Objective It is widely believed that there are multiple sources of pain at a tissue level in osteoarthritis (OA). MRIs provide a wealth of anatomic information and may allow identification of specific features associated with pain. We hypothesized that in knees with OA, bone marrow lesions (BMLs), synovitis, and effusion would be associated with weight-bearing and (less so with) non-weight-bearing pain independently. Methods In a cross-sectional study of persons with symptomatic knee OA using univariate and multivariate logistic regressions with maximal BML, effusion, and synovitis defined by Boston Leeds Osteoarthritis Knee Score as predictors, and knee pain using weight-bearing and non-weight-bearing Western Ontario and McMaster University OA Index pain questions as the outcome, we tested the association between MRI findings and knee symptoms Results 160 participants, mean age 61 (±9.9), mean BMI 30.3 (±4.7) and 50% female, stronger associations were seen with weight-bearing compared with non-weight-bearing knee pain with adjusted risk ratios (RRs) of weight-bearing knee pain, for increasing maximal BML scores of 1.0 (referent) (maximal BML = 0), 1.2, 1.9, and 2.0 (p for trend = 0.006). For effusion scores, adjusted ORs of knee pain were 1.0, 1.7, 2.0, and 2.6 (p for trend = 0.0004); and for synovitis scores, adjusted ORs were 1.0, 1.4, 1.5, and 1.9 (p for trend = 0.22). Conclusion Cross-sectionally, maximal BML and effusion scores are independently associated with weight-bearing and less so with non-weight-bearing knee pain, supporting the idea that pain in OA is multifactorial. These MRI features should be considered as possible new treatment targets in knee OA.
Herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) establish latent infections in the peripheral nervous system following primary infection. During latency both virus genomes exhibit limited transcription, with the HSV-1 LATs and at least four VZV transcripts consistently detected in latently infected human ganglia. In this study we used real-time PCR quantitation to determine the viral DNA copy number in individual trigeminal ganglia (TG) from 17 subjects. The number of HSV-1 genomes was not significantly different between the left and right TG from the same individual and varied per subject from 42.9 to 677.9 copies per 100 ng of DNA. The number of VZV genomes was also not significantly different between left and right TG from the same individual and varied per subject from 37.0 to 3,560.5 copies per 100 ng of DNA. HSV-1 LAT transcripts were consistently detected in ganglia containing latent HSV-1 and varied in relative expression by >500-fold. Of the three VZV transcripts analyzed, only transcripts mapping to gene 63 were consistently detected in latently infected ganglia and varied in relative expression by >2,000-fold. Thus, it appears that, similar to LAT transcription in HSV-1 latently infected ganglia, VZV gene 63 transcription is a hallmark of VZV latency.Herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) are neurotropic alphaherpesviruses that are endemic in the human population. Under normal conditions, both viruses are acquired early in life: HSV-1 often as an inapparent asymptomatic infection of the mouth and lips (38) and VZV as childhood chickenpox (1). Following primary infection, both viruses establish latent infections in sensory ganglia. Reactivation of latent HSV-1 typically results in localized epithelial eruptions (cold sores) which shortly resolve with few, if any, consequences. Reactivation of VZV involves the skin innervated by one to three dermatomes lasting for weeks (shingles) and the excruciating pain can persist long after skin lesions are cleared (reviewed in reference 18). In the normal population, the frequency of HSV-1 reactivation wanes with age, while VZV reactivation occurs usually once and is associated with the elderly (32). The differences in the frequency and severity of HSV-1 and VZV reactivation may be attributed to a number of factors that are yet to be elucidated. Some possible explanations that have been proposed include the cell type harboring latent virus, the virus burden during latency, and the virus genes transcribed during latency, including interactions with host factors (5,6,12,18,23,30). The neuronal site of HSV-1 latency has been firmly established in both human and animal models (31). Lacking an animal model, the site of latent VZV has been shown to be predominantly neuronal in human ganglia removed at autopsy; however, nonneuronal satellite cells are also implicated as a reservoir of latent VZV (11, 15; and reviewed in reference 19).
Objective-The performance characteristics of hyaline articular cartilage measurement on magnetic resonance imaging (MRI) need to be accurately delineated before widespread application of this technology. Our objective was to assess the rate of natural disease progression of cartilage morphometry measures from baseline to 1 year in knees with osteoarthritis (OA) from a subset of participants from the Osteoarthritis Initiative (OAI).Methods-Subjects included for this exploratory analysis are a subset of the approximately 4700 participants in the OAI Study. Bilateral radiographs and 3T MRI (Siemans Trio) of the knees and clinical data were obtained at baseline and annually in all participants. 160 subjects from the OAI Progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic OA based on a screening reading done at the OAI clinics were eligible for this exploratory analysis. One knee from each subject was selected for analysis. 150 participants were included. Using sagittal 3D DESSwe (double echo, steady-state sequence with water excitation) MR images from the baseline and 12 follow-up month visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalised cartilage volume (volume normalised to bone surface interface area), and percentage denuded area (total cartilage bone interface area denuded of cartilage).Results-Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardised response mean (SRM), ie, mean change divided by the SD change were calculated. On average the subjects were 60.9 years of age and obese, with a mean body mass index of 30. Despite being extraordinarily prevalent OA remains a condition that is poorly understood, and a condition for which available effective therapeutic options are limited to symptomatic treatment. The development of therapies aimed at joint preservation in OA is constrained by the slow progress of the condition, its heterogeneous clinical manifestations and the need for long-term follow-up to observe changes in structure. NIH Public AccessNew technologies may improve the assessment of early disease development, and progression, and could greatly facilitate measurement of structural outcomes in OA clinical trials. Foremost among these is magnetic resonance imaging (MRI), a sensitive non-invasive method for assessing joint morphology. 5 6 MRI is ideally suited for imaging arthritic joints as: (1) it is free of ionising radiation; (2) it defines both calcified as well as soft tissue joint components; and (3) its tomographic viewing perspective obviates morphological distortion, magnification and superimposition. MRI of the knee can directly visualise hyaline articular cartilage and cover the whole joint in one examination, meaning that the cartilage defects in the joint can be visualised directly regardless of their location. 5Although yet to be formally accepted by regulatory authorities, many experts now agree that MRI may b...
Objective. Magnetic resonance imaging (MRI) and radiography are established imaging modalities for the assessment of knee osteoarthritis (OA). The objective of our study was to compare the responsiveness of radiographic joint space width (JSW) with MRI-derived measures of cartilage morphometry for OA progression in participants from the Osteoarthritis Initiative (OAI). Methods. This study examined the baseline and 12-month visits of a subset of 150 subjects from the OAI. Measurement of radiographic JSW was facilitated by the use of automated software that delineated the femoral and tibial margins of the joint. Measures of medial compartment minimum JSW and JSW at fixed locations were compared with cartilage morphometry measures derived from MRI. The results were stratified by Kellgren/Lawrence (K/L) scale grade and by tibiofemoral anatomic axis angle. In order to examine the relative responsiveness of various techniques, we calculated the standardized response mean (SRM) between the 2 visits. Results. The SRM for radiographic JSW measured at the optimal location was ؊0.32 compared with ؊0.39 for the most responsive MRI measure. For the subgroup with a K/L scale grade of 2 or 3, the most responsive SRM values were ؊0.34 for radiographic JSW and ؊0.42 for MRI. Conclusion. Our study demonstrates that new measures using a software analysis of digital knee radiographic images are comparable with MRI in detecting OA progression, and potentially superior when considering the cost-effectiveness of the 2 imaging modalities.
This study shows a moderate but significant association between changes in JSW and changes in cartilage volume or thickness in knee joint of osteoarthritic patients.
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