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ID PMID Title PublicationDate abstract
12518070 [Comparative safety of traditional non-steroidal anti-inflammatory drugs and COX-2 selecti 2002 Dec 7 SIDE EFFECTS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: Digestive disorders and skin and mucosal reactions, more rarely neurosensorial, renovascular, gyneco-obstetrical and hematological disorders are the main side effects of non-steroidal anti-inflammatory drugs. DIGESTIVE USEFULNESS OF COXIBS: Coxibs reduce the risk of symptomatic complicated or uncomplicated gastroduodenal ulcers by 1 to 1.5 per 100 patient-years compared with conventional NSAID. They do however induce a similar number of dyspeptic disorders and are contraindicated in case of inflammatory bowel disease. Extra-digestive tolerance is comparable with that for classical NSAID. PLATELET AGGREGATION AND THROMBOSIS: If the patient's vascular status requires an anti-platelet agent, aspirin must be combined with the coxib which in itself cannot provide cardiovascular protection.
14498766 Atlizumab: anti-IL-6 receptor antibody-Chugai, anti-interleukin-6 receptor antibody-Chugai 2003 Atlizumab [Actemra, MRA] is a humanised anti-interleukin-6 receptor monoclonal antibody. It was originated by the Japanese company Chugai Pharmaceutical and is being developed for the treatment of rheumatoid arthritis, Crohn's disease, multiple myeloma and the lymphoproliferative disorder giant lymph node hyperplasia (Castleman's disease). In October 2002, a majority share (50.1%) in Chugai Pharmaceutical was acquired by Roche. Nippon Roche was merged into Chugai Pharmaceutical, which is now Roche's exclusive pharma representative in Japan. The relationship between Chugai Pharmaceutical and Roche has been defined through a jointly agreed governance agreement, by which Chugai Pharmaceutical will be an autonomously managed company. Chugai Pharmaceutical is now Roche's exclusive pharma representative in Japan and will have rights to develop and market Roche products in Japan. As part of the transaction, Roche gained rights of first refusal for licencing, marketing or co-developing any Chugai Pharmaceutical products which are available for partnering. In the first quarter of 2003, Chugai Pharmaceutical and Roche formed an agreement to co-develop and co-promote atlizumab. The companies will co-promote the drug in the UK, France and Germany. Roche will co-develop and promote atlizumab worldwide, except in Japan, South Korea and Taiwan. Chugai Pharmaceutical has retained co-promotion rights in the US, Italy and Spain. Atlizumab completed phase II development for giant lymph node hyperplasia in Japan in 2002, where it has been granted orphan drug status. In April 2003, a regulatory filing was submitted in Japan for use of atlizumab in the treatment of giant lymph node hyperplasia. In May 2000, Chugai Pharmaceutical and the US company Protein Design Labs reached an agreement whereby Chugai Pharmaceutical will receive nonexclusive, worldwide licences for an undisclosed number of its antibody targets under Protein Design Labs' antibody humanisation patents. One of the targets included is the human interleukin-6 receptor. Chugai Pharmaceutical will pay Protein Design Labs 6.04 million US dollars in signing and licencing fees. Chugai Pharmaceutical will also pay annual maintenance fees and royalties on any future product sales.
11956298 Arthritogenic monoclonal antibodies from K/BxN mice. 2002 Apr 15 Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patients we have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI specificities were present at extraordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid. None of the anti-GPI mAbs induced arthritis when injected individually into healthy recipients, but most were effective when combined in pairs or larger pools. Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to GPI with Kd in the 10(-9) M range, with no indication of cooperative binding between complementing pairs. Pathogenicity was not associated with recognition of a particular epitope, but the ability to form mAb/GPI multimers by simultaneous recognition of different epitopes was clearly required, consistent with the known role of complement and FcRs in this model. Sequence analysis revealed structural similarities amongst the mAbs, indicating that a particular subset of B cells may evade tolerance in K/BxN mice, and that affinity maturation by somatic mutation likely takes place. These results confirm that GPI itself, rather than a cross-reactive molecule, is the target of pathogenic Igs.
15086386 High expression of interleukin-1beta in the corneal epithelium of MRL/lpr mice is under th 2004 May MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr), spontaneously develop polyarthritis, sialoadenitis and dacryoadenitis, resembling rheumatoid arthritis (RA), and also corneal involvement such as keratopathy and scleritis, which is a major complication in RA patients. In this study, we found that the expression levels of IL-1beta and MMP-1 mRNAs in cornea were high in both MRL/lpr and MRL/Mp-+/+ strains of mice at an age younger than when they develop any inflammatory lesions. This was not true of other inbred strains, even those bearing the lpr gene, and also not of (NZB x NZW) F1 lupus mice. There was no significant difference in the expression of IL-1alpha and TGFbeta in cornea in these strains. Using crosses between MRL/lpr and C3H/HeJ-lpr/lpr (C3H/lpr) mice, at least the expression of IL-1beta was found to be under the control of the MRL genetic background, likely with a recessive mode of inheritance. Considering that IL-1beta in cornea was detected particularly in the epithelial layer, the high expression of IL-1beta in cornea is most likely involved in the genetic predisposition for corneal involvement and possibly also for arthritis in an MRL strain of mice.
15677401 Posttraumatic stress disorder and physical illness: results from clinical and epidemiologi 2004 Dec Research indicates that exposure to traumatic stressors and psychological trauma is widespread. The association of such exposures with posttraumatic stress disorder (PTSD) and other mental health conditions is well known. However, epidemiologic research increasingly suggests that exposure to these events is related to increased health care utilization, adverse health outcomes, the onset of specific diseases, and premature death. To date, studies have linked traumatic stress exposures and PTSD to such conditions as cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, chronic fatigue syndrome, musculoskeletal disorders, and other diseases. Evidence linking cardiovascular disease and exposure to psychological trauma is particularly strong and has been found consistently across different populations and stressor events. In addition, clinical studies have suggested the biological pathways through which stressor-induced diseases may be pathologically expressed. In particular, recent studies have implicated the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) stress axes as key in this pathogenic process, although genetic and behavioral/psychological risk factors cannot be ruled out. Recent findings, indicating that victims of PTSD have higher circulating T-cell lymphocytes and lower cortisol levels, are intriguing and suggest that chronic sufferers of PTSD may be at risk for autoimmune diseases. To test this hypothesis, we assessed the association between chronic PTSD in a national sample of 2,490 Vietnam veterans and the prevalence of common autoimmune diseases, including rheumatoid arthritis, psoriasis, insulin-dependent diabetes, and thyroid disease. Our analyses suggest that chronic PTSD, particularly comorbid PTSD or complex PTSD, is associated with all of these conditions. In addition, veterans with comorbid PTSD were more likely to have clinically higher T-cell counts, hyperreactive immune responses on standardized delayed cutaneous hypersensitivity tests, clinically higher immunoglobulin-M levels, and clinically lower dehydroepiandrosterone levels. The latter clinical evidence confirms the presence of biological markers consistent with a broad range of inflammatory disorders, including both cardiovascular and autoimmune diseases.
14578453 Premature telomeric loss in rheumatoid arthritis is genetically determined and involves bo 2003 Nov 11 In rheumatoid arthritis, peripheral blood T cells have age-inappropriate telomeric erosion. We examined whether HLA-DRB1*04 alleles, the major susceptibility genes for this disease, confer risk for T cell senescence. In healthy individuals, HLA-DRB1*04 alleles were associated with excessive loss of telomeres in CD4+ T cells. Accelerated telomeric erosion occurred during the first two decades of life and was followed by reduced homeostatic T cell proliferation during adulthood. Premature telomeric loss also affected granulocytes, suggesting that the hematopoietic stem cell is the primary target. Telomeric repair mechanisms were intact in HLA-DRB1*04+ donors. We propose that HLA-DRB1*04 alleles or genes in linkage disequilibrium regulate stem cell replication and contribute to the accumulation of senescent and autoreactive T cells in rheumatoid arthritis.
12740670 Fever of unknown origin: a review of 20 patients with adult-onset Still's disease. 2003 May In this study we aimed to investigate the findings in patients with adult-onset Still's disease (AOSD) admitted with fever of unknown origin (FUO) during the last 18 years in our unit, in order to discover the ratio of such patients to all patients with FUO during the same period, and to determine the clinical features of AOSD in FUO. The number and the aetiologies of the patients with FUO diagnosed between 1984 and 2001, and the clinical features of those with AOSD, were taken from the patient files. The diagnosis of AOSD was reanalysed according to the diagnostic criteria of Cush et al. [11]. The presumed diagnoses before a diagnosis of AOSD was established were also noted. The chi(2) and Fisher's exact tests were used for statistical analysis. We studied 130 patients with a diagnosis of FUO, 36 (28%) of whom had collagen vascular diseases. Of these 36 patients, 20 (56%, 12 female, 8 male, mean age 34 years, range 16-65) had AOSD. Clinical and laboratory findings were as follows: fever (100%), arthralgia (90%), rash (85%), sore throat (75%), arthritis (65%), myalgia (60%), splenomegaly (40%), hepatomegaly (25%), lymphadenopathy (15%), anaemia (65%), neutrophilic leukocytosis (90%), increased erythrocyte sedimentation rate (100%), elevated transaminase levels (65%), a negative RF (100%), and a negative FANA (80%). Antibiotics had been prescribed in 18 (90%) of cases. The presumed infectious diagnoses were streptococcal tonsillitis/pharyngitis (50%), infective endocarditis (four patients), sepsis (two patients) and acute bacterial meningitis (two patients). The presumed non-infectious diagnoses were acute rheumatic fever (three patients), seronegative rheumatoid arthritis (two patients) and polymyositis (two patients). Sixteen patients were followed for a mean duration of 30 months (range 2-59). A remission was obtained with indomethacin in three cases (19%), and with prednisolone in the remainder. Relapse was detected in three cases (19%). AOSD is one of the most frequent aetiologies of FUO. During the diagnostic course of a patient with FUO, a maculopapular rash and/or arthralgia and/or sore throat should raise the suspicion of AOSD. Because the disease has heterogeneous clinical findings, certain bacterial infections (e.g. streptococcal pharyngitis and sepsis) are generally considered and the prescribing of antibiotics is common.
12391388 Asthma and multiple sclerosis: an inverse association in a case-control general practice p 2002 Nov BACKGROUND: Th1/Th2 imbalance is hypothesized to up-regulate some diseases and down-regulate others. Compared to controls, multiple sclerosis (MS) (Th1-mediated) has been linked to a reduced risk of allergy and asthma (Th2-mediated), based on patient questionnaire studies and a review of asthma medication. AIM: To investigate whether MS is associated with a reduced risk of Th2-associated diseases and an increased risk of Th1-associated diseases. DESIGN: Retrospective matched case-control study. METHODS: Three hundred and twenty MS patients and controls matched for age, gender, location and smoking were selected from the Welsh General Practice Morbidity Database from 1995-99. Case and control records were assessed for Th1-mediated and Th2-mediated diseases. RESULTS: Overall, 346 MS patients were identified, giving a prevalence of 127 per 100 000. There was an inverse relationship between multiple sclerosis (MS) and asthma (OR 0.33; 95%CI 0.15-0.77). No statistically significant relationships emerged between other Th2-associated (eczema, dermatitis) or any Th1-associated (rheumatoid arthritis, thyroid disorders, inflammatory bowel disease [IBD], type 1 diabetes) diseases and MS, although no patient in either group had treated type 1 diabetes. A trend existed for IBD, with 5/320 of cases affected and no controls; OR infinity; 95%CI 1.30-infinity; p=0.063. DISCUSSION: This inverse association between MS and asthma is compatible with a Th1/Th2 imbalance. Although the Th1/Th2 theory is probably an over-simplification in MS, a shift from Th1 cytokine dominance towards Th2 may provide drug-targeting routes for MS.
12519387 T cell activation by soluble C1q-bearing immune complexes: implications for the pathogenes 2003 Jan Both innate and adaptive immune systems are thought to participate in the pathogenesis of rheumatoid arthritis in adults and children. The experiments reported here were undertaken to examine how immune complexes, potent stimulators of inflammation, may regulate cells of the adaptive immune system. Human T cells were prepared from peripheral blood by negative selection and incubated with bovine serum albumin (BSA)-anti-BSA immune complexes that were formed in the presence or absence of human C1q. C1q-bearing immune complexes, but not unopsonized complexes, elicited both TNF-alpha and IFN-gamma secretion from human T cells. Secretion of both cytokines was time- and dose-dependent. Cross-linking C1q on the cell surface of T cells produced the same results. Cytokine secretion was not inhibited by blocking the C3b receptor (CR1, CD35) on T cells prior to incubation with immune complexes. Reverse transcriptase polymerase chain reaction (RT-PCR) of immune complex-stimulated cells revealed accumulation of both TNF-alpha and IFN-gamma mRNA within 2 h post-stimulation. IL-2 was not detected in cell culture supernatants, but IL-2 receptor alpha chain (CD25) was detected in low density on a small proportion of T cells activated by C1q-bearing immune complexes. Secretion of both cytokines was inhibited partially, but not completely, by IL-10. These experiments show that immune complexes, potent inflammatory mediators, may activate T cells through a novel mechanism. These findings have implications for chronic inflammatory diseases in humans.
12571841 Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma. 2003 Feb OBJECTIVE: To define the cytokine profile within rheumatoid subcutaneous nodules, and to determine whether the destructive inflammatory process in this lesion displays features of a lymphocyte-driven Th1 or Th2 granuloma. METHODS: Subcutaneous nodules excised from 10 patients with rheumatoid arthritis were examined. Transcripts for interleukin 1beta (IL-1beta) IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-15, IL-18, and for tumor necrosis factor alpha (TNFalpha) and interferon-gamma (IFNgamma) were detected by reverse transcription-polymerase chain reaction of extracted RNA. RESULTS: Nine of 10 nodules contained transcripts for IFNgamma. We observed no evidence for the expression of IL-2, IL-4, or IL-5 among the lymphokine genes analyzed. Transcripts for TNFalpha, IL-1beta, IL-10, IL-15, and IL-18 were present in all 10 nodules. Transcripts for IL-12 were present in all but one nodule. Expression of IL-13 messenger RNA was observed in only 5 nodules. CONCLUSION: The cytokine profile within the rheumatoid nodule (i.e., presence of IFNgamma but not IL-2, and prominent expression of IL-1beta and TNFalpha together with IL-12, IL-18, IL-15, and IL-10) is similar to the profile of cytokines in the synovial lesion of rheumatoid arthritis, which is generally accepted as being attributable to a Th1-mediated inflammatory mechanism. Our results suggest that damage to affected synovial membrane or subcutaneous tissue is caused by the same inflammatory mechanisms, and that the nodule is a Th1 granuloma.
15764033 D-penicillamine-induced pemphigus successfully treated with combination therapy of mizorib 2004 Jul A 63-year-old woman had D-penicillamine-induced pemphigus with a high index value of circulating autoantibodies against desmoglein 1. Because of the lack of response to prednisolone monotherapy, the patient was treated with a combination therapy of mizoribine and low-dose prednisolone. The skin eruption was improved by this combination with a declined value of circulating anti-desmoglein 1 antibody. Currently, a remission of 2 months has been achieved, and prednisolone could be tapered.
12073659 [The role of adrenal and gonadal hormones in the pathogenesis of autoimmune polyarthritis] 2002 May 19 A growing body of recently published results suggest the role of adrenal androgens in the onset and development of chronic inflammatory process due to autoantigens. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA)--the major androgen products of the adrenal gland--have immunosuppressive effect inhibiting interleukin-6 production and substantially determining acute phase reaction. Decreased serum levels of DHEA and DHEAS has been observed in most of autoimmune diseases. Recent data suggest that adrenal hypoandrogenism comes from disturbed neuroendocrine, regulation due to hypothalamic effect of the inflammatory cytokines. On the other side, decreased adrenal androgen activity negatively influences the anabolic tonus of steroid hormone system while a relative enhancement of catabolic pressure occurs by the glucocorticoids. Moreover, the hypothalamus-hypophysis-gonadal axis can also be involved, resulting shifts in serum levels of prolactin, estrogens and gonadal androgens. All these hormonal changes can be summarised in decreasing the immunosuppressive tonus. This hypothesis connects the endocrine dysregulation with the development of autoimmune disorders. The new results promise not only a basically different theory of chronic inflammation but they will permit using new diagnostic tools as well as inducing substantially new and more effective therapeutic approaches.
12064831 Antigen induced arthritis (AIA) can be transferred by bone marrow transplantation: evidenc 2002 Jun OBJECTIVE: To investigate the role of bone marrow cells (BMC) in the induction of antigen induced arthritis (AIA), the expression of 3 major proinflammatory cytokines, interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, was examined in the bone marrow (BM) of mice with AIA. We also examined whether AIA could be transferred by bone marrow transplantation (BMT). METHODS: Expression of IL-1beta, TNF-alpha, and IL-6 in BMC was assessed by immunohistochemistry throughout the course of AIA. BMT experiments were performed using 2 different mouse genotypes, wild type (IL-6+/+) and IL-6 deficient (IL-6-/-) mice, as a donor. The gradation of AIA was evaluated histologically. RESULTS: IL-6 was highly expressed in the BM at induction as well as during progression of AIA, while TNF-alpha showed a marginal expression, and no significant expression of IL-1beta was detected throughout the course of AIA. In BMT experiments, all irradiated IL-6+/+ mice developed typical AIA by transplantation of BMC from immunized IL-6+/+ mice, whereas almost no irradiated IL- 6+/+ mice transplanted with BMC from the immunized IL-6-/- mice developed definite arthritis. CONCLUSION: These results suggest that BMC play a critical role and IL-6 is a key cytokine for the induction and progression of AIA. There may be clinical benefits in the blockade of IL-6 and BMT in the treatment of rheumatoid arthritis.
12881830 Reliability, validity, and responsiveness of the modified Kapandji index for assessment of 2003 Jul OBJECTIVE: To determine the reliability, validity, and responsiveness of the modified Kapandji index (MKI). DESIGN: Prospective study. A cohort of patients planned for surgery of the wrist and/or fingers was evaluated within 48 hours before surgery and at least 6 months after surgery. SETTING: Patients were in hospitalized or private care in France. PARTICIPANTS: Patients with rheumatoid arthritis according to criteria of the American College of Rheumatology. Forty-two patients (36 women; mean age, 57.5y; range, 22-80y) were included in the reliability study. Fifty patients (42 women; mean age, 54.18y; range, 19-77y) were included in the validity study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical outcome measures included the MKI, the overall mobility score of the wrist and fingers, the finger mobility score, a visual analog scale (VAS) of pain in the hands and wrists, morning stiffness duration, total score of tenderness, total score of swelling, grip and pinch strength, the Hand Functional Index (HFI), and the Cochin rheumatoid hand disability scale. Reliability was studied with the intraclass correlation coefficient (ICC) and the Bland and Altman method. Convergent and divergent validity were assessed with the Spearman correlation coefficient. Responsiveness was assessed by the paired t test, the effect size, and the standardized response mean (SRM). RESULTS: Interobserver reliability was good with an ICC of.90, and the Bland and Altman analysis showed homogeneous distribution of the differences, with no systematic trend. The MKI correlated well with the other mobility measures (HFI, the finger mobility score measured with the finger goniometer), indicating a good convergent validity, and the expected divergent validity with the other outcome measures (grip and pinch strength, total score of swelling, total score of Ritchie Articular Index, Cochin scale, VAS of pain) was observed. The 50 patients in the validity study were evaluated twice, before and after surgery, at a mean interval +/- standard deviation of 7.16+/-2.10 months (range, 6-15mo). Thirty-six patients (72%) were very satisfied or satisfied with the results of surgery, 7 (14%) were not satisfied or dissatisfied, and 7 (14%) were dissatisfied or very dissatisfied. The SRM and effect size values of the MKI were -.19 and -.10, respectively. Individual changes in the score had the best correlation (r(s)=.51) with overall patient satisfaction. CONCLUSIONS: The MKI has excellent validity and reliability. Individual changes in the score are clinically relevant. This index can be used in clinical practice and in therapeutic trials; it needs further study concerning its use for hand surgery.
14760808 Longer use of COX-2-specific inhibitors compared to nonspecific nonsteroidal antiinflammat 2004 Feb OBJECTIVE: To compare COX-2-specific inhibitor therapy with conventional nonspecific nonsteroidal antiinflammatory drugs (NS NSAID), and investigate the effect of demographic and disease factors on NSAID duration of use. METHODS: A total of 3639 patients with rheumatoid arthritis (RA), osteoarthritis, and fibromyalgia starting therapy of celecoxib, rofecoxib, naproxen, or ibuprofen were surveyed at 6-month intervals for up to 2.5 years. Detailed demographic and disease severity variables were also measured. Time to discontinuation, discontinuation rates, and effect of covariates were determined by Weibull parametric survival analyses, controlling for a wide variety of demographic and disease severity factors. RESULTS: The median duration of use for celecoxib, rofecoxib, naproxen, and ibuprofen was 15, 13, 10, and 10 months, respectively. Duration of use of celecoxib and rofecoxib, as measured by survival times, was significantly longer than those of naproxen and ibuprofen. The celecoxib survival time was significantly longer than the rofecoxib survival time (p = 0.005). Disease severity was not associated with survival times, but survival was related to younger age and male sex. In addition, ulcer diagnosis was a strong predictor of early termination. After adjustment for severity, survival times for RA and non-RA patients were the same. CONCLUSION: COX-2-specific inhibitors have a longer duration of use than NS NSAID. Among the COX-2-specific inhibitors, celecoxib has a longer survival time than rofecoxib. In addition, COX-2-specific inhibitors also have longer survival times than noted in the literature of NS NSAID in RA community practice. Duration of use can be an indicator of treatment effectiveness and/or drug acceptability, and provides additional interpretation beyond the results of clinical trials.
14749154 An observational, retrospective, cohort study of dosing patterns for rofecoxib and celecox 2003 Dec OBJECTIVE: This study assessed prescribing patterns for rofecoxib and celecoxib in the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA), as well as differences in prescribing patterns across physician specialties. METHODS: This was an observational, retrospective, cohort study of a large, US pharmacy claims database. Eligible patients were initiating therapy with rofecoxib or celecoxib and had succeeds, equals 90 days' supply of medication, as well as > or =1 medical claim specific to OA or RA between June 1, 2000, and May 31, 2001. Analyses were stratified according to diagnosis, prescribing physician specialty, and patient demographics. The main outcome measure was mean daily usage (ie, mean daily dose [milligrams]; mean number of pills per day; and mean daily consumption [denoted as DACON], calculated as daily dose divided by most frequently prescribed strength). This was primarily a descriptive study. Tests of statistical significance were not performed because the large sample size would have rendered small differences significant. RESULTS: A total of 58,574 patients with OA (81.8% [n=47,935]) or RA (18.2% [n=10,639]) received 220,627 prescriptions for rofecoxib or celecoxib (47.7% [n=27, 924] and 52.3% [n=30, 650] of patients, respectively) during the study period. Overall, the most frequently prescribed strengths were rofecoxib 25 mg and celecoxib 200 mg. In both OA and RA, the most frequently prescribed mean daily dose of rofecoxib was 25 mg. In OA, the most frequently prescribed mean daily dose of celecoxib was 200 mg; in RA, it was 400 mg. Both pills per day and DACON were higher for celecoxib than rofecoxib. The DACON for rofecoxib was unrelated to physician specialty. Rheumatologists prescribed celecoxib at 20% to 40% higher mean daily doses than did primary care physicians, orthopedic specialists, or other specialists. Regardless of physician specialty, the DACON appeared higher for patients with RA than OA, for men than women, and for younger (aged <65 years) than older patients. CONCLUSIONS: In this analysis, relative to the most frequently prescribed strength, celecoxib-treated patients with OA and RA had higher DACONs than rofecoxib-treated OA and RA patients across all subgroups. These observations may have economic implications in terms of direct effects on cost and the need for formularies to consider overall use patterns in addition to pill costs. However, these conclusions are limited by lack of clinical information (other than an OA or RA diagnosis), inability to ascertain actual use, and potential for selection bias.
12580916 Anti-avian antibodies and rheumatoid factor in pigeon hypersensitivity pneumonitis. 2003 Feb BACKGROUND: Although several immunological abnormalities may be present in pigeon hypersensitivity pneumonitis (HP), few specific hallmarks have been described. OBJECTIVE: To determine whether the presence of rheumatoid factor (RF) could be useful to discriminate pigeon HP from asymptomatic breeders (AB) and other interstitial lung diseases. METHODS: Fifty-three patients with pigeon HP, 47 AB, 31 idiopathic pulmonary fibrosis (IPF) patients and a rheumatoid arthritis (RA) group were studied. IgM RF was determined through enzyme-linked immunosorbent assay (ELISA) and western blot using human IgG and IgG Fc fragment as antigens. IgG and IgA anti-avian antibodies (AA) against pigeon serum antigen were also measured. The use of F(ab')2 fraction of peroxidase-labelled anti-human immunoglobulins prevented endogenous interferences. Possible cross-binding of RF with avian antigens and the reactivity against human IgG by AA were studied. RESULTS: RF tests were frequently positive in HP (52.8%) in comparison to AB (4.2%) and IPF (12.9%; P = 2.6 x 10-10 and 4.1 x 10-5). Therefore, the presence of RF in pigeon HP showed a sensitivity of 52% and was highly specific considering the results of AB and IPF (95 and 87%, respectively). The RA group revealed positive RF but negative AA tests. RF activity was confirmed through western blot using purified IgG Fc fragment. Overlapping levels of IgG and IgA AA were found in HP and AB. The frequency of AA was low in IPF. The cross-reaction of RF with avian antigens was excluded, and no reactivity against human IgG by AA was detected. Other endogenous interferences were ruled out. CONCLUSION: No single immunological test may definitively distinguish pigeon HP from AB and other interstitial lung disorders; however, positive RF, together with high AA levels, seems to be useful in differentiating the diagnosis.
12498817 Streptococcal cell wall arthritis: kinetics of immune cell activation in inflammatory arth 2002 Dec The streptococcal cell wall model of arthritis in Lewis rats consists of an acute, non-T-cell-dependent initiation phase, followed by a remission and then a chronic, inflammatory T-cell-dependent phase. In this report, we define pertinent changes in the cognate and noncognate immune system of the Lewis rats during various phases of the disease. We examined changes in the population size of various cell types using lineage-specific markers in three different tissues (blood, spleen, and lymph nodes) over 28 days. Our results indicate that the T cell and monocyte populations were significantly altered in PG-PS-treated rats and the activation status of these cells parallel initiation, remission, and chronic phases of joint inflammation. Activation of B cells also increases in certain tissues in the chronic phase of the disease. In summary, our results confirm the involvement of both innate and cognate immunity in the development of arthritis and demonstrate that monocytes, in addition to T cells, play a substantive role in the induction and maintenance of the inflammatory process in this rat model.
12496713 [Etanercept--infliximab switch in rheumatoid arthritis 14 out of 131 patients treated with 2002 Nov 23 OBJECTIVE: Patients with severe rheumatoid arthritis and resistant to at least three DMARDS can benefit from anti-TNFalpha (tumor necrosis factor) therapy. In some patients, because of inefficacy or adverse events, treatment with one of the two available TNFalpha drugs (etanercept and infliximab) must be stopped. In this study, we explored the results in efficacy and tolerance of switching from one anti-TNFalpha to the other. PATIENTS: Between August 1999 and January 2002, we administered one of the two anti TNFalpha drugs to 131 patients: 67 patients received infiximab and 64 etanercept. RESULTS: Among the 67 patients treated with infliximab, 17 patients had to stop treatment. In 8 of them (4 allergies, 2 infections and 2 non responders) the switch from infliximab to etanercept was beneficial for 5 patients, 2 patients did not respond and 1 patient withdrew for personal reasons. Among the 64 patients treated with etanercept, 13 had to stop treatment. In 6 of them (2 adverse events, 4 failures) the switch from etanercept to infliximab was beneficial for 3 patients, 2 did not respond and 1 withdrew because of adverse events. CONCLUSION: In all, 14 patients with severe rheumatoid arthritis and treated by one of the two TNFalpha drugs (and in whom treatment was stopped because of adverse events or inefficacy) benefited from the switch to the other anti- TNFalpha, with excellent response in 8 out of 14 patients.
12634236 Oral corticosteroid prescribing in women over 50, use of fracture prevention therapy, and 2003 Apr OBJECTIVE: To identify the most common diseases and age of corticosteroid use in women over 50, dosage in last year, duration of oral corticosteroid use, prescription for fracture prevention (drug used), and referrals for bone densitometry. METHODS: General practice records from 41 practices in Shropshire identified 62,230 women aged >50 from a population of 80,082. Data on fractures, duration of corticosteroid use, dose in the study year (1 April 1997-31 March 1998), use of fracture prevention therapy and bone densitometry were sampled from one out of three records. RESULTS: 3.2% were prescribed corticosteroids; 633 patients investigated in detail aged 70.1 (SD 10.5) years, had been prescribed 1526 (SD 1727) mg prednisolone (median 1040 mg) for 3.31 (SD 3.20) years (median 2.0 years). Patients with asthma/lung disease, most common in the younger group, had the lowest annual corticosteroid use; patients with rheumatoid arthritis (RA), polymyalgia rheumatica/temporal arteritis (PMR/TA), who were more likely to be elderly, had the highest annual use. Between the age of 70 and 79 years patients with RA had significantly more hip fractures than the other groups, and corticosteroid prescribing was most common. Bisphosphonates or hormone replacement therapy were prescribed for 48% aged 50-59 years but only 32% at 70-79 years (p<0.01); patients with asthma and RA being less likely recipients (p<0.01). Referrals for bone densitometry had occurred in 20.2%,with 60.2% having osteoporosis. Referrals were more common in those taking corticosteroids for longer periods (p<0.01). CONCLUSIONS: The elderly had the most prescriptions for corticosteroid treatment but the fewest for effective fracture prevention therapy. Patients with RA, PMR/TA had the greatest corticosteroid dosage, for the longest time. Patients with RA sustained more hip fractures than other groups but were least likely to have effective fracture prevention therapy prescribed.