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ID PMID Title PublicationDate abstract
18691998 Treatment persistence with adalimumab, etanercept, or infliximab in combination with metho 2008 Jul BACKGROUND: Anti-tumor necrosis factor (TNF) biologic agents are effective in treating rheumatoid arthritis (RA). Information on patient persistence with biologic anti-TNF therapies is limited, and the effects of persistence on the costs of therapy are unknown. OBJECTIVES: The aims of this study were to compare treatment persistence with adalimumab, etanercept, or infliximab in combination withmethotrexate (MTX) and evaluate the effects of persistence on overall health care costs. METHODS: This retrospective study used data from the PharMetrics managed care administrative claims database. Data from patients with RA who received combination treatment with an anti-TNF agent plus MTX and had > or = 24 months of continuous plan eligibility were collected. The 3 anti-TNF cohorts were adalimumab + MTX (adalimumab group), etanercept + MTX (etanercept group), and infliximab + MTX (infliximab group). Treatment persistence was defined as the number of days between the first and last anti-TNF treatment and was reported as a percentage of the 1-year period after treatment initiation. Costs were compared between patients with treatment persistence rates > or = 80% or <80%. Demographics, comorbidities, disease severity, and RA-related costs were assessed using descriptive statistics. Univariate and multivariate analyses were applied to identify differences in mean persistence between the 3 cohorts. RESULTS: Data from 1242 patients were included (77.7% female; mean age, 50.0 years). The mean persistence rate in the overall population was 74.6%, and the mean treatment time was 272.3 days. The infliximab group had a higher persistence rate compared with the etanercept and adalimumab groups (78.0% vs 72.8% and 70.8%, respectively; P < 0.005). In all patients combined, those with treatment persistence > or = 80% had higher mean total health care costs compared with those with treatment persistence <80% ($19,271.52 vs $15,598.46; P < 0.001), largely due to higher pharmacy costs. However, nonpharmacy costs were lower in the > or = 80% persistence cohort ($3091 vs $4601; P = 0.015). CONCLUSIONS: In this population of patients with RA, overall treatment persistence was high, with patients treated with infliximab + MTX having significantly higher persistence compared with those treated with adalimumab + MTX or etanercept + MTX. While pharmacy costs were higher in patients with > or = 80% persistence, nonpharmacy costs were lower.
18836607 Total wrist arthroplasty. 2008 Aug In the article, I review the history of total wrist arthroplasty designs; give an overview of and design rationale for the ReMotion (Small Bone Innovations, Morrisville, PA) total wrist arthroplasty; describe the indications, technique, and postoperative care for this implant; and present some early, very encouraging results.
18984608 Contemporary patterns of care and disease activity outcome in early rheumatoid arthritis: 2009 Jan OBJECTIVES: To report from the Early Rheumatoid Arthritis Network (ERAN), time from symptom onset to start of therapy, treatment choices and disease outcome in early RA. METHODS: Patients with newly diagnosed RA were prospectively enrolled from 19 centres in the UK and Eire. Standardized information was collected on case report forms at first presentation, 3-6 months, 1 yr and annually thereafter. The choice and intensity of drug treatment was left to the discretion of individual centres. RESULTS: A total of 808 patients were recruited between 2002 and 2007, with a mean follow-up of 16 (0-60) months. Of them, 62% fulfilled four or more ACR criteria for RA at first visit. The median time from onset of symptoms to referral to secondary care was 4 months [interquartile range (IQR) 2-9, n = 655] and to start of first DMARD 8 months (IQR 4-13, n = 638). DMARDs were prescribed in 97% of the patients, initially as monotherapy in 91%, and as combination therapy in 9%. The second DMARD (n = 220) was a switch to another as monotherapy in 52% and step-up to combination therapy in 48%. The proportions with a 28-joint disease activity score >5.1 at baseline and 3 yrs were 46 and 19%, >3.2 were 84 and 54% and <2.6 were 6 and 33%, respectively. CONCLUSIONS: Patients presenting with RA in ERAN do not receive DMARDs promptly, largely due to delays in referral to secondary care. Contemporary treatment practice is to start with DMARD monotherapy, and to use combination DMARDs as second-line therapy in approximately half of them. Over 3 yrs the proportion of patients continuing to have active disease remains high.
16269431 Observational study on efficacy, safety, and drug survival of anakinra in rheumatoid arthr 2006 Jun BACKGROUND: The efficacy and safety of anakinra, a recombinant human interleukin 1 (IL1) receptor antagonist used in rheumatoid arthritis, has been documented in five randomised controlled studies. However, long term post-marketing efficacy data are lacking. OBJECTIVE: To evaluate the efficacy, safety, and drug survival of anakinra in clinical practice. METHODS: All patients with rheumatoid arthritis who started anakinra in six hospitals between May 2002 and February 2004 were included in a two year prospective, in part retrospective, cohort study. Efficacy was assessed using the 28 joint disease activity score (DAS28) and the EULAR response criteria. Safety was evaluated using the common toxicity criteria. Drug survival and prognostic factors were analysed using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: After three months, 55% of the patients (n = 146) showed a response (43% moderate, 12% good). A subset of patients continuing anakinra after 18 months had a sustained clinical response compared with patients who switched to other disease modifying antirheumatic drug treatment (DAS28 improvement, 2.46 v 1.79). Drug survival was 78%, 54%, and 14% after three, six, and 24 months, respectively. The reason for discontinuation was lack of efficacy in 78% and adverse events in 22%. Except for higher drug survival in women (odds ratio = 0.51, 95% confidence interval, 0.27 to 0.97), no prognostic factors were found. Adverse events were reported 206 times in 111 patients, the most common being injection site reactions (36%). Serious adverse events occurred in 12% of the patients, with one classified as related. CONCLUSIONS: The short term efficacy and safety profile of anakinra are comparable to those found in randomised clinical studies. However, the drug survival of anakinra after two years is low, mostly because of lack of efficacy.
17129374 Induction of multiple matrix metalloproteinases in human dermal and synovial fibroblasts b 2006 Infections of body tissue by Staphylococcus aureus are quickly followed by degradation of connective tissue. Patients with rheumatoid arthritis are more prone to S. aureus-mediated septic arthritis. Various types of collagen form the major structural matrix of different connective tissues of the body. These different collagens are degraded by specific matrix metalloproteinases (MMPs) produced by fibroblasts, other connective tissue cells, and inflammatory cells that are induced by interleukin-1 (IL-1) and tumor necrosis factor (TNF). To determine the host's contribution in the joint destruction of S. aureus-mediated septic arthritis, we analyzed the MMP expression profile in human dermal and synovial fibroblasts upon exposure to culture supernatant and whole cell lysates of S. aureus. Human dermal and synovial fibroblasts treated with cell lysate and filtered culture supernatants had significantly enhanced expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-10, and MMP-11 compared with the untreated controls (p < 0.05). In the S. aureus culture supernatant, the MMP induction activity was identified to be within the molecular-weight range of 30 to >50 kDa. The MMP expression profile was similar in fibroblasts exposed to a combination of IL-1/TNF. mRNA levels of several genes of the mitogen-activated protein kinase (MAPK) signal transduction pathway were significantly elevated in fibroblasts treated with S. aureus cell lysate and culture supernatant. Also, tyrosine phosphorylation was significantly higher in fibroblasts treated with S. aureus components. Tyrosine phosphorylation and MAPK gene expression patterns were similar in fibroblasts treated with a combination of IL-1/TNF and S. aureus. Mutants lacking staphylococcal accessory regulator (Sar) and accessory gene regulator (Agr), which cause significantly less severe septic arthritis in murine models, were able to induce expression of several MMP mRNA comparable with that of their isogenic parent strain but induced notably higher levels of tissue inhibitors of metalloproteinases (TIMPs). To our knowledge, this is the first report of induction of multiple MMP/TIMP expression from human dermal and synovial fibroblasts upon S. aureus treatment. We propose that host-derived MMPs contribute to the progressive joint destruction observed in S. aureus-mediated septic arthritis.
17023808 Low frequency of anticyclic citrullinated peptide antibodies in psoriatic arthritis but no 2006 Oct BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) antibodies are highly specific for the diagnosis of rheumatoid arthritis (RA). The clinical distinction between RA and psoriatic arthritis (PsA) is often difficult to establish; therefore, the presence of rheumatoid factor (RF) and anti-CCP antibodies could be useful. Seven percent to 40% of patients with longstanding psoriasis will develop PsA at some point. Therefore, it is important to study the positivity of these antibodies in these two interrelated populations. OBJECTIVE: The aim of this study was to determine the seropositivity of anti-CCP antibodies in patients with psoriasis and PsA and to compare it with that seen in patients with other inflammatory, noninflammatory (osteoarthritis) arthritides and healthy controls. PATIENTS AND METHODS: Serum anti-CCP antibodies were measured in 106 patients with cutaneous psoriasis, 72 patients with PsA, 41 healthy controls (HC), 41 patients with undifferentiated or early inflammatory arthritis (UA), and 41 patients with RA and 41 with osteoarthritis using a commercial second-generation enzyme-linked immunosorbent assay. We considered a positive result to be >20 UI/mL, as recommended by the manufacturer. RESULTS: Of 106 patients with PsA, 55 were women and 51 men. The mean age was 42.87 +/- 17.71 years and the mean disease duration was 5.3 +/- 2.10 years. Anti-CCP antibodies were not present in patients with psoriasis without arthritis. In contrast, 7 of 72 (9.72%) patients with PsA were positive for anti-CCP antibodies with a median titer of 7.16 units. Only one patient with PsA was positive for RF. Most of these patients were female with polyarticular joint involvement. Distal interphalangeal involvement was present in 4 and 2 had dactylitis. We found clear differences when we compared patients with PsA with patients with psoriasis (P = 0.001). Of the 43 patients with UA studies, 4 initially exhibited a low titer positive anti-CCP antibody, and at follow up, another patient developed anti-CCP antibodies and later developed RA. None of the patients with UA developed PsA at 5-year follow up. Thirty-two of the 41 patients had a positive anti-CCP antibody and the mean +/- standard deviation of the anti-CCP units was 80.61 +/- 55.5.2. Six of the 41 (14.6%) patients with osteoarthritis studied had positive anti-CCP with a mean titer of 7.388. None of the healthy controls exhibited positively for anti-CCP antibodies. CONCLUSION: Anti-CCP antibodies may be found in patients with PsA and not in our patients with only cutaneous psoriasis. These antibodies may also be found in some patients with osteoarthritis and rarely in patients with UA; such patients will be of interest to follow prospectively.
17530686 Participation in patient self-management programs. 2007 Jun 15 OBJECTIVE: Participation in evidenced-based arthritis self-management programs (SMPs) has not been well documented. The purpose of this study was to investigate the participation rate and participant characteristics in a closed cohort of subjects in a geographic region where arthritis SMPs have been offered multiple times and continuously for 2 decades. METHODS: Data were from osteoarthritis (OA) and rheumatoid arthritis subjects participating in the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) who resided in the San Francisco (SF) Bay area who had responded to questions about ever participating in an SMP. Differences between participants and nonparticipants were examined by t-tests and chi-square tests. RESULTS: Questions added to the Health Assessment Questionnaire were returned by 1,176 patients; 618 resided in the SF Bay area. Of the SF Bay area sample, 41.9% had participated in an SMP. Small group SMPs, which had been offered multiple times, in diverse settings, continuously over the past 2 decades, were attended by the highest proportion (28%) of participants. Characteristics of participants and nonparticipants in the SF Bay area were similar ( approximately 70 years old, 15 years of education, and the majority had OA [ approximately 72%]). However, a higher proportion of participants were white (88% versus 82%; P = 0.046) and female (82% versus 73%; P < 0.05). CONCLUSION: When arthritis SMPs were offered multiple times in diverse settings and continuously over many years, >40% of the cohort was reached. More research is needed with larger samples and different geographic regions to identify participation rates in more diverse populations.
18617467 [The pulmonological manifestations of rheumatoid arthritis]. 2008 Jul 20 In their review article the authors overview the primary and secondary pulmonary complications of rheumatoid arthritis with the help of bibliographic data. They emphasize the pulmonological complications of disease modifying antirheumatic drugs used for the pharmaceutical therapy of rheumatoid arthritis, of which they discuss the methotrexate induced pulmonary diseases. Methotrexate participates nearly in all of additive double and triple--O'Dell-scheme--combined disease modifying antirheumatic drugs therapy. Because of that, the early detection of drug-induced pulmonological complications is important. For rheumatologists the treatment of methotrexate resistant rheumatoid arthritis is always getting a higher and higher challenge. Biological therapeutical drugs act as cytokine antagonists, by blocking TNF-alpha and, compared to disease modifying antirheumatic drugs, they can more effectively inhibit the progression of the disease. These are the biological response modifiers. Their main representatives are infliximab, adalimumab, and etanercept. At the end, the authors discuss secondary pulmonary complications caused by biological response modifiers, e.g. the biological response modifiers associated pulmonary tuberculosis, bacterial tracheobronchitis, bacterial pneumonia, bronchiectasia, pulmonary oedema, rapid fibrosing alveolitis, and coccidioidomycosis. At 3% of patients with rheumatoid arthritis, treated with biological response modifiers, who live in Arizona, California, Nevada, pulmonary and systemic mycosis--coccidioidomycosis can appear with a 15% of mortality. As a consequence of frequent earthquakes, the spores getting into the air from the ground infect immunosuppressed patients treated with biological response modifiers. The authors draw attention to the fact that patients who receive biological therapy and travel to the above-mentioned endemic or earthquake-active regions, have a potential high risk, so it is indispensable that they are informed by the doctor. Testing and use of newer and newer groups of biological response modifiers are expected in the near future in the therapy of rheumatoid arthritis. Nowadays--in patients, who are non-reactive for TNF-alpha inhibitor treatment--the use of B-lymphocyte inhibitor rituximab, characteristic in non-Hodgkin lymphoma therapy is possible. The pulmonary complications of rheumatoid arthritis therapy of that cytokine are not known yet. Today, antirheumatic therapy results in a significant improvement of patients' life-quality, whilst the more and more modern therapeutical methods cause more complications.
17762459 Reactivation of pulmonary tuberculosis in a patient with rheumatoid arthritis during treat 2007 Aug This single case report describes reactivation of previous pulmonary tuberculosis (TBC) after 23 months of treatment with the IL-1 receptor antagonist anakinra. This patient had severe acute rheumatoid arthritis (Disease Activity Score >6). Initially, he received treatment with 10 mg prednisolone daily along with oral methotrexate 15 mg weekly. Methotrexate was discontinued after 3 months because of repeated liver enzyme elevation. After the disease became more active, he was treated with the IL-1 receptor antagonist along with 10 mg prednisolone daily. One month later, the patient improved significantly, and prednisolone was decreased to 5 mg on alternate days and discontinued after another 3 months. After 23 months of anakinra monotherapy, the patient developed pulmonary TBC and was put on quadruple anti-TBC treatment, which resulted in excellent recovery. Six years before, the patient had pulmonary TBC and received triple anti-TBC treatment for 9 months with complete clinical and radiologic remission. We believe this is the first reported case of TBC reactivation during anakinra treatment.
17260192 Total hip arthroplasty for rheumatoid arthritis in younger patients: 2,557 replacements in 2006 Dec BACKGROUND: The results of total hip arthroplasty (THA) in young patients with rheumatoid arthritis (RA) have been reported in only a few studies. On a nationwide level, the outcome of THA in these patients is unknown. We evaluated the population-based survival of THA in patients under 55 years of age with RA and factors affecting the survival. PATIENTS: Between 1980 and 2003, 2,557 primary THAs performed for RA in patients less than 55 years of age were reported to the Finnish Arthroplasty Register. RESULTS: Proximally circumferentially porous-coated uncemented stems had a 15-year survival rate of 89% (95% CI 83-94) with aseptic loosening as endpoint. The risk of stem revision due to aseptic loosening was higher with cemented stems than with proximally porouscoated uncemented stems implanted during the same period (RR 2.4; p < 0.001). In contrast, Cox regression analysis showed that the risk of cup revision was significantly higher for all uncemented cup concepts than for all-polyethylene cemented cups with any cup revision as endpoint. There were no significant differences in survival between the THR concepts. INTERPRETATIONS: Uncemented proximally circumferentially porous-coated stems and cemented all-poly-ethylene cups are currently the implants of choice for young patients with RA.
16778393 Disease-specific proteins from rheumatoid arthritis patients. 2006 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly destroys cartilages or bones at the joints. This inflammatory disorder is initiated by self-attack using own immune system, but the detail of pathological mechanism is unclear. Features of autoantigens leading to autoimmune disease are also under veil although several candidates including type II collagen have been suggested to play a role in pathogenesis. In this report, we tried to identify proteins responding to antibodies purified from RA patients and screen proteins up-regulated or down-regulated in RA using proteomic approach. Fibronectin, semaphorin 7A precursor, growth factor binding protein 7 (GRB7), and immunoglobulin mu chain were specifically associated with antibodies isolated from RA synovial fluids. In addition, some metabolic proteins such as adipocyte fatty acid binding protein, galectin-1 and apolipoprotein A1 precursor were overexpressed in RA synovium. Also, expression of peroxiredoxin 2 was up-regulated in RA. On the contrary, expression of vimentin was severely suppressed in RA synoviocytes. Such findings might give some insights into understanding of pathological mechanism in RA.
16645972 Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. 2006 May OBJECTIVE: Spontaneous reports of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with leflunomide, a disease-modifying antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we conducted a population-based epidemiologic study. METHODS: A cohort of 62,734 patients with RA to whom a DMARD had been dispensed between September 1, 1998 and December 31, 2003 was formed using the PharMetrics claims database. A nested case-control design was used, in which each case of serious ILD requiring hospitalization was matched to 100 controls according to age (calendar time) and equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of serious ILD associated with DMARD use. RESULTS: There were 74 cases of serious ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence interval (95% CI) 1.1-3.6]). Among subjects with no previous methotrexate use and no history of ILD, the risk associated with leflunomide treatment was not elevated (RR 1.2 [95% CI 0.4-3.1]), but it was elevated among the remaining subjects (RR 2.6 [95% CI 1.2-5.6]). Patients with a history of ILD were twice as likely to have been prescribed leflunomide as any other DMARD. CONCLUSION: The reports of ILD associated with leflunomide use are likely the result of channeling of high-risk patients to leflunomide treatment, particularly those with a history of methotrexate use or preexisting ILD. Patients with no history of ILD and no previous methotrexate use show no excess risk of developing ILD with leflunomide treatment.
18647855 Evidence for association of an interleukin 23 receptor variant independent of the R381Q va 2009 Aug OBJECTIVE: The rare allele of a non-synonymous interleukin 23 receptor (IL23R) single nucleotide polymorphism (SNP) rs11209026 (p.Arg381Gln) confers strong protection against Crohn disease (CD) and psoriasis. Other IL23R variants also exhibit association with CD, genetically independent of rs11209026. In rheumatoid arthritis (RA), IL23 is an important determinant of the production of IL17A, a cytokine of consequence in inflammation and bone destruction. While there is no previous support for strong association of IL23R with RA, the possibility of a weaker role for IL23R variants in the aetiology of RA cannot be eliminated. METHODS: A New Zealand RA cohort was tested for association with six IL23R SNPs and the resulting data combined with a reanalysis of the Wellcome Trust Case Control Consortium data and a previously published Spanish data set. The combined data set totals over 3000 Caucasian cases and 3800 controls, which has sufficient power to detect a risk of as low as odds ratio (OR) = 1.2. RESULTS: Our data emphasise the lack of association of rs11209026 with RA (OR 1.01, 95% confidence interval (CI) 0.88 to 1.16, p = 0.86). However there was some evidence for association of rs1343151 with RA (OR 1.14, 95% CI 1.06 to 1.22, p = <0.001). CONCLUSIONS: While requiring further replication, these data further support a role for the IL17A/IL23 pathway in RA. Understanding how different variants of IL23R associate, at varying levels of strength, with contrasting groups of immune-mediated diseases (CD, psoriasis, ankylosing spondylitis, RA) will enhance knowledge on the aetiology of these diseases.
18058674 [Treatment of chronic recurrent synovial fistula following radiosynoviorthesis: two case r 2007 Dec Chronic recurrent synovial fistulae of the knee are uncommon. They can occur after traumatic injuries, as complication after surgical treatment or in patients with rheumatoid arthritis as spontaneous complication after trauma. No consensus exists about the adequate treatment and literature on this subject is scarce. Two cases are presented in which synovial fistula had occurred after radiosynoviorthesis. Previous conservative and conventional surgery failed to solve the problem as the fistulae remained chronic and recurrent. However both, radical debridement and plastic reconstruction by either a fasciocutaneous or a myocutaneous gastrocnemius flap were successful.
17564031 [Psychosomatic associations in internal diseases. Part II]. 2007 The role of psychic factors in the most common somatic diseases (chronic obstructive pulmonary disease, bronchial asthma, peptic ulcer, h4epatitis, rheumatoid arthritis, systemic lupus erythematosus, cancer, and chronic renal failure) is considered in Part II of the review. A significant connection between anxiety and depression and the occurrence, course, and prognosis of many diseases is shown. The appropriateness and effectiveness of treatment of mental disorders is evaluated on the basis of randomized studies.
17543148 Fibroblast-like synoviocyte-chondrocyte interaction in cartilage degradation. 2007 Mar OBJECTIVE: In vitro models for joint diseases often focus on a single cell type, such as chondrocytes in osteoarthritis (OA) or fibroblast-like synoviocytes (synoviocytes) in rheumatoid arthritis (RA). However, these joint diseases affect the whole joint and interaction between chondrocytes and synoviocytes may play an important role in disease pathology. The current study was designed to study the use of the alginate recovered chondrocyte method as a model for cartilage degradation and to study interaction between chondrocytes and synoviocytes. METHODS: Bovine chondrocytes were cultured in alginate beads for 1 week, subsequently chondrons were retrieved and seeded into transwells. Every two days cartilage-slices were analysed for proteoglycan content (colorimetric, Blyscan GAG kit), collagen content (HPLC) and collagen HP and LP crosslinking (HPLC). For degradation experiments, monocultures of cartilage-slices labelled with (35)S and cocultures with synoviocytes were stimulated with IL-1beta or TNF-alpha. After 7 days, (35)S release was measured taken as a measure of cartilage degradation. RESULTS: After biochemical analysis, three week old cartilage-like slices were chosen to perform cartilage-degradation experiments. Synoviocytes were able to induce cartilage degradation only in the presence of living chondrocytes. In addition, the cytokines interleukin 1 (IL-1beta) and tumor necrosis factor (TNF-alpha) were only able to induce cartilage degradation by chondrocytes, not by synoviocytes. CONCLUSION: These data indicate that the alginate recovered chondrocyte method provides a novel model for cartilage degradation in which the interaction between synoviocytes and chondrocytes can be studied.
16804090 Quest for arthritis-causative genetic factors in the rat. 2006 Oct 3 Experimental rat models of arthritis are extensively studied with a view to understand the genetic underpinnings of rheumatoid arthritis (RA). Genome scans using these models have led to the detection of arthritis regulatory quantitative trait loci (QTLs) on all but three chromosomes of the rat. Whereas some of the QTLs are model specific, others overlap between models. Some arthritis susceptibility and/or severity QTLs identified by genetic linkage analyses are corroborated by substitution mapping using congenic strains, whereas others are not. In these cases, testing alternate arthritis models proved to be useful to identify QTL effects. Nevertheless, development and testing of congenic substrains containing progressively shorter introgressed regions have not only fine mapped the location of the arthritis QTLs but also resulted in the identification of multiple QTLs within several originally identified individual QTL. Most of these studies progressed rapidly since 2001, when the rat genome sequence was published. Proof of principle for substitution mapping as a successful method for QTL gene discovery is provided by the positional cloning of Ncf1 as one of the arthritis QTLs in rats. This finding is encouraging for similar sustained dissection of all the other arthritis QTLs mapped in the rat. Identification of rat arthritis QTLs is expected to pave the way for discovery of yet-unidentified arthritis-causative genetic elements and/or pathways for RA in humans and potential development of targeted therapeutics. This review catalogs some of the recent advances made in QTL discovery projects of experimentally induced rat models of arthritis.
17978540 Hemophagocytic syndrome associated with rheumatoid arthritis. 2007 We report a patient with rheumatoid arthritis (RA) who showed bicytopenia with hyperferritinemia and hepatic dysfunction ascribable to hemophagocytic syndrome (HPS) 2 weeks after commencement of bucillamine. Pathology of the bone marrow showing infiltration of macrophages confirmed the diagnosis of HPS. On the basis of renal dysfunction with an increase in fibrin degradation products, disseminated intravascular coagulation was considered to be concurrent with HPS. Oral prednisolone and cyclosporine A were started right after cessation of bucillamine, and yielded complete normalization of hepatic and renal function and hematology. As there was neither disease activity of RA nor associated infection throughout the clinical course, bucillamine was suspected of being the cause of HPS in our patient. HPS is a very rare complication in RA, but should be actively considered when abnormalities in laboratory data, especially pancytopenia and hepatic dysfunction, quickly worsen.
18027239 Phospholipase A2 sensitive liposomes for delivery of small interfering RNA (siRNA). 2007 Small interfering RNA (siRNA) is potent and highly specific for gene silencing and there is currently a lot of enthusiasm for developing siRNA into a drug. However, for most therapeutic applications of siRNA, delivery systems are needed. These delivery systems have multiple requirements and should on one hand ideally be stable carriers protecting the siRNA from degradation and on the other hand assist the siRNA in overcoming membrane barriers for intracellular delivery to the cytosol. Long-circulating liposomes, which are sensitive to secretory phospholipase A(2) (sPLA(2)) are feasible delivery systems for systemic administration of drugs due to their passive targeting to pathological tissue via the enhanced permeability and retention (EPR) effect and their site-specific, enzyme-triggered release of encapsulated drug in response to sPLA(2) which exists locally at elevated levels at, e.g,. sites of inflammation. However, recent data suggest that endosomal membrane destabilizing approaches could be addressed to design sPLA(2)-sensitive liposomes as successful delivery systems for siRNA to the RNA interference pathway in the cytoplasm upon systemic administration.
16650588 Positive affect as a factor of resilience in the pain-negative affect relationship in pati 2006 May OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a factor of resilience in the relationships between pain and negative affect (NA) in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks. Multilevel modeling was applied to study the within-week relationships among the variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05, P<.01) indicating a weaker relationship between pain and NA in weeks with more PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001), depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive affect is most influential in reducing NA during weeks of higher pain and may be a factor of resilience, helping patients experiencing pain fluctuations as less distressful than at lower levels of PA.