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Review Sarcoidosis presenting as primary Sjogren's syndrome. free! 2001
Levy O, Topilski M, Brazowski E, Yaron M, Tishler M. · Department of Medicine B, Assaf Harofeh Medical Center, Zerifin, Israel. · Isr Med Assoc J. · Pubmed #11344808 links to free full text
This publication has no abstract.
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Clinical Conference The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 and MMP-3 in patients with resistant rheumatoid arthritis. 2006
Litinsky I, Paran D, Levartovsky D, Wigler I, Kaufman I, Yaron I, Yaron M, Caspi D, Elkayam O. · Department of Rheumatology, Sourasky Medical Center, and Sackler, Faculty of Medicine, University of Tel Aviv, 6 Weizman Street, Tel Aviv 64239, Israel. · Cytokine. · Pubmed #16487722 No free full text.
Abstract: OBJECTIVE: The purpose of this open pilot study was to assess possible mechanisms of the effects of leflunomide by studying the influence of the drug on the serum levels of MMP-1, MMP-3, IL-10, IL-6 and their possible correlation with clinical disease parameters. PATIENTS AND METHODS: Thirty patients with long standing active rheumatoid arthritis were enrolled in this study. All patients failed at least 5 DMARDs in the past and were on stable treatment for at least 3 months before starting the protocol. The patients received a loading dose of 100 mg for 3 days followed by 20 mg/day thereafter and followed up monthly for 6 months. Disease activity was assessed at baseline, 2 weeks, and every month of therapy thereafter using the following variables: tender joint count, swollen joint count, morning stiffness duration, pain, tiredness, physician's and patient's global assessment, using VAS, ESR and CRP. Clinical effects of the treatment regimen were calculated using the American College of Rheumatology (ACR) criteria for clinical response. Adverse events were recorded. Serum levels of MMP-1, MMP-3, IL-10 and IL-6 were measured before and 3 months after starting the protocol. RESULTS: Except for tiredness, a statistically significant improvement in all clinical and laboratory parameters of disease activity was reached after 3 months. At this time point the ACR-20 response rate was 46.2%. The levels of MMP-1, MMP-3, IL-6 and IL-10 decreased significantly after 3 months. A statistically significant correlation between serum levels of MMP-1, IL-10 and IL-6 and clinical and laboratory parameters was also shown. After 6 months, 16 out of 30 patients withdrew from the study [adverse events (35.4%), lack of efficacy (9.7%), and low compliance (6.4%)]. CONCLUSIONS: Leflunomide was clinically efficacious in this group of long standing resistant RA in an open study "real life" design. These results comply with those reported in previous clinical trials. Serum MMP-1, MMP-3, IL-10 and IL-6 levels decreased significantly. Despite high withdrawal rate, no serious adverse effects were recorded.
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Clinical Conference Safety and efficacy of vaccination against hepatitis B in patients with rheumatoid arthritis. free! 2002
Elkayam O, Yaron M, Caspi D. · Department of Rheumatology, Tel Aviv Sourasky Medical Centre and the Sackler Faculty of Medicine, University of Tel Aviv, Israel. · Ann Rheum Dis. · Pubmed #12079904 links to free full text
Abstract: BACKGROUND: Hepatitis B infection and vaccination against it have been implicated in the potential triggering or flare of some autoimmune diseases, including rheumatoid arthritis (RA). However, the safety of hepatitis B vaccination in patients with pre-existing RA is not known. OBJECTIVES: To assess the safety and antibody response of immunisation with a recombinant DNA hepatitis B vaccine in patients with RA. PATIENTS AND METHODS: The study comprised 44 patients with RA, of whom 22 received three doses (the second and third dose being given after one and six months) of a recombinant DNA hepatitis B vaccine (study group) and 22 did not receive the vaccine (control group). Both groups had comparable proportions of women and similar mean age (51 years). Clinical assessment before and two and seven months after the first immunisation included evaluation of daytime pain with a 10 cm visual analogue scale, duration of morning stiffness, and number of tender and swollen joints. Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured at each visit. Antibodies to hepatitis B surface antigen (HBsAg) were determined by a commercial enzyme linked immunosorbent assay (ELISA) test kit. RESULTS: Hepatitis B vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease. The measures of disease activity of the patients and controls during the study period did not differ significantly: p=0.76 for daytime pain, p=0.1 for morning stiffness, p=0.24 and p=0.3 for tender and swollen joints respectively, p=0.08 for CRP, and p=0.12 for ESR. Fifteen of the 22 patients responded to vaccination, with an antibody level against HBsAg of 10 IU/l after seven months. Lack of response was associated with older age and higher scores of daytime pain. CONCLUSIONS: Hepatitis B vaccination is safe in RA and produces antibodies in 68% of the patients.
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Clinical Conference Increased salivary interleukin-6 levels in patients with primary Sjögren's syndrome. 1999
Tishler M, Yaron I, Shirazi I, Yossipov Y, Yaron M. · Department of Rheumatology, Ichilov Hospital, Tel Aviv, Israel. · Rheumatol Int. · Pubmed #10220831 No free full text.
Abstract: This study's purpose was to evaluate salivary interleukin-6 (IL-6) levels in patients with primary Sjögren's syndrome (SS). Salivary and serum IL-6 concentrations were evaluated by ELISA in 36 patients with SS and compared with 19 patients complaining of dry mouth and with normal controls. Salivary IL-6 levels were significantly elevated (P < 0.01) in the 36 patients with SS as compared to the 19 patients with dry mouth (200.5 +/- 43.6 and 12.6 +/- 6.8 pg/ml, respectively). No significant differences were noted in the serum IL-6 levels between these two groups (105.8 +/- 17.1 and 84.8 +/- 17.1 pg/ml, respectively). Both salivary and serum IL-6 levels in the normal controls were below the level of detection of the assay. Positive correlation (r = 0.8613, P < 0.0001) was found between salivary IL-6 levels and the focus score of labial biopsies in SS patients. Elevated salivary IL-6 levels appear to be a consequence of local production and may reflect the component of salivary gland inflammation in SS.
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Article Active leflunomide metabolite inhibits interleukin 1beta, tumour necrosis factor alpha, nitric oxide, and metalloproteinase-3 production in activated human synovial tissue cultures. free! 2003
Elkayam O, Yaron I, Shirazi I, Judovitch R, Caspi D, Yaron M. · Department of Rheumatology, Tel Aviv Sourasky Medical Center, Israel. · Ann Rheum Dis. · Pubmed #12695157 links to free full text
Abstract: BACKGROUND: Leflunomide is now an approved agent for the management of adult rheumatoid arthritis (RA). Its active metabolite A771726 inhibits de novo pyrimidine biosynthesis. Although considered to be an immunosuppressive agent, its mechanism of action remains obscure. OBJECTIVES: Evaluation of the leflunomide active metabolite A771726 (LEF) effect on interleukin 1beta (IL1beta), tumour necrosis factor (TNFalpha), nitric oxide (NO), and stromelysin (metalloproteinase-3 (MMP-3)) production by activated human synovial tissue in culture. METHODS: Synovial tissue was obtained during surgery from patients undergoing total knee replacement owing to RA or osteoarthritis (OA), cut into small pieces, and cultured in Petri dishes with test materials as previously described. IL1beta, TNFalpha, NO, and MMP-3 were measured in the culture media after 48 hours incubation with different doses of LEF by methods previously described. RESULTS: LEF (0.3, 3, and 9 micro g/ml) inhibited IL1beta production in the presence of lipopolysaccharide (LPS; 3 micro g/ml) in a dose dependent manner (p<0.01) at LEF 0.3 micro g/ml. TNFalpha production in the presence of IL1beta (1 ng/ml) was also inhibited in a dose dependent manner (p<0.05 at LEF 0.3 micro g/ml). NO and MMP-3 production in the presence of LPS (3 micro g/ml) was inhibited as well (p<0.01 at LEF 1 micro g/ml and at LEF 0.3 micro g/ml, respectively). Synovial cell viability evaluated by the tetrazolium salt XTT was unaffected by the LEF concentration used. There was no qualitative difference in the response of OA and RA synovial tissue. CONCLUSION: Leflunomide may modulate the rheumatoid articular process by inhibition of local production of IL1beta, TNFalpha, NO, and MMP-3.
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Article Rapid and complete resolution of proteinuria due to renal amyloidosis in a patient with rheumatoid arthritis treated with infliximab. free! 2002
Elkayam O, Hawkins PN, Lachmann H, Yaron M, Caspi D. · Department of Rheumatology, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. · Arthritis Rheum. · Pubmed #12384913 links to free full text
Abstract: We describe herein a patient with rheumatoid arthritis who developed proteinuria due to AA amyloidosis, in whom the inflammatory disease was rapidly and completely suppressed by treatment with infliximab. This response was accompanied by resolution of the proteinuria and stabilization of the amyloid deposits as seen on serial (123)I-labeled serum amyloid P scintigraphy.
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Article Immunogenicity and safety of pneumococcal vaccination in patients with rheumatoid arthritis or systemic lupus erythematosus. 2002
Elkayam O, Paran D, Caspi D, Litinsky I, Yaron M, Charboneau D, Rubins JB. · Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Clin Infect Dis. · Pubmed #11740700 No free full text.
Abstract: Prevention of bacterial infection, which is a leading cause of morbidity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is a priority. However, the safety and immunogenicity of the pneumococcal vaccine in such patients remain controversial. We evaluated the currently available pneumococcal vaccine in patients with RA or SLE. Pneumococcal vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease activity in either group. One month after vaccination, patients in both groups had significant increases in geometric mean concentrations of pneumococcal polysaccharide-specific IgG to all 7 serotypes tested, as did control subjects. However, 14 (33.3%) of 42 patients with RA and 5 (20.8%) of 24 patients with SLE responded either to none or to only 1 of the 7 polysaccharides. Pneumococcal vaccination is generally safe and immunogenic in patients with RA or SLE, but a subset of patients may remain unprotected by the currently available vaccine.
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Article Accelerated Fas-mediated apoptosis of monocytes and maturing macrophages from patients with systemic lupus erythematosus: relevance to in vitro impairment of interaction with iC3b-opsonized apoptotic cells. free! 2001
Shoshan Y, Shapira I, Toubi E, Frolkis I, Yaron M, Mevorach D. · Laboratory for Cellular and Molecular Immunology, Department of Medicine, Hadassah University Hospital, Jerusalem, Israel. · J Immunol. · Pubmed #11698475 links to free full text
Abstract: Impaired handling of apoptotic cells has been suggested as an important factor in the development of systemic lupus erythematosus (SLE), and a role for complement in the removal of apoptotic cells was shown recently. We studied the in vitro function of macrophages from 40 patients with SLE and their matched controls in the removal of heterologous apoptotic cells opsonized by iC3b. Interaction index of apoptotic cells opsonized by iC3b was significantly lower in patients with SLE and averaged 71% +/- 37 of that of healthy individuals (p < 0.002) and 69% +/- 35 of patients with rheumatoid arthritis (p < 0.007). SLE patients had increased apoptosis of both freshly isolated monocytes (p < 0.001) and maturing macrophages (p < 0.04) that led to decreased density of monocyte-derived macrophages. Apoptosis was inhibited by adding soluble Fas receptor indicating Fas-mediated apoptosis. As demonstrated in both healthy controls and patients with SLE, decreased macrophage density by itself caused significant decreased uptake of apoptotic cells by the remaining macrophages. Maintaining normal density in SLE patients either by an increased initial density or by using soluble Fas restored the interaction capacity of the individual macrophages in the majority of patients. We concluded that impaired in vitro interaction of iC3b-opsonized apoptotic cells with macrophages from patients with SLE was mainly associated with Fas-dependent accelerated apoptosis of the monocytes/macrophages. Accelerated apoptosis of phagocytes may represent a novel in vitro mechanism of impairment of interaction with apoptotic cells that, apart from reducing the number of professional phagocytes, alters the function of the remaining macrophages.
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Article A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis. free! 2001
Paran D, Elkayam O, Mayo A, Paran H, Amit M, Yaron M, Caspi D. · Tel-Aviv Sourasky Medical Centre, Tel-Aviv University, Israel. · Ann Rheum Dis. · Pubmed #11502617 links to free full text
Abstract: OBJECTIVE: To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA). METHODS: Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20). RESULTS: Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1). CONCLUSION: Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.
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Article Clinical and immunological characteristics of elderly onset Sjögren's syndrome: a comparison with younger onset disease. 2001
Tishler M, Yaron I, Shirazi I, Yaron M. · Department of Rheumatology, Tel Aviv Souraski Medical Center and Tel Aviv University Sackler School of Medicine, Israel. · J Rheumatol. · Pubmed #11327252 No free full text.
Abstract: OBJECTIVE: To compare the clinical and laboratory characteristics of patients with primary Sjögren's syndrome (SS) with an elderly onset to those with a younger onset. METHODS: The study group comprised 85 consecutive patients (79 women and 6 men) attending the Sjögren's clinic. Primary SS was diagnosed according to the San Diego criteria. Elderly onset disease (EOD) was determined as the appearance of symptoms suggestive of SS after age 65. Clinical and laboratory variables for EOD were compared to those of a younger onset disease (YOD). Salivary and serum samples of all patients were examined for concentrations of interleukin 6 (IL-6) and hyaluronic acid (HA). RESULTS: Seventeen patients with SS (20%) matched the definition of EOD and their median disease onset was 71 years (range 65-80). No significant differences were noted in the clinical disease manifestations between the 2 groups of patients. Rheumatoid factor and anti-Ro(SSA) antibodies were more common in the YOD group (p = 0.012 and p = 0.023, respectively). Significant elevations of salivary IL-6 and HA levels were detected in the YOD group compared to the EOD group with SS (17.3 +/- 3.6 vs 8.8 +/- 2.1 pg/ml and 230.2 +/- 41.1 vs 128.8 +/- 33.3 ng/ml, respectively) (p < 0.0001). CONCLUSION: EOD SS has somewhat milder clinical symptoms with fewer immunological manifestations than YOD. The elevations of salivary IL-6 and HA in the younger group of SS patients support in part the differences in the inflammatory process between the 2 groups.
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Article Clinical, radiologic, demographic, and occupational aspects of hand osteoarthritis in the elderly. 2001
Caspi D, Flusser G, Farber I, Ribak J, Leibovitz A, Habot B, Yaron M, Segal R. · Departments of Rheumatology and Radiology, Tel Aviv (Souraski) Medical Center, Tel Aviv, Israel. · Semin Arthritis Rheum. · Pubmed #11303305 No free full text.
Abstract: OBJECTIVE: Osteoarthritis (OA) of the hand is common in elderly patients. The aim of this study was to characterize OA frequency, severity, and distribution and to trace interrelationships between these findings and the demographic, occupational, and medical data from elderly Jewish nonrheumatologic patients. METHODS: Study participants were 253 consecutive patients admitted to a geriatric center for a variety of nonrheumatic medical conditions. Excluded patients were those with rheumatoid arthritis; neurologic, orthopedic, or other conditions that would interfere with symmetric hand function; and mental or medical states that would interfere with history taking and radiographic studies. Patient occupations were graded as workload degree (on a scale of 1 to 3) and as the total occupational score (workload degree multiplied by the duration of each job). Clinical findings of Heberden nodes, Bouchard nodes, and malignment, graded on a scale of 0 to 3, were summed as the clinical OA score. Hand radiographs were independently read (modified Altman method), grading 5 parameters in each joint on a scale of 0 to 3, summed as a radiologic OA score. Statistical analyses included the Student t test, chi(2) test, ANOVA, Pearson correlation, and partial correlation coefficients. RESULTS: Among 253 elderly patients (171 women, 82 men; mean age, 79 years) OA was frequent (occurring in about 80% of patients), involving most severely the second and third distal interphalangeal, right first interphalangeal, and both first carpometacarpal joints. The prevalence of OA was similar in women and men, with higher scores in women, and reached significance only in the distal interphalangeal joints. Metacarpophalangeal joints were more involved in men. Age had a clear influence on OA scores. Ethnicity affected OA severity, with Ashkenazi Jews having significantly higher scores than Sepharadi Jews. Dominant hands had significantly higher global OA scores as well as isolated joint scores (except for the first carpometacarpal joint). Occupational load, housekeeping tasks, and the number of children did not influence the total or specific joint OA scores. Associated conditions such as obesity, diabetes, hypothyroidism, and chondro calcinosis were not associated with more pronounced OA. CONCLUSIONS: Hand OA was prevalent in our elderly cohort, and its severity was influenced by inherent traits such as age, female gender, ethnicity, and handedness. In contrast, acquired factors such as workload, number of children, and associated diseases did not appear to influence OA expression.
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Article Clinical significance of low titer anti-nuclear antibodies in early rheumatoid arthritis: implications on the presentation and long-term course of the disease. 2001
Caspi D, Elkayam O, Eisinger M, Vardinon N, Yaron M, Burke M. · Department of Rheumatology, Tel Aviv (Sourasky) Medical Center, Israel. · Rheumatol Int. · Pubmed #11269531 No free full text.
Abstract: The objective of this study was to evaluate the clinical significance of anti-nuclear antibodies (ANA) detected in the early stages of rheumatoid arthritis (RA), by a retrospective comparison of the clinical, laboratory, and therapeutic characteristics of patients with or without ANA. The files of 99 longstanding seropositive RA patients were reviewed. Data relating to demographics, medical history, family history, physical findings, extra-articular complications, laboratory tests, drugs [dosage, duration. efficacy, combinations, adverse effects (AEs)], intra-articular injections, and surgery were recorded. Patients with or without ANA at presentation of their disease were compared using chi-square and t-tests. Fifty-two ANA positive (group 1) and 47 ANA negative (group 2) patients were enrolled in the study. All were comparable in terms of their mean age, age at diagnosis, follow-up duration (approximately 10.5 years), and male:female (M:F) ratio. On admission, pain complaints were more pronounced in group 1 (P = 0.004 in the feet), but the physical findings did not differ. Deformities and nodules developed in similar numbers. Extra-articular complications were evenly distributed; vasculitis, however, was significantly more prevalent in ANA positive (10/52) than in ANA negative (2/47) patients. Thyroid disease was more common in group 2 (10/47 vs 3/52). Laboratory tests (presentation and maximal values) were similar, with the exception of higher anti-DNA (but within normal ranges) and gamma-globulin% in group 1. Group 1 used more drugs prior to diagnosis. Corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) were evenly used. Combination therapy, joint injections, and surgery were more prevalent in group 2. AEs to various DMARDs were more common in group 1. Although similar in many aspects, RA patients with ANA tend to present with more pain complaints, a higher risk of vasculitis and AEs relating to use of DMARDs, while those without ANA needed more aggressive therapeutic modalities.
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Article Serum levels of hyaluronic acid in patients with psoriatic arthritis. 2000
Elkayam O, Yaron I, Shirazi I, Yaron M, Caspi D. · Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Clin Rheumatol. · Pubmed #11147755 No free full text.
Abstract: The purpose of this study was to evaluate the serum levels of hyaluronic acid (HA) in a group of patients with psoriatic arthritis (PsA), with special emphasis on the relationships between HA levels and clinical parameters of joint and skin activity. Thirty-four patients with PsA, 34 patients with rheumatoid arthritis (RA) and 49 healthy volunteers participated in the study. Assessment of joint disease in patients with PsA included duration of morning stiffness, number of tender and swollen joints, right and left grip, the presence of inflammatory back pain and Schober's test. The current severity of skin involvement was graded according to the Psoriasis Area Severity Index (PASI). Serum levels of HA were measured by a radiometric assay. The mean HA serum levels of patients with PsA and RA were significantly increased in comparison with healthy controls (107 +/- 39.6 microg/dl in patients with PsA, whereas in patients with RA it was 168 +/- 32.4 microg/dl and 36.7 +/- 5.5 microg/dl in healthy controls). A highly significant correlation was found between levels of HA and index of skin involvement, but no association was found between HA levels and clinical parameters of joint severity. We conclude that in this cohort of patients with PsA, HA levels clearly reflected psoriatic skin involvement although it did not correlate with joint disease.
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Article Insufficiency fractures in rheumatic patients: misdiagnosis and underlying characteristics. 2000
Elkayam O, Paran D, Flusser G, Wigler I, Yaron M, Caspi D. · Department of Rheumatology, Sourasky Medical Center, Tel Aviv University, Israel. · Clin Exp Rheumatol. · Pubmed #10895375 No free full text.
Abstract: OBJECTIVE: To report 9 patients with rheumatic diseases referred to our observation due to presumed exacerbation of their rheumatic disease, subsequently diagnosed as stress insufficiency fractures, and to characterize the clinical profile of patients prone to this complication. METHODS: The medical history of the patients was reviewed with special emphasis on their rheumatic disease, its course, duration and management, their menopausal state, location and characteristics of the fracture, its presentation and the initial presumed diagnosis, the delay in diagnosis, imaging diagnostic tests performed and outcome. Three representative case reports are presented. RESULTS: All 9 patients were women, 8 of them aged 50 years old or more, 8 with rheumatoid arthritis and 1 with polymyalgia rheumatica. They were all treated with corticosteroids and had reduction in their bone mass density when evaluated. Three of the patients presented with subcapital fracture of the femur, 4 had fractures of metatarsal bones and 2 had fractures of the distal tibia. In only one patient was a stress fracture initially suspected. Diagnosis was delayed by a mean of 31 days. CONCLUSION: The diagnosis of stress fractures in patients with rheumatic diseases may often be delayed or missed, and thus improperly treated. Increased awareness of this entity is of importance for prompt diagnosis and correct management.
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Article Serum amyloid A-derived peptides, present in human rheumatic synovial fluids, induce the secretion of interferon-gamma by human CD(4)(+) T-lymphocytes. 2000
Yavin EJ, Preciado-Patt L, Rosen O, Yaron M, Suessmuth RD, Levartowsky D, Jung G, Lider O, Fridkin M. · Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel. · FEBS Lett. · Pubmed #10788622 No free full text.
Abstract: Serum amyloid A (SAA) is a major acute-phase protein whose biochemical functions remain largely obscure. Human rheumatic synovial fluids were screened by high performance liquid chromatography mass spectrometry for SAA-derived peptides, specifically the sequence AGLPEKY (SAA(98-104)) which was previously shown to modulate various leukocyte functions. Two such fluids were found to contain a truncated version of SAA(98-104). Synthetic SAA(98-104) and several of its analogs were shown capable of binding isolated human CD(4)(+) T-lymphocytes and stimulating them to produce interferon-gamma. Given the high acute-phase serum level of SAA and its massive proteolysis by inflammatory related enzymes, SAA-derived peptides may be involved in host defense mechanisms.
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Article Hydroxychloroquine treatment for primary Sjögren's syndrome: its effect on salivary and serum inflammatory markers. free! 1999
Tishler M, Yaron I, Shirazi I, Yaron M. · Department of Rheumatology, Tel Aviv Souraski Medical Center, Tel Aviv University Sackler School of Medicine, Israel. · Ann Rheum Dis. · Pubmed #10364906 links to free full text
Abstract: OBJECTIVE: To evaluate the effect of hydroxychloroquine treatment on interleukin 6 (IL6), hyaluronic acid (HA), and soluble interleukin 2 receptor (sIL2R) concentrations in the saliva and serum of patients with primary Sjögren's syndrome (SS). METHODS: Fourteen SS patients treated with hydroxychloroquine 200 mg/day for 12 months were investigated in an open prospective study. Clinical parameters of efficacy and routine biochemical and haematological data to assess drug safety and tolerability were determined every three months. Salivary and serum IL6, sIL2R, and HA values were determined at study entry, 6 and 12 months, using ELISA and radiometric assays. RESULTS: After hydroxychloroquine treatment, salivary IL6 concentrations decreased from 13.2 (1.2) to 7.3 (1.1) pg/ml (mean (SEM)) (p < 0.0001). Similarly, salivary HA concentrations were also reduced from 577.8 (120) to 200 (34) ng/ml (mean (SEM) (p < 0.003). Serum IL6 concentrations decreased from 5.4 (0.6) to 2.9 (0.2) pg/ml (mean (SEM) (p < 0.001), while serum HA concentrations remained unchanged. No change has been detected in salivary or serum sIL2R concentrations after 12 months of treatment with hydroxychloroquine. Treatment also resulted in significant reduction in erythrocyte sedimentation rate, serum gamma globulin, and C reactive protein values while only partial clinical improvement was noted in some patients. A more pronounced decrease of salivary IL6 and HA levels was found in the two patients in whom a reduction in the swelling of the parotid gland was noted. CONCLUSION: In this open label study of hydroxychloroquine treatment for SS a significant reduction of some salivary inflammatory markers was seen at the end of 12 months. Although during the treatment period only a partial clinical effect could be noted, the findings suggest that a double blind controlled study of hydroxychloroquine in SS is indicated.
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Article Salivary and serum soluble interleukin-2 receptor in primary Sjögren's syndrome. 1999
Tishler M, Yaron I, Shirazi I, Levartovsky D, Yaron M. · Department of Rheumatology, Ichilov Hospital, Tel Aviv-Sourasky Medical Center, Israel. · Arch Oral Biol. · Pubmed #10348356 No free full text.
Abstract: Salivary and serum concentrations of soluble interleukin-2 receptor (sIL-2R) were studied in a group of patients with Sjögren's syndrome and a group suffering from dry mouth. Salivary sIL-2R levels was significantly higher (57.9+/-15.1 vs 16.7+/-4.7 pg/ml) (p < 0.05) in the group of 26 patients with Sjögren's syndrome than in the dry-mouth group. Both the salivary and the serum sIL-2R of normal controls were below the level of detection. No significantly statistical differences were noted between the concentrations of serum sIL-2R in either abnormal groups. No correlations were found between salivary or serum sIL-2R and the erythrocyte sedimentation rate, C-reactive protein, the presence of various autoantibodies or the focus score from lip biopsies in the group of patients with Sjögren's syndrome. The results show that, although the salivary sIL-2R does not actually reflect the extent of inflammation, it might have an important role in the diagnosis of Sjögren's syndrome.
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