Corneal involvement in rheumatoid arthritis: an vivo confocal study

PURPOSE. To analyze the in vivo morphology of corneal cells and nerves in patients with rheumatoid arthritis (RA), with or without secondary Sj\uf6gren\u2019s syndrome (SSII), and to investigate the correlations between corneal alterations and RA activity. METHODS. Fifty patients with RA and 30 age- and gender-matched control subjects were studied. SSII was diagnosed according to the American-European Consensus Group criteria, and RA activity was evaluated by the Lansbury index (LI). Confocal microscopy was used to investigate corneal thickness, the number of epithelial and stromal cells, and keratocyte hyperreflectivity. In addition, the sub-basal plexus was assessed for the number, tortuosity, and reflectivity of the nerve fibers and the presence of beadlike formations. RESULTS. Sixteen percent of patients with RA also had SSII. Between the SSII and non-SSII groups, no significant differences were found in the LI or in the clinical and confocal variables. Significant differences were present between patients with RA and control subjects for all the variables studied except nerve reflectivity. In patients with RA with and without SSII, LI correlated significantly with the number of beadlike formations and the number of hyperreflective, activated keratocytes. CONCLUSIONS. Confocal microscopy of patients with RA showed several changes in corneal cells and nerves. The number of beadlike formations and the number of activated keratocytes could be interpreted as confocal signs of ocular surface disease activity. These correlations with the index of systemic disease activity, LI, may provide insight regarding the pathogenic mechanisms of dry eye in patients with RA

El error de observación y su influencia en los análisis morfológicos de restos óseos humanos. Datos de variación discreta.

        RESUMEN A partir de la década de 1960 se incrementó el empleo de los rasgos no métricos del cráneo en los análisis de relaciones poblacionales. Si bien uno de los supuestos en que se bas6 el uso de estos rasgos es la facilidad de estandarizar su registro, varios trabajos sugieren que el error interobservador en los rasgos discretos es elevado. En consecuencia, los objetivos del trabajo son evaluar el error intra e interobservador en el registro de rasgos craneales no métricos y analizar el efecto del error interobservador sobre las distancias biológicas calculadas. Con este fin, se analizó una muestra arqueológica procedente del Valle inferior del Río Negro -10 con deformación pseudocircular y 10 con deformación planolámbdica-. Se seleccionaron ocho variables discretas del cráneo que fueron relevadas por cuatro observadores. El error de observación fue evaluado mediante un diseño experimental de bloques aleatorios con tres repeticiones y el empleo del índice Kappa y la prueba de McNemar. La distancia biológica entre las dos muestras se estimó mediante la Medida Media de Divergencia y un análisis de escalamiento multidimensional. Los resultados obtenidos indican que el error intraobservador disminuyó mediante la aplicación del diseño experimental, que el error interobservador se incrementó en las sucesivas series y que las diferencias entre los observadores alteraron los resultados de las medidas de distancia calculadas entre las muestras.   ABSTRACT Since the early 1960s, there was an increasing interest in the application of non-metric cranial traits to the analysis of relationships between populations. One of the assumptions for the use of these traits is based upon the simplicity to standardize the recordings. However, several papers suggest that the interobserver error on such recordings is high. Therefore, the goals of this paper are to evaluate the intra and interobserver error on the scoring of nonmetric cranial traits, as well as to analyze the effect of the interobserver error in the biological distances estimated with them. An archeological sample (n=20) from the lower stretch Valley of Rio Negro Valley (Rio Negro Province, Argentina) was analyzed. Eight discrete variables from the skull were recorded independently by four observers. The observation error was evaluated by means of a randomized complete blocks design, with three repetitions, and employing the Kappa index and the McNemar test. The biological distance between the two samples was estimated through the Mean Measure of Divergence and a multidimensional scaling test. Our results indicate that 1) the intraobserver error Diminishes with the application of observational designs; 2) the interobserver error increases in successive series and; 3) the differences among observers modify the results of calculated biodistance between samples

Rituximab vs mycophenolate and vs cyclophosphamide pulses for induction therapy of active lupus nephritis: A clinical observational study

Objective. We report the first comparison between rituximab (RTX) and either MMF or CYC pulses in the treatment of active LN. Methods. Fifty-four patients with active LN received three methylprednisolone pulses for 3 consecutive days followed by oral prednisone and RTX 1 g at days 3 and 18 (17 patients) or MMF 2-2.5 g/day (17 patients) or six CYC pulses (0.5 g every fortnight) (20 patients). At 4 months MMF, AZA or ciclosporin were associated to prednisone as a consolidation/maintenance therapy in all groups. The outcomes of the three groups were compared at 3 and 12 months. Results. Patients in the RTX group were older, had a longer duration of SLE and LN, had more renal flares, had higher activity and had higher chronicity indexes at renal biopsy than the other two groups. Four patients in each group had acute renal dysfunction and 3c50% had nephrotic syndrome. At 3 months, proteinuria was reduced by 50% in 58.8% of patients on RTX, in 64.7% on MMF and in 63.1% on CYC. At 12 months, complete remission was present in 70.6% of patients on RTX, in 52.9% on MMF, and in 65% on CYC. Partial remission was reached in 29.4% on RTX, 41.2% on MMF, and 25% on CYC. Conclusion. RTX seems to be at least as effective as MMF and CYC pulses in inducing remission. Considering that patients treated with RTX had more negative renal prognostic factors, this drug should be considered a viable alternative for the treatment of active LN

Raised levels of circulating endothelial cells in systemic sclerosis

OBJECTIVE: Circulating endothelial cells (CECs) have been described in different conditions with vascular injury. Vascular abnormalities play a key role in the pathogenesis of Systemic Sclerosis (SSc). The aim of our study was to look for the presence of CECs in SSc patients and to evaluate their clinical significance. METHODS: We studied 52 SSc patients and 40 healthy controls (HC). Five-parameter, 3-color flow cytometry was performed with a FACScan. CECs were defined as CD45 negative, CD31 and P1H12 positive, and activated CECs as CD45 negative and P1H12, CD62, or CD106 positive. RESULTS: Total and activated CEC counts were significantly higher in SSc patients when compared with HC and positively correlated with disease activity score. We found a significant association between CECs and disease activity; as regard with organ involvement, CEC number correlate with the severity of pulmonary hypertension. CONCLUSIONS: Raised counts of CECs may represent direct evidence of active vascular disease in SSc as regard as visceral involvement, the association between CECs and pulmonary hypertension suggest a relevant role for CECs as a marker of prominent endothelial involvement

Endothelial progenitor cells in systemic sclerosis: their possible role in angiogenesis

BACKGROUND: Recently, several studies have demonstrated the presence of circulating endothelial progenitors (CEPs) responsible for angiogenesis. Notably, these cells are able to migrate to ischemic tissues and differentiate in situ in mature endothelial cells. Aim of this study was to assess the presence of CEPs in the peripheral blood of patients with Sistemic Sclerosis (SSc) and evaluate their significance as an attempt of re-vascularization MATERIAL AND METHODS: Samples of peripheral blood from 40 healthy subjects and 56 patients with SSc were studied. Five-parameter, 3-color flow cytometry was performed with a FACScan. CEPs were defined as CD45 negative, CD34 and CD133 positive. In addition, plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by commercial ELISA (R&D Systems). RESULTS: Levels of CEPs (CD133+/CD34+/CD45-) were significantly higher in patients with SSc in comparison to HC (P = 0.01). No correlation was found between CEPs and any clinical parameter of disease neither activity score. CEPs were significantly higher in the group of patients with early disease, while their number decreased in the late phases of disease. Plasma levels of VEGF, but not bFGF, were significantly higher in SSc in comparison to HC (P<0.001) but no correlation was found between VEGF concentrations and CEP number. CONCLUSIONS: The presence of CEPs in patients with SSc suggest that sclerodermic hypoxic tissues could induce the mobilization of bone-marrow derived cells in an attempt to provided new vessels, in the early phase of the disease, at least