Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
21852963 Pervasive sharing of genetic effects in autoimmune disease. 2011 Aug Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA) which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44%) immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA)<0.01). We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.
21729637 [Kyphotic deformities of the cervical spin]. 2011 PURPOSE OF THE STUDY: The development of a cervical kyphotic deformity can be associated with a degenerative disease, trauma, tumour, developmental anomaly and also a surgical procedure. Post-operative kyphosis can develop after both the anterior and posterior surgical approaches. The deformity can also result from systemic diseases, such as ankylosing spondylitis or rheumatoid arthritis. The aim of the study was to make the clinical and radiographic evaluation of a group of patients with kyphotic deformity treated at our department. MATERIAL: Between May 2005 and April 2010, a total of 102 patients underwent correction of cervical kyphosis at our department. (Center for Spinal Surgery). Of them, 90 patients with complete medical records and post-operative periods longer than 6 months were included in this study. There were 36 men and 54 women ranging in age from 13 to 90 years and with an average of 56.7 years. In six patients cervical kyphosis was caused by an inveterate injury, in 71 by degenerative disease, in six it developed in association with rheumatoid arthritis, and in seven patients it was due to previous surgery. Patients with acute trauma, tumour, infectious disease or congenital anomaly were not included. METHODS: All patients were examined before surgery by radiography in antero-posterior and lateral projection, including flexion- extension bending films, and by CT scanning of ultrathin cross-sections with sagittal, frontal and recently also 3D reconstructions. Magnetic resonance imaging in three planes was also performed. On the basis of the results and clinical examination, the operative strategy was planned. Surgery was carried out from the anterior or the posterior approach, or the combined approach was used. Three-stage surgery was performed in one patient. The surgical outcome was assessed using the Nurick score and Neck Disability Index (NDI), the Visual Analogue Scale (VAS) was used to evaluate pain intensity or paraesthesia. Statistical analysis was done using the Chi-square test and paired t-test. RESULTS: The average NDI value was 25.5 before surgery and 14.3 and 14.9 at one and two years after surgery, respectively. Compared with the pre-operative state, improvement or no changes were recorded in 89.7 % of the patients; transient deterioration occurred in 10.3 %. Improvements found were as follows: by one degree in 46.2 % of the patients, by two degrees in 18 %, by three degrees in 5.1 % and by five degrees in 2.6 % of the patients. The condition remained unchanged in 18 % of the patients. The average outcome was an improvement by one degree. The average pre-operative Nurick score was 0.7; an average post-operative value of 0.6 was recorded at both one and two years of follow-up. The average VAS value for neck and radicular pain was 5.7 pre-operatively, and 2.5 and 2.7 at one and two post-operative years, respectively. Out of 90 patients, complete bone union was achieved at 6 months after surgery in 88 patients (97.8 %). The average pre-operative value for the cervical curvature index (Ishihara) was -13.7; the average pre-operative cervical kyphosis was -14.4 degrees, ranging from -2.2 to -44.0 degrees. After surgery, the average Ishihara index was +15.3 and the average lordosis was +13.5 degrees, with a range of -16.0 to + 37.4 degrees. DISCUSSION: A single/isolated anterior approach can be used for fixed deformities without ankylosing spondylitis. It allows for decompression of the anterior pathology and for correction of cervical kyphosis with use of instrumentation and structural graft. A combined ventral-dorsal approach is appropriate in fixed deformities or deformities involving the cervico-thoracic junction. The main principle of correction is to lengthen the cervical spinal column in the front and to shorten it at the back by anterior decompression with or without instrumentation and by subsequent posterior stabilisation. An isolated/single dorsal correction can be used in the case of successful correction by traction or specific head positioning on the table without anterior nerve compression. In severe fixed deformities such as Bekhterev's disease, the chin can be so close to the chest as to interfere with eating and breathing. The deformity most often develops at the cervico-thoracic junction and requires treatment by osteotomy. CONCLUSIONS: The results of the study showed a marked improvement in the patients' quality of life after kyphosis correction, improved neurological status and an improved posture seen on radiograms of the cervical spine. The study also revealed a higher number of potential complications associated, in particular, with corrective osteotomy. The best results were achieved with the combined surgical approach; however, the choice of a surgical method was independent of the patient's clinical status.
21368688 Safety, efficacy, and dosing of recombinant human bone morphogenetic protein-2 for posteri 2011 Jul BACKGROUND: Considerable attention has focused on concerns of increased complications with recombinant human bone morphogenetic protein-2 (rhBMP-2) use for anterior cervical fusion, but few reports have assessed its use for posterior cervical fusions. OBJECTIVE: To assess the safety, efficacy, and dosing of rhBMP-2 as an adjunct for instrumented posterior cervical arthrodesis. METHODS: All patients treated by the senior author with posterior cervical or cervicothoracic instrumented fusion using rhBMP-2 from 2003 to 2008 with a minimum of 2 years of follow-up were included. Diagnosis, levels fused, rhBMP-2 dose, complications, and fusion were assessed. RESULTS: Fifty-three patients with a mean age of 55.7 years (range, 2-89 years) and an average follow-up of 40 months (range, 25-80 months) met inclusion criteria. Surgical indications included basilar invagination (n = 6), fracture (n = 6), atlantoaxial instability (n = 16), kyphosis/kyphoscoliosis (n = 22), osteomyelitis (n = 1), spondylolisthesis (n = 1), and cyst (n = 1). Fifteen patients had confirmed rheumatoid disease. The average rhBMP-2 dose was 1.8 mg per level, with a total of 282 levels treated (average, 5.3 levels; SD, 2.8 levels). Among 53 patients, only 2 complications (3.8%) were identified: a superficial wound infection and an adjacent-level degeneration. No cases of dysphagia or neck swelling requiring treatment were identified. At the last follow-up, all patients had achieved fusion. CONCLUSION: Despite many of the patients in the present series having complex pathology and/or rheumatoid arthritis, a 100% fusion rate was achieved. Collectively, these data suggest that use of rhBMP-2 as an adjunct for posterior cervical fusion is safe and effective at an average dose of 1.8 mg per level.
22528818 A patient with Leiden V mutation, multiple sclerosis, psoriasis, and sicca syndrome: could 2012 Sep The paper describes the case of a patient affected by a combination of genetic and autoimmune diseases (multiple sclerosis, psoriatic arthritis, Leiden V mutation, and sicca syndrome) and hypertension. The psoriatic arthritis was treated with celecoxib and multiple sclerosis with fingolimod. The patient developed high fever and endocarditis, resulting in severe mitral regurgitation, atrial fibrillation, and congestive heart failure. Evidence is suggestive of adverse effects of potent immunosuppressive and anti-inflammatory therapies with biologic agents and the cardiovascular system. Fingolimod increases susceptibility to infections and induced endocarditis resulting in severe mitral regurgitation, atrial fibrillation, and congestive heart failure. Managed care systems limit the contact among basic care physicians and specialists. However, the process by which the optimal decision may be reached for a patient with a complex pathology is shared decision making, where the risk of severe complications and medical expenses may be reduced.
22840991 Autoantibodies in Sjögren's syndrome: clinical presentation and regulatory mechanisms. 2012 Sep Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease mostly affecting the exocrine glands. A large number of autoantibodies have been detected in the serum of patients with pSS. Among them, anti-Ro/SSA and anti-La/SSB autoantibodies are the most common; they serve as disease markers and are involved in the pathogenesis of neonatal lupus syndrome (NLS). Other autoantibodies are associated with significant clinical phenotypes, such as cryoglobulins with development of non-Hodgkin's lymphoma, anti-centromere antibodies with Raynaud's phenomenon and anti-mitochondrial antibodies with liver pathology. As a result, pSS patients can be schematically categorized in subgroups according to their serological profile. Although the clinical utility of these autoantibodies is appreciated, little is known about the mechanisms related to their production and the regulation of the autoimmune response. In the present review, the clinical subsets of patients with pSS related to different autoantibodies as well as the regulating mechanisms of their production with special emphasis on idiotypic/anti-idiotypic network are discussed.
22208659 Epigenetics and Sjögren's syndrome. 2012 Aug There is growing evidence that epigenetics, the study of heritable changes in gene expression that do not involve mutations in the DNA itself, may play an essential role in autoimmune diseases (AID). In Sjögren's syndrome (SS), a chronic AID characterized by an epithelis of the exocrine glands, epigenetic studies have focused on three mechanisms: DNA methylation and its consequences including human endogenous retrovirus (HERV) expression; microRNA expression; and protein post-translational modifications associated with autoantibody production. Although in its infancy, comprehension of the epigenetic (dys)regulation in SS may help us to understand: why SS affects predominantly middle-aged women; why genetically predisposed individuals develop SS but not others; why flare-ups occur; why treatment responses differ between patients; and why some patients develop lymphoma. From these studies will arise a better comprehension of the pathophysiology of SS as well as development of new diagnostic and prognostic biomarkers, and novel therapeutics for prevention and perhaps early intervention.
21895886 Deep sequencing of short RNAs reveals novel microRNAs in minor salivary glands of patients 2012 Mar OBJECTIVES: Sjögren's syndrome is a complex autoimmune disease of the salivary gland with an unknown etiology, so a thorough characterization of the transcriptome would facilitate our understanding of the disease. We use ultradeep sequencing of small RNAs from patients with Sjögren's syndrome and healthy volunteers, primarily to identify and discover novel miRNA sequences that may play a role in the disease. METHODS: Total RNA was isolated from minor salivary glands of healthy volunteers and patients with either high or low salivary flow and sequenced on the SOLiD platform. Prediction of mature miRNAs from the sequenced reads was carried out using miRanalyzer, and expression was validated using Taqman qPCR assays. RESULTS: We validated the presence of six previously unidentified miRNA sequences in patient samples and in several cell lines. One of the validated novel miRNAs shows promise as a biomarker for salivary function. CONCLUSION: Sequencing small RNAs in the salivary gland is largely unprecedented, but here, we show the feasibility of discovering novel miRNAs and disease biomarkers by sequencing the transcriptome.
22312161 Increased interleukin (IL)-7Rα expression in salivary glands of patients with primary Sjo 2012 Jun OBJECTIVE: To identify interleukin (IL)-7Rα expression in the labial salivary gland (LSG) of patients with primary Sjögren's syndrome (pSS) and non-Sjögren's syndrome sicca (nSS-sicca) and to study its correlation with glandular inflammation and IL-7 expression. METHODS: The presence of infiltrating immune cells and IL-7Rα cells in inflamed LSG of patients with pSS (n=12) and nSS-sicca controls (n=7) was studied by immunohistochemistry and fluorescence activated cell sorting analysis upon tissue digestion (n=15 and n=13, respectively). Additionally, the correlations of IL-7Rα cells with hallmark disease parameters of pSS, major infiltrating inflammatory cells and IL-7 were assessed. RESULTS: In the LSG of patients with pSS increased numbers of IL-7Rα cells were found as compared with nSS-sicca patients. IL7Rα cells strongly correlated with the lymphocytic focus score, IL-7 expression, the decrease in percentage of IgA plasma cells and numbers of CD3 T cells, CD20 B cells, and CD1a and CD208 myeloid dendritic cells. Analysis of isolated cells from the LSG demonstrated strongly increased percentages of IL-7Rα CD3 T cells in pSS as compared with nSS, showing abundant IL-7Rα expression on both CD4 and CD8 T cells. Other CD45 leucocytes and CD45- tissue cells scarcely expressed IL-7Rα. Percentages of IL-7Rα T cells also significantly correlated with glandular inflammation. CONCLUSIONS: This study shows the presence of increased IL-7Rα T cells in the LSG of patients with pSS and their association with the severity of sialadenitis, disease parameters and IL-7 expression. Considering the immunostimulatory ability of IL-7Rα T cells and IL-7, this suggests that IL-7(R)-dependent T cell-driven immune activation plays an important role in inflammation in pSS.
22709856 The T cell in Sjogren's syndrome: force majeure, not spectateur. 2012 Sep Sjogren's syndrome (SS) is characterized by infiltration of exocrine glands with T and B lymphocytes, leading to glandular dysfunction and frequently accompanied by hypergammaglobulinemia and autoantibodies. The role of T cells, which predominate in the lesions, has attracted much interest. CD4 T cells seem to be responding to autoantigens on apoptotic cells, such as the Ro and La antigens, or to the cytoskeletal antigen α-fodrin. Physical injury to ocular surfaces may also lead to T cell mediated responses to self antigens and perpetuate disease. Within the salivary glands, T cell responsiveness is further promoted by the special capacity of salivary epithelial tissue to provide costimulation and enhanced antigen presentation. Cytokines are key mediators of the T cell contribution to pathology, with roles attributed both to Th1 and Th2 cells. Recently, striking data implicate Th17 cells in the stimulation of B cells, and a role for the related cytokine IL-21 produced by follicular T helper cells is now appreciated. Dysfunction of T regulatory cells has been shown to have a role in the exuberant production of cytokines by Th17 cells. Beyond their role in provoking B cell hyperactivity and immunoglobulin secretion, T cells are directly involved in destruction of glands through Fas and perforin-mediated cytotoxicity. Animal models of SS have confirmed the role of T cell derived cytokines in disease and support a role for effector-memory cells in pathogenesis. Further elucidation of the role of T cells will open avenues for better treatment of SS, whose current management is still mainly supportive.
24964485 Complete transition from failing restorations to implant-supported fixed prostheses in a p 2012 Nov In a case involving a patient with scleroderma, the authors demonstrate how to treatment plan and sequence the transition from a failing restored dentition to complete implant-supported fixed prostheses with sequential extractions and implant placements. The article also presents surgical and prosthodontic considerations for a complete-mouth implant-supported fixed rehabilitation while achieving optimal esthetics without compromising function in patients with this condition. Sequential treatment provided the patient with fixed provisional restorations during treatment in multiple, short surgical appointments with less psychosocial trauma. This case posed treatment challenges due to limited oral access, unpredictable disease progression, and limited data on the success of treatment with endosseous dental implants in these patients.
22685592 Mesenchymal stromal cells improve salivary function and reduce lymphocytic infiltrates in 2012 BACKGROUND: Non-obese diabetic (NOD) mice develop Sjögren's-like disease (SS-like) with loss of saliva flow and increased lymphocytic infiltrates in salivary glands (SGs). There are recent reports using multipotent mesenchymal stromal cells (MSCs) as a therapeutic strategy for autoimmune diseases due to their anti-inflammatory and immunomodulatory capabilities. This paper proposed a combined immuno- and cell-based therapy consisting of: A) an injection of complete Freund's adjuvant (CFA) to eradicate autoreactive T lymphocytes, and B) transplantations of MSCs to reselect lymphocytes. The objective of this was to test the effectiveness of CD45(-)/TER119(-) cells (MSCs) in re-establishing salivary function and in reducing the number of lymphocytic infiltrates (foci) in SGs. The second objective was to study if the mechanisms underlying a decrease in inflammation (focus score) was due to CFA, MSCs, or CFA+MSCs combined. METHODOLOGY/PRINCIPAL FINDINGS: Donor MSCs were isolated from bones of male transgenic eGFP mice. Eight week-old female NOD mice received one of the following treatments: insulin, CFA, MSC, or CFA+MSC (combined therapy). Mice were followed for 14 weeks post-therapy. CD45(-)/TER119(-) cells demonstrated characteristics of MSCs as they were positive for Sca-1, CD106, CD105, CD73, CD29, CD44, negative for CD45, TER119, CD11b, had high number of CFU-F, and differentiated into osteocytes, chondrocytes and adipocytes. Both MSC and MSC+CFA groups prevented loss of saliva flow and reduced lymphocytic infiltrations in SGs. Moreover, the influx of T and B cells decreased in all foci in MSC and MSC+CFA groups, while the frequency of Foxp3(+) (T(reg)) cell was increased. MSC-therapy alone reduced inflammation (TNF-α, TGF-β), but the combination of MSC+CFA reduced inflammation and increased the regenerative potential of SGs (FGF-2, EGF). CONCLUSIONS/SIGNIFICANCE: The combined use of MSC+CFA was effective in both preventing saliva secretion loss and reducing lymphocytic influx in salivary glands.
22888089 Quantitative proteomics of parotid saliva in primary Sjögren's syndrome. 2012 Oct The diagnosis of primary Sjögren's syndrome (pSS) is difficult due to the lack of specific laboratory and clinical tests. As an initial step for the global discovery of changes in the abundance of parotid salivary proteins in pSS, a pooled sample was compared to that from healthy control subjects by multidimensional protein identification technology (MudPIT). A total of 1246 proteins were identified by MudPIT. The abundance of 477 of these proteins did not change, 529 were only detected in either the pSS or HC sample, while 206 of these proteins were significantly upregulated ≥ twofold and 34 were downregulated ≤ 0.5. Ingenuity Pathway Analyses of differentially expressed proteins identified by MudPIT resulted in the identification of 100 significant pathways. The same samples were quantified in parallel using RP MS. Fifty-eight of 71 proteins identified by RP overlapped with MudPIT results. Five proteins were further analyzed by targeted label-free quantification to confirm the similar relative differential expression observed by RP and MudPIT approaches. The present study supports the use of MS for global discovery and validation of marker proteins for improved and early diagnosis of pSS.
22300712 Sex steroids in Sjögren's syndrome. 2012 Aug The purpose of the review is to consider pathomechanisms of Sjögren's syndrome (SS), which could explain the female dominance (9:1), the most common age of onset (40-50 years) and targeting of the exocrine glands. Estrogens seem to specifically protect secretory glandular acinar cells against apoptosis whereas lack of estrogens during menopause and climacterium specifically leads to increased apoptosis of the exocrine secretory cells. Male gonads produce testosterone and convert it in exocrine glands to dihydrotesterosterone (DHT), which is anti-apoptotic and protects against acinar cell apoptosis. Estrogen-deficient women need to produce dehydroepiandrosterone (DHEA) in the adrenal glands and convert it to DHT in exocrine glands in a complex and branching reaction network in which individual enzymatic reactions are catalyzed in forward and backward directions by a myriad of different isoforms of steroidogenic enzymes. Tailoring DHT in peripheral tissues is much more complex and vulnerable in women than in men. In SS the intracrine steroidogenic enzyme machinery is deranged. These endo-/intracrine changes impair acinar remodeling due to impaired integrin α1β1 and integrin α2β1 expression so that the intercalated duct progenitor cells are unable to migrate to the acinar space, to differentiate to secretory acinar cells upon contact with laminin-111 and laminin-211 specifically found in the acinar basement membrane. The disarranged endo-/intracrine estrogen/androgen balance induces acinar cells to release microparticles and apoptotic bodies and to undergo apoptotis and/or anoikis. Membrane particles contain potential autoantigens recognized by T- (TCRs) and B-cell receptors (BCRs) and danger-associated molecular patterns (DAMPs) recognized by Toll-like receptors (TLRs). In membrane particles (or carrier-complexes) antigen/adjuvant complexes could stimulate professional antigen capturing, processing and presenting cells, which can initiate auto-inflammatory and autoimmune cascades, break the self-tolerance and finally lead to SS.
22292142 Esthetic rehabilitation of a severely worn dentition with minimally invasive prosthetic pr 2012 Apr Restorative treatment of the severely worn dentition is typically indicated to replace deficient tooth structure, limit the advancement of tooth destruction, improve oral function, and enhance the appearance of the teeth. Minimizing removal of additional tooth structure while also fulfilling the desire of patients to have highly esthetic restorations can present a prosthetic challenge when the existing tooth structure is already diminished. This article presents a comprehensive minimally invasive prosthetic treatment approach using a lithium disilicate all-ceramic material for the esthetic rehabilitation of a severely worn dentition for a female patient diagnosed with Söjgren syndrome.
22871259 Secreted human Ro52 autoantibody proteomes express a restricted set of public clonotypes. 2012 Dec Long-lived secreted autoantibody responses in systemic autoimmunity are generally regarded to be polyclonal and to express a diverse B-cell repertoire. Here, we have used a proteomic approach based on de novo sequencing to determine the clonality and V region structures of human autoantibodies directed against a prototypic systemic autoantigen, Ro52 (TRIM21). Remarkably, anti-Ro52 autoantibodies from patients with primary Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis or polymyositis were restricted to two IgG1 kappa clonotypes that migrated as a single species on isoelectric focusing; shared a common light chain paired with one of two closely-related heavy chains; and were public in unrelated patients. Targeted mass spectrometry using these uniquely mutated V region peptides as surrogates detected anti-Ro52 autoantibodies in human sera with high sensitivity and specificity compared with traditional ELISA. Mass spectrometry-based detection of specific autoantibody motifs provides a powerful new tool for analysis of humoral autoimmunity.
23255063 Anti‑obesity effects of Actinidia polygama extract in mice with high‑fat diet‑induce 2013 Feb Actinidia polygama has been used as a herbal folk medicine for treating pain, gout, rheumatoid arthritis and inflammation. In the present study, the anti‑obesity properties of Actinidia polygama extract (APE) were investigated in mice with high‑fat diet‑induced obesity. APE treatment of high‑fat diet (HFD)‑fed obese mice significantly reduced body weight, adipose tissue mass and serum triglyceride and leptin levels relative to the HFD‑fed mice. Food intake did not differ between the HFD and HFD+APE groups, although the food efficiency ratio (FER) was significantly decreased in the HFD+APE group compared with the HFD group. Histological examination showed that the sizes of the adipocytes were significantly smaller in the HFD+APE group compared with the HFD group. Serum levels of aspartate transaminase were significantly decreased in the HFD+APE mice compared with the HFD‑fed mice, but serum levels of alanine transaminase (ALT), blood urea nitrogen and creatinine were not significantly changed in the HFD+APE mice compared with the levels in the normal diet (ND)‑fed and HFD‑fed mice. These results suggest that APE may be useful for treating metabolic diseases, including obesity and hyperlipidemia, without toxic side‑effects.
23214207 A study on parasites in Mexican rheumatic disease patients. 2012 Aug Blastocystis hominis is a common human parasite with infection rates up to 50% in developing countries, and giardiasis is the commonest intestinal one in Mexico. No doubt, various parasites as Giardia lamblia and Entamoeba histolytica can cause rheumatic diseases. This study coproparasitoscopic analysis evaluated the cysts by B. hominis, G. lamblia, E. hartmani, E. coli and E. histolytica in Mexican rheumatic disease patients. Also, ELISA was used to detect E. histolytica, Ascaris lumbricoides, Toxocara canis, and Trichinella spiralis in Mexican patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Thirty-six patients (24 with AS and 12 with RA) and 77 healthy control individuals were enrolled in this study. The frequencies of protozoan cysts were comparable in rheumatic disease patients (AS and RA) and healthy control donors (33 and 25 vs. 26%, respectively; p > 0.05). The frequency of antibodies to T. canis was significantly higher in AS patients than in healthy control donors (16 vs. 2.6%, respectively; p = 0.027), whereas no differences were observed for the prevalence of antibodies for the other parasites (E. histolytica, A. lumbricoides and T. spiralis) (p > 0.05). This information indicates the need to intensify educational efforts for the prevention of parasite infections associated with AS disease that cannot be controlled only by drugs.
23203276 Distinguishing health benefits of eicosapentaenoic and docosahexaenoic acids. 2012 Nov 13 Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) are recommended for management of patients with wide-ranging chronic diseases, including coronary heart disease, rheumatoid arthritis, dementia, and depression. Increased consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is recommended by many health authorities to prevent (up to 0.5 g/day) or treat chronic disease (1.0 g/day for coronary heart disease; 1.2–4 g/day for elevated triglyceride levels). Recommendations for dietary intake of LC n-3 PUFAs are often provided for α-linolenic acid, and for the combination of EPA and DHA. However, many studies have also reported differential effects of EPA, DHA and their metabolites in the clinic and at the laboratory bench. The aim of this article is to review studies that have identified divergent responses to EPA and DHA, and to explore reasons for these differences. In particular, we review potential contributing factors such as differential membrane incorporation, modulation of gene expression, activation of signaling pathways and metabolite formation. We suggest that there may be future opportunity to refine recommendations for intake of individual LC n-3 PUFAs.
23043859 Comparison of indirect immunofluorescence and line immunoassay for autoantibody detection. 2013 Jan OBJECTIVES: The aim of the present paper is to evaluate the diagnostic performance of indirect immunofluorescence (IIF) and line immunoassay (LIA) for autoantibody (autoAb) detection and provide sufficient information to interpret the results of autoAb tests. METHODS: The study included 1,052 patients for whom IIF and LIA tests had been performed simultaneously for a systemic autoimmune disease work-up. All patients were divided into either the systemic autoimmune group or non-autoimmune group, and the systemic autoimmune group was further divided into systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome, systemic sclerosis (SSc), and dermatomyositis/polymyositis (DM/PM). The diagnostic performance of IIF and LIA was analysed according to the distribution of IIF patterns and autoAbs identified by LIA. RESULTS: The overall sensitivity/specificity of IIF and LIA for systemic autoimmune disease was 63.5%/80.3% and 66.1%/83.2%, respectively. IIF showed higher sensitivity for SLE than LIA, but the sensitivity of LIA was higher for Sjögren's syndrome and DM/PM. The speckled pattern was the most commonly observed pattern in systemic autoimmune diseases with the exception of SSc. In the majority of systemic autoimmune diseases and their various IIF patterns, both anti-Ro-52 and anti-SS-A were the most prevalent autoAbs. In addition, a majority of the systemic autoimmune diseases showed specific dominant positive patterns or a combination of IIF and LIA results that were disease specific. CONCLUSIONS: Utilising both methods together not only increased the sensitivity in most cases but also provided more information from the combination of results, augmenting their interpretation with the advantage of simultaneous identification of autoAbs.
23031611 Integration of complementary and alternative medicine in primary care: what do patients wa 2012 Dec OBJECTIVE: To explore patients' perspectives towards integration of Complementary and Alternative Medicine (CAM) in primary care. METHODS: A mixed-methods approach was used. This included a survey on use, attitudes and disclosure of CAM, an e-panel consultation and focus group among patients with joint diseases. RESULTS: A total of 416 patients responded to the survey who suffered from osteoarthritis (51%), rheumatoid arthritis (29%) or fibromyalgia (24%). Prevalence of CAM use was 86%, of which 71% visited a CAM practitioner. Manual therapies, acupuncture and homeopathy were most frequently used. A minority (30%) actively communicated CAM use with their General Practitioner (GP). The majority (92%) preferred a GP who informed about CAM, 70% a GP who referred to CAM, and 42% wanted GPs to collaborate with CAM practitioners. Similar attitudes were found in the focus group and upon e-panel consultation. CONCLUSIONS: Most patients in primary care want a GP who listens, inquires about CAM and if necessary refers to or collaborates with CAM practitioners. PRACTICE IMPLICATIONS: To meet needs of patients, primary care disease management would benefit from an active involvement of GPs concerning CAM communication/referral. This study presents a model addressing the role of patients and GPs within such an integrative approach.