the development of hip/knee osteoarthritis (OA) has not been clearly defined. The purpose of this study was to develop a method to quantify PA-related joint stress and to assess its influence on the risk of hip/knee OA. METHODS: Participants in a large longitudinal study, without knee/hip OA (n = 5284), were asked about their PA participation in 1986. PA-related joint stress was calculated using information on the frequency, intensity, and duration of individual types of PA, and incorporated a quantification of joint stress. Self-reported, physician-diagnosed hip/knee OA was ascertained by survey in 1990, 1995, and 1999 (average length of follow-up: 12.8 years). METHODS: The joint stress PA score was not associated with an increased risk of hip/knee OA. Also, among walkers and runners there was no association between the frequency, pace, or weekly training mileage and hip/knee OA. Older age, previous joint injury and surgery, and higher body mass index were confirmed as independent risk factors for hip/knee OA. CONCLUSIONS: Participation in PA as an adult does not increase the risk of hip/knee OA and there does not seem to be a threshold of increasing risk with increased training among walkers and runners.

Female↗

Objective clinical evaluation of function. Gait analysis.

Automated gait analysis allows us to document and quantify objectively normal gait, functional deficits, and patient response to therapeutic intervention. Instrumentation for this analysis at the Mayo Clinic Gait Laboratory includes three-dimensional electrogoniometers for measurement of relative joint rotation at the hip, knee, and ankle; footswitches that record foot-floor contact sequences; instrumented mats that measure step length and width; piezoelectric force plates for measurement of floor reaction forces; and two walkways that simulate a variety of ground conditions. We use a DEC-PDP 11/34 computer for acquisition, storage, and analysis of data and for generation of a gait report form that displays a patient's results relative to normal and previous evaluations. Applications of these techniques include assessment of function preoperative and postoperative total joint arthroplasty, quantification of gait faults, and documentation of effectiveness of exercise and gait training techniques. We have demonstrated the reliability of the techniques, accumulated a sizeable normal data bank, and developed a concise, effective data summary for communication with referring practitioners.

Amputees↗

Crystal-induced inflammation in canine joints. I. An experimental model with quantification of the host response.

Injection of sodium urate or calcium pyrophosphate crystals into the stifle joints of anesthetized dogs almost invariably induced an acute exudative response. This response was quantified by serial measurements of intra-articular pressure, pH and leukocyte concentration. Pressure rose progressively and reflected intra-articular volume increase. The hydrogen ion concentration increased as the reaction progressed and correlated in a given exudate with the leukocyte concentration. Analysis of sequential physiologic and biochemical changes occurring in this model of crystal-induced inflammation may provide insight into the mechanisms of acute gouty arthritis in man.

Animals↗

A comparative analysis of bone and cartilage metabolism in two strains of guinea-pig with varying degrees of naturally occurring osteoarthritis.

OBJECTIVE: To evaluate the interaction of bone and cartilage in knee osteoarthritis (OA) pathogenesis in two guinea-pig strains with appreciable differences in bone metabolism. DESIGN: Two guinea-pig strains were evaluated for their susceptibilities to OA using semi-quantitative histological grading of knee joints and quantification of biomarkers including urinary excretion of hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP) collagen cross-links, serum osteocalcin (OC), and synovial fluid levels of keratan sulfate (KS). RESULTS: At 12 months of age, Strain 13 guinea-pigs had minimal to mild histological evidence of OA compared to the Hartley strain guinea-pigs. The Hartley strain, with more severe OA, had a higher rate of bone formation (serum osteocalcin) and bone resorption (HP and LP) evident at a young age with persistence of a greater rate of bone formation at 12 months of age. The Strain 13 possessed much thicker subchondral bone at the outset (2 months) compared to the Hartley; however, the Hartley strain showed the greatest increase in subchondral bone thickness coincident with the development of cartilage degeneration. Thus, the process of subchondral bone thickening, in contrast to the absolute initial subchondral bone thickness, was a hallmark of OA in the guinea-pig. Moreover, Strain 13 had lower intraarticular proteoglycan turnover. Levels of synovial fluid keratan sulfate were positively correlated with the severity of histological OA. CONCLUSIONS: This pilot study represents the first evidence of differential susceptibility to OA in guinea-pigs. Comparison of these two strains of guinea-pig has revealed that increased metabolism within the affected tissues, cartilage and bone, is associated with the development and progression of OA. This work demonstrates that the Strain 13 is a viable age-matched control to the Hartley strain and merits a more in depth evaluation of the contribution of bone and bone metabolism to OA.

Amino Acids↗

Quantification of mRNA levels in joint capsule and articular cartilage of the murine knee joint by RT-PCR: kinetics of stromelysin and IL-1 mRNA levels during arthritis.

We developed a method to isolate well defined joint specimens from different compartments of normal and arthritic murine knee joints in which mRNA levels of stromelysin and IL-1 were semiquantified using RT-PCR. Joint capsule specimens were isolated on medial and lateral sides of the patella with a biopsy punch. Cartilage layers were isolated from patellae after a mild decalcification with EDTA. EDTA treatment had no effect on the amount and efficiency of amplification of mRNA when tested on isolated chondrocytes. After induction of experimental arthritis, stromelysin mRNA was elevated approximately 50 times in both joint capsule and cartilage. IL-1 was elevated 100 times in joint capsule but only 10 times in cartilage. Kinetic analysis of mRNA levels in cartilage during arthritis showed a prolonged elevation of stromelysin mRNA compared to IL-1. The variation in mRNA levels between joints of individual mice proved to be low, showing that sampling of the specimens and subsequent RT-PCR can be performed reliably. The current method offers a valuable approach to study gene expression in knee joints during murine experimental arthritis.

Animals↗

Computerized digital imaging techniques provided by digital X-ray radiogrammetry as new diagnostic tool in rheumatoid arthritis.

PURPOSE: Our study evaluates digital x-ray radiogrammetry (DXR) and Radiogrammetry Kit (RK) as a new diagnostic method for the measurement of disease-related osteoporosis including quantification of joint space narrowing dependent on the severity of rheumatoid arthritis (RA). MATERIALS AND METHODS: A total of 172 unselected patients with RA underwent computerized measurements of bone mineral density (BMD) and metacarpal index (MCI) by DXR, as well as a semiautomated measurement of joint space distances at the metacarpal-phalangeal articulation (JSD-MCP 2-5), both were analyzed from plain radiographs of the nondominant hand. RESULTS: Correlations between DXR-BMD and DXR-MCI vs. parameters of RK were all significant (0.34 < R < 0.61; p < 0.01). An expected negative association was observed between RK parameters and the different scoring methods (-0.27 < R < -0.59). The maximum relative decrease in BMD vs. MCI as measured by DXR between the highest and lowest RA severity group was -27.7% vs. -27.5% (p < 0.01) for the modified Larsen Score, whereas the minimal value of relative DXR-BMD and DXR-MCI reduction could be documented for the Sharp Erosion Score (-20.8% vs. -26.8%; p < 0.01). The relative reduction of mean JSD-MCP using RK significantly varied from -25.0% (Sharp Erosion Score) to -41.2% (modified Larsen Score). In addition, an excellent reproducibility of DXR and RK could be verified. CONCLUSION: DXR in combination with RK could be a promising, widely available diagnostic tool to supplement the different scoring methods of RA with quantitative data, allowing an earlier and improved diagnosis and more precision in determining disease progression.

Adolescent↗

In vivo quantification of the cat patellofemoral joint contact stresses and areas.

A new method for in vivo measurement of patellofemoral joint contact areas, stresses, and patellar displacements, with joint loading approximating physiologic conditions was developed. Joint contact measurements were obtained using pressure sensitive film inserted directly between articular joint surfaces. Two-dimensional joint kinematics were measured using a high-speed video based motion analysis system. Joint loading, provided by quadriceps muscle stimulation, was measured with an implantable force transducer (IFT). Variations in joint mechanics as a function of joint flexion angle, joint loading and joint stability (anterior cruciate ligament intact or transected) were determined for four adult male cats. The contact measurements obtained with the pressure sensitive film displayed high repeatability with a standard error of +/- 6.8% of the mean value of the median pressure and +/- 4.4% of the mean contact area value. Substantial differences in joint mechanics were reliably detected with the new technique. The influence of experimental procedures, such as incisions in the joint capsule and insertion of pressure sensitive film between the articular surfaces, produced minimal changes in the joint kinematics during muscular contraction.

Animals↗

ProteoformDB: A Built-In Application to Generate Proteoform Database.

Proteins play essential functions through their complex regulations on cell-type-specific expression, localization, and molecular complexes. Protein complexity is further enhanced by proteoforms, which are the diverse molecular forms that each gene can produce through genomic alterations, transcriptional variations, translational regulations, and protein modifications. Profiling of proteoforms is a promising method for gaining a deeper understanding of the role of proteins in biological pathways and disease mechanisms. Here, we developed ProteoformDB, an application tool for generating proteoform databases, and we cataloged a total of over one million unique single-site human proteoforms. We showed that ProteoformDB can serve as a valuable resource to document the experimentally identified proteoforms in a database, supporting protein characterization in quantitative proteomics for both total protein abundances and modified protein forms.

Humans↗

Model dependence in quantification of spike interdependence by joint peri-stimulus time histogram.

Multineuronal recordings have enabled us to examine context-dependent changes in the relationship between the activities of multiple cells. The joint peri-stimulus time histogram (JPSTH) is a much-used method for investigating the dynamics of the interdependence of spike events between pairs of cells. Its results are often taken as an estimate of interaction strength between cells, independent of modulations in the cells' firing rates. We evaluate the adequacy of this estimate by examining the mathematical structure of how the JPSTH quantifies an interaction strength after excluding the contribution of firing rates. We introduce a simple probabilistic model of interacting point processes to generate simulated spike data and show that the normalized JPSTH incorrectly infers the temporal structure of variations in the interaction parameter strength. This occurs because, in our model, the correct normalization of firing-rate contributions is different than that used in Aertsen, Gerstein, Habib, and Palm's (1989) effective connectivity model. This demonstrates that firing-rate modulations cannot be corrected for in a model-independent manner, and therefore the effective connectivity does not represent a universal characteristic that is independent of modulation of the firing rates. Aertsen et al.'s (1989) effective connectivity may still be used in the analysis of experimental data, provided we are aware that this is simply one of many ways of describing the structure of interdependence. We also discuss some measure-independent characteristics of the structure of interdependence.

Brain↗

Biochemical and biomechanical properties of lesion and adjacent articular cartilage after chondral defect repair in an equine model.

BACKGROUND: Chondral defects may lead to degradative changes in the surrounding cartilage, predisposing patients to developing osteoarthritis. PURPOSE: To quantify changes in the biomechanical and biochemical properties of the articular cartilage adjacent to chondral defects after experimental defect repair. STUDY DESIGN: Controlled laboratory study. METHODS: Specimens were harvested from tissue within (lesion), immediately adjacent to, and at a distance from (remote area) a full-thickness cartilage defect 8 months after cartilage repair with genetically modified chondrocytes expressing insulin-like growth factor-I or unmodified, control chondrocytes. Biomechanical properties, including instantaneous Young's and equilibrium aggregate moduli, were determined by confined compression testing. Biochemical properties, such as water and proteoglycan content, were also measured. RESULTS: The instantaneous Young's modulus, equilibrium modulus, and proteoglycan content increased, whereas water content decreased with increasing distance from the repaired lesion. The instantaneous Young's and equilibrium moduli of the adjacent articular cartilage were 80% and 50% that of remote area samples, respectively, whereas water content increased 0.9% and proteoglycan content was decreased by 35%. No significant changes in biomechanical and biochemical properties were found either in the lesion tissue or in adjacent cartilage with genetic modification of the chondrocytes. CONCLUSION: Articular cartilage adjacent to repaired chondral defects showed significant remodeling 8 months after chondral defect repair, regardless of whether genetically modified or unmodified cells were implanted. CLINICAL RELEVANCE: Changes in the biochemical and biomechanical properties of articular cartilage adjacent to repaired chondral defects may represent remodeling as part of an adaptive process or degeneration secondary to an altered distribution of joint forces. Quantification of these changes could provide important parameters for assessing progress after operative chondral defect repair.

Animals↗