Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

OBJECTIVE: To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). METHODS: Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. RESULTS: Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p < 0.001) as well as with immunosuppressive therapy (p < 0.01). Significant differences were found in VEGF (p < 0.001), ET-1 (p < 0.001), sE-selectin (p < 0.01), and sTM (p < 0.001) serum concentrations between SLE patients with a capillaroscopic score > 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). CONCLUSIONS: Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Serum autoantibodies profile and increased levels of circulating intercellular adhesion molecule-1: a reflection of the immunologically mediated systemic vasculopathy in rheumatic diseases?

The clinical manifestation of systemic vasculitis may be postulated as a consequence of immune response abnormalities in the course of connective tissue diseases (CTD). The aim of this study was to elucidate the significance of the different autoantibodies and soluble intercellular adhesion molecule 1 (sICAM-1) being shed into the circulation in the diagnosis of vasculitis in rheumatic diseases. Sera of 86 patients with rheumatic diseases (54 with rheumatoid arthritis (RA) and 32 with CTD) were analyzed for the concentrations of sICAM-1 levels by the enzyme-linked immunosorbent assay (ELISA). Control sera were obtained from 30 healthy individuals. Anti-nuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies and anti-proteinase 3 (PR-3) antibodies (cytoplasmic specific anti-neutrophil cytoplasmic autoantibodies, cANCA) were assessed by the ELISA method. Fifty out of the 86 patients had systemic lesions. A pathological picture of the vascular loop under nailfold capillary microscopy was found in 84 patients. In 19 patients the microvascular changes were advanced, in 35 moderate and in 30 mild. All patients with articular manifestations had pathological changes under capillary microscopy. Patients with advanced changes under capillary microscopy had longer disease durations than patients with a mild intensity of vasculitis. The serum concentrations of sICAM-1 were significantly increased in RA and CTD patients compared with 30 controls (in both cases p<0.001). Moreover, RA and CTD patients with systemic vasculitis showed significantly higher levels of sICAM-1 than those without vascular involvement (p<0.001 and p<0.005 respectively). ANA were observed in significantly elevated concentration among RA and CTD patients with the systemic damage compared with patients without organ injury (p<0.001 and p<0.05 respectively). Also, cANCA levels were two-fold higher, but only among CTD patients with systemic damage (p<0.05). Serum concentrations of sICAM-1 were elevated in the patients showing the presence of ANA antibodies (p<0.05). Significant correlations between ANA level and disease duration and hemoglobin concentration were observed. The concentrations of cANCA correlated with those of rheumatoid factor and of dsDNA with patient age. We conclude that systemic lesions in the course of RA and CTD are accompanied by the microvascular injury observed under nailfold capillary microscopy. Our data suggest that sICAM-1, ANA and cANCA serum levels may reflect the extent of the vascular involvement in RA and CTD patients.

Serum alpha-1-antitrypsin and alpha-1-antichymotrypsin after surgical treatment and during postoperative clinical course of human gastric cancer.

The usefulness of alpha-1-antitrypsin (A1AT) and alpha-1-antichymotrypsin (A1AChy) in monitoring the adequacy of surgical treatment in patients with gastric cancer was studied. In 32 patients A1AT and A1AChy serum levels were studied before and after radical or palliative surgery at regular intervals during a 3-50-month follow-up. After palliative surgery, A1AT and A1AChy concentrations were significantly higher than in patients treated radically who showed a decreasing tendency of both antiproteases. In patients with progressive disease after surgery an increase of both antiproteases was observed. A1AT and A1AChy levels in the remission group tended to decrease but the values did not normalize as compared to healthy subjects. It was suggested that the increasing levels of A1AT and A1AChy during chemotherapy after radical surgery for gastric cancer may point to the progress of the disease.

Comparison of blood and synovial fluid lymphocyte subsets in rheumatoid arthritis and osteoarthritis.

Immunoregulatory T-cell deficiency is thought to underlie pathogenesis of rheumatoid arthritis (RA) as a systemic autoimmunopathy. The aim of this study was a simultaneous analysis of peripheral blood and synovial lymphocyte subsets (Ly-SS) of RA patients as compared to patients with locally active osteoarthritis (OA). Peripheral blood Ly-SS and paired synovial fluid Ly-SS from 87 RA patients were analysed by two dimensional flow cytometry (Simulset Becton Dickinson) as compared to 15 OA patients. The control group consisted of 32 healthy subjects. The peripheral blood analysis from RA and OA patients revealed a significant decrease of CD8+ T-cells and increase of CD4+: CD8+ ratio when compared to the control group. The blood of RA patients showed a significant increase of HLA DR+ and IL 2R+ T cells as compared to OA group. The synovial fluid from RA and OA patients showed a significant increase of CD3+, CD8+, HLA DR+ T-cells and decrease of CD4+:CD8+ ratio and CD19+ cells in comparison to the peripheral blood. This study shows, that the OA T-cell system seems not to be activated in peripheral blood in opposition to RA patients. Synovial fluid Ly-SS in OA, however, showed only quantitative but not qualitative differences. OA seems to be mainly a local inflammatory response depending on T-cells, when lymphocyte T activity in blood is diminished.

Cytokines and soluble CD4 and CD8 molecules in rheumatoid arthritis: relationship to systematic vasculitis and microvascular capillaroscopic abnormalities.

Vascular involvement in rheumatoid arthritis (RA) is associated with a wide range of extra-articular complications. Damage to internal organs occurs through a widespread disorder of the microvasculature. Vasculitis, as an integral part of the disease process, is associated with immune system abnormalities. To evaluate the relationship between capillaroscopic abnormalities, extra-articular involvement and immunological alterations, serum levels of soluble CD4 (sCD4), CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) were determined by an enzyme-linked immunosorbent assay in 80 RA patients. In all patients with signs of extra-articular manifestations, severe or moderate changes in nailfold capillaroscopy were found. Serum levels of TNF-alpha, IL-6, sIL-6R and sCD4 were significantly higher in RA patients compared with 30 healthy subjects. RA patients with clinical signs of systemic vasculitis showed significantly higher levels of TNF-alpha and IL-6 compared with those without vascular involvement. Moreover, a significant correlation between sCD4 levels and the capillaroscopy findings was found. These results point to a pathogenic role of the cytokine network in rheumatoid vasculitis and further may suggest an important role of cellular immune activation in the pathogenesis of microvascular damage.

Circulating intercellular adhesion molecule 1 in rheumatoid arthritis--relationship to systemic vasculitis and microvascular injury in nailfold capillary microscopy.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane bound molecule that plays an important role in the pathogenic inflammatory responses observed in vasculitis. The aim of this study was to determine whether levels of soluble ICAM-1 sICAM-1) shedding into the circulation reflect the vascular injury found in nailfold capillaroscopy as well as systemic vasculitis in RA patients. We determined serum levels of sICAM-1 and soluble interleukin-2 receptor (sIL-2R) by an enzyme-linked immunosorbent assay in 79 RA patients. Serum levels of sICAM-1 were significantly increased in RA patients compared to 30 healthy controls. RA patients with clinical signs of systemic vasculitis showed significantly higher levels of sICAM-1 than those without vascular involvement. Although no significant correlation between sICAM-1 levels and the capillaroscopy findings were found, 75% of the patients with severe vascular changes in capillaroscopy exceeded normal sICAM-1 cut off value. Serum sICAM-1 concentrations correlated significantly with the erythrocyte sedimentation rate and serum sIL-2R, but not with the duration of RA, radiological stages, Ritchie index, age or type of treatment. These findings suggest that increased levels of sICAM-1 in serum of RA patients reflect systemic vascular involvement rather than a local vascular injury.

Von Willebrand factor antigen in assessment of vasculitis in patients with connective tissue diseases.

Von Willebrand factor antigen (vWF:Ag) is synthesized and secreted by endothelial cells. In the present study we tried to assess the relationship between plasma level of vWF:Ag and vascular damage in patients with vasculitis. The study was carried out on 59 patients with connective tissue diseases. Vasculitis was diagnosed by biopsies of the skin. The patients with vasculitis had a significantly elevated level of vWF:Ag; however, no significant correlation between the amount of plasma vWF:Ag and the degree of vasculitis was found. The obtained results show that the plasma level of vWF:Ag may reflect the presence of vascular, especially endothelial, damage in patients with connective tissue diseases.

[The joint changes and presence of HLA-B27 antigen in patients with ulcerative colitis]. / Zmiany stawowe oraz wystepowanie antygenu HLA-B27 u chorych z wrzodziejacym zapaleniem jelita grubego.

The extra-bowel manifestation can be found among patients with ulcerative colitis (UC). The most common are the joint changes. A group of 18 patients with ulcerative colitis was investigated. The physical and radiological signs of joint inflammation and presence of HLA-B27 antigen in blood were examined. Appearance of HLA-B27 antigen among 28% of patients with ulcerative colitis can support involvement of autoimmunologic mechanism in joint inflammation. The joint changes (swelling of small joints of hand, presence of nodes, sacroileitis, and particularly spondyloarthritis) were observed in 50% of patients.

Morphological changes of the vocal fold mucosa in hyperfunctional dysphonia diagnosed by psychoacoustic and videostroboscopic methods.

PURPOSE: The aim of the study was to provide a morphological assessment of the laryngeal mucosa in patients with hyperfunctional dysphonia diagnosed by psychoacoustic and videostroboscopic methods. MATERIAL AND METHODS: Forty patients with voice quality disorders of hyperfunctional dysphonia were recruited for participation in the study. The diagnosis of dysphonia was based on the Voice Rating Scale GRBAS, and endoscopic and stroboscopic assessment of the vocal folds. Acoustic assessment was carried out using following parameters: fundamental frequency, Jitter, Shimmer, Noise to Harmonic Rate and Yanagihara (YG) scale. In order to evaluate the morphology of the vocal fold mucosa transmission electron microscopy was performed using postoperative material obtained from the larynx. Results of clinical and morphological analysis were compared with the reference group. The morphological material was obtained from patients with hypopharyngeal cancer without pathological changes of the vocal folds. RESULTS: The psychoacoustic assessment using the perceptual GRBAS scale enables the appropriate diagnostics of hyperfunctional dysphonia, which was confirmed by evaluation of acoustic parameters and YG scale analysis. In 40 patients with voice quality disorders causing by hyperfunctional dysphonia, in morphological assessment of the laryngeal mucosa, 4 (10%) patients demonstrated the presence of oedema and signs of intensive dysphonia in psychoacoustic and stroboscopic examination. CONCLUSIONS: Oedema of the laryngeal mucosa confirmed by stroboscopic and ultramorphological examination may coexist with hyperfunctional dysphonia. The presence of the laryngeal oedema in patients with hyperfunctional dysphonia has the negative impact on voice quality in psychoacoustic assessment with the use of the GRBAS and YG scales.

Comparison of the long-term effectiveness of physiotherapy programs with low-level laser therapy and pulsed magnetic field in patients with carpal tunnel syndrome.

PURPOSE: The aim of the study was to compare the long term effects of low - level laser therapy (LLLT) and pulsed magnetic field (PMF) in the rehabilitation of patients with carpal tunnel syndrome (CTS). METHODS: The study included 38 patients with idiopathic CTS, confirmed by electroneurographic (ENG) examination. All patients were randomly assigned to 2 groups: group L (18 patients) treated with LLLT and group M (20 patients) with PMF therapy. Clinical assessment, including day and night pain, the presence of paresthesia, functional tests (Phalen, Tinel, armband tests) and pain severity according to the Visual Analogue Scale (VAS) was conducted before treatment, after the first series of 10 sessions, after a two-week break, after the second series of 10 sessions and six months after the last series. RESULTS: After LLLT a significant reduction of day and night pain was observed at each stage of treatment and 6 months after the last series (p<0.05). However, in group M, a significant reduction of both day and night pain was demonstrated only after the second series (p<0.05). A reduction of the incidence of Phalen's symptoms were noticed in both groups, however, only in group L the improvement was significant (p<0.05). In groups L and M a significant reduction of pain intensity was observed at every stage of treatment (p<0.05). CONCLUSIONS: Although after LLL as well as PMF therapy clinical improvement was observed, the most significant differences were registered after the second series and persisted for up to 6 months in both groups.

The levels of alpha 1-antitrypsin and alpha 1-antichymotrypsin in the sera of patients with gastrointestinal cancers during diagnosis.

Protease inhibitors, such as alpha 1-antitrypsin (A1AT) and alpha 1-antichymotrypsin (A1AChy) have been considered in searching for new biochemical tumor markers useful at initial diagnosis, staging, and monitoring of cancer diseases after surgery. Levels of both antiproteases in serum of 32 patients with gastric cancer and 61 patients with colorectal cancer at initial diagnosis were studied. A significant increase of A1AT and A1AChy was found in the initial stages of both cancer groups as compared to healthy blood donors. A significant correlation between A1AT and A1AChy serum level and cancer stages was observed. The antiprotease serum concentrations progressively increased with increasing severity of gastric and colorectal cancers. The A1AChy level correlated with the histologic grade of both cancers and were higher in Grade III than in Grade II. These findings could be useful in the early diagnosis of gastric and colorectal cancers and in complex preoperative diagnostic procedure to estimate the stage of disease.

Apoptosis in autoimmune diseases.

Physiological cell death (apoptosis) is a natural mechanism for the removal of redundant and abnormal cells, in the absence of inflammation, during normal development. This review focuses on recent developments concerning connections between defective regulation of programmed cell death and aethiology of autoimmune diseases. The pharmacological manipulation of apoptosis maybe will offer new possibilities for the prevention and treatment of these illnesses.

[Advances in pathogenesis of anemia in rheumatoid arthritis]. / Postepy patogenetyczne w niedokrwistosci w reumatoidalnym zapaleniu stawów.

The growing importance of anaemia in rheumatoid arthritis (RA) let us to analyze the problems connected with etiopathology and diagnosis of this disease. The main attention was put on iron metabolism disturbances in the pathomechanism of the anaemia in RA.