Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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24427583 | Multi-frequency tympanometry: clinical applications for the assessment of the middle ear s | 2013 Jul | The aim of the present paper was to review the current knowledge on multi-frequency tympanometry and explore its role as a diagnostic tool in various otologic conditions. Literature review in Medline and other database sources. Prospective controlled, prospective comparative, and prospective cohort studies, animal studies, retrospective studies and systematic reviews. Multi-frequency tympanometry provides more accurate and detailed information about the middle ear dynamics than standard tympanometry. Otosclerosis and rheumatoid arthritis characteristically increase the resonant frequency (RF) of the middle ear. Ossicular chain discontinuity, atelectatic tympanic membrane, and otitis media with effusion typically decrease the RF of the middle ear. Multifrequency tympanometry can also assess the stage of rheumatoid arthritis in the presence of middle ear involvement. The RF can be affected by the mechanical impedance of the cochlea, and multi-frequency tympanometry can be helpful in the diagnostic workup of LVAS. Multi-frequency tympanometry can be a useful tool to predict the diagnosis of various middle ear pathologies preoperatively, due to the ensuing changes in the RF of the mechano-acoustic system of the middle ear, which can be accurately determined when this methodology is applied. | |
21794134 | "I could cry, the amount of shoes I can't get into": A qualitative exploration of the fact | 2011 Jul 27 | BACKGROUND: Studies have reported that women with rheumatoid arthritis (RA) are not wearing NHS supplied therapeutic footwear; therefore it is likely they are wearing footwear sourced through retailers. Previous research gives limited information (largely associated with cosmesis) on people's perceptions on the relationships that exist between retail footwear, well-being and quality of life. This study aimed to explore the perceptions of women with RA regarding their choice of retail footwear and identify the factors influencing retail footwear selection. METHODS: Eleven women with RA wearing normal retail footwear were recruited from an out-patient podiatry clinic in the south east of England. Semi-structured interviews were carried out and an interpretative phenomenological approach was adopted for data collection and transcript analysis. RESULTS: Six key themes were revealed from the analysis: (1) the nature of foot complaints and deformities, (2) aesthetic appearance and design of footwear, (3) body image, (4) psychosocial aspects, (5) Perceptions of footwear and (6) the therapeutic value of retail shoes. These contributed to an overarching concept of loss of choice associated with retail footwear. In particular, the areas discussed most frequently throughout were themes (2), (3) and (4), which were notably more 'emotional' in nature. CONCLUSIONS: Limitations in retail footwear for these women have impacted on their individuality, linking significantly with their body image. The loss of choice in footwear as a consequence of the disease impacts negatively on emotions, wellbeing and was identified in reduced self-perceived quality of life. | |
22792128 | Living life without B cells: is repeated B-cell depletion a safe and effective long-term t | 2012 Apr 1 | The continued efficacy of B-cell depletion in rheumatoid arthritis (RA) depends on repeated cycles of anti-CD20 treatment to maintain low levels of B cells. It is surprising that this significant manipulation of the humoral immune system is remarkably safe with repeated treatment and that rates of adverse effects remain stable, and may even decline, over subsequent courses. Although responses to vaccines and probably to new antigens are diminished, adaptive immunity nevertheless functions adequately despite markedly restricted B-cell numbers. In the 10 years or so since the widespread use of B-cell depletion, there is little to suggest that a long-term paucity of B cells puts patients at risk for malignancy or opportunistic infections, nor that it leads to treatment-resistant RA or complications. While time will tell whether this major alteration of the immune system has other consequences, it is remarkable that drastic reduction of B-cell numbers over the long term is tolerated so well, and that it maintains efficacy in RA therapy. | |
22211138 | Depression in patients with rheumatoid arthritis: description, causes and mechanisms. | 2011 | Two sets of contributory factors to depression among patients with rheumatoid arthritis (RA) are generally examined - the social context of the individual and the biologic disease state of that person's RA. This article will review the evidence for both. RA affects patients both physically and psychologically. Comorbid depression is common with RA and leads to worse health outcomes. Low socioeconomic status, gender, age, race/ethnicity, functional limitation, pain and poor clinical status have all been linked to depression among persons with RA. Systemic inflammation may also be associated with, cause, or contribute to depression in RA. Understanding the socioeconomic factors, individual patient characteristics and biologic causes of depression in RA can lead to a more comprehensive paradigm for targeting interventions to eliminate depression in RA. | |
22204770 | Environmental triggers and epigenetic deregulation in autoimmune disease. | 2011 Dec | The study of epigenetic mechanisms in the pathogenesis of autoimmune diseases is receiving unprecedented attention from clinicians and researchers in the field. Autoimmune disorders comprise a wide range of genetically complex diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. Together they affect a significant proportion of the population and have a great economic impact on public health systems. Epigenetic mechanisms control gene expression and are influenced by external stimuli, linking environment and gene function. A variety of environmental agents, such as viral infection, hormones, certain drugs, and pollutants, have been found to influence the development of autoimmune diseases. On the other hand, there is considerable evidence of epigenetic changes, particularly DNA methylation alterations, in diseases like systemic lupus erythematosus, rheumatoid arthritis, or multiple sclerosis. However, the gap in our understanding between the specific effects of external agents and the influence on epigenetic profiles has not yet been filled. Here we review a number of studies describing epigenetic alterations in autoimmune diseases and a range of environmental factors that influence the development of autoimmune diseases. We also discuss potential mechanisms linking environment and epigenetics, consider the prospects for future epigenetic studies addressing the relationship between environment and epigenetics, and comment on the use of drugs with an epigenetic-reversing effect in the clinical management of these diseases. | |
22991848 | [A case of MRSA infection in multiple artificial joints successfully treated with conserva | 2012 Jul | We report herein on a case with multiple MRSA prosthetic arthritis and osteomyelitis successfully treated medically. Our patient was a 64-year-old Japanese woman with a previous medical history of malignant rheumatoid arthritis and multiple surgical interventions with an atlantoaxial fixation in 2003, artificial joint replacement of both knee joints in 2006, and of the right hip joint in September, 2007. She was initially hospitalized due to MRSA arthritis in the right hip in October, 2007. Thereafter, multiple joint infections occurred sequentially in the right knee joint in January 2008 and the left hip joint in June 2008. More recently, the patient was re-admitted in January 2009 due to cervical osteomyelitis with MRSA infection. The patient had been treated with a combination of vancomycin and rifampin for 17 weeks and followed by sulfamethoxazole/trimetoprim in the out-patient setting up to the present. Although the complete resolution of multiple deep MRSA infections with prosthetic arthritis and osteomyelitis is not expected without removing the infectious sources, our patient was successfully treated with chronic antibiotic suppressive therapy. Therefore, we report on our case with a literature review. | |
22131069 | Epirubicin potentiates recombinant adeno-associated virus type 2/5-mediated TRAIL expressi | 2012 May | OBJECTIVE: Synovial cells in rheumatoid synovium display abnormal proliferation, which leads to joint destruction. TRAIL has been described as a proapoptotic factor in fibroblast-like synoviocytes (FLS). This study was undertaken to investigate the functions of rAAV2/5-TRAIL in human FLS and in arthritic mice. METHODS: Primary human FLS were infected with rAAV2/5-TRAIL in the presence or absence of epirubicin. Transgene expression was monitored by both enzyme-linked immunosorbent assay and flow cytometry. The disease-modulating activity of epirubicin plus rAAV2/5-TRAIL was investigated in mice with collagen-induced arthritis (CIA). RESULTS: Subtoxic doses of epirubicin potentiated rAAV2/5-mediated TRAIL expression in FLS and simultaneously enhanced the sensitivity of FLS to TRAIL. Epirubicin treatment up-regulated death receptor 4 (DR-4) and DR-5 expression and down-regulated FLIP expression, thereby enhancing the activation of procaspase 3, procaspase 8, and procaspase 9. An in vivo study showed that the combination of rAAV2/5-TRAIL gene therapy and epirubicin chemotherapy provided augmented antiarthritic effects in a mouse model of CIA. The intraarticular injection of rAAV2/5-TRAIL combined with epirubicin treatment significantly reduced the severity and incidence of CIA and joint swelling in the animals. Histologic evaluations revealed that inflammatory cell infiltration, cartilage destruction, and bone erosion were significantly reduced in the joints of the mice receiving the synthetic treatment. Results of a viral genome copy number assay indicated that epirubicin dramatically augmented the expression of rAAV2/5-TRAIL without altering its tissue distribution. CONCLUSION: These results suggest that epirubicin enhances the antiarthritic effect of rAAV2/5-TRAIL and that combination treatment might be an important therapeutic alternative, with practical significance for rheumatoid arthritis. | |
22751600 | Adalimumab in psoriatic arthritis. | 2012 Jul | Open prospective studies and randomized controlled trials (RCT) have shown the short-term efficacy of adalimumab (ADA) in psoriatic arthritis (PsA) and psoriasis. ADA effectively treated all varied musculoskeletal manifestations characteristic of PsA, including peripheral arthritis, spinal disease, enthesitis, and dactylitis. ADA significantly inhibited structural changes on radiographs, lessened disability, and improved quality of life in patients with active PsA. One study showed the efficacy of 24-week ADA therapy on bone marrow edema and erosions, as measured by magnetic resonance imaging. The clinical and radiographic efficacy of ADA demonstrated during short-term treatment was sustained during longterm treatment. ADA was generally well tolerated and its safety profile was similar to that reported in studies of ADA in rheumatoid arthritis. Overall, ADA has a favorable risk-benefit profile in PsA. The combination of ADA and cyclosporine seems to be more effective than ADA monotherapy in patients with active PsA and inadequate response to methotrexate; however, this observation must be confirmed in RCT. | |
21665248 | New concepts in pain research and pain management of the rheumatic diseases. | 2011 Dec | OBJECTIVES: To provide an update on advances in pain research and practical guidelines for pain management in the rheumatic diseases. METHODS: A selected literature review and authors' conference consensus. RESULTS: There is emerging evidence that augmented pain regulation, as found in fibromyalgia, is important in rheumatoid arthritis and osteoarthritis. These findings are applicable to optimal management paradigms in the rheumatic diseases. CONCLUSIONS: Fibromyalgia and other forms of chronic widespread pain have taught us important lessons about pain epidemiology and pain pathways. | |
22717204 | Evanescent and persistent pruritic eruptions of adult-onset still disease: a clinical and | 2012 Dec | OBJECTIVE: Persistent pruritic eruptions (PPE) are common among our patients with adult-onset Still disease (AOSD). We aimed to characterize the clinicopathologic features of the AOSD-associated evanescent and persistent rashes. METHODS: We reviewed the clinicopathologic features of the skin lesions from all AOSD cases diagnosed in our hospital during 1988 to 2009. The diagnoses were based on Yamaguchi criteria for AOSD. RESULTS: Altogether, there were 36 patients (6 men and 30 women) with age of onset ranging from 17 to 67 years (average 35.7 years). Evanescent rash was recorded in 31 patients (86%) and PPEs in 28 (78%). PPEs usually appeared at the disease onset and manifested as widespread, pruritic, erythematous urticarial or violaceous to brownish flat-topped (lichenoid) papules and plaques over the trunk, neck, face, and extensor sides of the extremities. PPEs were classified clinically as urticarial papules (n = 21), lichenoid papules (n = 18), prominent linear and dermographism-like (n = 11), dermatomyositis-like (n = 7), prurigo pigmentosa-like (n = 4), and lichen amyloidosis-like (n = 2). The clinical activity score was 5.78 ± 1.11 (range 4 to 8) for the series and 6.57 ± 0.98 and 5.57 ± 1.07, respectively, for the groups with and without dermatomyositis-like PPE (P = 0.0314). Five patients died, 3 of them with dermatomyositis-like PPE. Histopathologically, the evanescent rash (8 specimens) showed a superficial perivascular infiltrate of lymphocytes and neutrophils, whereas the PPEs (32 specimens) revealed solitary or cluster necrotic keratinocytes in the superficial epidermis with infiltration of lymphocytes and neutrophils in the upper and mid dermis. CONCLUSIONS: PPEs were very common among our patients with AOSD. Recognition of the characteristic clinical and pathologic features of PPE can facilitate diagnosis of AOSD. Therefore, biopsy of atypical eruptions in AOSD patients is recommended because it is likely that the highly distinctive histopathologic features will allow these eruptions to be readily classified. | |
22212410 | Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular aci | 2013 Jul | We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia. | |
22112034 | Oral distress in primary Sjögren's syndrome: implications for health-related quality of l | 2011 Dec | The aims of the study were to evaluate oral distress in patients with primary Sjögren's syndrome (pSS) compared with age- and sex-matched Norwegian normative data, to estimate the occurrence of oral symptoms in pSS, and to evaluate the impact of oral distress on health-related quality of life (HRQoL). The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used to assess HRQoL, and the Oral Health Impact Profile 14 (OHIP-14) was used to measure oral distress. Of the 246 pSS patients invited to participate in the study, 177 (72%) responded. Data were analysed for the female participants (n = 163). Significant deviations from normative estimates were found in all OHIP-14 item results, and the findings indicated a high level of oral distress among the pSS patients. Health-related quality of life was decreased among pSS patients, with the largest deviations from normative estimates related to general health and role physical. The patients with high levels of oral distress scored significantly lower than patients with low levels of oral distress in five of the SF-36 subscales, indicating that oral conditions have a marked impact on general quality of life. In conclusion, oral distress in pSS is pronounced and severe, and should receive increased attention with a view to improving the quality of life for these patients. | |
22098691 | Unusual presentation of a case of Sjogren's syndrome with neurological and ocular manifest | 2012 Apr | Sjogren's syndrome is an autoimmune disease that commonly presents to the ophthalmologist as a dry eye disease. We report an unusual presentation of a case of Sjogren's syndrome. A 33-year-old man presented with lid swelling, pseudomembraneous conjunctivitis with central corneal epithelial defect and history of limb weakness for past 2 years. There was progressive enlargement of the epithelial defect and conjunctival-scleral necrosis developed during follow-up. Evaluation for underlying connective tissue disorder was positive for SS-B/La antibody and, the rheumatoid factor, anti nuclear antibody, anti neutrophil cytoplasmic antibody titres were negative. Patient was diagnosed as a case of Primary Sjogren's syndrome. Resolution of the conjunctival-scleral necrosis occurred following treatment with combination of cyclosporine and prednisolone. Paramedian tarsorrhaphy was performed to promote healing of the corneal epithelium. The corneal epithelium healed, conjunctival-scleral necrosis resolved completely and the visual acuity improved to 6/36 in the right eye after 3 months of immunosuppressive therapy. The immunosuppressive therapy was discontinued after completion of 6 months of treatment. After 6 months follow-up of stopping immunosuppressive therapy, the ocular and systemic condition is stable. | |
21881287 | Successful treatment of HTLV-1-related overlap syndrome using tacrolimus. | 2011 | A 56-year-old HTLV-I-positive woman, initially diagnosed as having Sjögren's syndrome, presented with muscle weakness, myalgia, face erythema and leg edema. Based on the presence of various autoantibodies, the diagnosis of overlap syndrome (dermatomyositis/Sjögren's syndrome) was made. Treatment with high-dose corticosteroid plus cyclosporine improved her symptoms. However, three months after the start of these treatments, exacerbation of myositis occurred. A muscle biopsy revealed prominent perivascular accumulation of mononuclear cells with perifascicular atrophy, which were consistent with dermatomyositis. Tacrolimus, which was substituted for cyclosporine led to marked improvement of the myositis symptoms. | |
22002845 | Population pharmacokinetic-pharmacodynamic-disease progression model for effects of anakin | 2011 Dec | A population pharmacokinetic-pharmacodynamic-disease progression (PK/PD/DIS) model was developed to characterize the effects of anakinra in collagen-induced arthritic (CIA) rats and explore the role of interleukin-1β (IL-1β) in rheumatoid arthritis. The CIA rats received either vehicle, or anakinra at 100 mg/kg for about 33 h, 100 mg/kg for about 188 h, or 10 mg/kg for about 188 h by subcutaneous infusion. Plasma concentrations of anakinra were assayed by enzyme-linked immunosorbent assay. Swelling of rat hind paws was measured. Population PK/PD/DIS parameters were computed for the various groups using non-linear mixed-effects modeling software (NONMEM® Version VI). The final model was assessed using visual predictive checks and nonparameter stratified bootstrapping. A two-compartment PK model with two sequential absorption processes and linear elimination was used to capture PK profiles of anakinra. A transduction-based feedback model incorporating logistic growth rate captured disease progression and indirect response model I captured drug effects. The PK and paw swelling versus time profiles in CIA rats were fitted well. Anakinra has modest effects (I ( max ) = 0.28) on paw edema in CIA rats. The profiles are well-described by our PK/PD/DIS model which provides a basis for future mechanism-based assessment of anakinra dynamics in rheumatoid arthritis. | |
23153973 | Clinical profile of coexisting conditions in type 1 diabetes mellitus patients. | 2012 Apr | AIMS: Type 1 diabetes mellitus (T1DM) is associated with various genetic and autoimmune diseases implicated in its etiopathogenesis. We hereby profile the clinical association of such diseases among patients from our center. METHODS: Consecutive patients of T1DM presenting to department of Endocrinology from May 1997 to December 2011 were retrospectively analyzed in context of associated clinical profile. RESULTS: Among 260 patients diagnosed as T1DM, 21 (8%) had hypothyroidism, 4 (1.5%) had hyperthyroidism and 2 (0.7%) had primary adrenal insufficiency. Eighteen patients (7%) had celiac disease, 9 (3.5%) had Turner's syndrome, 5 patients (1.9%) had Klinefelter's syndrome, whereas Down's syndrome and Noonan's syndrome was present in 2 and 1 patients (0.7%) respectively. One patient had Wolframs' syndrome and 1 patients had myasthenia gravis. Systemic lupus erythematosus and rheumatoid arthritis were present in 3 and 1 patients respectively. Total of 5 patients with cerebral palsy, 4 cases with deaf mutism, 4 cases with acute psychosis and 16 patients with depression were noted. Mean age of study patients was 20.8±9.8 years (range, 3-23 years). CONCLUSION: Various conditions including genetic (Down, Turner, Noonan, and Klinefelter's), autoimmune (thyroid and adrenal disorders, myasthenia gravis, SLE, rheumatoid arthritis) and central nervous system diseases were the associated diseases encountered in our patients. Routine screening is required for early diagnosis and treatment of associated co morbidities. | |
20655576 | Neuromyelitis optica spectrum disorder as an initial presentation of primary Sjögren's sy | 2011 Feb | OBJECTIVES: Longitudinal myelitis in patients with Sjögren's syndrome (SS) is a rarely reported occurrence. Here, we present a patient with longitudinal myelitis who was found to have both primary SS and a positive antibody to aquaporin-4 (NMO-IgG). We review the recent literature concerning the overlap between primary SS-associated myelitis and the presence of NMO-IgG, suggestive of a neuromyelitis optica spectrum disorder (NMOSD). METHODS: A patient with longitudinal myelitis, SS, and a positive NMO-IgG is presented. A review of the relevant English literature based on a PubMed and Embase search is then discussed. The keywords used were Sjögren's syndrome, myelitis (longitudinal and transverse), neuromyelitis optica, and Devic's disease. RESULTS: Our patient fulfills the criteria for both primary SS and NMOSD. Several small studies have shown that most SS patients with longitudinal myelitis are positive for the antibody to aquaporin-4. Additionally, minor salivary gland biopsies of patients with NMO or NMOSD have evidence of lymphocytic inflammation, suggesting that there may be an overlap in the mechanism of NMOSD and longitudinal myelitis secondary to primary SS. This overlap in mechanism may have important ramifications with regard to prognosis and treatment of SS-related myelitis. CONCLUSION: The presentation of longitudinal myelitis in a patient with SS should be considered a possible NMOSD. Checking for the presence antiaquaporin-4 antibodies provides important prognostic information and may help to guide treatment decisions. | |
23374667 | [MALT-type parotid lymphoma--a case report and the review of the literature]. | 2013 Jan | Primary lymphomas of the salivary glands are rare. It is estimated that they constitute no more than 5% of all lymphomas in different locations. The most common subtype developing in parotid glands is marginal zone B-cell mucosa associated lymphoid tissue type lymphoma (MALT) that belongs to a group of low-grade tumours. There are many factors associated with the incidence of that proliferative process: environmental and infectious agents as well as immune deficiency states. We describe a case of primary non-Hodgkin's lymphoma of the parotid gland arising in the background of previously undiagnosed and untreated Sjögren's syndrome in a 52-year-old woman. The article concerns a short review of the literature regarding etiology, symptoms, treatment and survival prognosis in that rare disease as well. MALT lymphomas should always be considered in the differential diagnosis of the tumors and swelling of the parotid gland area. A special, regular monitoring should include all patients with Sjögren's syndrome as those with the proven greater risk of developing that proliferative disease. The role of the laryngologist in the case of MALT-type lymphoma of the parotid gland should focus on a diagnosis and possible tumor cytoreduction with maximal saving of the facial nerve. The essential treatment of this pathology is one of the oncologists and haematologists. | |
23009759 | Emerging trends in Sjögren's syndrome: basic and translational research. | 2012 Sep | This review will address the 'state of the art' of novel genomic and proteomic biomarkers for primary Sjögren's syndrome (pSS) and the current status and potential of gene transfer to salivary glands in restoring the function of salivary glands. | |
22928476 | Comparison of autologous serum eye drops with different diluents. | 2013 Jan | PURPOSE: To compare the effect of autologous serum eye drops with different diluents in patients with dry eyes and persistent epithelial defects. METHODS: Patients of Sjögren's syndrome (Group I), non-Sjögren's syndrome (group II) with dry eye, and persistent epithelial defects (Group III) were included. The eyes of each group were randomly treated with one of the following autologous serum eye drops: 100% serum (AS(100)), 50% serum with normal saline (AS(50NS)); 50% serum with sodium hyaluronate (AS(50HA)); or 50% serum with ceftazidime (AS(50CEF)). The differences in dry eye symptoms, Schirmer test I, tear break-up time (TBUT), corneal staining, and speed in epithelial healing were studied. RESULTS: In Group I, AS(100) showed fewer symptoms than AS(50NS), AS(50HA) and AS(50CEF) (all p < 0.01). AS(100) showed significantly better effect than AS(50NS), AS(50HA) and AS(50CEF) in decreasing corneal staining at the time point of 12-week post-treatment (p = 0.041, p < 0.001 and p < 0.001, respectively). In Group II, AS(100) was more effective than AS(50CEF) in decreasing symptoms and decreasing corneal staining (all p < 0.05). There was no significant difference in symptom and corneal staining between AS(100) and AS(50NS). In Group III, AS(100) was the most effective in achieving quick epithelial closure. CONCLUSION: In the eyes with Sjögren syndrome and persistent epithelial defects, AS(100) was the most effective in decreasing symptoms, corneal epitheliopathy and promoting fast closure of wound. In the eyes with non-Sjögren syndrome, AS(100) and AS(50NS) have similar effects in decreasing symptoms and corneal epitheliopathy. |