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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19881269 | Formulation and evaluation of press coated tablets for pulsatile drug delivery using hydro | 2009 Nov | The aim of present investigation was to develop press coated tablet for pulsatile drug delivery of ketoprofen using hydrophilic and hydrophobic polymers. The drug delivery system was designed to deliver the drug at such a time when it could be most needful to patient of rheumatoid arthritis. The press coated tablets containing ketoprofen in the inner core was formulated with an outer shell by different weight ratio of hydrophobic polymer (micronized ethyl cellulose powder) and hydrophilic polymers (glycinemax husk or sodium alginate). The release profile of press coated tablet exhibited a lag time followed by burst release, in which outer shell ruptured into two halves. Authors also investigated factors influencing on lag time such as particle size and viscosity of ethyl cellulose, outer coating weight and paddle rpm. The surface morphology of the tablet was examined by a scanning electron microscopy. Differential scanning calorimeter and Fourier transformed infrared spectroscopy study showed compatibility between ketoprofen and coating material. | |
19701696 | Somatization is associated with physical health-related quality of life independent of anx | 2009 Oct | PURPOSE: To test the relative importance of anxiety, depression and somatization as correlates of physical health-related quality of life (HRQOL) in several chronic physical disorders. METHODS: In a cross-sectional study of patients with colorectal cancer (N = 162), glaucoma (N = 100), rheumatoid arthritis (N = 168), systemic sclerosis (N = 56) and systemic lupus erythematosus (N = 56), we assessed specific disease severity and used the Symptom Distress Checklist (SCL-90) for psychologic dimensions. Outcome was assessed with the WHO Quality of Life Instrument, Short Form using hierarchical regression to determine independent correlates of HRQOL. RESULTS: After adjustment for demographic features, stage of cancer and pain (final models), the SCL-90 somatization score was the only psychologic distress covariate significantly correlated to physical HRQOL in all diseases (Betas between -0.33 and -0.49) except in systemic sclerosis and scleroderma, where depression was also a correlate. In glaucoma patients, the SCL-90 somatization score was the only significant covariate for physical HRQOL in the final model. CONCLUSIONS: Since reported number of bodily symptoms is both associated with physical HRQOL and treatable in its own right, our findings suggest a possible new avenue to improve the HRQOL in patients with chronic physical disease. Whether this offers greater benefit than treatments for anxiety and depression needs further research. | |
19595612 | CD40 and autoimmunity: the dark side of a great activator. | 2009 Oct | CD40 is a tumor necrosis factor receptor superfamily member expressed by immune and non-immune cells. CD40:CD154 interactions mediate T-dependent B cell responses and efficient T cell priming. Thus, CD40 is a likely candidate to play roles in autoimmune diseases in which activated T and B cells cause pathology. Diseases in which CD40 plays a pathogenic role include autoimmune thyroiditis, type 1 diabetes, inflammatory bowel disease, psoriasis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. This review discusses the role of CD40:CD154 interaction in human and mouse autoimmunity, human polymorphisms associated with disease incidence, and disrupting CD40:CD154 interactions as an autoimmune therapy. | |
19519441 | Overview of the role of macrophage migration inhibitory factor (MIF) in inflammatory bowel | 2009 | An array of investigations has revealed that macrophage migration inhibitory factor (MIF) plays an important role in the exacerbation of a wide range of inflammatory diseases. For the past two decades, we have extensively studied MIF's pathophysiological roles in human diseases, and have accumulated evidence elucidating its molecular mechanisms in the pathogenesis of immune disorders and inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel diseases (IBD). In a study of IBD, we demonstrated for the first time that anti-MIF antibody suppressed the degree of dextran-sulfate sodium (DSS)-induced colitis, indicating its potential therapeutic use for IBD patients. Following that report, a number of researchers, including us, clarified that MIF was profoundly involved in various gastrointestinal disorders, such as hepatitis and pancreatitis. We recently revealed that a MIF-deficient mouse was resistant to a challenge of DSS, and showed few clinical and pathological signs. Currently, we are developing new therapeutic approaches targeting MIF in inflammatory disorders, particularly IBD. We here overview MIF's pathophysiological function, mainly in IBD, and introduce two therapeutic approaches, anti-MIF antibody treatment and MIF-antisense therapy, via a drug delivery system using 1,3-beta glucan. | |
19502675 | Problems in the rehabilitation of patients following total shoulder replacement surgery - | 2009 Mar | BACKGROUND: There are a number of indications for total joint replacement surgery, mainly degenerative changes with limited function, rheumatoid arthritis, post-traumatic changes, arthropathy accompanying rotator cuff injuries. Problems in the rehabilitation of patients following partial or total shoulder joint replacement surgery result from the anatomy and biomechanics of the shoulder, including extensive joint mobility range, relatively weak muscle stabilization and a frequent need to reconstruct the rotator muscles and joint capsule. The aim of this paper is to present problems in the rehabilitation of a patient following total shoulder replacement surgery. DESCRIPTION OF A CASE: A female patient (St. G., 69) was involved in a traffic accident and, immediately after the accident, underwent surgery with stabilisation of the bone fragments with Kirschner wires. Five years following the operation, the patient was qualified for total shoulder replacement surgery on account of pain, limited mobility and muscle weakness. One year later, the patient was admitted to the Rehabilitation Department at the Regional Hospital No. 2 in Rzeszów for rehabilitation. The main goals of the rehabilitation were improvement of neuromuscular control of the scapula, reduction of pain, restoration of the function of muscles supplying the glenohumeral joint, and improvement of the range of joint mobility. SUMMARY AND DISCUSSION: Total shoulder replacement is a difficult operative procedure and its outcomes are often unsatisfactory to the patient. Pain reduction and improvement of limb function are good postoperative outcomes. A satisfactory result of total shoulder replacement depends on the experience of the operator, physiotherapist and an appropriate rehabilitation programme. CONCLUSION: Rehabilitation following partial shoulder replacement should be designed not only to increase shoulder joint mobility, but also to restore the entire stabilization mechanism, and improve upper limb function. | |
19491002 | Tetrada of the possible mycophenolate mofetil embryopathy: a review. | 2009 Jul | Mycophenolate mofetil (MFM) is an immunosuppressant agent used in organ transplantation, rheumatoid arthritis and lupus nephritis. Experimental data show that doses roughly equivalent to those used clinically in transplant patients may cause fetal resorption and malformations in pregnant rats and rabbits. There are limited data regarding the use of MFM in pregnant women. The human experience is based on 9 case reports, 1 case series, and 2 registry data. The most frequent structural anomalies described in 12 newborns exposed to MFM were as follows: microtia (11); auditory canal atresia (8); cleft lip and palate (6); micrognathia (4); hypertelorism (4); ocular coloboma (3); short fingers (2) and hypoplasic nails (2). The distinctive and unique phenotype associated with MFM exposure during pregnancy (EMFO tetrada: Ear, Mouth, Fingers, Ocular/Organ malformation) raised the hypothesis that MFM may be a real teratogenic drug. Appropriate recommendations to prevent this possible new embryopathy are given. | |
19465928 | Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiati | 2009 Jun | Two distinct helper T (TH) subsets, TH1 and TH17, mediate tissue damage and inflammation in animal models of various immune diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases and allergic skin disorders. These experimental findings, and the implication of these TH subsets in human diseases, suggest the need for pharmacological measures to manipulate these TH subsets. Here we show that prostaglandin E2 (PGE2) acting on its receptor EP4 on T cells and dendritic cells not only facilitates TH1 cell differentiation but also amplifies interleukin-23-mediated TH17 cell expansion in vitro. Administration of an EP4-selective antagonist in vivo decreases accumulation of both TH1 and TH17 cells in regional lymph nodes and suppresses the disease progression in mice subjected to experimental autoimmune encephalomyelitis or contact hypersensitivity. Thus, PGE2-EP4 signaling promotes immune inflammation through TH1 differentiation and TH17 expansion, and EP4 antagonism may be therapeutically useful for various immune diseases. | |
19330908 | Sesquiterpene lactones with antinociceptive and antipyretic activity from two Centaurea sp | 2009 Mar 18 | ETHNOPHARMACOLOGICAL RELEVANCE: Several Centaurea species are used to alleviate pain and inflammatory symptoms in rheumatoid arthritis, high fever, and head ache in Turkish folk medicine. AIM OF THE STUDY: The effectiveness of extracts, fractions and subfractions from dried Centaurea solstitialis L. subsp. solstitialis (CSS) (Asteraceae) roots and aerial parts were studied on mice. MATERIALS AND METHODS: The antinociceptive and antipyretic effects of Centaurea solstitialis L. subsp. solstitialis have been investigated by using p-benzoquinone-induced writhing reflex for antinociceptive activity and Freund's Complete Adjuvant-induced pyrexia model for antipyretic activity assessment in mice. RESULTS: The ethanolic extract from the aerial parts of the plant was shown to possess significant antinociceptive (p < 0.01) and antipyretic activities (p < 0.01). The extract was then submitted to subsequent solvent extractions and chromatographic processes. Through bioassay-guided fractionation and isolation procedures two sesquiterpene lactones, solstitialin A and acetyl solstitialin, were isolated and defined as the active components of CSS. On the other hand, a comparative study was conducted on another species, Centaurea depressa Bieb., which has no similar folkloric utilization. Following the same fractionation chart same compounds were defined as the active ingredients. CONCLUSION: Results of the present study proved that aerial part of CSS possesses antinociceptive and antipyretic activities supporting the folkloric assertion in Turkish folk medicine. However, these effects seem not limited to CSS, some other Centaurea species, in fact, having no folkloric use might be equally active. | |
19318799 | Intralymphatic histiocytosis. A clinicopathologic study of 16 cases. | 2009 Apr | Intralymphatic histiocytosis is a rare condition characterized by the presence of dilated lymphatic vessels containing aggregates of mononuclear histiocytes (macrophages) within their lumina. The phenomenon seems to occur almost exclusively within the reticular dermis. Although its pathogenesis remains uncertain, there has been speculation about the possible relationship between intralymphatic histiocytosis and intravascular reactive angioendotheliomatosis. In addition, several examples historically have been associated with rheumatoid arthritis. We describe our experience with 16 cases of intralymphatic histiocytosis. Clinically, the lesions were located predominantly on the upper and lower limbs, and they consisted of asymptomatic and poorly demarcated erythematous plaques and livedo reticularis-like lesions. They were characterized histopathologically by dilated vascular structures involving the reticular dermis. Some of these dilated vessels had empty lumina, whereas others contained variable number of mononuclear histiocytes. An inflammatory response of variable intensity from case to case was also present in the adjacent dermis. The dilated vessels exhibited thin walls with irregular shapes, and a single discontinuous layer of flat endothelial cells lined their lumina. Immunohistochemically, the endothelial cells lining the dilated lumina expressed immunoreactivity for CD31, CD34, podoplanin, D2-40, Lyve-1, and Prox-1, which confirmed their nature as lymphatic endothelial cells. Intralymphatic mononuclear histiocytes expressed CD68 (PGM1), although some cases also had variable immunoexpression for myeloperoxidase, CD31, and podoplanin. In the 4 cases that employed double immunohistochemistry, with podoplanin + CD68 (PGM1) or with Lyve-1 + CD68 (PGM1), each marker highlighted their specific target cells unequivocally; the endothelial cells expressed podoplanin or Lyve-1 immunoreactivity, and intralymphatic histiocytes showed CD68 (PGM1) immunoexpression. Our findings expand on the previously described morphologic and immunohistochemical features of intravascular histiocytosis. We also discuss the possible relationship between intralymphatic histiocytosis and the so-called reactive intravascular angioendotheliomatosis. | |
19142624 | APRIL in B-cell malignancies and autoimmunity. | 2009 | A Proliferation Inducing Ligand (APRIL) was first identified as a cytokine expressed predominantly by tumour tissues and was not found in most normal tissues. The activity of this new cytokine, in terms of its ability to stimulate tumour cell proliferation in vivo, determined the catchy acronym of yet another TNF family cytokine: APRIL. Reports showing an association between APRIL and cancer have since been prolific, in particular, those showing a link with B cell malignancies. Evidence is accumulating that APRIL is also a player in several autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and Sjoegren's syndrome. However, we now know that APRIL also plays an important role in the immune system and in lymphocyte biology. In this chapter we outline the physiological role of APRIL in immunity and describe what is known regarding the role of APRIL in B cell malignancies and autoimmune disease. | |
21475699 | Cachexia as a major underestimated and unmet medical need: facts and numbers. | 2010 Sep | Cachexia is a serious, however underestimated and underrecognised medical consequence of malignant cancer, chronic heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cystic fibrosis, rheumatoid arthritis, Alzheimer's disease, infectious diseases, and many other chronic illnesses. The prevalence of cachexia is high, ranging from 5% to 15% in CHF or COPD to 60% to 80% in advanced cancer. By population prevalence, the most frequent cachexia subtypes are in order: COPD cachexia, cardiac cachexia (in CHF), cancer cachexia, and CKD cachexia. In industrialized countries (North America, Europe, Japan), the overall prevalence of cachexia (due to any disease) is growing and currently about 1%, i.e., about nine million patients. The relative prevalence of cachexia is somewhat less in Asia, but is a growing problem there as well. In absolute terms, cachexia is, in Asia (due to the larger population), as least as big a problem as in the Western world. Cachexia is also a big medical problem in South America and Africa, but data are scarce. A consensus statement recently proposed to diagnose cachexia in chronic diseases when there is weight loss exceeding 5% within the previous 3-12Â months combined with symptoms characteristic for cachexia (e.g., fatigue), loss of skeletal muscle and biochemical abnormalities (e.g., anemia or inflammation). Treatment approaches using anabolics, anti-catabolic therapies, appetite stimulants, and nutritional interventions are under development. A more thorough understanding of the pathophysiology of cachexia development and progression is needed that likely will lead to combination therapies being developed. These efforts are greatly needed as presence of cachexia is always associated with high-mortality and poor-symptom status and dismal quality of life. It is thought that in cancer, more than 30% of patients die due to cachexia and more than 50% of patients with cancer die with cachexia being present. In other chronic illnesses, one can estimate that up to 30% of patients die with some degree of cachexia being present. Mortality rates of patients with cachexia range from 10% to 15% per year (COPD), to 20% to 30% per year (CHF, CKD) to 80% in cancer. | |
21375035 | [Natural history of carpal tunnel syndrome--a review]. | 2010 Jul | The review of the literature on the natural history of the carpal tunnel syndrome is presented. It is shown that the condition is characterised by non-uniform and unpredictable clinical course, in which besides the progressive type of evolution, a regressive one (characterised by spontaneous resolution of symptoms) and type of stable clinical picture (with episodes of exacerbation and resolution of symptoms) exist. Proportion of prevalence of particular types of clinical courses is not precisely estimated, but it appears that at least a half of the cases is of non-progressive type. Non-operative treatment of the condition may be effective in those particular cases, without risk of the development of severe neurological complications as a consequence of impairment of the median nerve. The evidence form analysed studies shows that in carpal tunnel syndrome, the clinical symptoms and signs and nerve conduction disturbances have different natural histories. Clinical features are subjected to greater temporal fluctuations than electrophysiological findings, and they frequently do not correlate one with another. There is not common opinion about efficacy of intervention in extreme carpal tunnel syndrome, characterised by severe conduction disturbances in electrophysiological tests and fixed neurological deficits, however surgical decompression of the carpal tunnel appears to be more promising than decline of the treatment. The natural history of the syndrome occurred in the course of other diseases (or conditions, e.g. pregnancy) is different, depending on the type of the disease itself. In the commonest systemic diseases associated with carpal tunnel syndrome, such as diabetes, hypothyroidism and rheumatoid arthritis, there is not common opinion about their prognostic effect on the natural course of the syndrome. | |
21261172 | Extracorporeal photopheresis: a review on the immunological aspects and clinical applicati | 2010 Dec | Extracorporeal photopheresis (ECP) was hailed as a new therapeutic concept for the treatment of diseases caused by aberrant T lymphocytes since it was first described more than twenty years ago. Advances in molecular biology and immunology have allowed a greater understanding of the mechanisms involved in ECP. As a result, ECP is being increasingly considered as a safe and promising immunomodulatory therapy with diverse clinical applications. At present ECP is approved by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL). ECP is considered a relatively safe and promising immunomodulatory therapy with diverse clinical applications reported in the literature. ECP has been used in the treatment of patients following acute allograft rejection in cardiac, lung, renal or liver transplantation, graft-versus-host disease, systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis and pemphigus vulgaris. The use of ECP as a novel form of therapy is in constant evolution with newer studies focusing on the treatment of patients with Crohn's disease and the immunological effects of ECP in children with type 1 diabetes mellitus. However, because the exact mechanism by which ECP exerts its effects remains to be described in detail and because important questions regarding the use of ECP in the clinical setting, such as length of therapy or design of specific protocols, concomitant use of immunosupressive therapy, patient characteristics, long term side effects, assessment of therapy efficacy and cost effectiveness continue to remain unanswered, the exact role of ECP cannot be fully established except in the case of patients with CTCL and GvHD. Nevertheless, future clinical studies with ECP can be done with the objective of designing more appropriate treatment protocols based on expected patient response and with a side effect profile that is fairly tolerable. | |
21161563 | Lactoferrin inhibits the inflammatory and angiogenic activation of bovine aortic endotheli | 2011 May | OBJECTIVE: Lactoferrin (Lf) is known to have anti-cancer and anti-inflammatory activities; however, its therapeutic mechanism has not been defined. In this study, to explain the therapeutic mechanism of Lf, we examined the effect of Lf on endothelial cell activation, leukocyte integration, and angiogenesis in vitro. METHODS: Endothelia-leukocyte adhesion assays were used to assess primary cultures of bovine aortic endothelial cells (BAECs) activation following LPS treatment. The mRNA expression of ICAM-1 and proinflammatory cytokines was measured using RT-PCR. Each step of angiogenesis was evaluated in vitro, including endothelial cell proliferation, migration, and tube formation. Proliferation was examined using WST-1 and BrdU incorporation assays, while wound migration assays were used to evaluate cell migration; capillary-like tube formation assays on Matrigel were used to assess tube formation. RESULTS: Lf reduced the adhesion of human monocyte-like THP-1 cells to BAECs by 45%. Lf also reduced mRNA expression of ICAM-1 and proinflammatory cytokines in BAECs. Lf significantly inhibited BAEC proliferation, migration, and tube formation. CONCLUSIONS: Lf exerted a potent effect on BAEC activation, suggesting that it might function via an endothelia-based mechanism in the treatment of various diseases, including rheumatoid arthritis and cancer. | |
21159896 | Concordance study of 3 direct-to-consumer genetic-testing services. | 2011 Mar | BACKGROUND: Several companies offer direct-to-consumer (DTC) genetic testing to evaluate ancestry and wellness. Massive-scale testing of thousands of single-nucleotide polymorphisms (SNPs) is not error free, and such errors could translate into misclassification of risk and produce a false sense of security or unnecessary anxiety in an individual. We evaluated 3 DTC services and a genomics service that are based on DNA microarray or solution genotyping with hydrolysis probes (TaqMan® analysis) and compared the test results obtained for the same individual. METHODS: We evaluated the results from 3 DTC services (23andMe, deCODEme, Navigenics) and a genomics-analysis service (Expression Analysis). RESULTS: The concordance rates between the services for SNP data were >99.6%; however, there were some marked differences in the relative disease risks assigned by the DTC services (e.g., for rheumatoid arthritis, the range of relative risk was 0.9-1.85). A possible reason for this difference is that different SNPs were used to calculate risk for the same disease. The reference population also had an influence on the relative disease risk. CONCLUSIONS: Our study revealed excellent concordance between the results of SNP analyses obtained from different companies with different platforms, but we noted a disparity in the data for risk, owing to both differences in the SNPs used in the calculation and the reference population used. The larger issues of the utility of the information and the need for risk data that match the user's ethnicity remain, however. | |
21120503 | Comparative proteome analysis of peripheral blood mononuclear cells in systemic lupus eryt | 2012 Mar | To identify and quantify protein profiles from peripheral blood mononuclear cells (PBMC) of systemic lupus erythematosus (SLE) patients with isobaric Tagging for Relative and Absolute protein Quantification (iTRAQ)-based proteomic technology and to find differentially expressed proteins in SLE. PBMC were collected from patients of six stable SLE, six active SLE, six rheumatoid arthritis (RA), and six healthy donors. After protein extraction and concentration, the pooled protein content was labeled with iTRAQ reagents and then subjected to multiple chromatographic fractionation and tandem mass spectrometry. ProteinPilotâ„¢ 3.0 software and a database of IPI (International Protein Index) human 3.62 were used for database searching and statistical analysis. A total of 452 proteins were identified. Of these, 67 unique proteins were observed twofold or more alteration in levels across groups. The proteins determined support existing knowledge and uncover novel biomarker candidates. These results indicate that iTRAQ-based technology can serve as a useful aid for identification and quantification proteins from PBMC. | |
21083302 | Determination of calcium in synovial fluid samples as an aid to diagnosing osteoarthritis. | 2010 Feb | BACKGROUND: Microscopic inorganic crystals are commonly observed in the synovial fluid of patients suffering from arthritic diseases. Basic calcium phosphate (BCP) crystals are known to occur quite commonly in the joint fluid of osteoarthritis (OA) patients and are insoluble at physiological pH. Current analysis of patient synovial fluid depends on light microscopy and staining with Alizarin Red-S. Both methods cannot identify crystals < 1µm in size and are highly subjective. This article investigates the use of o-cresolphthalein complexone (OCP), a colorimetric reagent, to quantify calcium from crystals isolated from synovial fluid samples as a means of identifying the presence of BCP and, hence, improving the diagnosis of OA. RESULTS: Inorganic crystals were isolated following degradation of the biological sample matrix with hyaluronidase. 1-M HNO(3) was used for crystal dissociation into ions and the colorimetric response of OCP to calcium was measured in a basic environment of 2-amino-2-methyl-1-propanol. The average calcium content in OA patient samples was up to 40% higher than in rheumatoid arthritis (RA) patient samples. RA samples were used as a comparison, because they are generally accepted to be crystal free. Within the OA group, higher levels of calcium were detected in three out of 12 synovial fluid samples, which correlated with a significantly greater number of BCP crystals detected during microscopic examination. CONCLUSIONS: A simple method based on colorimetry for measurement of calcium content and semiquantification of BCP crystals in synovial fluid samples has been described. Sample pretreatment following addition of hyaluronidase proved to be effective in reducing viscosity and aiding the dissociation of BCP crystals in synovial fluid samples. | |
20950265 | A timely review of state-of-the-art chronopharmaceuticals synchronized with biological rhy | 2010 Dec | Extensive research into circadian rhythms and their influence on biological systems has given rise to the science of chronobiology and subsequently chronotherapy, the science of delivering drugs in synchrony with biological rhythms. The field of chronotherapeutics paves the way for advances and complexities in current drug delivery technology. The ultimate goal of current chronopharmaceutical research strives to design ideal chronotherapeutic drug delivery systems that respond to such therapeutic needs. Considering the fact that physiological events such as heart rate, blood pressure, plasma concentration of hormones, plasma proteins and enzymes display constancy over time, drug delivery systems with constant release profiles have thus been favored. However, due to circadian rhythms, the conventional paradigm of constant drug delivery may not be what is needed. Instead, precisely timed drug delivery systems are required in order to correlate drug delivery with circadian rhythms to provide maximum therapeutic efficacy for chronotherapeutic diseases when most needed. The aim of this review paper is to outline the concepts in designing chronopharmaceuticals from a clinical viewpoint of major chronotherapeutic diseases such as asthma, allergic rhinitis, cardiovascular disorders, rheumatoid arthritis and cancer as well as relatively minor niche areas of interest such as in glaucoma, diabetes, immunity, pain, gastric ulcers, epilepsy and even HIV/AIDS that would require chronotherapy. In addition this review paper attempts to concisely assimilate and explicate the role of circadian rhythms in these various disease states and provide a focused overview of the current state-of-the-art in designing strategies for chronopharmaceutical formulations employed for treating chronotherapeutic diseases. | |
20734544 | Development and use of touch - screen computer-assisted self interviewing in Portuguese pa | 2010 Apr | AIM: The major purpose of this study was to evaluate alternative automated methods of collecting data on health related quality of life (HR-QoL). In order to achieve this, we developed a study with the following objectives: (1) to evaluated the feasibility of electronic version in patients with different chronic pathologies of the immune system using Short Form 36version2 (SF-36v2), (2) to evaluate the construct validity of SF-36v2 using the electronic data capture, and (3) to compare electronic version questionnaires with paper questionnaires in terms of patients' acceptance, data quality, and reliability. METHODS: Out-patients with chronic immune diseases (HIV infection, lupus, scleroderma, rheumatoid arthritis, Behçet and Sjögren), were randomly selected to completed electronic and paper SF-36v2 (n=50) before consultation in Clinical Immunology Unit, in Hospital Santo António-Centro Hospitalar do Porto (CI-HGSA). RESULTS: There were very high correlations in SF-36v2 responses (p< .001) between the paper and electronic forms. Internal reliability coefficients (Cronbach's alpha) showed good internal consistency for all reported responses in either, computer and paper. There were no missing data in electronic version or paper. About 84% of the patients prefer to use the computer version in future. CONCLUSION: The electronic HR-QoL assessment is technically possible and it can provide reliable and valid clinically significant information which can either be used in routine care appointments. | |
20727711 | Somatic hypermutation and antigen-driven selection of B cells are altered in autoimmune di | 2010 Dec | B cells have been found to play a critical role in the pathogenesis of several autoimmune (AI) diseases. A common feature amongst many AI diseases is the formation of ectopic germinal centers (GC) within the afflicted tissue or organ, in which activated B cells expand and undergo somatic hypermutation (SHM) and antigen-driven selection on their immunoglobulin variable region (IgV) genes. However, it is not yet clear whether these processes occurring in ectopic GCs are identical to those in normal GCs. The analysis of IgV mutations has aided in revealing many aspects concerning B cell expansion, mutation and selection in GC reactions. We have applied several mutation analysis methods, based on lineage tree construction, to a large set of data, containing IgV productive and non-productive heavy and light chain sequences from several different tissues, to examine three of the most profoundly studied AI diseases - Rheumatoid Arthritis (RA), Multiple Sclerosis (MS) and Sjögren's Syndrome (SS). We have found that RA and MS sequences exhibited normal mutation spectra and targeting motifs, but a stricter selection compared to normal controls, which was more apparent in RA. SS sequence analysis results deviated from normal controls in both mutation spectra and indications of selection, also showing differences between light and heavy chain IgV and between different tissues. The differences revealed between AI diseases and normal control mutation patterns may result from the different microenvironmental influences to which ectopic GCs are exposed, relative to those in normal secondary lymphoid tissues. |