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ID PMID Title PublicationDate abstract
16583474 Myelopathies secondary to Sjögren's syndrome: treatment with monthly intravenous cyclopho 2006 Apr OBJECTIVE: Central nervous system manifestations in Sjögren's syndrome (SS) include focal deficits, optic neuritis, and myelopathies. Acute and chronic myelopathies are frequently severe and sometimes respond poorly to corticosteroids. The efficacy of intravenous (IV) cyclophosphamide (CYC) has been suggested in single case reports. METHODS: We describe the potential usefulness of IV CYC in SS patients with severe myelopathies. Fourteen patients [with acute (n = 6) and chronic (n = 8) myelopathies] were treated with monthly CYC infusions (700 mg/m2) in addition to 500 mg of corticosteroids for one year. We evaluated the disability before and after CYC treatment using a walking distance calculation and the Expanded Disability Status Scale (EDSS). RESULTS: CYC treatment was well tolerated in all cases without serious adverse events. Nine patients (including the 6 with acute myelopathy) were improved after CYC treatment. Three patients were stabilized and 2 patients with chronic myelopathies had moderate progression of disability. The mean walking distance increased from 48.2 m before to 180.4 m after CYC treatment (p < 0.02). Mean EDSS score decreased from 6.6 to 5.7 (not significant). We found a correlation between the length of time before CYC treatment and clinical improvement for both the walking distance (p < 0.02) and the EDSS score (p < 0.05). CONCLUSION: Although a randomized multicenter controlled study is warranted to confirm our findings, IV CYC infusions seem to be useful for the treatment of myelopathies secondary to SS, particularly in acute but also in progressive cases. This treatment should be strongly considered as soon as possible when disease progression is observed.
16547690 Sjögren's syndrome in patients with ankylosing spondylitis. 2007 Feb There are few reports about the coexistence of Sjögren's syndrome (SS) and ankylosing spondylitis (AS). To evaluate the frequency of SS in patients with AS. We studied 70 patients with AS presenting to the university outpatient clinic between January 2002 and November 2003. All the patients were asked about sicca symptoms by using sicca questionnaire. Rheumatoid factor, anti-nuclear antibody, anti-Ro, and anti-La antibodies were examined for each of the patients. Salivary flowmetry for the existence of xerostomia, Schirmer's test, and break-up time for the existence of xerophtalmia were performed in all patients with AS. Minor salivary gland biopsy was performed on the patients with at least three positive responses to the sicca questionnaire and positive xerostomia/xerophtalmia tests. Biopsies were regarded as pathological when they showed focal grade iii and grade IV sialoadenitis according to Chisholm grading criteria. Among 70 AS cases, 56 (80%) were men, 14 (20%) were women, and the mean age was 42 years old. Minor salivary gland biopsy was performed on the 16 patients. Of 16 minor salivary gland biopsies, 7 were assessed as pathological--5 of them showed grade III, and 2 of them showed grade IV sialoadenitis. Of these seven patients, one was anti-Ro-positive, and two were anti-La-positive. There was no patient with normal salivary gland biopsy and anti-Ro and/or anti-La positivity. In our study group, 7 (10%) of 70 AS patients had concomitant SS. Therefore, it seems likely that AS may have pathogenetic association with SS.
18682951 Health-related quality of life in patients with common rheumatic diseases referred to a un 2009 Jan The aim of the present study was to assess the health-related quality of life (HRQoL) in patients with common rheumatic diseases referred to a rheumatology clinic and to compare it to the HRQoL of the general population. All patients with a new referral to the Department of Rheumatology of the Helsinki University Central Hospital were asked to participate in the study during the period from May 2002 to April 2003. A total of 295 patients with various rheumatic diseases were included in the analysis: 99 patients with rheumatoid arthritis (RA), 47 with arthralgia and fibromyalgia, 43 with other chronic arthritis (spondyloarthritis, psoriatic arthritis, enteropathic arthritis), 44 with osteoarthritis (OA), 22 with active reactive arthritis (ReA), 17 with systemic rheumatic diseases, 9 adults with juvenile idiopathic arthritis (JIA) and 14 with other diagnoses. HRQoL was measured by a disease specific instrument, the Stanford health assessment questionnaire (HAQ) and by a generic instrument, 15D. The mean baseline 15D score of the 295 included patients (0.822, SD 0.114) was significantly lower than of the general population (0.903, SD 0.098). Patients with OA and chronic arthritis reported the poorest HRQoL scores (both 0.810 on a 0-1 scale). In patients with RA and ReA the 15D score improved in a statistically significant and clinically important manner during the 8-month follow-up. Discomfort and symptoms caused by the disease were alleviated in a statistically significant manner in patients with RA as well as in those with arthralgia and fibromyalgia, chronic arthritis, ReA and systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. The HRQoL of patients with common rheumatic diseases at referral to rheumatology clinic is significantly lower than the HRQoL of age-standardized general population. The most affected patients are those with OA, chronic arthritis and RA. A significant improvement in HRQoL with conventional interventions was achieved in patients with RA and ReA.
17195210 Tenosynovitis and osteoclast formation as the initial preclinical changes in a murine mode 2007 Jan OBJECTIVE: To determine the nature of the initial changes of joint inflammation occurring before, at the time of, and shortly after onset of clinically apparent arthritis. METHODS: Human tumor necrosis factor (TNF)-transgenic mice were assessed for clinical, histologic, immunophenotypic, serologic, and molecular changes at the preclinical phase of arthritis, at the onset of disease, and at the stage of early clinical disease. In addition, the effects of a genetic osteoclast deficiency and pharmacologic inhibition of TNF were studied in these initial phases of disease. RESULTS: Initial articular changes were observed even before the start of clinical symptoms. Infiltration of the tendon sheaths by granulocytes and macrophages as well as formation of osteoclasts next to the inflamed tendon sheaths were the first pathologic events. Tenosynovitis rapidly led to remodeling of the sheaths into pannus-like tissue, which formed osteoclasts that invaded the adjacent mineralized cartilage. Early lesions were associated with up-regulation of interleukin-1 (IL-1) and IL-6 as well as activation of p38 MAPK and ERK. In contrast, absence of osteoclasts led to uncoupling of tenosynovitis from invasion into cartilage and bone. TNF blockade also attenuated the pathologic changes associated with tenosynovitis. CONCLUSION: Structural damage begins even before the onset of clinical symptoms of arthritis and involves the tendon sheaths as well as adjacent cartilage and bone. These results suggest that tenosynovitis is an initiating feature of arthritis and that joint destruction starts right from the onset of disease. Our findings thus underscore the importance of immediate initiation of an effective therapy in patients with rheumatoid arthritis.
16710131 [Symptomatic periodic paralysis secondary to primary Sjogren's syndrome]. 2006 May INTRODUCTION: Hypokalaemic periodic paralysis can be primitive or secondary to potassium deficiency which can arise from several causes. Primary Sjogren's syndrome is a rare cause related to kidney involvement. CASE REPORT: A 50-year-old woman has been admitted for hypotonic tetraparesis which had appeared a few days earlier. History taking revealed three previous similar episodes with a notion of oral and lacrimal dryness. Laboratory tests revealed severe hypokalaemia, hyperchloremia, alkaline urinary pH and a minima 24h proteinuria. Additional investigations led to the diagnosis of a primary Sjogren's syndrome defined on the basis of international criteria. Kidney biopsy revealed tubular-interstitial nephritis. Oral corticosteroïd therapy and potassium supplementation led to symptom improvement. A recurrent episode also responded to treatment. Additional urinary alkalinisation has prevented further relapse. DISCUSSION: Primary Sjogren's syndrome is an exocrine disease causing systemic disorders. Tubular-interstitial nephropathy may occur in 25 percent of patients leading to distal tubular acidosis defined by the association of hypokalaemia, hyperchloremia and alkaline urinary pH. When hypokalaemia is severe, periodic paralysis may occur. CONCLUSION: Primary Sjogren's syndrome can lead to nephropathy and subsequent hypokalaemic periodic paralysis. Urinary alkalinisation is essential to prevent this catastrophic presentation from recurring.
18756337 Sjögren's syndrome associated with multiple myeloma. 2008 Aug There have been very few reported cases of multiple myeloma (MM) which had Sjögren syndrome (SS) as the first presentation. We report a 63-year-old Moroccan woman with IgA-lambda-type MM presenting as SS and who responded to anti-myeloma treatment. The patient, treated for SS, was admitted to our department for persistent and increasing thoracic pain. Clinical examination was normal. Laboratory investigations showed haemoglobin of 10 g/dL. Erythrocyte sedimentation rate was 80 mm/hr. Monoclonal spike was found in the betaglobulin region of the serum protein electrophoresis. Immunofixation identified it as IgA lambda and the level was 3.7 g/dL. The bone marrow contained 35 percent plasma cells, with atypical features. Radiographs showed diffuse lytic lesions. Treatment with vincristine, adriamycin and dexamethasone (VAD) was started and bisphosphonate was administered regularly. After three cycles of VAD therapy, the MM regressed without any evidence of SS symptoms. The development of MM in the setting of SS is unusual and the aetiopathogenic mechanism still unknown. However, some elements orient toward a common pathway for these two diseases, like the clinical remission of SS after treatment of the MM, such as described in our patient.
18701557 Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: 2009 Aug BACKGROUND: Mikulicz's disease (MD) has been considered as one manifestation of Sjögren's syndrome (SS). Recently, it has also been considered as an IgG(4)-related disorder. OBJECTIVE: To determine the differences between IgG(4)-related disorders including MD and SS. METHODS: A study was undertaken to investigate patients with MD and IgG(4)-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG(4)-positive multiorgan lymphoproliferative syndrome (IgG(4)+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG(4) (>135 mg/dl) and infiltration of IgG(4)(+) plasma cells in the tissue (IgG(4)+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG(4)+MOLPS and 31 patients with typical SS were compared. RESULTS: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG(4)+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG(2), IgG(4) and IgE levels were significantly increased in IgG(4)+MOLPS. Histological specimens from patients with IgG(4)+MOLPS revealed marked IgG(4)+ plasma cell infiltration. Many patients with IgG(4)+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG(4)+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG(4)+MOLPS treated with glucocorticoids showed marked clinical improvement. CONCLUSION: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG(4)+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG(4)+MOLPS.
18361813 [Patterns of anti-nuclear antibodies in patients with primary biliary cirrhosis and primar 2008 Jan 15 OBJECTIVE: To investigate the anti-nuclear antibody (ANA) patterns in the diagnosis of primary biliary cirrhosis (PBC) and primary Sjögren syndrome (SS). METHODS: Serum samples from 61 cases of PBC, 28 cases of primary SS, and 11 cases of overlap syndrome of PBC and SS were collected to detect the ANA with indirect immunofluorescence staining, and the difference in ANA patterns was analyzed between the PBC and SS patients. RESULTS: Antinuclear antibodies were detected in 85.2% of the PBC patients, with the following hierarchy of specificities: 37.7% being rim-like, 21.3% being discrete speckled, 18.0% being speckled, 8.2% being multiple nuclear dots, and 4.9% being anti-lamin; 89.3% of the primary SS patients was ANA positive with speckled antibody, only one of them presented discrete speckles (3.6%); and all of the PBC patients overlapped with SS (100%) were positive in ANA, and their contexture of ANAs was similar to those of the PBC patients: 45.5% being rim-like, 18.2% being discrete speckled, 18.2% being speckled, 18.2% being anti-lamin, and 9.1% being multiple nuclear dots. Rim-like pattern and multiple nuclear dots were statistically significant for the diagnosis of PBC, compared with primary SS (chi(2) = 14.236, 3.781, P < 0.01, < 0.05). CONCLUSION: The ANA patterns of PBC are different from those of primary SS. Among them, rim-like pattern and multiple nuclear dots are highly specific nuclear patterns of PBC and may be useful in diagnosing individuals without anti-mitochondrial antibodies.
18234228 Progressive multifocal leukoencephalopathy and CD4+ T-lymphocytopenia in a patient with Sj 2008 May 15 We report progressive multifocal leukoencephalopathy (PML) and CD4+ T-lymphocytopenia in a 71-year-old man with Sjögren syndrome (SjS). The patient was admitted to our hospital because of progressive dementia and gait disturbance. T2-weighted MR images showed high-intensity lesions in his left frontal white matter thalamus, cerebellum and brainstem. A pathological diagnosis of PML was made by brain biopsy. SjS is frequently accompanied with immunological complications; however, there are few reports on PML in patients with SjS. Recently, isolated CD4+ T-lymphocytopenia is reported to be one of the based immunological conditions associated with the development of PML. In the present case, CD4+ T-lymphocytopenia was also observed on admission, which is also associated with SjS.
17545193 Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in 2008 Jan OBJECTIVE: Dehydroepiandrosterone (DHEA) administration has been reported to improve fatigue, psychological distress, and physical disability. These are common features of primary Sjögren syndrome (pSS). We investigated the effects of DHEA administration on fatigue, well-being, and functioning in women with pSS. METHODS: In a double-blind, randomised placebo-controlled clinical trial, 60 female patients with pSS received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being, and physical functioning. In addition, pain, sicca complaints and disease activity parameters were measured. Patients were assessed before treatment, after 3, 6, and 12 months on study medication, and 6 months after cessation of treatment. RESULTS: Patients from both the DHEA- and placebo-treated group improved on general fatigue (p<0.001), mental well-being (p = 0.04), and depressive mood (p = 0.008). Physical functioning did not change (p = 0.44). Of the secondary outcome variables, complaints of a dry mouth diminished during treatment in both groups (p = 0.006), the erythrocyte sedimentation rate showed a decrease for the DHEA group (p = 0.02), and complaints of dry eyes improved in the placebo group (p = 0.01). The belief to have used DHEA was a stronger predictor for improvement of fatigue and well-being than the actual use of DHEA. CONCLUSIONS: Our study does not support a superior effect of DHEA over placebo in female patients with pSS. Both DHEA and placebo induce improvement of fatigue and well-being. This may suggest possibilities for cognitive behavioural interventions.
17289550 The mosaic of B-cell subsets (with special emphasis on primary Sjögren's syndrome). 2007 Jan Major breakthroughs have occurred with classification of B-cells into populations and subpopulations. With respect to their expression of CD5, they comprise the B1 and B2 populations, with the former further divided into B1a and B1b subpopulations. The oncologic process starts from transitional type 1 (T1) and T2 immature B-cells, through marginal zone or germinal center B-cells, ending up with memory B-cells and plasma cells (PCs). They may also be categorized based on their functional commitment with polarized B effector (Be)1 and Be2, with B-activating factor of the tumor-necrosis factor-producing B-cells, and with short-lived and long-lived PCs. Such a seemingly homogeneous family of cells has thus turned out to be a genuine mosaic of B-lymphocyte subsets.
16802369 Salivary gland epithelial cells: a new source of the immunoregulatory hormone adiponectin. 2006 Jul OBJECTIVE: Adiponectin is an adipocytokine that displays insulin-sensitizing and immunoregulatory properties. Adipocyte development in association with fibrosis is frequently detected in primary Sjögren's syndrome lesions, connoting a healing process. The aim of this study was to examine the expression of adiponectin in minor salivary gland biopsy specimens obtained from patients with primary SS and controls. METHODS: The expression of adiponectin in minor salivary gland biopsy specimens and in long-term-cultured non-neoplastic salivary gland epithelial cell (SGEC) lines obtained from patients with primary SS and control subjects was examined, using immunohistochemistry and immunoblotting, respectively. The expression of adiponectin, adiponectin receptor 1 (AdipoR1), and AdipoR2 messenger RNA (mRNA) by SGECs was investigated by reverse transcription-polymerase chain reaction. RESULTS: Immunohistochemical analysis for adiponectin revealed positive staining of adipocytes from primary SS lesions as well as ductal epithelial cells from both patients with primary SS and controls. All of the SGEC lines tested were shown to express adiponectin, AdipoR1, and AdipoR2 mRNA, whereas adiponectin protein expression was detected by immunoblotting in SGECs from patients with primary SS but not in those from controls. The analysis of concentrated culture supernatants also revealed increased adiponectin expression by SGECs from patients with SS compared with controls. CONCLUSION: Our findings provide novel evidence that adiponectin is produced by SGECs. The high constitutive expression of adiponectin by SGECs from patients with primary SS is likely attributable to aberrant activation of these cells. Although the significance of adiponectin expression remains unknown, it is possible that adiponectin functions in an autocrine manner, as suggested by concurrent expression of the relevant receptors.
16949042 Patients with inflammatory arthritic diseases harbor elevated serum and synovial fluid lev 2006 Oct 20 In K/BxN mice, anti-glucose-6-phosphate isomerase (G6PI) IgG antibodies (Abs) cause joint-specific inflammation and destruction. Anti-G6PI Abs are also present in humans with inflammatory arthritis, especially among patients with rheumatoid arthritis (RA). A contributing factor to the induction of such autoantibodies may be upregulated expression of the corresponding antigen G6PI in affected tissues and/or increased levels of G6PI in the circulation. To determine G6PI levels and the presence of free G6PI and/or G6PI-containing immune complexes in sera and synovial fluids (SF) of patients with different arthritides, serum and SF obtained concomitantly from 91 clinically well-defined arthritis patients were assessed in a blinded manner for G6PI enzymatic assay and for G6PI protein concentration by ELISA. Sera and SF from patients with immune-based inflammatory arthritis contained significantly higher levels of G6PI enzymatic activity compared to sera or SF from patients with non-immune-based inflammatory arthritis or healthy controls. In addition, significantly higher levels of total G6PI protein concentration (including both enzymatically active and inactive forms) were present in sera of RA patients vs. those with other immune-based or non-immune-based inflammatory arthritis.G6PI in sera and SF were present both as G6PI-containing immune complexes and as free G6PI, with the majority of free G6PI existing as tetramers with lesser amounts of dimers and monomers. Levels of G6PI enzymatic activity in the sera of most immune-based inflammatory arthritis patients are elevated and may reflect ongoing inflammation and cell destruction. The high serum levels of enzymatically inactive forms of G6PI in RA relative to those in other arthritic diseases are partially due to G6PI-containing immune complexes, a portion of which also contains C1q. Overall, our study supports the notion that elevated G6PI levels present in patients with immune-based inflammatory arthritis may contribute to elevated levels of anti-G6PI Abs and G6PI/anti-G6PI immune complexes. This, in turn, may trigger production of proinflammatory cytokines and perpetuate the inflammatory process.
17304382 Systemic lupus erythematosus presenting as parotitis and secondary Sjogren's syndrome. 2007 Feb A 38-year-old woman presented with right-sided parotid swelling, dry mouth and dry eyes of one year duration. Her Schirmer's test and sialometry were positive and histopathology showed lymphoplasmacytic infiltration. She also had concomitant normochromic , normocytic anaemia and mild haematuria. Her anti-nuclear antibody titre was also positive, 1:640, with a speckled pattern on immunofluorescence. We discuss the atypical presentation of systemic lupus erythematosus, particularly parotitis and secondary Sjogren's syndrome.
19848036 [Per Henrik Ling and his impact on gymnastics]. 2008 Per Henrik Ling (1676-1839) is one of the most wellknown Swedes of all times. He studied different subjects and became a fencing-master. After studies of the antique Greece and, above all, after being informed of the German physical functional training, he created the Swedish gymnastics, in part according to antique model. In 1813 he founded the Gymnastic Central Institute in Stockholm with the obligation to educate gymnastic teachers for military and school needs. He was a versatile person, lively, sensitive, original and choleric with intense manners, excellent judgement and an extraordinary pedagogic capability. Therefore, a great deal of attention was paid to his work. However, he was also called eccentric, overstrung, touchy and stubborn. Ling had a high work capacity, but it deteriorated little by little during his last two decades. Obviously, the cause was his lingering joint pains (rheumatoid arthritis?), which impeded his physical activities, but above all his fatal lung tuberculosis. His reports on gymnastic subjects are remarcably few. Ling was also a prolific author of pure literature. He was appointed professor in 1825, fellow of the Swedish Medical Society in 1831 and member of the Swedish Academy in 1835. The gymnastics had four categories: pedagogic, military, medical and aesthetic. All movements should be performed correctly under a leader's direction. Free standing exercises in group were introduced and they were advantageous pedagogically as well as practically over the earlier predominant training. The medical gymnastics played an important, later even dominant, role in Ling's daily work but he could interest only a few physicians in his sphere. After Ling's death the medical gymnastics was exposed to a strong and entitled critique and little by little it became modernized. Also his pedagogic gymnastics was scrutinized and successively modified, and it can still be traced in some modern programs of physical training.
17553349 [Paharmacological mechanisms of cellular immunity of overall alkali of tongbiling for the 2007 Jun AIM: To investigate the effect of the overall alkali of Traditional Chinese Medicine tongbiling(TBL) which comprises brucine and strychnine alkaloids on collagen induced-arthritis(CIA) and study its paharmacological mechanisms of cellular immunity. METHODS: Bovine CII was emulsified in Freund's incomplete adjuvant. Wistar rats were injected with Type II collagen intradermally at the base of the tail. After swelling, CIA groups were, randomly divided into physiological saline group and treatment group. Then the swelling of the rats' hindlimbs was evaluated. The whole body of the rats treated on 35 th days was photographed by mammography X-Ray. 96 joints in erosion scoring system and 100 joints in joint spacing narrow(JSN) scoring system were used to observe the joint destruction of CIA from X-Ray comprehensively and objectively. After the rats were killed, the third proximal claw pad of the right hindlimb and left forelimb were stained by HE dying, Neutrophil, lymphocyte, plasmacyte infiltration and hyperplasia of synoviocytes were assessed. Then MTT and Western blot were used to determine the effect of the overall alkali of TBL on proliferation of Jurkat cells and ERK1/2 phosphorylation of Jurkat cells, respectively. RESULTS: Inflammation of CIA joints was aggravated quickly. The swelling of CIA rats treated by MTX and overall alkali of TBL for 35 days was relieved (P<0.05). MTX and overall alkali of TBL inhibited the hyperplasia of synoviocytes. Overall alkali of TBL inhibited the infiltration of lymphocyteS and plasmacytes. Overall alkali of TBL inhibited the proliferation and ERK1/2 phosphorylation of Jurkat cells. CONCLUSION: Overall alkali of TBL could relieve joint inflammation and destruction of CIA rats by blocking the MAPK cell signalling pathway to inhibit the activation and proliferation of T cells. Our study might provide an experimental basis for treatment of rheumatoid arthritis with overall alkali of TBL.
18524804 The Sjögren's Syndrome Damage Index--a damage index for use in clinical trials and observ 2008 Aug OBJECTIVE: To validate a tool for assessment of accumulated damage in patients with Primary SS (PSS). METHODS: Of the total 114 patients fulfilling American-European Consensus Group (AECG) criteria for PSS 104 were included in the study and assessed by rheumatologists at T (time) = 0 months and T = 12 months. On each occasion, damage and activity data, and autoantibody status were collected. SF-36 and Profile of Fatigue and Discomfort-Sicca Symptoms Inventory (PROFAD-SSI) questionnaires were completed. Cross-sectional analysis of this data was subject to a process of expert validation by 11 ophthalmologists, 14 oral medicine specialists and 8 rheumatologists. Items were removed from the index if >or= 50% of respondents recommended exclusion. Statistical validation was performed on remaining items. Spearman's rank analysis was used to investigate associations between damage scores and other disease status measures and Wilcoxon matched-pair analysis to assess sensitivity to change in the damage score. RESULTS: Based on the expert validation, a 29-item damage score was agreed incorporating ocular, oral and systemic domains. Total damage score correlated with disease duration at study entry (r = 0.436; P < 0.001), physical function as measured by SF-36 (r = 0.250, T = 0 months; r = 0.261 T = 12 months) and activity as measured by the Sjögren's Systemic Clinical Activity Index (r = 0.213, T = 0 months; r = 0.215, T =12 months). Ocular damage score correlated with the 'eye dry' domain of PROFAD-SSI (r = 0.228, T = 0 months; r = 0.365, T = 12 months). Other associations not present on both assessments were considered clinically insignificant. On Wilcoxon analysis, the index was sensitive to change over 12 months (z = -3.262; P < 0.01). CONCLUSION: This study begins validation of a tool for collection of longitudinal damage data in PSS. We recommend further trial in both the experimental and clinical environment.
17040883 [Acute polyarthritis during a parvovirus B19 primary infection]. 2006 Sep Parvovirus B19 classically causes erythema infectiosum in children, febrile arthralgia or acute erythroblastopenia in adult. The clinical spectrum of adult primary infection is sometimes misleading. We report an observation of an acute rheumatoid-like arthritis following primary parvovirus B19 infection in a 42-year-old woman.
18984038 Differences in the injury/sprouting response of splenic noradrenergic nerves in Lewis rats 2009 Feb Sympathetic nerves in the spleen undergo an injury and sprouting response with development of adjuvant-induced arthritis (AA), a model of rheumatoid arthritis (RA). The objective of the present study was to determine whether this injury and sprouting response is disease-specific or occurs in a non-specific manner similar to injury and sprouting responses following sympathectomy with specific neurotoxins. Changes in noradrenergic (NA) innervation in spleens from Lewis rats 28 days following adjuvant treatment to induce arthritis and/or local 6-hydroxydopamine (6-OHDA) treatment to destroy NA nerves were examined using immunocytochemistry for tyrosine hydroxylase (TH). We observed significant increases in sympathetic innervation of hilar regions, sites of nerve entry into the spleen, and a striking decline in innervation of splenic regions distant to the hilus in arthritic compared to non-arthritic rats. While increased hilar and decreased distal NA innervation in arthritic rats was strikingly similar to that of non-arthritic 6-OHDA-treated rats, there were differences in splenic compartments innervated by sympathetic nerves between these groups. In 6-OHDA-treated rats, NA nerves re-innervated splenic compartments normally innervated by sympathetic nerves. In arthritic rats, sympathetic nerves returned to normally innervated splenic compartments, but also abundantly innervated red pulp. These findings suggest that splenic sympathetic nerves undergo a disease-associated injury/sprouting response with disease development that alters the normal pattern and distribution of NA innervation. The altered sympathetic innervation pattern is likely to change NA signaling to immune cell targets, which could exert long-term regulatory influences on initiation, maintenance, and resolution of immune responses that impact disease pathology.
18668557 Efficient suppression of murine arthritis by combined anticytokine small interfering RNA l 2008 Aug OBJECTIVE: Blocking tumor necrosis factor (TNF) effectively inhibits inflammation and joint damage in rheumatoid arthritis (RA), but 40% of RA patients respond only transiently or not at all to the current anti-TNF biotherapies. The purpose of this study was to develop an alternative targeted therapy for this subgroup of RA patients. As proof of concept, we tested the efficiency of an RNA interference (RNAi)-based intervention that targets proinflammatory cytokines in suppressing murine collagen-induced arthritis (CIA). METHODS: Two synthetic short interfering RNA (siRNA) sequences were designed for each of the proinflammatory cytokines interleukin-1 (IL-1), IL-6, and IL-18. Their silencing specificity was assessed according to lipopolysaccharide-induced messenger RNA expression in J774.1 mouse macrophages as compared with control siRNA. For in vivo administration, siRNA were formulated as lipoplexes with the RPR209120/DOPE liposome and a carrier DNA and were injected intravenously (0.5 mg/kg) into DBA/1 mice with CIA. RESULTS: Weekly injections of anti-IL-1, anti-IL-6, or anti-IL-18 siRNA-based lipoplexes significantly reduced the incidence and severity of arthritis, abrogating joint swelling and destruction of cartilage and bone, both in the preventative and the curative settings. The most striking therapeutic effect was observed when the 3 siRNA were delivered in combination. The siRNA lipoplex cocktail reduced all pathologic features of RA, including inflammation, joint destruction, and the Th1 response, and overall parameters of RA were improved as compared with anti-TNF siRNA lipoplex-based treatment. CONCLUSION: Our results present a novel option for in vivo RNAi-based antiinflammatory immunotherapy. Our findings indicate that intravenous administration of a lipoplex cocktail containing several anticytokine siRNA is a promising novel antiinflammatory therapy for RA, as well as a useful and simple tool for understanding the pathophysiology of RA and for evaluating new therapeutic candidates.