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ID PMID Title PublicationDate abstract
20546088 Persistent pruritic papules and plaques: a characteristic histopathologic presentation see 2010 Sep BACKGROUND: 'Persistent pruritic papules and plaques' of Still's disease represents a recently described eruption seen in a subset of patients. Most cases reported in the literature to date have been associated with adult-onset Still's disease. METHODS: We present the clinical and histopathologic examinations of three female patients ranging in age from 15 to 54 years. RESULTS: Our three patients each presented with clinical findings consistent with Still's disease. The youngest patient suffered from the juvenile form of Still's disease (systemic-onset juvenile rheumatoid arthritis). Each patient had a persistent, pruritic eruption with histopathologic findings of dyskeratosis confined to the upper layers of the epidermis as well as a sparse superficial dermal infiltrate containing scattered neutrophils. CONCLUSIONS: These cases confirm the characteristic clinical and histopathologic findings of 'persistent papules and plaques of Still's disease' and show the potential for this eruption in both the adult and juvenile age groups.
20962439 Efficacy and safety of mizoribine by one single dose administration for patients with rheu 2010 OBJECTIVE: Mizoribine (MZR) is an immunosuppressant that inhibits nucleic acid metabolism and is a relatively safe disease-modifying anti-rheumatic drug (DMARD). We evaluated the efficacy and safety of one single dose per day for patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: In this study 32 patients with RA received MZR therapy. We evaluated the average dose of MZR and prednisolone, response to treatment and peak plasma level of MZR. RESULTS: The average dose of MZR was 146.1±31.2 (range: 50-200) mg/day. The average dose of prednisolone was 4.63±3.59 (range: 0-14) mg/day. The average plasma level of MZR, measured after 3 hours, was 2.20±0.49 µg/mL in the responder group and 1.59±0.82 µg/mL in the non-responder group (p=0.020). The treatment with MZR for 24 weeks was completed by 71.9% of patients and the proportion of patients who achieved a good and moderate response rate according to the European League Against Rheumatism (EULAR) criteria was 56.3% at 24 weeks. The plasma level of MZR which was greater than or equal to 2.12 µg/mL was significantly correlated with the clinical response (p<0.01). Only one of thirty-two cases discontinued the treatment, because of skin eruption. CONCLUSION: This study included patients that could not be treated with other DMARDs and/or biologic agents because of age, interstitial pneumonia and other complications. We show that MZR may be a useful and relatively safe therapy for patients in this group.
19330336 [Favorable response of pulmonary rheumatoid nodule to Rituximab]. 2009 Jun Pulmonary rheumatoid nodules can be found in over 4% of patients with rheumatoid arthritis. Diagnostically they have to be differentiated from malignant and infectious processes. The present article describes a case of pulmonary rheumatoid nodule which responded well to Rituximab therapy.
20549669 Understanding the molecular mechanisms of the multifaceted IL-10-mediated anti-inflammator 2010 Sep Analysis of the molecular mechanisms governing the ability of IL-10 to keep inflammation under control has highlighted the existence of a great degree of plasticity and specificity with regard to innate immune cells. In this respect, neutrophils represent a perfect example of innate immune cells conditioned by external signals (for instance, by LPS), as well as by intracellular regulatory pathways, that render them optimally responsive to IL-10 only when required. The focus of this review are the recent experimental findings that have uncovered the sophisticated and complex molecular mechanisms responsible for the modulation of pro- and anti-inflammatory cytokine production by IL-10 in neutrophils and other innate immune cells. Understanding how IL-10 exerts its anti-inflammatory response, particularly in the case of neutrophils, will provide novel clues leading, hopefully, to the therapeutic control of neutrophil-driven inflammatory reactions, such as septic infections, rheumatoid arthritis, osteoarthritis and chronic obstructive pulmonary disease.
20203093 Qualitative research ethics: enhancing evidence-based practice in physical therapy. 2010 Apr BACKGROUND: Increasing challenges to health care systems and the prominence of patient-centered care and evidence-based practice have fostered the application of qualitative approaches in health care settings, prompting discussions of associated ethical issues in a range of disciplines. OBJECTIVES: The purposes of this work were to identify and describe the application and value of qualitative health research for physical therapy and to identify ethical considerations in a qualitative research study. DESIGN: This was a qualitative interview study with telephone follow-ups. METHODS: Forty-six participants were interviewed about their early experiences with rheumatoid arthritis. They also were asked what motivated them to volunteer for the study. To inform the discussion of ethics in qualitative health research, this study drew on the in-depth interviews, took a descriptive approach to the data, and applied the traditional ethical principles of autonomy, justice, and beneficence to the study process. RESULTS: Ethical issues emerged in this qualitative health research study that were both similar to and different from those that exist in a positivist paradigm (eg, clinical research). With flexibility and latitude, the traditional principle approach can be applied usefully to qualitative health research. CONCLUSIONS: These findings build on previous research and discussion in physical therapy and other disciplines that urge a flexible approach to qualitative research ethics and recognize that ethics are embedded in an unfolding research process involving the role of the subjective researcher and an active participant. We suggest reflexivity as a way to recognize ethical moments throughout qualitative research and to help build methodological and ethical rigor in research relevant to physical therapist practice.
19996617 Disease activity and cytokine production in mitogen-stimulated peripheral blood mononuclea 2010 OBJECTIVE: To test whether there are differences in the levels and ratios of 6 pro- and 3 anti-inflammatory cytokines produced by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) subjects compared to controls. SUBJECTS AND METHODS: 79 participants (42 seropositive RA patients and 37 healthy controls) were enrolled in this study. The production levels in mitogen-stimulated PBMCs of the 6 proinflammatory cytokines (IFN-gamma, TNF-alpha, TNF-beta, IL-8, IL-17, IL-18) and 3 anti-inflammatory cytokines (IL-4, IL-10, IL-13) were assayed by ELISA using kits obtained from Immunotech SA. The ratios of pro- to anti-inflammatory cytokines were calculated for all participants. RESULTS: There were significantly elevated levels of IL-8 and IL-10, and reduced levels of IFN-gamma, IL-4, and IL-17 in mitogen-stimulated PBMC culture supernatants of RA subjects compared to controls. Of the 18 pro-/anti-inflammatory cytokine ratios, 3 ratios (TNF-alpha/IL13, IL-8/IL-4 and IL-8/IL-13) were significantly higher in RA patients compared to controls; and 6 were higher in controls (IFN-gamma/IL-4; IFN-gamma/IL-10; IFN-gamma/IL-13; TNF-beta/IL10; IL-17/IL-10; IL-18/IL-10). CONCLUSIONS: Activated PBMCs of RA patients, regardless of disease activity, showed higher-level production of IL-8 and IL-10 compared to controls; lower-level production of IFN-gamma, IL-4, and IL-17; and elevated ratios of TNF-alpha/IL-13, IL-8/IL-4 and IL-8/IL-13.
20171051 Total hip arthroplasty with an uncemented tapered femoral component in patients younger th 2011 Jan The purpose of the present study was to evaluate the outcome of primary uncemented total hip arthroplasty in patients younger than 50 years using the Taperloc (Biomet, Warsaw, Ind) femoral component. We evaluated 94 hips in 79 patients at a mean follow-up of 16 years (range, 11-18.5 years). The average age of the patients at the time of surgery was 36 years (range, 20-49 years). Three femoral components had been revised, none for aseptic loosening. Complete clinical and radiographic follow-up was obtained on the 91 hips that had not undergone femoral component revision. The mean Harris hip score increased from 54 points (range, 20-72) before surgery to 93 points (range, 68-100) at the time of this review. Radiographically, 89 stems (98%) were determined to have fixation by bone ingrowth, 2 (2%) demonstrated stable fibrous ingrowth, and no femoral component was loose. Distal femoral osteolysis was identified in 1 hip (1%). These findings indicate that excellent clinical and radiographic results can be achieved in young patients with the Taperloc femoral component at a mean follow-up of 16 years.
20701456 Could antibodies against serum amyloid A function as physiological regulators in humans? 2011 Mar The natural structuring of the immune system is responsible for the functional physiological state of the body. The development of natural autoantibodies involved in homeostasis relies on the ability to distinguish between exposed/masked and altered/non-altered self antigens. The objectives of this article were to address the relationships between antigen and autoantibodies against serum amyloid A (SAA), define SAA protein concentrations in 219 blood donor (BD) sera and determine their autoantibody levels and search for possible clinical associations with autoimmune and thrombotic diseases. Just recently, an increasing number of reports have indicated significantly decreased levels of autoantibodies against pro-inflammatory molecules, such as anti-TNF-alpha, anti-IL-6, or anti-CRP found in diseased conditions, as compared to healthy donors, or even to less severe disease conditions. In accord with this line of thought, our data indicate a predominant presence of anti-SAA autoantibodies in healthy BDs (above 95% as tested by the immunoblot analysis, n = 41). Using ELISA, high levels of anti-SAA antibodies were confirmed with a median OD = 0.996 for the BD group (n = 219). This suggests that anti-SAA antibodies might have a physiological role in homeostasis and/or the innate immune system and could actually be a part of the natural antibody repertoire. Significantly, lower median levels were found in patients with arterial thrombosis. Based on 219 BD sera, we could establish a new median value of 20 μg/ml for SAA antigen and a cut-off value of 114.7 μg/ml (97.5th percentile). Significantly, higher concentrations of SAA were observed for antiphospholipid syndrome, rheumatoid arthritic, and SLE patients.
20463186 Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients w 2010 Sep OBJECTIVE: To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab (RTX) plus MTX in patients with active RA. METHODS: Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint was proportion of patients achieving ACR20 at Week 48. RESULTS: At Week 48, ACR20 responses were not statistically significantly different between the dose regimens. Compared with RTX 2 x 500 mg (n = 134) or dose escalation (n = 119), ACR and European League Against Rheumatism (EULAR) outcomes in the RTX 2 x 1000 mg group (n = 93) were consistently higher, with significantly more patients achieving EULAR responses (P = 0.0495). At Week 48, rituximab 2 x 1000 mg was associated with a higher proportion of patients who, following retreatment, maintained or improved their Week 24 responses. Dose escalation from 2 x 500 to 2 x 1000 mg did not appear to be associated with improved outcomes compared with continual 2 x 500 mg. All RTX regimens demonstrated comparable safety. CONCLUSIONS: RTX 2 x 500 and 2 x 1000 mg could not be clearly differentiated, although some efficacy outcomes suggest improved outcomes in the rituximab 2 x 1000 mg group. Retreatment from Week 24 resulted in a sustained suppression of disease activity through to Week 48.
19248121 Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with inflixi 2009 Mar 15 OBJECTIVE: To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan. METHODS: Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed. RESULTS: The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived. CONCLUSION: PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.
20091031 Minor influence of humeral component size on torsional stiffness of the Souter-Strathclyde 2010 Dec The use of Souter-Strathclyde total elbow prostheses is a well-studied replacement therapy for reconstruction of the elbow, but loosening of the humeral component is still of concern at long-term follow-up. In this study we looked at the effect of humeral component size and bone mineral density with respect to the bone size, torsional stiffness and torque to failure in cadaveric bones. Fourteen cadaveric humeri were available for testing purposes and four different humeral component size categories were used. First, we calculated the bone quality using dual-energy X-ray absorptiometry (DEXA). The torsional stiffness of the prosthetic humeri was measured during two mechanical tests: Firstly, the applied torque was recorded during a torsion fatigue test. The change of torsional stiffness between the tenth and last cycle was calculated. Secondly, a simple torsion test was performed and the torque to failure was recorded. No significant differences in outcome were seen between sizes of humeral components, even after correction for the bone size. Torsional stiffness and torque to failure were significantly correlated with bone mineral density and not with component size. In conclusion, bone quality seems to be a major eminent factor in the fixation of the humeral component in elbow replacement surgery.
20306217 Combination therapy with dexamethasone and osteoprotegerin protects against arthritis-indu 2010 Sep OBJECTIVE: To investigate the influence of a combined therapy consisting of dexamethasone and osteoprotegerin (OPG) on bone alterations and disease activity in antigen-induced arthritis (AIA) in the rat. METHODS: AIA rats received dexamethasone (0.25 mg kg(-1) day(-1), i.p.), OPG (2.5 mg kg(-1) day(-1), i.p.), or a combination of both at regular intervals for 21 consecutive days. At the end of the treatment, bone structure was analyzed by histomorphometry. Primary spongiosa was measured using linear scanning. RESULTS: AIA led to significant periarticular and axial bone loss. Dexamethasone monotherapy substantially suppressed joint swelling without inhibiting bone loss of the secondary spongiosa, whereas OPG monotherapy showed no anti-inflammatory effect. Despite reduction of bone resorption, OPG did not inhibit AIA-induced bone loss. In contrast, the combination of dexamethasone and OPG not only produced an anti-inflammatory effect, but also resulted in inhibition of periarticular and axial bone loss. OPG increased trabecular number of the primary spongiosa whilst combination therapy led to an increase in both trabecular number and trabecular width. CONCLUSION: The principle of combining a glucocorticoid together with inhibition of the receptor activator of NF-kappaB ligand (RANKL) may be an effective bone-saving therapy in rheumatoid arthritis.
21114589 Salivary flow rate and periodontal infection - a study among subjects aged 75 years or old 2011 May OBJECTIVE: To analyse the relation of stimulated and unstimulated salivary flow rates to periodontal infection in home-dwelling elderly people aged 75 years or older. SUBJECTS AND METHODS: This study was based on a subpopulation of 157 (111 women, 46 men) home-dwelling, dentate, non-smoking elderly people (mean age 79.8, SD 3.6 years) from the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly Study). The data were collected by interview and oral clinical examination. RESULTS: Persons with very low (< 0.7 ml min⁻¹) and low stimulated salivary flow rates (0.7- < 1.0 ml min⁻¹) had a decreased likelihood of having teeth with deepened (≥ 4 mm) periodontal pockets, RR: 0.7, CI: 0.5-0.9 and RR: 0.7, CI: 0.5-0.9, respectively, when compared with those with normal stimulated salivary flow. Persons with a very low unstimulated salivary flow rate (< 0.1 ml min⁻¹) had a decreased likelihood of having teeth with deepened (≥ 4 mm) periodontal pockets, RR 0.8, CI: 0.6-1.0, when compared with subjects with low/normal unstimulated salivary flow. CONCLUSIONS: In a population of dentate, home-dwelling non-smokers, aged 75 years or older, low stimulated and unstimulated salivary flow rates were weakly associated with a decreased likelihood of having teeth with deep periodontal pockets.
19261537 Interleukin-21 (IL-21)-mediated pathways in T cell-mediated disease. 2009 Apr Interleukin-21 (IL-21) is produced mostly by activated CD4+ T cells and controls the differentiation and functional activity of effector T helper cells, counteracts the suppressive effects of regulatory T cells, and stimulates non-immune cells to make inflammatory mediators. IL-21-driven tissue damage has been demonstrated in a number of organs, such as the gut, pancreas, and brain. Therefore new treatment modalities to neutralise IL-21 in vivo would be a valuable addition to the therapeutic armamentarium to combat immune-mediated inflammation. Here we describe the emerging role of IL-21 in the initiation and progress of the tissue-damaging inflammatory response in immune-mediated pathologies.
21154169 Corticorelin, a synthetic human corticotropin-releasing factor analog, for the treatment o 2010 Dec Corticorelin is a synthetic analog of the naturally occurring human peptide corticotropin-releasing factor (CRF). Several studies have indicated the ability of CRF to reduce the brain edema caused by brain tumors. Peritumoral brain edema (PBE), caused by an intracerebral tumor, manifests several features of vasogenic edema, which is a type of edema characterized by disruption of the blood-brain barrier. Traditionally, PBE has been treated using corticosteroids, primarily dexamethasone. Introduced more than four decades ago, dexamethasone revolutionized the treatment of PBE, but the side effects and withdrawal symptoms associated with corticosteroids propelled the investigation of other drugs. Clinical trials with the synthetic human CRF (hCRF) corticorelin (Xerecept, NEU-3002; Celtic Pharmaceutical Holdings) have indicated that this drug has a distinct advantage over classical corticosteroids in the treatment of PBE. Fewer and/or milder side effects have been reported for corticorelin compared with dexamethasone, although at higher doses of corticorelin several side effects, including hypotension and transient flushing, have been reported. Nevertheless, corticorelin was reasonably well tolerated in patients and healthy volunteers, and may be a good candidate for reducing PBE and associated neural damage, as well as improving neurological symptoms.
19596466 Metabolic cost and mechanical work for the step-to-step transition in walking after succes 2009 Dec The aim of this study was to investigate whether impaired ankle function after total ankle arthroplasty (TAA) affects the mechanical work during the step-to-step transition and the metabolic cost of walking. Respiratory and force plate data were recorded in 11 patients and 11 healthy controls while they walked barefoot at a fixed walking speed (FWS, 1.25 m/s) and at their self-selected speed (SWS). At FWS metabolic cost of transport was 28% higher for the TAA group, but at SWS there was no significant increase. During the step-to-step transition, positive mechanical work generated by the trailing TAA leg was lower and negative mechanical work in the leading intact leg was larger. Despite the increase in mechanical work dissipation during double support, no significant differences in total mechanical work were found over a complete stride. This might be a result of methodological limitations of calculating mechanical work. Nevertheless, mechanical work dissipated during the step-to-step transition at FWS correlated significantly with metabolic cost of transport: r=.540. It was concluded that patients after successful TAA still experienced an impaired lower leg function, which contributed to an increase in mechanical energy dissipation during the step-to-step transition, and to an increase in the metabolic demand of walking.
20037896 Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammato 2010 Mar PURPOSE: To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. RESULTS: After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. CONCLUSIONS: It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.
20097037 Total hip arthroplasty using a cylindrical cementless stem in patients with a small physiq 2011 Jan We performed total hip arthroplasty using an anatomic medullary locking cementless stem for small-physique patients from 1988 to 1995. We conducted a retrospective study of 50 joints in 44 cases, including 40 developmentally dysplastic hips followed for 12 to 20 years (average, 15.1 years). Average height and body weight were 152 cm and 56 kg (5.0 ft and 124 lb), respectively, with an average body mass index of 24.2. Twelve joints (24%) were revised for acetabular-sided failures. Forty-eight stems (96%) showed bone ingrowth fixation, and there were no unstable stems. The simple cylindrical shape of the distal portion of the AML stem was less affected by deformity of the proximal femur of developmental dysplasia of the hip in patients with a small physique, and both clinically and radiologically good results were confirmed at long-term follow-up.
20858147 Post-approval trials of new medicines: widening use or deepening knowledge? Analysis of 10 2011 May OBJECTIVE: To investigate the main aims of the post-approval randomized controlled trials (RCTs) on etanercept and the extent to which they were designed to gain more comparative information. METHODS: A search of the literature (Medline, Embase), trial registries (Clinical Trials.gov, Controlled Trials.com), and market authorization reports from the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) was carried out to identify all RCTs. A comparison of trial data identified unpublished trials and multiple publications relating to the same study. All RCTs completed and/or published after initial market approval was regarded as post-approval. RESULTS: Up until 2008, we found 84 post-approval trials, 11 (13%) trials on approved extensions of indication, another 30 (36%) trials on the approved indications, and 43 (51%) trials on indications not (yet) approved. Nearly half of the studies on indications not yet approved were initiated and funded by independent sponsors. After the initial approval of etanercept, six head-to-head trials were conducted on the approved indications. Overall, the main objectives of post-approval trials with etanercept were found to confirm efficacy and safety in new indications, and to gather additional information for optimal use on the approved indications. CONCLUSION: Post-approval RCTs on etanercept focus more on studies searching for new indications than on deepening knowledge about use. Ten years after the market entry of etanercept, one of the reasonable demands of clinical practice, for more comparative information, still remains unanswered.
20860546 Population pharmacokinetic evaluation of a fully human IgG monoclonal antibody in patients 2010 Sep ABX-IL8 is a fully human IgG₂ monoclonal antibody generated using transgenic mouse technology (Xenomouse®) that binds to human Interleukin-8 with high affinity and specificity. The objective of this study was to evaluate the pharmacokinetic (PK) properties of ABX-IL8 in patients with active inflammatory diseases. Patients with psoriasis and rheumatoid arthritis received single or multiple short intravenous infusions of ABX-IL8 or placebo. Serum concentrations of ABX-IL8, baseline serum IgG and IgG₂ concentrations and Anti-Drug Antibody (ADA) response to ABX-IL8 were determined using relevant immunoassays. Pharmacokinetic analyses of the serum ABX-IL8 concentration-time data were performed. Following single-dose administration of ABX-IL8, dose proportional increases in drug exposure were observed. Consistent with the disposition properties of the endogenous IgG antibodies, ABX-IL8 appeared to be primarily distributed into the plasma compartment and the extra-vascular fluid and the steady-sate volume of distribution (61 ± 14 to 71 ± 14 mL/kg) was comparable to that for the endogenous antibodies. Following the multiple-dose administration, PK properties of the antibody were linear with dose and time. Steady-state clearance (2.6 ± 1.1 to 2.7 ± 1.4 mL/day/kg) was similar to that observed following the single dose administration and no ADA response was detected throughout the study. PK variability and serum exposure to ABX-IL8 following administration of the fixed doses were comparable to those observed following administration of the weight-adjusted doses; the impact of body weight on clearance was minimal and this correlation did not translate into requirements for body weight-adjusted dosing. Additionally, age and disease type (psoriasis or RA) had no impact on ABX-IL8 pharmacokinetics.