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ID PMID Title PublicationDate abstract
12841422 The Martin and Park Environmental Demands (MPED) Questionnaire: psychometric properties of 2003 Feb BACKGROUND AND AIMS: The present study examines the usefulness of a newly developed instrument, the Martin and Park Environmental Demands (MPED) Questionnaire, to measure the level of self-reported environmental demands of day-to-day events faced by adults aged 35 to 84 years, particularly as these demands influence forgetfulness in taking medications. METHODS: The MPED has two scales including Busyness, which addresses the density or pace of daily events to which an individual attends; and Routine, addressing the predictability or routinization of events independent of density. The MPED was administered to a sample of 121 rheumatoid arthritis patients, along with a baseline assessment battery measuring age, education, employment status, household size and other factors that might influence self-perception of Busyness and Routine. RESULTS: The scale showed good internal consistency and external validity. Higher levels of environmental demand were negatively correlated with age and positively correlated with employment, household size and medication-taking errors. There was a significant independent association between Busyness and adherence errors even after controlling for the effects of these sociodemographic variables. CONCLUSIONS: The MPED is recommended when trying to assess the general daily level of environmental demands.
14690141 A correlative study of clinical and histological findings of revision hip arthroplasty for 2003 OBJECTIVE: Primary hip arthroplasty in rheumatoid arthritis (RA) and other forms of inflammatory joint disease (IJD) is generally thought to be associated with a less favourable outcome in terms of implant survival and other complications. Whether the duration of implant survival correlates with the degree of rheumatoid-like inflammatory changes in periprosthetic tissues is uncertain. METHODS: Histopathological changes in periprosthetic tissues obtained following revision surgery of 34 total hip replacements on 27 patients with IJD (RA 18 cases: ankylosing spondylitis three cases; juvenile chronic arthritis six cases) were examined. RESULTS: A heavy diffuse lymphocyte and plasma cell infiltrate +/- lymphoid aggregates was noted in 29% of cases in whom the mean implant survival was 5.6 years (range: 2-8 years). Where little or no lymphocytic infiltrate was noted in periprosthetic tissues, the mean implant survival was 8.6 years (range: 1-17 years). Revision arthroplasty was not undertaken for early or late infection of a primary hip replacement. CONCLUSIONS: Our findings indicate that implant survival is less in those cases where there is a heavy lymphocyte and plasma-cell infiltrate in periprosthetic tissues. These findings suggest that the presence of a heavy chronic inflammatory-cell infiltrate in periprosthetic tissues is likely to be a contributory factor in causing early implant failure in RA.
15180891 Targeting B cells for the treatment of rheumatoid arthritis. 2003 The role of B cells in rheumatoid arthritis (RA) has been debated for decades. However, recent clinical trial data indicating that depletion of B cells in RA patients is of therapeutic benefit has validated the importance of this cell type in the pathogenesis of the disease. Elucidation of the molecular basis of B cell development and activation has allowed the identification of a number of possible therapeutic targets that are appealing for drug development. This review discusses briefly a number of these molecules and the rationale for targeting them for the treatment of RA.
12086294 Development and clinical application of COX-2-selective inhibitors for the treatment of os 2002 Osteoarthritis (OA) and rheumatoid arthritis (RA) are among the most prevalent chronic illnesses and leading causes of disability in the United States. The clinical symptoms of OA and RA, pain and inflammation, are biologic processes mediated in part by prostanoids-prostaglandins, prostacyclin, and thromboxanes. The intermediate enzymes responsible for prostaglandin biosynthesis, cyclooxygenase (COX)-1 and COX-2, have been the target of arthritis therapy using nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). An understanding of the biochemistry and molecular pharmacology of COX enzymes has allowed for the development of agents that specifically inhibit COX-2. COX-2-selective inhibitors have efficacy in OA and RA that is similar to that of NSAIDs but with a lower potential for upper gastrointestinal injury, a serious side effect of nonselective NSAIDs. COX-2-selective inhibitors have been increasingly used in the treatment of OA and RA as well as other inflammatory arthropathies including ankylosing spondylitis and gout. Clinical trials with two currently available drugs, rofecoxib and celecoxib, have demonstrated efficacy comparable to nonselective NSAIDs but with a lower risk of gastrointestinal side effects. In general, these drugs are well tolerated in patients with aspirin-sensitive asthma. Rofecoxib is well tolerated in patients with sulfonamide sensitivities; further studies are needed to fully characterize the utility of celecoxib in these patients. Clinical experience shows that because of their improved GI safety, rofecoxib and celecoxib, and newer COX-2-selective inhibitors (valdecoxib, etoricoxib, parecoxib), represent a significant advance in the treatment of arthritis and other related inflammatory conditions.
14680510 Quantitative biomarker analysis of synovial gene expression by real-time PCR. 2003 Synovial biomarker analysis in rheumatoid arthritis can be used to evaluate drug effect in clinical trials of novel therapeutic agents. Previous studies of synovial gene expression for these studies have mainly relied on histological methods including immunohistochemistry and in situ hybridization. To increase the reliability of mRNA measurements on small synovial tissue samples, we developed and validated real time quantitative PCR (Q-PCR) methods on biopsy specimens. RNA was isolated from synovial tissue and cDNA was prepared. Cell-based standards were prepared from mitogen-stimulated peripheral blood mononuclear cells. Real time PCR was performed using TaqMan chemistry to quantify gene expression relative to the cell-based standard. Application of the cellular standard curve method markedly reduced intra- and inter-assay variability and corrected amplification efficiency errors compared with the C(t) method. The inter-assay coefficient of variation was less than 25% over time. Q-PCR methods were validated by demonstrating increased expression of IL-1beta and IL-6 expression in rheumatoid arthritis synovial samples compared with osteoarthritis synovium. Based on determinations of sampling error and coefficient of variation, twofold differences in gene expression in serial biopsies can be detected by assaying approximately six synovial tissue biopsies from 8 to 10 patients. These data indicate that Q-PCR is a reliable method for determining relative gene expression in small synovial tissue specimens. The technique can potentially be used in serial biopsy studies to provide insights into mechanism of action and therapeutic effect of new anti-inflammatory agents.
15355748 B cells: new ways to inhibit their function in rheumatoid arthritis. 2004 Oct The apparent efficacy of B-cell depletion in autoimmune diseases has increased interest in targeting B cells. One goal of next generation therapies is to develop treatments that block B-cell activation and preserve resting nonautoimmune cells that maintain B cell memory. To do so, one needs to understand how B cells are activated and what receptors and intracellular signaling pathways regulate this process. This paper will summarize B-cell activation pathways and illustrate how these are being targeted in the development of new treatments for rheumatoid arthritis.
15105987 [The caput-ulnae-syndrome. Pathogenesis, clinic and therapy]. 2004 Jun The ulnar head has a central function in stabilizing the wrist. In the treatment of caput ulnae syndrome, the radiocarpal joint must, therefore, always be considered. The integrity of the ulnar head and TFCC are of major importance for the rheumatoid wrist. Therefore, surgical treatment should be carried out early, and is indicated for drug-resistant synovitis and monarthritis of the wrist. Early synovectomy of the radiocarpal and distal radioulnar joint (DRUJ) can be done as an open procedure or, when extensor tendon synovitis is absent, as an arthroscopic procedure. In most cases, however, treatment of manifest caput ulnae syndrome, sometimes even with rupture of the extensor tendons, is necessary. In these cases, resection of the ulnar head together with a dorsal wrist stabilization is indicated. Less often, arthrodesis of the DRUJ with segmental resection of the ulna or an arthroplasty are indicated. When choosing the procedure, the type and stage of wrist changes have to be considered. The DRUJ usually has to be treated together with the radiocarpal joint. Its isolated treatment is rarely indicated.
14872477 Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been un 2004 Feb OBJECTIVE: To examine whether dose escalation of intramuscular (IM) methotrexate (MTX) up to 45 mg/week improves disease control in patients who have active rheumatoid arthritis (RA) despite receiving conventional doses (15 mg/week) of IM MTX, and to obtain preliminary data on patient tolerability and adverse effects of higher doses of IM MTX. METHODS: Patients >18 years of age who had active RA, defined as a European League Against Rheumatism (EULAR) Disease Activity Score in 28 joints (DAS28) of >3.2, and who had received 15-20 mg/week of oral MTX for at least 2 months were switched (week 0) to 15 mg/week of IM MTX for 6 weeks. Patients whose DAS28 remained >3.2 at both week 4 and week 6 were randomized, in a double-blind manner, either to continue to receive 15 mg/week IM MTX with monthly placebo escalation or to receive escalating doses of IM MTX monthly up to 45 mg/week. The dose of MTX or placebo was escalated every 4 weeks if the DAS28 was >2.5. Safety assessments and determination of the DAS28 were performed every 2 weeks and monthly, respectively. Disease activity parameters from the American College of Rheumatology (ACR) core disease activity set and health status as recorded on the Medical Outcomes Study Short-Form 12 were determined at baseline (week 0) and final assessment (week 22). The primary outcome was the percentage of patients in each group achieving a target DAS28 of <3.2. Secondary outcomes comprised the percentage of patients whose DAS28 improved by >1.2, the percentage of patients achieving a 20% improvement in the ACR core disease activity measures (ACR20), and the percentage of patients achieving a good response, a moderate response, or no response in accordance with the EULAR response criteria. RESULTS: Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean +/- SD DAS28 was 5.6 +/- 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups -15% to +15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups -18% to +18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group. CONCLUSION: Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15 mg/week IM MTX, increasing the dose up to 45 mg/week does not improve disease control. Higher doses of IM MTX were generally well tolerated and not associated with an increase in serious adverse reactions to the drug.
11845015 Coronary artery disease and rheumatoid arthritis. 2002 Mar Patients with rheumatoid arthritis (RA) have a reduced life expectancy when compared with the general population. Cardiovascular death is considered the leading cause of mortality in patients with RA; it is responsible for approximately half the deaths observed in RA cohorts. The prevalence of cardiovascular comorbidity is difficult to assess accurately, because cardiovascular disease (CVD) has a tendency to remain silent in the rheumatoid patient. It is not clear why rheumatoid patients have higher rates of coronary disease. Traditional cardiovascular risk factors do not seem to be wholly responsible for the increased cardiovascular risk. Novel cardiovascular risk factors, including inflammatory markers, have been identified over the past few years. It may be that these new cardiovascular risk factors are responsible for accelerating coronary heart disease in patients with RA. This article reviews recent literature relating to the epidemiology of cardiovascular disease in the context of RA.
12031032 Cutaneous palisaded allergic granuloma associated with rheumatic disease. 2002 Apr A 62-year-old man presented with a 5-year history of symmetric, hard papules on both of his elbows. These lesions were completely asymptomatic, but they were of cosmetic concern to the patient. Summer and trauma reportedly exacerbated the appearance of new papules, which tended to evolve spontaneously, harden, and subsequently ulcerate. The patient's main medical problem was a long-standing history of rheumatoid arthritis treated with low-dose oral prednisone. Physical examination revealed multiple scattered papules bilaterally on the extensor surfaces of the forearms. These were 2-10 mm in size, red to violaceous, and hard. Some of the lesions had ulcerated centers or slight umbilication (Fig. 1A,B). Histologic examination revealed several granulomas in the mid- to deep dermis with central basophilic fibrillar collagen necrosis (Fig. 2A). The necrotic areas were interspersed with bands of neutrophils, lymphocytes, and leukocytoclastic debris. The periphery of these basophilic granulomas was lined by palisading histiocytes (Fig. 2B).
11953967 Determination of the minimal clinically important difference in rheumatoid arthritis joint 2002 Apr OBJECTIVE: To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method. METHODS: The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID. RESULTS: The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%). CONCLUSION: This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change.
12730518 Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up 2003 Sep OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.
12428576 [Dance therapy in the treatment of psychiatric and somatic disorders]. 2002 The article is an attempt of review of recent achievements in dance therapy. It presents possibilities of introducing dance into the treatment of psychiatric disturbances (psychoses, dementias, neurotic disorders) and somatic disorders (rheumatoid arthritis, osteoporosis, terminal stages). The authors basing on the contemporary literature describe positive results of dance therapy in various clinical situations.
12618524 Inducible costimulator is essential for collagen-induced arthritis. 2003 Mar CD4(+) helper Th cells play a major role in the pathogenesis of rheumatoid arthritis. Th cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a novel costimulatory receptor expressed on activated T cells. We, as well as others, recently demonstrated its importance in Th2 cytokine expression and Ab class switching by B cells. In this study, we examined the role of ICOS in rheumatoid arthritis using a collagen-induced arthritis model. We found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation. These mice, when immunized with collagen, exhibited reduced anti-collagen IgM Ab's in the initial stage and IgG2a Ab's at the effector phase of collagen-induced arthritis. Furthermore, ICOS regulates the in vitro and in vivo expression of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These data indicate that ICOS is essential for collagen-induced arthritis and may suggest novel means for treating patients with rheumatoid arthritis.
15188354 Increased synovial tissue NF-kappa B1 expression at sites adjacent to the cartilage-pannus 2004 Jun OBJECTIVE: To compare the expression of the Rel/NF-kappa B subunits, NF-kappa B1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis. METHODS: Synovial tissue was selected at arthroscopy from sites adjacent to the CPJ and from the suprapatellar pouch of patients who were referred to an early arthritis clinic. Tissue samples from patients with osteoarthritis (OA) undergoing knee arthroplasty were also studied. Rel/NF-kappa B subunit activation and expression were measured by electrophoretic mobility shift assay and supershift analyses and by immunohistochemistry. RESULTS: Tissue samples were obtained from 10 patients with rheumatoid arthritis (RA), 7 with a seronegative arthropathy (SnA), and 6 with OA. Rel/NF-kappa B was abundantly expressed in all samples. In both RA and SnA synovial tissue, the absolute number of NF-kappa B1+ cells at the CPJ was significantly higher than at non-CPJ sites (P = 0.006 and P = 0.02, respectively). The proportion of cells expressing NF-kappa B1 was also significantly higher at the CPJ compared with non-CPJ sites (P = 0.003 in RA, P = 0.009 in SnA). The numbers of RelA+ cells were consistently lower throughout. In RA synovial tissue, but not in SnA synovial tissue, both the absolute number and the proportion of RelA+ cells were significantly higher at the CPJ than at non-CPJ sites (P = 0.003 and P = 0.01, respectively). In OA synovial tissue, the numbers of cells expressing NF-kappa B1 and RelA were similar to those observed at the non-CPJ sites in all inflammatory tissues studied. CONCLUSION: In this study of early inflammatory arthritis, expression of NF-kappa B1 in synovial tissue was highest at sites most likely to be associated with joint erosion. These observations are consistent with a critical role of NF-kappa B1 in joint destruction, and support the rationale for specific therapeutic inhibition of NF-kappa B in RA.
12408395 Syringomyelia caused by loosening of multistrand cables following C1-2 Brooks-type fusion 2002 Oct The authors report a very rare case of syringomyelia caused by loosening of multistrand cable wires following C1-2 Brooks-type fusion in a 36-year-old woman with a 13-year history of rheumatoid arthritis (RA). The syrinx vanished immediately after removal of the cables, and 2 years later no recurrence of symptoms or deterioration has occurred. The authors contend that multistrand titanium cables should not be used to fix a graft-assisted C1-2 construct in patients with RA, although this material is good for fixing rods. The phenomenon observed in this case adds to our understanding of the pathogenesis of noncommunicating syringomyelia.
13130462 Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in 2003 Sep OBJECTIVE: To compare the quantitative and qualitative information obtained by Doppler ultrasound (US) measurements of the wrist joints and the small joints of the hand with the information obtained by postcontrast magnetic resonance imaging (MRI) and to correlate the imaging results with clinical observations in patients with rheumatoid arthritis (RA). METHODS: Twenty-nine consecutive RA patients were studied; 196 joints (29 wrist and 167 finger joints) were examined by both US and MRI. Parameters of inflammation were the color fraction and the resistance index (RI) obtained with color Doppler US and the thickness of enhanced synovium (in mm) and the MRI score obtained with postcontrast MRI. Clinical examination and measurements of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level were performed on the same day as the imaging studies. RESULTS: There was a highly significant association between US indices of inflammation and postcontrast MRI scores. The mean values for both the color fraction and the RI were significantly different in the group without joint swelling compared with the other groups. The mean RI values were significantly different in the group without joint tenderness compared with the other groups. The mean thickness of enhanced synovium on postcontrast MRI was significantly different between the group without joint swelling and the other groups, but this difference was statistically significant only for the comparison of the group without joint tenderness versus the group with maximum tenderness. No association between the MRI or US estimates of inflammation and values on the visual analog scale for pain, Health Assessment Questionnaire, duration of morning stiffness, ESR, or CRP was found. CONCLUSION: Estimates of synovial inflammatory activity by Doppler US and postcontrast MRI were comparable. Estimation of synovial inflammatory activity by the RI and color fraction parameters of US appears to be a promising method of detecting and monitoring inflammatory activity in patients with RA.
11920397 Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a 2002 Mar OBJECTIVE: To determine time trends in the epidemiology of rheumatoid arthritis (RA) in a population-based cohort. METHODS: An inception cohort of residents of Rochester, Minnesota > or = 18 years of age who first fulfilled the American College of Rheumatology 1987 criteria between January 1, 1955 and December 31, 1994 (applied retrospectively, as appropriate) was assembled and followed up until January 1, 2000. Incidence rates were estimated and were age- and sex-adjusted to the 1990 white population of the US. A birth cohort analysis was performed, and survival rates over time were examined. RESULTS: The incidence cohort comprised 609 patients, 445 (73.1%) of whom were female and 164 (26.9%) were male, with a mean age at incidence of 58.0 years. The overall age- and sex-adjusted annual incidence of RA among Rochester, Minnesota, residents > or = 18 years of age was 44.6/100,000 population (95% confidence interval 41.0-48.2). While the incidence rate fell progressively over the 4 decades of study, from 61.2/100,000 in 1955-1964, to 32.7/100,000 in 1985-1994, there were indications of cyclical trends over time. Birth cohort analysis showed diminishing incidence rates through successive cohorts following a peak in the 1880-1890 cohorts. Incidence rates increased with age until age 85, but peaked earlier in women than in men. The survival rate in RA patients was significantly lower than the expected rate in the general population (P < 0.001), and no improvement was noted over time. CONCLUSION: The secular trends demonstrated in this study population, including the progressive decline in the incidence of RA over the last 40 years, suggest that an environmental factor may play a role in the etiology of RA.
14677008 Efficacy of cyclophosphamide combined with prednisolone in patients with AA amyloidosis se 2003 Dec Secondary amyloid A (AA) amyloidosis is an uncommon yet important complication of rheumatoid arthritis (RA). It is one of the most relentless of the extra-articular features of RA, and suitable treatments have not yet been found. We studied the efficacy of cyclophosphamide (CYC) combined with prednisolone (PSL) in amyloidotic patients who had serum amyloid A (SAA) 1.3 genotype, which is a risk factor for secondary amyloidosis in Japanese RA patients. Fifteen RA patients who were SAA1.3 homo- and heterozygotes with biopsy-confirmed AA amyloidosis were treated with a combination of CYC and PSL. Laboratory variables of C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), serum albumin (Alb), serum creatinine (Cre) and Lansbury's index were carried out by statistical analysis of changes between before and during the medication. According to the Mann-Whitney rank test, CRP, RF, ESR, Alb and Cre levels improved significantly with the combination treatment (p<0.05). Also, paired t-tests showed significance in Lansbury's index between before and during the medication (p=0.007). CYC combined with PSL ameliorated not only laboratory markers but also clinical rheumatoid activity in patients with amyloidosis secondary to RA, whose genotypes were SAA1.3 homo- and heterozygous. CRP, ESR, RF, Alb and Cre will be surrogate markers of therapeutic efficacy. The combination of CYC and PSL appears to be beneficial for Japanese RA patients who are SAA1.3 homo- and heterozygous carriers, associated with secondary AA amyloidosis.
11808787 Oral intake of Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 prevents collagen-in 2002 Jan Oral intake of some lactic acid bacteria can have beneficial effects on the host by activating immune responses and enhancing resistance to infection by pathogens. In this study, effects of Lactobacillus sp. on the development of autoimmune disease were examined in mice with collagen-induced arthritis (CIA). CIA, a model of some types of rheumatoid arthritis (RA), can be induced in DBA/1J mice by immunizing them with bovine type II collagen (bCII). Oral intake of skimmed milk (SM) fermented with Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (SM/OLL1073R-1) was found to markedly inhibit the development of CIA in these mice, compared with a control group fed the control foodstuff. The inhibitory effect of SM fermented with L. delbrueckii subsp. bulgaricus OLLI 102 (SM/OLL1102) or fresh SM was weaker than that of SM/ OLL1073R-1. A deMan Rogosa Sharpe (MRS) broth culture of OLL1073R-1 without any major components of SM had the same inhibitory effect as SM/OLL1073R-1, suggesting that the inhibitory effect of SM/OLL1073R-1 is attributable not only to SM components but also to OLL1073R-1 cells, their metabolites, or both. We found that SM/OLL1073R-1 and SM caused reduced secretion of the cytokine IFN-gamma by lymph node cells (LNCs) in response to bCII. However, SM/OLL1102 did not affect the secretion of IFN-gamma. A polysaccharide fraction secreted by OLL1073R-1 also exhibited the inhibitory effects on both development of CIA and secretion of IFN-gamma.