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ID PMID Title PublicationDate abstract
11495189 Iron and vitamin deficiencies, endocrine and immune status in patients with primary Sjögr 2001 May OBJECTIVES: To study the prevalence of iron and vitamin deficiencies, endocrine disorders and immunological parameters in patients with primary Sjogren's syndrome (1 degree SS). DESIGN AND SUBJECTS: At the time of the establishment of the diagnosis of 1 degree SS in 43 consecutive patients, a clinical examination including haematological analyses was performed. The patients' medical records were also reviewed. SETTING: Patients referred for diagnosis to The University Hospital, Linköping, a secondary or tertiary referral hospital serving the middle part of southern Sweden. RESULTS: In total, current or previously treated iron and vitamin deficiencies were registered for 63% of the 1 degree SS patients (iron 51%, vitamin B12 25%, folate 9%). Current low ferritin was noted in 24%, low iron saturation in 37%, decreased vitamin B12 in 13% and folate in 9%. Thyroid disease was found in a total of 33% and 30% had had autoimmune thyroiditis. Three patients (7%) had verified diabetes mellitus. Erythrocyte sedimentation rate (ESR) was raised in 65% of the patients and 84% had a polyclonal increase of Ig. Rheumatoid factor (RF) was detected in 85%, antinuclear antibody (ANA) in 74%, anti-SS-A in 88% and anti-SS-B in 73% of the patients. CONCLUSION: Iron and vitamin deficiencies and thyroid diseases are common in patients with 1 degree SS. Since these disorders often are treatable and may affect the patients' distress as well as their immune and exocrine function, an active, recurrent search for deficiencies, endocrine diseases and other frequently recorded disorders is recommended.
11283468 [Subacute neuropathy, multiple cancers, and Gougerot-Sjögren syndrome: contribution of an 2001 Feb We report the case of a patient presenting a subacute, predominantly sensory neuropathy. The work up revealed a Sjögren's syndrome and a breast carcinoma. The presence of anti-Hu antibodies, identified by Western Blot using purified recombinant HuD protein, and the absence of the Hu antigen in the breast carcinoma ruled out the responsibility of the Sjögren's syndrome or breast carcinoma. In this context, the most likely diagnosis was a subacute neuropathy associated with small cell lung cancer, which was indeed discovered 3 years later.
11133854 Improvement of lacrimal function by topical application of CyA in murine models of Sjögre 2001 Jan PURPOSE: The object of this study was to evaluate improvement of lacrimal gland (LG) function after topical cyclosporin A (CyA). METHODS: Topical CyA (0.01% and 0.1%) was applied to two mouse models of Sjögren's syndrome, the NFS/sld after thymectomy and the nonobese diabetic (NOD) mouse, and the functional integrity of the lacrimal gland was evaluated by measuring basal and stimulated tear secretion and its histologic integrity by examining it for apoptosis and lymphocyte invasion. RESULTS: After treatment with CyA at 0.1% in the NFS/sld mice, tear function increased, and there was a decrease in lymphocyte infiltration of the LG and a decrease in apoptotic figures among the acinar cells. In the NOD mice, tear function also improved, but there was no associated decrease in lymphocyte infiltration. However, the expression of Fas ligand (FasL) in NOD mice by infiltrating lymphocytes was suppressed with 0. 1% CyA eye drops. CONCLUSIONS: CyA appears to improve tear secretion in mouse models of Sjögren's syndrome by preventing lymphocyte-induced apoptosis of acinar cells. In one model this was achieved by preventing lymphocyte infiltration and in the other by reducing expression of FasL expression on infiltrating lymphocytes.
10654279 In vivo assessment of synovial microcirculation and leukocyte-endothelial cell interaction 1999 Dec OBJECTIVE: The microcirculation and leukocyte-endothelial cell interaction in synovial tissue of an inflamed joint are known to play a crucial role in the pathogenesis of rheumatoid arthritis. The aim of this study was to characterize the in vivo changes in the microvasculature and in leukocyte-endothelial cell interactions in the mouse synovial tissue using intravital fluorescence microscopy in three stages of antigen-induced arthritis. The expression of E- and P-selectin and ICAM-1 were also studied using immunohistochemistry. METHODS: Antigen-induced arthritis (AiA) was produced in Balb/c mice. The severity of arthritis at three different phases was quantified using a clinical and histological score. For the intravital fluorescence microscopy measurements, the patella tendon was partially resected for visualization of the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes, functional capillary density (FCD) and RBC velocity were quantitatively measured in synovial microvessels. Expression of ICAM-1, E- and P-selectin was assessed by immunohistochemistry. RESULTS: There was a significant increase in the leukocyte rolling fraction in postcapillary venules in the acute phase of AiA (from 0.26 +/- 0.05 in controls to 0.45 +/- 0.04 8 d after AiA induction). The number of leukocytes adherent to the endothelium was significantly elevated in all phases of arthritis (from 121 +/- 27 in controls to 376 +/- 62 mm2 63 d after AiA-induction). Functional capillary density was significantly enhanced in the acute (332 +/- 15 cm/cm2) and intermediate phases (320 +/- 15 cm/cm2) compared to control values (227 +/- 15 cm/cm2). Arthritis resulted in a distinct increase in the expression of ICAM-1 on the synovial endothelium in all phases of AiA. E- and P-selectin expression were detected only in the acute phase. CONCLUSION: Our model provides new insights into the microcirculatory changes which occur in the synovial tissue of an arthritic joint.
11014358 Suppression of streptococcal cell wall-induced arthritis by human chorionic gonadotropin. 2000 Sep OBJECTIVE: To determine whether human chorionic gonadotropin (HCG) contributes to pregnancy-associated immunosuppression, as observed clinically by an amelioration of symptoms in human autoimmune diseases, including rheumatoid arthritis, during pregnancy. METHODS: Administration of HCG was initiated 2 days prior to an arthritogenic dose of streptococcal cell wall (SCW) in nonpregnant female rats, and the development and severity of SCW-induced arthritis was monitored. Inflammatory mediators, including plasma nitrite/nitrate and cytokine levels, were measured. Inducible nitric oxide synthase (iNOS) protein and cytokine messenger RNA expression in joint tissue were compared between treated and untreated arthritic animals. RESULTS: Systemic administration of HCG resulted in a dose-dependent reduction in the clinical arthritis index. Consistent with the amelioration of clinical symptoms, HCG significantly reduced the inflammatory cell infiltration, pannus formation, and bone and cartilage degradation. Mechanistically, HCG therapy was associated with suppression of the overzealous production of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-1beta, which contribute to synovial pathology in animals with SCW-induced arthritis. Circulating nitric oxide and the amount of iNOS protein were also reduced. Furthermore, circulating transforming growth factor beta levels were elevated by the HCG, all of which suggest monocytes/macrophages as a potential target. CONCLUSION: These findings indicate that HCG exerts a protective effect in this experimental arthritis model, through modulation of inflammatory mediators.
10728759 Induction of tolerance with intranasal administration of human cartilage gp-39 in DBA/1 mi 2000 Mar OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) was recently identified as a candidate autoantigen in the pathogenesis of rheumatoid arthritis. In the present studies, we investigated the capacity of HC gp-39 to interfere in clinical disease induced by an unrelated autoantigen, type II collagen (CII), by the induction of cross-tolerance. METHODS: DBA-1j/Bom mice were immunized with bovine CII/complete Freund's adjuvant and were given intraperitoneal booster injections of CII on day 21. Tolerance was induced via the intranasal pathway with either the disease-inducing antigen (CII), a control antigen (ovalbumin), or HC gp-39 either before priming with CII or near the day of the booster injection. Arthritis was monitored visually, and joint pathology was examined histologically and radiologically. In addition, CII antibody levels in serum were analyzed by enzyme-linked immunosorbent assay. RESULTS: In contrast to treatment before priming, intranasal application of HC gp-39 after immunization markedly suppressed disease activity and prevented joint destruction, whereas application of ovalbumin or CII was ineffective. Interference of HC gp-39 with the immune response to CII was demonstrated by decreased anti-CII antibody levels. The combined data indicate that intranasal treatment with HC gp-39 may trigger modulatory or regulatory mechanisms that interfere with the expression of disease in murine collagen-induced arthritis. CONCLUSION: HC gp-39 is the first cross-tolerance-inducing protein in arthritis that down-modulates a spectrum of disease features when given in a semitherapeutic protocol.
10827521 [Hypokalemic pareses secondary to renal tubular acidosis]. 2000 Jan 30 A 24 year old woman presented with flaccid paralysis, severe hypokalaemia and hyperchloremia, metabolic acidosis. Immunological tests and labial glandular biopsy indicated primary Sjögren's syndrome as the underlying cause of her distal renal tubular acidosis. The patient recovered after alkali and potassium substitution and was put on oral treatment with potassium citrate.
10468169 Neurological involvement in primary Sjögren's syndrome: clinical and instrumental evaluat 1999 To evaluate nervous system involvement in a cohort of Italian patients with primary Sjögren's syndrome (pSS), 87 unselected patients (83 female, and four male) observed consecutively at our institution over a period of 5 years were screened by clinical and instrumental (MRI, SPECT, electrophysiological testing, CSF analysis) investigations for peripheral and central neurological abnormalities. Seroimmunological parameters and extraglandular features other than neurological manifestations were also evaluated. Seven patients had central nervous system (CNS) disease (8%), mostly non-focal dysfunction, and 12 had peripheral nervous system (PNS) disease (13.8%), mostly mild or severe sensory or sensory-motor polyneuropathies. One patient had concomitant CNS and PNS involvement. Compared with CNS disease, PNS involvement occurred in older patients (> 50 years), independent of the disease duration. Patients with and without neurological abnormalities did not differ for seroimmunological parameters (including antiphospholipid antibodies) or extraglandular manifestations. From a statistical point of view, the only relevant finding was the detection of a slight increase in serum IgA and IgM levels (p < 0.05) in patients with an intact nervous system. Neurological involvement in pSS, be it central or peripheral, is not a rare finding. A careful clinical neurological evaluation, combined with a multiplicity of instrumental investigations, is recommended in the global assessment of pSS patients.
10201480 Celiac disease and markers of celiac disease latency in patients with primary Sjögren's s 1999 Apr OBJECTIVE: Many autoimmune diseases occur concomitantly with celiac disease. We investigated prospectively the occurrence of celiac disease and small-bowel mucosal inflammation in patients with primary Sjögren's syndrome. METHODS: A total of 34 patients with primary Sjögren's syndrome and 28 controls underwent small bowel biopsy. Villous morphology, jejunal intraepithelial lymphocytes, and mucosal HLA-DR were evaluated and DQA and DQB alleles, serum antiendomysial, and antigliadin antibodies were examined. RESULTS: Five (14.7%) of 34 Sjögren's syndrome patients were found to have celiac disease. The density of jejunal intraepithelial gammadelta+ T cells was increased in all celiac and in four nonceliac patients. All celiac patients, 69% of nonceliac Sjögren's syndrome patients, and 11% of control subjects showed enhanced HLA-DR expression (p < 0.001). HLA DQ2 was present in 19 (56%) patients with Sjögren's syndrome, including all five with celiac disease. CONCLUSIONS: The findings show a close association between Sjögren's syndrome and celiac disease. Even among nonceliac patients with primary Sjögren's syndrome, an ongoing inflammation is often present in the small bowel mucosa.
9849649 Essential fatty acid status in cell membranes and plasma of patients with primary Sjogren' 1998 Oct In 41 primary Sjögren's syndrome patients we compared fatty acid levels within erythrocyte phospholipids, plasma phospholipids, plasma triglycerides and plasma cholesterol esters, with the immunopathological and clinical disease status. Docosahexaenoic acid was the essential fatty acid (EFA), the levels of which correlated (inversely) most closely with the clinical disease status (r=-0.33 to -0.50). Levels of dihomogammalinolenic acid and eicosapentaenoic acid correlated inversely to levels of IgM rheumatoid factors (r=-0.33) and anti-SSA/Ro antibodies (r=-0.40) respectively. Moreover, levels of anti-SSA/Ro antibodies (r=-0.34-0.40) correlated with levels of the proinflammatory arachidonic acid. Sigma n-3 EFA/sigma n-6 EFA ratios correlated significantly to the quantitative estimates of immunopathological and clinical disease status. Our data are in agreement with current understanding of pro- and anti-immunoinflammatory roles within EFA metabolism, and support the rationale for intervention studies.
11302868 A longitudinal cohort study of Finnish patients with primary Sjögren's syndrome: clinical 2001 May OBJECTIVE: To evaluate outcome in a cohort of Finnish patients with primary Sjögren's syndrome (pSS). METHODS: Clinical and laboratory data from the time of diagnosis and follow up were collected from 110 patients with pSS (107 women, three men) diagnosed in 1977-1992 in central Finland. The standardised incidence ratio for cancers was determined as the ratio of the observed number of cases to the expected number based on regional population rates. Eighty one of the 93 patients still alive were interviewed, and clinical and laboratory examinations performed in 1994-1997. RESULTS: The mean (SD) erythrocyte sedimentation rate (33 (22) v 45 (28) mm/1st h), serum IgG (18.8 (7.4) v 22.5 (8.5) g/l), and serum IgM (1.6 (1.1) v 2.0 (1.2) g/l) at the control visit were significantly (p<0.0001) lower than those at baseline. A similar change was observed in a subgroup of patients never treated with glucocorticosteroids or disease modifying antirheumatic drugs. Three non-Hodgkin's lymphomas were diagnosed (standardised incidence ratio 13; 95% confidence interval 2.7 to 38). In a logistic regression model, the patients with pSS with subsequent lymphoma were found to have higher baseline levels of serum beta2 microglobulin than the others (odds ratio 1.9; 95% confidence interval 1.1 to 3.4). CONCLUSION: The results suggest that mean concentrations of serum IgG and IgM in patients with pSS decline with time, possibly reflecting diminishing inflammatory activity. As in previous studies, the incidence of non-Hodgkin's lymphomas in this cohort of patients with pSS was significantly higher than in the reference population.
10503559 The influence of age on disease manifestations and serological characteristics in primary 1999 We have studied the influences of age on clinical manifestations and serological abnormalities in primary Sjögren's syndrome (pSS). The 67 patients included were diagnosed according to the preliminary European classification criteria for pSS, and disease manifestations were assessed according to a newly developed quantitative and qualitative classification model. We found that the age at diagnosis correlated to the presence of autoantibodies anti-SSA/SSB (r=-0.31, <0.02), rheumatoid factor (RF) (r=-0.33, p<0.01) and serum levels of IgG (r=-0.27, p<0.05). Young patients diagnosed before 45 years of age had the highest positivity of the autoantibodies anti-SSA/SSB (62.5%), RF (62.5%) and high levels of s-IgG (68.8%), while the corresponding values for old patients diagnosed after 60 years of age were anti-SSA/SSB: 20.8%, RF: 20.8%, and high s-IgG: 29.2%. None of these parameters correlated to age at onset nor disease duration. By applying a model for evaluating disease manifestations, no correlation between the global index nor the indices for subgroups of disease manifestations was found to age at onset, age at diagnosis, nor disease duration. We conclude that there is a significant influence of age on serological abnormalities in pSS, but not on disease manifestations.
10495053 Painful tonic/dystonic spasms in Sjogren's syndrome. 1999 Sep Three patients with Sjogren's syndrome are presented in whom frequent tonic/dystonic spasms of the limbs developed during the course of the illness. These patients' clinical findings suggested spinal cord involvement, a localization that was confirmed by magnetic resonance imaging in two patients. In one patient the painful movements responded to treatment with phenytoin and in one other to baclofen. Sjogren's syndrome should be considered in the differential diagnosis of conditions that produce tonic/dystonic limb spasms.
9892572 Pseudomonas aeruginosa orbital phlegmon in a patient treated for myelodysplastic syndrome 1999 Jan 26 Pseudomonas aeruginosa orbital infections have been described very rarely in patients with neutropenia after chemotherapy. We report the case of a woman with the unusual association of Sjögren's disease and myelodysplasia, who suffered from a Pseudomonas aeruginosa orbital phlegmon after chemotherapy for her myelodysplastic syndrome. Partial intestinal antibiotic decontamination with ciprofloxacine did not prevent the infection. She was treated successfully with intravenous ceftazidime, netilmicin and granulocyte-colony stimulating factor (G-CSF). The normalization of the granulocyte count seems to play a crucial role for recovery. We present the clinical and radiological findings, discuss the therapy and review the literature concerning ocular infections due to Pseudomonas. Other infections due to this germ in immunocompromised hosts are briefly reviewed.
9152077 Adie syndrome as the initial sign of primary Sjögren syndrome. 1997 May PURPOSE: To report Adie syndrome as the initial sign of primary Sjögren syndrome. METHODS: Case report. RESULTS: Adie syndrome was associated with necrotizing gingivitis and xerostomia. Antibodies against Ro (SS-A) were present. Prednisone and antimalarial drugs were ineffective in treating Adie syndrome but improved the necrotizing gingivitis. CONCLUSION: Search for Sjögren syndrome is mandated in patients with Adie syndrome. The latter condition is likely related to ganglionitis, a mechanism responsible for peripheral nervous system involvement in primary Sjögren syndrome.
11710726 Amelioration of arthritis in two murine models using antibodies to oncostatin M. 2001 Nov OBJECTIVE: Oncostatin M (OSM) is a member of the interleukin-6 cytokine family, with well-documented effects on cell growth and differentiation. OSM also has proinflammatory and cartilage degradative properties. The aim of this study was to investigate the significance of OSM in arthritis pathology using a neutralizing antibody in arthritis models. METHODS: Collagen-induced arthritis (CIA) was established in male DBA/1 mice. Reverse transcriptase-polymerase chain reaction was used to detect OSM messenger RNA (mRNA) message levels in arthritic joints. Neutralizing anti-OSM antibody or control immunoglobulin was administered on days 1 and 3 after disease onset. Animals were assessed for clinical arthritis for 2 weeks, followed by a histologic analysis of paws. Pristane-induced arthritis (PIA) was produced in male CBA mice dosed with anti-OSM or control immunoglobulin immediately before disease onset. Mice with PIA were assessed for clinical arthritis over a period of 100 days. RESULTS: Levels of mRNA for OSM, but not GAPDH, were elevated in arthritic joints of mice with CIA compared with those of normal controls. Mice with CIA treated with anti-OSM antibody showed significant amelioration of both the clinical severity (P < 0.01) and the number of affected paws (P < 0.01) compared with control animals. Histologic analysis confirmed these clinical findings, revealing a marked reduction in cellular infiltration of synovium and cartilage damage. In the PIA model, the incidence of arthritis was 65% in the control group compared with 0% in the anti-OSM-treated animals. CONCLUSION: These results demonstrate a key role for endogenously produced OSM as a potent mediator of joint pathology, and suggest that OSM might be a potentially important, novel therapeutic target for treatment of established rheumatoid arthritis.
11139426 Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase-inhibitor. 2000 Dec BAY 12-9566 (4-[4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) is a newly developed, synthetic matrix metalloproteinase (MMP) inhibitor (MMPI) that selectively inhibits MMP-2, MMP-3 and MMP-9 isozymes. We study the effect of BAY 12-9566 on inflammation and cartilage destruction in adjuvant-induced arthritis (AA) in rats. Rats were injected with adjuvant and treated for 21 days with vehicle, Indomethacin or BAY 12-9566. AA was assessed: by measuring arthritic index, paw volume, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr); by examining joint inflammation; and by microscopic morphometry of articular cartilages. Oral treatment of rats for 22 days with 50 mg kg(-1) body weight/d BAY 12-9566 showed decreased AA as determined by improvement in body weight gain (P<0.01), arthritic index (P<0.05) and swelling of paws contralateral to the adjuvant injection site (P<0.05). Neutrophil infiltration and collagen degradation were also significantly lower (P<0.01) in this treatment group. Cartilage destruction was successfully suppressed (P<0.01) in rats treated with either 50 mg kg(-1) body weight/d BAY 12-9566 or 1 mg kg(-1) body weight/d Indomethacin. These results indicate that BAY 12-9566 successfully suppressed inflammation and cartilage destruction in rats with AA. Moreover, these results also suggested that MMP-2, MMP-3 and MMP-9 are involved in arthritic diseases such as rheumatoid arthritis.
9277035 An outbreak of post-streptococcal reactive arthritis. 1997 Jun We describe an outbreak of an illness with fever, mono-, pauci- or polyarticular arthritis, and high antideoxyribonuclease B (ADNB) titres in 11 patients. Two patients had concomitant non-purulent conjunctivitis and one had endogenous endophthalmitis. There was no clinical or echocardiographic (6 patients) evidence of carditis. Blood culture grew Group A beta haemolytic streptococci in one patient. A simultaneous synovial fluid culture in this patient and similar cultures in four more patients yielded no microorganism. Most patients recovered completely, but one developed rheumatoid factor negative spondyloarthropathy. Monoarticular arthritis in several patients, the absence of carditis, and the presence of high ADNB titres without high anti-streptolysin O titres indicate that this was not acute rheumatic fever but post-streptococcal reactive arthritis (PSRA).
11781886 [Biographic risk factors and mental disorders in fibromyalgia]. 1999 Patients with fibromyalgia are compared with rheumatoid arthritis and coxarthrosis patients respecting biographic risk factors and comorbidity (mental disorders). As expected, in fibromyalgia there are higher biographic risk factors and more mental disorders than in the other groups. Moreover, there is a positive relation between mental disorders and biographic risk factors in fibromyalgia. Therefore patients with fibromyalgia are no uniform group, but can be divided in at least two subgroups: One subgroup with high biographic risk factors and mental disorders and another subgroup without increased biographic risk factors and without comorbidity (mental disorders). Consequences for psychosomatic theories are discussed.
11479371 Antibody-based targeting of angiogenesis. 2001 Aug The selective targeting of neovasculature opens new avenues for the diagnosis and therapy of angiogenesis-related diseases such as cancer, blinding ocular disorders, and rheumatoid arthritis. Here we review recent advances in the identification of markers of angiogenesis as well as in the isolation and use of antibodies (and their derivatives) for the in vivo targeting of both tumoral and nontumoral neovasculature.