This pilot study showed a clear diagnostic potential for new IVC tests combining halothane, the triggering agent of MH, and ryanodine acting at the calcium release channel, and should be considered as a first step in the investigation of combined tests.
Heterogeneity and multifactoriality complicate diagnostics and our understanding of pathogenesis of rheumatoid arthritis (RA). The only accepted serologic parameter (rheumatoid factor [RF]) is not disease specific, nor are any of several novel RA autoantibodies. We aimed at identifying profiles instead of individual autoreactivities allowing for unambiguous prediction of RA. Selected RA autoantigens were tested by ELISA (RF and anti-cyclic citrullinated peptide [anti-CCP]) or Western blot (heavy-chain-binding protein [BiP], heterogeneous ribonucleoprotein particle A2 [RA33/ hnRNP A2], calpastatin and calreticulin). Antibody reactivities were assayed from serum samples of 149 RA patients and 132 patients with other rheumatic diseases and from synovial fluids (SF) (58 RA, 65 non-RA). No single autoreactivity was sufficient for unambiguous prediction of RA. Frequencies of multiparameter profiles consisting of 3, 4, 5 and 6 autoreactivites were determined. Fifteen six-parameter serum profiles were exclusively expressed in RA patients, representing a cumulative sensitivity of 59%. Twelve SF profiles were exclusively expressed in 64% of RA patients. The self-learning classification algorithm CLASSIF1 was capable of accurately predicting RA when these profiles were present. Data profile analysis of RF/CCP/BiP/calpastatin/calreticulin/RA33 provided specific discrimination of 64% of RA. Most importantly, RA specific profiles were observed in 64% of patients with early disease (<12 months). For the first time, the accurate prediction of the class RA has been achieved by the use of multiparametric autoreactivity profiles. Because of early expression in disease, these profiles make it possible to start a disease-modifying therapy long before irreversible bone and joint destruction may develop. Additional RA-specific profiles are required to cover the entire group of RA patients. 2 Investigation of the reactivity patterns of antifilaggrin antibodies in sera and synovial fluids from patients with rheumatoid arthritis using citrullinated synthetic peptides
BackgroundFracture risk prediction in patient relies chiefly on bone mineral density (BMD) measurement. However, the decreased bone strength characteristic of osteoporosis is dependent not only on BMD, but also on other factors, most notably bone microarchitecture.ObjectivesThe purpose of this study was to investigate bone microarchitecture variables of cadaveric vertebrae using ultra-high field MRI (7 Tesla).MethodsTwenty four vertebrae (L2, L3, L4) from eight cadavers were studied using 7 Tesla MRI. Their Bone Mineral Density (BMD) were investigated using dual energy X Ray absorptiometry. Then, all specimens underwent mechanical compression tests to failure and the failure load (in Newton) and constraint (in Mpa) were measured. Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th), and Trabecular Spacing (Tb.Sp) were measured in MR images using a Digital topological analysis (Bone J). Measurements were performed by two observators in order to characterize the inter-rater reliability. Statistical analyses were performed using SPSS. Correlations between variables were analyzed using Spearman correlations and Stepwise regression. A p value of 0.05 was considered as significant.ResultsThe inter-rater reliability for bone microarchitecture parameters quantification was good. Tb.Th and Tb.Sp measured using high-field MRI were 0.52±0.18 and 0.48±0.10 respectively while the BV/TV fraction was 0.52±0.13. The mean BMD was 0.86±0.20 g/cm2. The failure load and the constraint measured during the compression tests were 2600±1267N and 1.57±0.81 Mpa respectively. Interestingly, the variables measured during the mechanical tests were significantlyThe failure load and constraint measured during the compression tests were significantly correlated with the BMD. Regarding the bone indices quantified using high-field MRI, a significant linear relationship was observed between the trabecular spacing and the BMD (R2=0.23, p=0.01 and the constraint values to failure (R2=0.18, p=0.04). A stepwise regression with backward elimination demonstrated that combining BV/TV and BMD improved the relationship with the constraints from an adjusted R2=0.384 for BMD alone to an adjusted R2=0.41 for BMD + BV/TV.ConclusionsIn the present study, we demonstrated for the first time that the variables characterizing the vertebral bone microarchitecture quantified using ultra-high field MRI were significantly correlated with biomechanical parameters. In addition, we illustrated that the vertebral bone strength was better described by a variable combining BMD and trabecular bone spacing.Disclosure of InterestNone declared
Background Vascular changes are consistent early findings in SSc and often proceed the development of fibrosis. Despite a severe reduction in the capillary density, signs of neoangiogenesis cannot be detected. Objectives To examine the role of VEGF and its receptors in the impaired angiogenesis of SSc. Methods Skin pO2 was measured intradermally using the pO2 histograph in 13 patients with SSc and in 5 healthy controls. Cultured SSc and normal skin fibroblasts were exposed to hypoxia and analysed for VEGF mRNA by real-time PCR (TaqMan). Immunohistochemistry with anti-VEGF-Receptor-1 and anti-VEGF-Receptor-2 antibodies was performed on skin biopsies of SSc patients and healthy controls. Serum samples of 47 patients with SSc and 21 healthy controls were analysed for VEGF by ELISA and correlated with clinical parameters. Results PO2 values from involved skin of SSc patients (23,7 ± 2,1 mmHg) were significantly lower compared to healthy controls (33,6 ± 4,1 mmHg) and non-involved skin areas (37,8 ± 8,6 mmHg, p < 0.05). After hypoxic exposure of cultured fibroblasts, VEGF mRNA was found to be upregulated compared to normoxic controls in SSc (3,7 ± 1,7 fold) and normal skin fibroblasts (3,0 ± 1,8 fold). The bioavailability of VEGF was not reduced, since the expression of VEGF-Receptor-1 and VEGF-Receptor-2 was found on endothelial cells of 4/5 patients with SSc, whereas no signal could be detected in healthy controls. In addition to the overexpression of VEGF mRNA in skin samples, serum levels of VEGF protein were significantly higher in SSc patients compared to healthy controls (mean 461 pg/ml, range 93-1153 pg/ml vs. 106 pg/ml, range 0-500 pg/ml, p < 0.001). Interestingly, levels of VEGF were upregulated in patients with pre-SSc (clinical evidence for SSc without fulfilling ACR criteria, mean 451 pg/ml, range 230-601 pg/ml, p < 0.05) and in patients with early disease stages (disease duration < 2 years, mean 569 pg/ml, range 135-1013 pg/ml, p < 0.01). Patients with diffuse disease and the presence of fingertip ulcers had higher levels of VEGF (mean 339 pg/ml, range 93-714 pg/ml) than healthy controls, but highly significant lower levels than patients without fingertip ulcers (mean 655 pg/ml, range 281-1151 pg/ml, p < 0.001). Conclusion Our results suggest a hypoxia mediated activation of the VEGF/VEGF-receptor axis in SSc. The correlation with clinical parameters indicate that elevated levels of VEGF are a feature of early disease stages and might be protective against the development of fingertip ulcers. Since the feasibility of a treatment with VEGF has just been approved in other ischaemic diseases, the application of VEGF may be a therapeutic option for the vascular insufficiency in SSc.
Objective: Psoriatic arthritis (PA) is an inflammatory rheumatism, mediated in part by TNFα and associated with bone loss. Anti-TNFα treatment should inhibit this phenomenon and reduce the systemic bone loss. Ultra-high field MRI (UHF MRI) may be used to quantify bone microarchitecture (BM) in-vivo. In this study, we quantified BM using UHF MRI in a PA patient and followed up the changes related to anti-TNFα treatment.Patients and methods: A non-treated PA patient with knee arthritis and 7 gender-matched controls were scanned using a gradient re-echo sequence at UHF MRI. After a year of Adalimumab treatment, the patient underwent a second UHF MRI. A PET-FNa imaging was performed before and after treatment to identify and localize the abnormal metabolic areas. BM was characterized using typical morphological parameters quantified in 32 regions of interest (ROIs) located in the patella, proximal tibia, and distal femur. Statistical analysis was assessed performing Student T-tests.Results: Before treatment, the BM parameters were statistically different from controls in 24/32 ROIs with differences reaching up to 38%. After treatment, BM parameters were normalized for 15 out of 24 ROIs. The hypermetabolic areas disclosed by PET-FNa before the treatment partly resumed after the treatment.Conclusion: Thanks to UHF MRI, we quantified in-vivo BM anomalies in a PA patient and we illustrated a major reversion after one year of treatment. Moreover, BM results highlighted that the abnormalities were not only localized in hypermetabolic regions identified by PET-FNa, suggesting that the bone loss was global and not related to inflammation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.