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ID PMID Title PublicationDate abstract
9103857 [Unilateral mixed-dust pneumoconiosis with aluminum deposition associated with interstitia 1997 Feb A 63-year-old stoneworker complained of fever and a productive cough. His chest roentgenogram showed a nodular mass and a diffuse interstitial shadow in the right lung. Angiography of the pulmonary artery revealed obstruction of the right upper trunk. Open-lung biopsy was done. Histologic examination showed mixed-dust pneumoconiosis with a massive focus of mixed-dust fibrosis with silicotic nodules, and diffuse interstitial fibrosis of pattern with lymphoid infiltration. Chemical analysis revealed a high content of aluminum in lymph node, which was thought to be due to inhalation of alumina used for lettering stones. The unilateral interstitial pneumonia was thought to have developed due to deposition of free silica and aluminum dust. Although this patient had been given a diagnosis of rheumatoid arthritis and the value of rheumatoid factor was high, the interstitial pneumonia was not believed to be associated with the collagen vascular disease.
10081047 [Gene transfer in the treatment of arthritis]. 1999 Jan Current concepts in treating arthritis by gene transfer are described, including different vector systems and strategies of gene transfer into target cells. Promissing antiarthritic gene products are a variety of growth factors which facilitate increased matrix synthesis and mitogensis in articular chondrocytes. Furthermore, rheumatoid joint destruction can be treated genetically by the transfer of certain antiinflammatory cytokine genes, which provide locally high concentrations of the antiinflammatory gene product. First clinical trails using the IRAP gene (interleukin I receptor antagonist protein) to eliminate the inflammatory reaction caused by interleukin I in rheumatoid joints are on its way. In order to investigate potential improvement in cartilage regeneration retroviral TGF-beta gene transfer in rabbit articular chondrocytes has been carried out. The TGF-beta group showed an in vitro increase in collagen type II neosynthesis by 304%, compared to normal chondrocytes.
10632676 Exacerbation of acute inflammatory arthritis by the colony-stimulating factors CSF-1 and g 2000 Feb CSF-1 and GM-CSF have been implicated in the pathogenesis of rheumatoid arthritis. We report the effects of CSF-1 and GM-CSF in the development of an acute methylated bovine serum albumin (mBSA)-induced murine arthritis model. Examination of histopathological features revealed that the systemic administration of CSF-1 or GM-CSF following mBSA administration into the knee resulted in the exacerbation of arthritis. This included synovial hyperplasia and joint inflammation, most evident at 7 and 14 days post-mBSA administration, and the appearance of erosive pannus tissue. The exacerbation by CSF-1 and GM-CSF was not sustained but declined in incidence and severity by 21 days post-mBSA administration, similar to the effects of IL-1beta in this model, reported here and previously. Macrophages expressing Mac-2 and F4/80 were a prominent feature of the pathology observed, particularly the infiltration of Mac-2+ macrophages seen in all mice administered CSF-1, GM-CSF or IL-1beta. Present in inflamed knees was a locally dividing population of cells which included Mac-2+ and F4/80+ macrophages. These studies demonstrate that CSF-1 and GM-CSF can exacerbate and prolong the histopathology of acute inflammatory arthritis and lend support to monocytes/macrophages being a driving influence in the pathogenesis of inflammatory arthritis.
9403335 Reduction of disease causative T-cells in experimental autoimmune disease models by a new 1997 Oct We investigated the mode of action of a new quinoline derivative, TAK-603 (ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl) quinoline-3-carboxylate), in adjuvant arthritis (AA), a model of rheumatoid arthritis. AA rat splenocytes transferred the arthritis to normal syngeneic rats upon inoculation, but the cells from AA rats treated with TAK-603 (6.25 mg/kg/day) caused only mild arthritis with significantly less foot pad swelling and a lower arthritis score. An effect of TAK-603 in the induction phase of AA was suggested. TAK-603 had little effect on CD4+ and CD8+ T-cell populations in the AA rat splenocytes. We therefore estimated the frequency of T-cells which are reactive to the so-called disease causative antigen using a limiting dilution assay (LDA). The ratio of T-cells responsive to PPD, which increased in AA rat splenocytes with the severity of the arthritis, was reduced in AA rats treated with TAK-603. Furthermore, the ratio of MBP (myelin basic protein)-reactive T-cells, which were generated in experimental allergic encephalomyelitis (EAE) rats, were also reduced by TAK-603 administration. These data suggest that TAK-603 acts on the immune system and reduces the number of cells reactive to the relevant antigen.
11123331 Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18. 2001 Jan 1 We have recently reported the presence and a potential proinflammatory role of IL-18 in the synovium of patients with rheumatoid arthritis. To obtain direct evidence that IL-18 plays an influential role in articular inflammation, we investigated the development of collagen-induced arthritis in a strain of mice lacking IL-18 (IL-18(-/-)) of DBA/1 background. IL-18(-/-) mice developed markedly reduced incidence of arthritis compared with heterozygous or wild-type mice. Of the IL-18(-/-) mice that developed arthritis, the severity of the disease was significantly reduced compared with the intact mice. This was accompanied by reduced articular inflammation and destruction evident on histology. IL-18(-/-) mice also had significantly reduced Ag-specific proliferation and proinflammatory cytokine (IFN-gamma, TNF-alpha, IL-6, and IL-12) production by spleen and lymph node cells in response to bovine type II collagen (CII) in vitro compared with wild-type mice, paralleled in vivo by a significant reduction in serum anti-CII IgG2a Ab level. Treatment with rIL-18 completely reversed the disease of the IL-18(-/-) mice to that of the wild-type mice. These data directly demonstrate a pivotal role of IL-18 in the development of inflammatory arthritis and suggest that antagonists to IL-18 may have therapeutic potential in rheumatic diseases.
10711573 Molecular basis of androgen receptor diseases. 2000 Feb androgens act through a single intracellular androgen receptor (AR) which is encoded by a single-copy gene in the X chromosome. Disruption of the AR by genetic mutation results in complete androgen insensitivity syndrome (CAIS) and the female phenotype in otherwise healthy 46XY individuals. Although CAIS is the best known phenotype, recent studies from our laboratory and elsewhere show that malfunction of the AR is associated with many androgen-regulated diseases or conditions that cross traditional clinical disciplines ranging from paediatrics (ambiguous genitalia), gynaecology (primary amenorrhoea), urology (prostate cancer), neurology (spinal bulbar muscular atrophy), reproductive medicine (male infertility), orthopedics (rheumatoid arthritis), oncology (breast cancer) and dermatology (hirsutism, baldness and acne). Of particular interest are the roles that polymorphic CAG trinucleotide repeat tracts and subtle mutations in the AR ligand-binding domain have in the aetiology of male infertility and prostate cancer, two conditions affecting large numbers of patients. Novel mechanisms of pathogenesis have been uncovered in these cases, and they involve defective protein-protein interactions with coregulator molecules such as TIF2 (transcriptional intermediary factor 2). Knowledge of the critical role that the AR plays in the pathogenesis of these diverse conditions has led to improved diagnostic methods and successful therapy.
11440462 C1-C2 transarticular screw fixation: technical aspects. 2001 Jul OBJECTIVE: I review posterior atlantoaxial fusion with transarticular screw fixation, including indications, complications, and operative technique, emphasizing my experience. METHODS: The indications for C1-C2 transarticular screw fixation include traumatic injuries to the atlantoaxial complex, instability resulting from inflammatory disease (rheumatoid arthritis), and congenital abnormalities (os odontoideum). All patients underwent stabilization using cannulated C1-C2 transfacetal screws by the method described by Magerl. Supplemental interspinous fusion with bicortical autologous iliac crest graft and titanium cable was used to restore the posterior tension band by use of the method described by Sonntag's group. Preoperatively, all patients underwent imaging with plain radiographs, magnetic resonance imaging, and axial computed tomography. Patients were maintained in a rigid cervical orthosis postoperatively. RESULTS: Measures used to improve safety and efficacy include patient positioning, fluoroscopic guidance, preoperative magnetic resonance imaging, axial computed tomography, and open reduction of C1-C2 subluxation before screw passage. In this series of 75 patients, fusion was obtained in 72 patients (96%). There were no instances of vertebral artery injury, errant screw placement, instrumentation failure, dural laceration, spinal cord injury, or hypoglossal nerve injury. CONCLUSION: C1-C2 transarticular screw fixation with a posterior tension band construct provides excellent fusion rates with few perioperative complications. Preoperative imaging and meticulous surgical technique improve outcomes.
12042961 Thin-section chest CT findings of primary Sjögren's syndrome: correlation with pulmonary 2002 Jun The purpose of this study was to describe thin-section CT findings of lung involvement in patients with primary Sjögren's syndrome (PSS), and to correlate them with pulmonary function tests (PFT). The chest thin-section CT examinations of 35 patients with proven diagnosis of PSS and respiratory symptoms were retrospectively assessed by two observers, in a first step independently with interobserver evaluation, and in a second step in consensus. The extent of the most frequent CT findings was scored. Correlation was made with PFT in 31 of these patients. Three main CT patterns were identified with good interobserver agreement (kappa coefficient 0.71): 19 of 35 (54%) large and/or small airways disease; 7 of 35 (20%) interstitial lung fibrosis (ILF); and 5 of 35 (14%) suggestive of lymphocytic interstitial pneumonia (LIP). The CT scans were normal in 2 patients (6%) and showed only dilatation of pulmonary vessels due to pulmonary arterial hypertension in two others (6%). Airway disease patients had predominantly obstructive profiles (mean FEV(1)/FVC ratio 69.7+/-12.7%, mean MEF(25) 50.1+/-22.9%), whereas patients with ILF and LIP had predominantly restrictive profiles and/or a decreased diffusing lung capacity (mean TLC 87.0+/-26.0 and 64.6+/-18.6%, mean DL(CO) 57.4+/-21.2 and 52.0+/-8.0%). Significant correlation ( p<0.01) was found between the scores of ground-glass attenuation and TLC ( r=-0.84) and DL(CO) ( r=-0.70) and between the score of air trapping and FEV1 ( r=-1.0). In patients with PSS and respiratory symptoms, thin-section CT may provide characterization of lung involvement which correlates with pulmonary function.
11673571 The prevalence of Sjögren syndrome in patients with primary progressive multiple sclerosi 2001 Oct 23 OBJECTIVE: To assess the prevalence of Sjögren syndrome (SS) in patients with primary progressive MS (PPMS). BACKGROUND: SS may be considered in the differential diagnosis of MS. Age at onset and clinical presentation are similar in SS and PPMS. However, occurrence of SS in definite cases of PPMS has been recently reported. METHODS: Proposed clinical and laboratory diagnostic criteria for SS were systematically assessed in 60 consecutive patients with PPMS. The authors questioned all patients about xerophthalmia and xerostomia, biopsied minor salivary glands, and performed a Schirmer test, a salivary gland scintigraphy, and anti-Ro (SSa) and anti-La (SSb) serologies. RESULTS: Ten patients (16.6%) met four or more criteria for SS. This prevalence is higher than in the general population (1 to 5%) and implies that SS can mimic PPMS. CONCLUSIONS: The authors propose that SS should be screened for systematically in patients with PPMS.
11517999 Neurological complications of primary Sjögren's syndrome. 2001 Jul OBJECTIVE: To better delineate the spectrum of neurological complications of primary Sjögren's syndrome (PSS). METHODS: A detailed neurological investigation was prospectively performed in a group of 25 consecutive patients with PSS followed in an internal medicine department between June 1996 and December 1997 (Internal Medicine group). In addition, eleven patients with neurological complications of PSS were identified in the Neurological Department of the same institution during the same period (Neurological group). RESULTS: In the Internal Medicine group, neurological complications were discovered in 10/25 (40%) patients. Peripheral nervous system involvement was present in 4/25 patients from the Internal Medicine group and in 10/11 patients from the Neurological group and consisted mainly of axonal sensorimotor/sensory polyneuropathy. A motor neuron syndrome was identified in two patients. CNS involvement occurred in 7/25 patients from the Internal Medicine group and in 4/11 patients from the Neurological group. Three patients had spinal cord involvement. Cognitive dysfunction was the most frequent finding (5/25 in the Internal Medicine group, 3/11 in the Neurological group) characterized either by subcortical or corticosubcortical dysfunction. Cognitive impairment was not attributed to mood disturbance and was not associated with specific laboratory or radiological abnormalities. CONCLUSION: Neurological complications of PSS are frequent since they were present in 40% (10/25) of patients in a consecutive series of patients from a department of Internal Medicine. Although PNS involvement predominates, complications of PSS affecting the brain or spinal cord are not rare, with subcortical dysfunction as the main finding.
10717899 Cerebral blood flow in Sjögren's syndrome using 99Tcm-HMPAO brain SPET. 2000 Jan Neuropsychiatric disturbances are frequent in connective tissue diseases. Little is known about the cerebral pathophysiology of Sjögren's syndrome, including cerebral blood flow disturbances. 99Tcm-HMPAO brain SPET was performed in 21 Sjögren's syndrome patients. We also studied 77 patients with systemic lupus erythematosus and 27 healthy individuals. Our results demonstrate the high rate of alterations in cerebral blood flow in Sjögren's syndrome, both psychoneurologically symptomatic and asymptomatic. Focal interhemispherical perfusion deficits were seen in 17 of 21 patients (80.9%) with Sjögren's syndrome: 13/15 symptomatic (86.6%) and 4/6 asymptomatic (66.6%). These changes were mostly localized in the prefrontal and frontal areas, occipital lobes and occipitoparietal area, and less frequently so in the temporal, parietal and central areas. Diffuse hypoperfusion of the frontal lobes (bilateral hypofrontality) was seen in 29% of patients in the Sjögren's group. An acetazolamide stress test was performed in seven patients. There was an increase in perfusion deficits in two patients, no change in two patients, and hypoperfusion decreased in three patients compared with baseline. The results indicate that most Sjögren's syndrome patients experience alterations in cerebral blood flow that are consistent with systemic lupus erythematosus, with heterogeneous reactivity to acetazolamide-induced hypercapnia. These alterations present as focal perfusion deficits and bilateral diffuse hypoperfusion of the lobes. The mechanism of cerebral blood flow alterations is unknown, although it might be the result of diffuse cerebral vasculitis.
11588161 Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproducti 2001 Oct 15 Rheumatoid arthritis is characterized by erosive inflammation of the joints, new bone proliferation, and ankylosis, leading to severely reduced locomotion and intense chronic pain. In a model of this disease, adjuvant-induced polyarthritis in the rat, neurons involved in pain transmission and control undergo plastic changes, especially at the spinal level. These changes affect notably neurons that contain opioids, such as enkephalins deriving from preproenkephalin A (PA) precursor protein. Using recombinant herpes simplex virus containing rat PA cDNA, we enhanced enkephalin synthesis in sensory neurons of polyarthritic rats. This treatment markedly improved locomotion and reduced hyperalgesia. Furthermore, the progression of bone destruction slowed down, which is the most difficult target to reach in the treatment of patients suffering from arthritis. These data demonstrate the therapeutic efficacy of enkephalin overproduction in a model of systemic inflammatory and painful chronic disorder.
10403918 Inducible nitric oxide synthase is expressed in joints of goats in the late stage of infec 1999 Jul We have studied the expression of the inducible form of nitric oxide synthase (iNOS) in joints of goats infected with the caprine arthritis encephalitis virus (CAEV). Nitric oxide generated by iNOS is thought to play an important role in the pathogenesis of various types of arthritis, especially rheumatoid arthritis (RA) in humans. Surprisingly, iNOS immunoreactivity was found only in joints of long-term infected goats with severe clinical arthritis, whereas-despite the presence of high numbers of inflammatory cells in the synovial tissue-no iNOS immunoreactivity was detected in mildly arthritic and in short-term experimentally infected goats. Most iNOS-positive cells expressed neither MHC class II nor CD68, which suggests that they were fibroblast-like synoviocytes. In situ hybridization studies showed that there was no correlation between iNOS immunoreactivity and detectable virus expression in the joint. In addition, infection of macrophages in vitro-the major host cells of CAEV in vivo-did not lead to increased iNOS mRNA expression. In response to stimulation, similar levels of iNOS expression were observed in infected and in uninfected macrophages. These findings suggest that the expression of iNOS is a feature of late-stage chronic arthritis and is not involved in the development of the inflammatory lesions. Both the lack of co-localization of iNOS protein and viral transcripts in the joint and the finding that CAEV does not stimulate the expression of iNOS in vitro further suggest that iNOS is not directly induced by the virus or the anti-viral immune response in the joint, that it may well, however, be involved in tissue remodelling or scar formation.
11501726 Volunteers' experiences of becoming arthritis self-management lay leaders: "It's almost as 2001 Aug OBJECTIVE: To determine whether undergoing training to become a lay leader and conducting an arthritis self-management course is associated with improvements in physical and psychological health status, arthritis self-efficacy, use of self-management techniques, and visits to the general practitioner. In addition, we aimed to describe the experiences of training and course delivery from the older volunteers' perspective. METHODS: 21 participants completed all assessments and had a median age of 58, median disease duration of 10 years, and either osteoarthritis (n = 13) or rheumatoid arthritis (n = 8). The study was a pretest-posttest design with qualitative data collected at 3 points in time: before training, 6 weeks after training, and 6 months after training. Quantitative data were collected through self-administered postal questionnaires at baseline and 6-month followup. RESULT: Six months after training, participants reported small, significant increases in arthritis self-efficacy for pain (P = 0.002), cognitive symptom management (P = 0.004), and communication with their physician (P = 0.024) and a small, significant decrease in depressed mood (P = 0.04). Qualitative data supported these findings, with participants reporting more confidence, happiness, and a changed outlook on life in general. Volunteerism was associated with altruistic behavior and with filling the vocational void caused by retirement. CONCLUSION: Findings support the value of volunteerism and training to become lay leaders in arthritis self-management programs. Volunteers reported positive changes both in themselves and in course participants. They enjoyed helping similar others and being involved in a worthwhile activity, and they valued their newly acquired status as lay leaders. Many had begun to apply their newfound knowledge about self-management to their own situation, reporting less pain and more willingness "to get on with life."
10215784 The relationship between facial annular erythema and anti-SS-A/Ro antibodies in three East 1999 Jan A distinct annular erythema developed on the cheeks of three East Asian women who had anti-SS-A/Ro (SSA) antibodies. The erythema was characterized by a wide, elevated border and central pallor. Histologically, there was a coat-sleeve-like infiltration of lymphocytes around the blood vessels, appendages, and secretory gland cells in the dermis. Immunohistological analysis clarified that the majority of infiltrating lymphocytes were CD4-positive T cells. Abnormal expression of HLA-DR antigens in the perivascular, appendage, and secretory gland cells in the dermis was also observed. The differential diagnosis of the three patients lay between Sjögren syndrome (SjS), Sjögren/systemic lupus erythematosus overlap syndrome and an asymptomatic clinical state. These results are consistent with recent findings of major histocompatibility complex class II expression on target organs in various autoimmune diseases. Based on these findings, erythema appears to represent a broad cutaneous manifestation of these diseases. Furthermore, the presence of SSA antibodies, aberrant HLA-DR expression, and sun exposure may be responsible for the development of erythema.
11692552 Malignant lymphoma in primary Sjogren's syndrome. 2001 Oct Sjogren's syndrome is a chronic inflammatory process involving primarily the exocrine glands. Its association with lymphoma is well documented. A low grade marginal-zone lymphoma related to mucosa-associated lymphoid tissue is the commonest lymphoid neoplasia in Sjogren's syndrome. We review the literature and comment on the molecular, clinical, histopathologic and therapeutic aspects of these tumors in Sjogren's syndrome.
11490514 Viral studies in rheumatic disease. 1998 Feb Rheumatic disease has long been thought to represent an interaction between environmental agents on a background of genetic susceptibility. In this review herpesviruses and retroviruses are considered as possible aetiological agents in autoimmune disease with a particular emphasis on Sjögren's syndrome. A possible role for cytomegalovirus, Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and human herpesvirus-8 (HHV-8) is reviewed. We conclude that there is no compelling evidence for the involvement of any of these herpesviruses. Retroviruses, however, are attracting increasing interest. In Man, both Human immunodeficiency virus (HIV) and human T lymphotropic virus type I (HTLV-I) infections cause autoimmune phenomena, including Sjögren's syndrome and arthritis in a minority of infected individuals. Similar reactions to retroviral infection are also seen in animal models. A possible role for the newly described human retrovirus-5 (HRV-5) is discussed, though current evidence does not support a role in Sjögren's syndrome. Other autoimmune diseases are under investigation.
9918250 Oral microbial flora in Sjögren's syndrome. 1999 Jan OBJECTIVE: To study presence of microorganisms associated with caries, gingivitis, oral opportunistic infections, and extent of hyposalivation in dentate patients with primary and secondary Sjögren's syndrome (SS). METHODS: An oral clinical examination was performed. The salivary flow was measured and a rinsing sample analyzed for presence of specific microorganisms. The results were compared to those of healthy controls matched for sex, age, and number of teeth. RESULTS: In patients with undetectable salivary flow at rest, mean number and proportion of mutans streptococci and lactobacilli showed a tendency to be increased, as well as the frequency of Candida. They also displayed an increased proportion of filled surfaces. In contrast, gingivitis and the numbers of microorganisms associated with gingivitis were comparable to those found in the healthy controls. CONCLUSION: Patients with SS and severe hyposalivation harbor oral flora associated with the development of caries and frequent presence of retention sites, indicating a need for efficient preventive dental care.
9690247 Evaluation of the levels of oral Candida in patients with Sjögren's syndrome. 1998 Jul OBJECTIVE: The purpose of this study was to investigate the levels of oral Candida in patients with Sjögren's syndrome METHODS: The Candida count and salivary flow rate of patients with Sjögren's syndrome were compared with those of healthy control subjects. Candida cultures were obtained from oral rinses. The numbers of colony-forming units were determined through use of the Spiral System. RESULTS: The mean Candida count of patients with Sjögren's syndrome was 1672 +/- 1455 colony-forming units per mL; the count of healthy control subjects was 0.00 colony-forming units per mL. The mean salivary flow rate of patients with Sjögren's syndrome was significantly lower than that of healthy control subjects (0.16 +/- 0.13 mL/min/gland vs 0.55 +/- 0.24 mL/min/gland, respectively; p = 0.0001). However, Spearman rank correlation analyses did not reveal a significant correlation between salivary flow rate and Candida count (in colony-forming units per mL) among patients with Sjögren's syndrome. CONCLUSIONS: Alteration in the oral microbial flora in patients with Sjögren's syndrome may be enhanced by the reduction in salivary output.
9643244 A comparison of three methods for detecting Candida albicans in patients with Sjögren's s 1998 Feb OBJECTIVE: An immediate chairside technique (Latex Candida) for the detection of Candida albicans was compared with a simple tube culturing technique (Oricult) and the traditional laboratory culturing technique in patients with Sjögren's syndrome. METHOD AND MATERIALS: Subjects with primary (n = 9) and secondary (n = 9) Sjögren's syndrome (mean age of 56.7 years; all female) and an age- and sex-matched group of control subjects (n = 9) were selected. Three different methods for culturing Candida albicans were performed for each subject. One culturette was plated on a trypticase soy-agar streptomycin-vancomycin medium plate and incubated for 48 hours at 37 degrees C. Another swab was plated on a reagent paper with the Latex Candida test kit. The third swab was placed in a culture media tube using the Oricult kit and incubated for 48 hours at 37 degrees C. RESULTS: All three techniques indicated a significant difference in the prevalence of Candida between the control group and both Sjögren's groups. The Latex Candida technique indicated that 78% of all Sjögren's subjects were positive for Candida, while the other two tests indicated that 83% were positive. CONCLUSION: The Latex Candida technique was comparable to Oricult and streptomycin-vancomycin culturing techniques for negative results and was correctly positive for 90% of cases.