Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 17159810 | Antilipoxygenase activity of copper complexes of aminoalkanoate type. | 2006 Dec | OBJECTIVES: Lipoxygenases (EC 1.13.11.12, LOX) catalyze the hydroperoxidation of polyunsaturated fatty acids (PUFA). This reaction leads to the production of conjugated hydro peroxide dienes of PUFA. In animals, LOX generate leukotriens (LT) and lipoxins, which belong to inflammatory mediators. It is believed that restricting LT synthesis by inhibition of LOX would have therapeutic utility for the treatment of a variety of inflammatory conditions (e.g. asthma, rheumatoid arthritis, psoriasis). METHODS & RESULTS: The process of production and elimination of radical intermediates in vitro can be monitored by determination of LOX activity. We assessed the concentration of PUFA hydroperoxides in our system with LOX-catalyzed enzyme reaction spectrophotometrically. The inhibition of LOX activity (LOX from cytosol fraction of rat lungs) with selected N-salicylideneaminoalkanoatocopper(II) complexes was tested. In our experiments, all compounds tested showed an inhibitory effect on LOX catalyzed hydroperoxidation of PUFA. Cu(II) (from CuSO(4).5H(2)O dilution) ions also inhibited this enzyme reaction, but all compounds studied had a 10 times higher anti-LOX activity. The most effective of these complexes was monohydrate aqua-(N-salicylidene-L-a-alaninato)copper(II) complex [Cu(sal-L-alpha-ala)(H(2)O)].H(2)O with IC(50) 1.86 x 10(-4) mol/l. CONCLUSIONS: These complexes are known for their anti-phlogistic and radioprotective properties and they can be classified as potential anti-radical compounds. The structure of these complexes is similar to the active site of Cu,Zn-SOD (superoxide dismutase) and superoxide radical scavenger activity of these complexes is known. We found that these copper complexes were capable to inhibit LOX activity, which may be related with their anti-radical properties. | |
| 17136494 | Engagement of CD44 up-regulates Fas ligand expression on T cells leading to activation-ind | 2007 Jan | Activation-induced cell death (AICD) plays a pivotal role in self-tolerance by deleting autoreactive T cells, but a defect of AICD results in expansion of autoreactive T cells and is deeply involved in the pathogenesis of rheumatoid arthritis. Although the process of AICD is mainly mediated by Fas Ligand (FasL)/Fas signaling, it remains unclear what induces FasL expression on T cells. In the present study, we found that CD44 was the most potent stimulator of FasL expression on human peripheral T cells. CD44 cross-linking rapidly up-regulated FasL expression on the T cell surface by delivery from the cytoplasm without new FasL protein synthesis. This up-regulation of FasL was mediated by activation of a tyrosine kinase, IP3 receptor-dependent Ca(2+) mobilization and actin cytoskeletal rearrangements. Furthermore, AICD induced by CD3 restimulation was inhibited by hyaluronidase as well as by soluble Fas, indicating an interaction between membrane-bound hyaluronan and the cell surface CD44 was involved in the up-regulation of FasL expression on T cells and subsequent AICD. We therefore propose that the engagement of CD44 on T cells can eliminate autoreactive T cells by expression of FasL and FasL-mediated AICD. | |
| 17005503 | Measuring autonomy in disabled people: Validation of a new scale in a UK population. | 2006 Sep | OBJECTIVE: To evaluate the validity and reliability of an English version of the Impact on Participation and Autonomy Questionnaire (IPA). The original Dutch IPA has been shown to load onto five factors. DESIGN: A validation study. SETTING: Outpatients clinics and people's homes. SUBJECTS: Two hundred and thirteen people with multiple sclerosis, rheumatoid arthritis, spinal cord injury, and general practice attendees, stratified by level of disability (median age 54, 42% male, 58% female). INCLUSION CRITERIA: English as first language, aged 18-75, Mental Status Questionnaire score >6. INTERVENTIONS: Self- and interviewer-administered outcome measures. MAIN MEASURES: IPA, including one new item (66 participants completed the IPA on a second occasion). OTHER MEASURES: Short Form-36 Health Survey (SF-36), London Handicap Scale, three domains of the Functional Limitations Profile (FLP): household management, social integration, emotion. RESULTS: Confirmatory factor analysis confirmed the construct validity of the IPA (Normal Fit Index = 0.98, Comparative Fit Index = 0.99), indicating a good fit to the model. Convergent and discriminant validity were confirmed by the predicted associations, or lack of, with the exception of a poor association between the 'social life/relationships' IPA subscale and FLP-emotion. Internal reliability of the IPA was confirmed (Cronbach alphas >0.8; item-total correlations for all subscales >0.5). Test-retest reliability was confirmed for all items (weighted kappas >0.6) and subscales (intraclass correlation coefficients >0.90). CONCLUSIONS: The English IPA is a valid, reliable and acceptable measure of participation and autonomy in people with a range of conditions and can make a unique and fundamental contribution to outcome assessment. Further research is required to examine the responsiveness of the IPA to change over time, its clinical utility and suitability for use with people from ethnic minorities and with older people. | |
| 16929123 | Joint symptoms: a practical problem of anastrozole. | 2006 | BACKGROUND: Anastrozole and tamoxifen have mild toxicity. However, we noticed that more patients treated with anastrozole complained of joint symptoms than expected. In particular, digital stiffness as is seen with rheumatoid arthritis is a problem. Some clinical trials of anastrozole in Europe and the United States reported musculoskeletal disorders as adverse events, however, joint symptoms were not described in detail. PATIENTS AND METHODS: At our clinic from August 2001 to March 2005, 53 postmenopausal women with estrogen receptor-positive breast cancer were treated with anastrozole. We calculated the incidence and classified the grade of joint symptoms by interviewing patients. We also investigated the patients' characteristics and their relevance to joint symptoms. RESULTS: Of 53 patients, 14 patients (26%) had joint symptoms (13 patients with digital stiffness and 3 patients with arthralgias of wrist and shoulders). Joint symptoms tended to occur in the patients who had previously undergone chemotherapy; however, there has no relationship between prior hormonal therapy and joint symptoms. Seven patients who discontinued anastrozole treatment showed improved symptoms. Five patients with grade 1 digital stiffness continued anastrozole treatment without additional treatment. Two patients with grade 1 digital stiffness, who took a Chinese herbal medicine showed improved symptoms and continued anastrozole treatment. CONCLUSION: Benefits to the patients may possibly be lost by discontinuation of anastrozole or changing to tamoxifen since the clinical superiority of anastrozole to tamoxifen has been reported. We should continue anastrozole in patients with low grade symptoms, while ensuring that patients are aware of the toxicity of anastrozole. | |
| 16827387 | [Post-anesthetic autologous blood donation used in knee and hip arthroplasty]. | 2006 Jun | OBJECTIVE: To explore the clinical application of the postanesthetic autologous donation and the postoperative transfusion during the knee and hip replacement surgeries. METHODS: Thirty-three patients (17 males, 16 females) admitted for the elective joint replacement surgeries from September 2004 to January 2005 were included in this study. Of the 33 patients, 5 were diagnosed with rheumatoid arthritis, 23 with femoral head necrosis, and 5 with knee osteoarthritis. Immediately after anesthesia, 400 ml of the blood was drawn and transfused after the surgery. The blood pressure was monitored during the blood drawing, postoperative blood parameters were recorded, surgical site drainage and signs of infections were observed, and the other clinical data were collected. RESULTS: Of the 33 patients, 27 only received autologous transfusion, including 21 patients who underwent the unilateral hip replacement and 6 patients who underwent the unilateral knee replacement. All these 6 patients with the unilateral knee replacement received the blood drained from the surgical sites in addition to the blood obtained from the post-anesthetic autologous donation. Another 6 cases with the bilateral hip and knee replacement received the blood drained from the surgical sites, the blood obtained from the post-anesthetic autologous donation and 400 ml of the allogeneic blood transfusion. The blood received postoperatively averaged 650 ml (range, 200-1 150 ml), haemoglobin (Hb) was averaged 88 g/L (68-102 g/L), and Hct was averaged 24.6% (20.5%-31.5%). Hb and Hct were lower after operation than before operation (P < 0.01). CONCLUSION: Postoperative blood transfusion following the postanesthetic and preoperative autologous donation can be successfully applied to most of the patients undergoing the knee or hip replacement so as to reduce complications of the allogeneic blood transfusion. | |
| 16637849 | Diffuse granulomatous necrotizing scleritis. | 2006 Apr | CASE REPORT: A 34-year-old man presented with anterior scleral thinning in the right eye (RE) and a painful nodular scleritis in the left eye (LE). Fundus examination showed a healed vasculitis and an inferior epiretinal neovascular membrane in the LE. Topical and systemic oral steroids and antiviral medication were prescribed. One year later, optic disc hyperaemia and swelling and macular oedema became apparent in the LE. Pulsed intravenous steroids were administered for 1 year, when a nasal septum perforation and vitreous haemorrhage in the LE were diagnosed. The eye was enucleated 3.5 years after the initial complaint. Necrotizing granulomatous tissue replacing the sclera and subconjunctival granulomatous tissue were observed. Six months later, oedema and neovascularization of the right optic disc were observed and cyclophosphamide was started, with regression of the clinical signs. No systemic abnormalities have so far become apparent. DISCUSSION: Posterior scleritis is most often observed in patients with no signs of associated systemic autoimmune disease. The diagnosis in this case is most probably one of Wegener's granulomatosis (WG). In WG, the diagnosis is based on necrotizing granulomas of the respiratory tract, generalized focal necrotizing vasculitis and focal necrotizing glomerulonephritis. Eye involvement with WG has been reported in up to 58% of cases. Evaluation of the scleritis patient should include a detailed medical history, chest X-rays, blood tests, autoantibody serology and analysis of urinary sediment. Cyclophosphamide is the treatment of choice for patients with ocular manifestations of WG, polyarteritis nodosa or rheumatoid arthritis, either alone or in combination with systemic steroids. Visual loss is expected in 85% of individuals with severe necrotizing posterior scleritis. | |
| 16540553 | The binding of lupus-derived autoantibodies to the C-terminal peptide (83-119) of the majo | 2006 Nov | OBJECTIVES: To evaluate the binding of lupus-derived autoantibodies, double-stranded DNA and nucleosomes to the positively charged C-terminal SmD1(residues 83-119) peptide and the full-length SmD protein. METHODS: The binding of lupus-derived monoclonal antibodies, sera from patients with systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis, dsDNA and nucleosomes to the SmD1(83-119) peptide or the full-length SmD protein was determined using different ELISA methods. RESULTS: Monoclonal anti-dsDNA antibodies and the serum of patients with systemic lupus erythematosus that are positive for anti-dsDNA antibodies react with the SmD1(83-119) peptide in ELISA. However, DNaseI treatment of the blocking reagents leads to a decreased reactivity. Purified dsDNA and nucleosomes bind to the SmD1 peptide but not to the full-length SmD protein. CONCLUSIONS: The SmD1(83-119) peptide is able to bind dsDNA and nucleosomes, and dsDNA or nucleosomes in applied reagents lead to an apparent reactivity of anti-dsDNA, anti-histone or nucleosome-specific antibodies with the SmD1(83-119) peptide in ELISA. | |
| 16439439 | Atherosclerosis in Takayasu arteritis. | 2006 Sep | OBJECTIVE: Chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis are associated with accelerated atherosclerosis. We hypothesised that atherosclerosis may also be increased in Takayasu arteritis. METHODS: The frequency of atherosclerotic plaques and the intima-media thickness (IMT) were investigated in 30 female patients with Takayasu arteritis (mean age (standard deviation), 35.4 (8.0) years), along with 45 sex-matched and age-matched patients with SLE (37.4 (6.8)) and 50 healthy controls (38.2 (5.7)). Plaques were scanned and IMT was measured at both sides of the common carotids, carotid bulb, and internal and external carotid arteries by B-mode ultrasonography. Traditional risk factors for atherosclerosis were also assessed. RESULTS: Most of the atherosclerotic risk factors were comparable between patients with Takayasu arteritis and SLE. More atherosclerotic plaques were observed among patients with Takayasu arteritis (8/30; 27%) and those with SLE (8/45; 18%) than among the healthy controls (1/50; 2%; p = 0.005). Logistic regression analyses showed that the presence of a plaque was associated only with age in both Takayasu arteritis and SLE (p = 0.04 and 0.02, respectively). The mean overall IMT was significantly higher among patients with Takayasu arteritis (0.95+/-0.31 mm) than among the patients with SLE (0.58+/-0.10 mm) and the healthy controls (0.59+/-0.08 mm; p<0.001). CONCLUSION: Patients with Takayasu arteritis have a high rate of atherosclerotic plaques, at least as frequent as that observed among patients with SLE. | |
| 16294372 | Differential expression of oestrogen receptors in human secondary lymphoid tissues. | 2006 Feb | Many autoimmune diseases including rheumatoid arthritis (RA), Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) occur much more frequently in women than in men. There is much evidence that oestrogen is the major cause of this gender difference. Interestingly, oestrogen relieves the symptoms of RA and SS but it exacerbates SLE. This contradictory effect of oestrogen on autoimmune diseases is not well understood. Most of the effects of oestrogen are mediated by two receptors: oestrogen receptor alpha and beta (ERalpha and ERbeta). To determine whether these contradictory effects of oestrogen relate to the involvement of distinct effects of the two ERs, we investigated expression of ERalpha and ERbeta in human secondary lymphoid tissues. We observed that, in tonsils, ERbeta is expressed in lymphocytes of germinal centres (GC) and the follicular mantle zone as well as in granulocytes, while ERalpha is expressed only in activated germinal centres but not in the follicular zone. ERbeta is the predominant ER in human leucocytes from peripheral blood, spleen and in leucocytes infiltrating cancers in both males and females. In addition, in different human lymphoma cell lines including Hodgkin lymphoma, Burkitt lymphoma, and multiple myeloma, ERbeta is abundant while ERalpha is not detectable. Our results indicate that ERbeta is the predominant type of ER in mature lymphocytes. We suggest that ERalpha and ERbeta have distinct roles in secondary lymphoid tissues and that further studies with ERbeta-specific agonists will help to elucidate the role of ERbeta in these tissues. | |
| 16256366 | Production of active recombinant mitogen-activated protein kinases through transient trans | 2006 Apr | Mitogen-activated protein (MAP) kinases are a family of serine/threonine protein kinases that play an important role in a myriad of cellular processes, including cell proliferation, differentiation, and apoptosis. Abnormal activation of MAP kinases has been shown to participate in a variety of human diseases which include cancer, septic shock, rheumatoid arthritis, diabetes, and cardiovascular diseases. Active MAP kinase enzymes are not only valuable for basic biomedical research but are also critical for the development of pharmacological inhibitors as therapeutic drugs in the treatment of relevant human diseases. MAP kinases produced in a bacterial system are poorly active due to a lack of proper phosphorylation at their characteristic threonine and tyrosine residues. To overcome these limitations, we have developed a mammalian expression system for high level expression and one-step purification of enzymatically MAP kinases. We cloned JNK1, p38, and p38-regulated MAP kinase-activated protein kinase-2 into the mammalian expression vector pEBG, and expressed these protein kinases as glutathione S-transferase fusion proteins in human embryonic kidney 293T cells through transient transfection. The protein kinases were activated in vivo through treating the transfected cells with sodium arsenite and affinity-purified using glutathione-Sepharose beads. The enzymatic activities of these protein kinases were demonstrated by Western blot analysis and in vitro kinase assays. Our results indicate that this system is an extremely powerful tool for generating valuable reagents, and could be very valuable for proteomic studies. | |
| 19608087 | Systemic CD5+ MALT lymphoma: presentation with Waldenstrom syndrome. | 2009 Aug | We report a case of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in a 75-year-old woman with a neuropathy related to high levels of serum immunoglobulin M and a history of rheumatoid arthritis and polymyositis. The patient developed a mass in the right submandibular salivary gland, and this mass demonstrated histopathologic features that are typical of MALT lymphoma, including infiltrates of small monocytoid B cells in the epithelium (forming "lymphoepithelial lesions"), a reactive background of florid germinal center hyperplasia, and follicular colonization by the monocytoid B cells. Many plasma cells in the background expressed cytoplasmic immunoglobulin M lambda, matching the serum spike. Flow cytometric analysis confirmed the presence of clonal mature B cells; however, unlike most MALT lymphomas, these cells coexpressed dim CD5. Clinical staging revealed evidence of systemic distribution with documented disease involving the bone marrow, the lung, and a paratracheal lymph node. Analysis of this unusual systemic MALT lymphoma, and a comparison with similar examples from the literature, illuminates relationships among MALT lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and Waldenstrom macroglobulinemia. | |
| 19244746 | [Advances in the study of immunopharmacological effects and mechanisms of extracts of Trip | 2008 Dec | Extracts of Chinese herb Tripterygium wilfordii Hook. f. (TWHF) have been found to have potent anti-inflammatory and immunosuppressive functions and widely used in China for treatment of rheumatoid arthritis. Also they have been considered to be the potential drugs in the treatment of tumor and acute graft rejections. With the progress of neuroimmunological research on neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson disease (PD) and multiple sclerosis (MS), the neuroprotective strategies to rescue neurons from immunological injury are currently being explored. Recently, studies have indicated that extracts of TWHF such as triptolide, tripchlorolide and (5R)-5-hydroxytriptolide are able to attenuate progression of these neuroimmunologic disorders in vitro and in vivo. Accumulating evidence has shown that they can promote neuronal survival and neurite growth and facilitate functional recovery of brain injury by invoking distinct mechanisms that are related to their neuroprotective roles as inhibitor of neuroinflammatory toxicity of activated-microglia, antioxidants, calcium channel blockers, neurotrophic actions, modulating T cell functions, inhibitor of transcriptional activation of NF-kappaB on genes and signaling. Significant pharmaceutical strategies against neuroimmunologic disorders will hopefully be discovered by understanding the valuable components of TWHF. | |
| 18962898 | Short leucine-rich glycoproteins of the extracellular matrix display diverse patterns of c | 2009 Feb | The extracellular matrix consists of structural macromolecules and other proteins with regulatory functions. An important family of the latter class of molecules found in most tissues is the small leucine-rich repeat proteins (SLRPs). We have previously shown that the SLRP fibromodulin binds directly to C1q and activates the classical pathway of complement. In the present study we further examine the interactions between SLRPs and complement. Osteoadherin, like fibromodulin, binds C1q and activates the classical pathway strongly while moderate activation is seen in the terminal pathway. This can be explained by the interaction of fibromodulin and osteoadherin with factor H, a major soluble inhibitor of complement. Also, chondroadherin was found to bind C1q and activate complement, albeit to a lesser extent. Chondroadherin also binds factor H. We confirm published data showing that biglycan and decorin bind C1q but do not activate complement. In this study a similar pattern is seen for lumican although its affinity for C1q is lower than for biglycan and decorin. Furthermore, using electron microscopy and radiolabeled SLRPs, we demonstrate two different classes of SLRP binding sites on C1q, to head and stalk respectively, where only binding to the head appears to be activating. We propose a role for SLRPs in the regulation of complement activation in diseases involving the extracellular matrix, particularly those characterized by chronic inflammation such as rheumatoid arthritis, atherosclerosis, osteoarthritis and chronic obstructive lung disease. | |
| 18955217 | A Proteomic Approach for the Diagnosis of 'Oketsu' (blood stasis), a Pathophysiologic Conc | 2008 Dec | 'Oketsu' is a pathophysiologic concept in Japanese traditional (Kampo) medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for 'Oketsu'. Sixteen rheumatoid arthritis (RA) patients were treated with keishibukuryogan (KBG), a representative Kampo medicine for improving 'Oketsu'. Plasma samples were diagnosed as either having an 'Oketsu' (n = 19) or 'non-Oketsu' (n = 29) state according to Terasawa's 'Oketsu' scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the 'Oketsu' scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the 'Oketsu' and 'non-Oketsu' states. Hierarchical clustering gave three major clusters (I, II, III). The majority (68.4%) of 'Oketsu' samples were clustered into one cluster as the principal component of cluster I. The remaining 'Oketsu' profiles constituted a minor component of cluster II and were all derived from patients cured of the 'Oketsu' state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for 'Oketsu'. A reduction in measurement/pre-processing conditions (from 55 to 16) gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine 'Oketsu' has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing 'Oketsu' using a combination of proteomic and bioinformatics-based classification methods. | |
| 18799089 | Development and characteristics of pannus-like soft tissue in osteoarthritic articular sur | 2008 Jul | OBJECTIVES: Pannus is invasive granulation tissue found on the articular cartilage having rheumatoid arthritis (RA). However, pannus-like tissue has also been found in osteoarthritis (OA). Our previous study showed that pannus-like tissue in OA (OA pannus) was frequently found in human OA samples. The purpose of the study is to investigate the development and the characteristics of OA pannus in a rat OA model. DESIGN: Ligaments of the knee joint were transected in Wister rats to induce OA. The knee joints were removed at weeks 1, 2, 4 and 6, and subjected to histological study. Samples were stained with hematoxylin and eosin (HE), Safranin-O and immuno-stained for vimentin, CD34, type II collagen and MMP-3. The whole knee joint of OA rats was implanted in SCID mice and kept for a further 3 weeks. Then the histological findings were evaluated in HE sections. RESULT: OA pannus appeared at week 2 and extend over the articular surface. OA pannus cells were positive for vimentin and/or CD34. At week 6, a part of articular surface was restored with matrix. OA pannus cells expressed MMP-3 as well as type II collagen. Histological study of rat OA knees implanted in SCID mice showed that OA pannus cells filled the joint space and invaded articular cartilage. CONCLUSIONS: The presence of OA pannus was found in a rat OA model and its features were similar to those in human OA. OA pannus had both catabolic and reparative features, and the latter feature were speculated to be dominant in the later phase of the disease under a certain environmental condition. | |
| 18798460 | [Anemic syndrome frequency in complicated obstetrical patients]. | 2008 Sep | BACKGROUND: The prevalence of anemia varies from country to country and there is not a trustworthy record. OBJECTIVE: To determine the frequency of anemia in obstetric patients and the association among healthy pregnancy and aggregate complications. PATIENTS AND METHOD: Was carried out as transversal, observational and comparative study. Obstetrical patients entered and responded in the period of a year, were formed a group with normal pregnancy and another with complicated pregnancy, with a total sample of 194 patients. In the statistical analysis was employed Student t test for independent groups, with value if p < 0.05. RESULTS: When was included all patients from both groups of study a general frequency of anemia was found in 22.4%. Hematological stage from group with normal pregnancy was mild anemia in 16.9% and anemia moderated in 4.1% of the cases. The anemia degrees in the group with associated illness and pregnancy were mild anemia in 19.2% and moderated anemia in 4.2%. Not any case was found with severe anemia. The statistical analysis showed difference significant among both groups p < 0.05. The most frequently causes of the obstetrical morbidity were preeclampsia severe (22.6%), type 2 diabetes (13.9%), gestational diabetes (12.2%) and the remainder with other complications that include to the hypertiroidism, rheumatoid arthritis, lupus, asthma and vein deep thrombosis. CONCLUSIONS: Frequency of anemia in this study was greater upon informing in the international literature. The obstetrical complication more frequently relates to diverse anemia degrees were the hypertensive stage during pregnancy. The anemia is presented with greater frequency in pregnancy patients with others associated illness. | |
| 18707564 | Financial disclosure and clinical research: what is important to participants? | 2008 Aug 18 | OBJECTIVE: To assess what participants in company-sponsored clinical trials wish to know about financial aspects of the study. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional questionnaire administered to 324 participants in six clinical trials conducted at the Royal Melbourne Hospital in 1999-2000 and 2006 for non-acute conditions (asthma, chronic obstructive pulmonary disease, osteoporosis, rheumatoid arthritis, diabetes and influenza vaccine efficacy). MAIN OUTCOME MEASURES: Participants' desire for information on study funding, investigators' conflicts of interest, and use of accrued funds. RESULTS: 259 participants (80%) completed the survey. Participants wanted to be informed about the identity of the project sponsor (148 participants; 57%), whether the investigators owned shares in the company (105; 41%) or received travel grants (83; 32%), how much funding was accrued at study completion (88; 34%), how accrued funds were used (98; 38%), and who approved their use (91; 35%). After adjusting for year of survey and level of education, younger subjects (aged | |
| 18686462 | ASA physical status classification is not a good predictor of infection for total knee rep | 2008 Jun | The American Society of Anesthesiologists Physical Status Classification System (ASA) ranks patients for risk of adverse events during a surgical procedure. The ASA classification is used as a surrogate for the patient's underlying severity of illness and has been recommended for use in Surgical Site Infection (SSI) and risk stratification. We assessed the predictive power of the ASA score for total knee replacement surgery infection, and compared it to a comorbidity score. All patients who had TKA (total knee arthroplasty) surgery performed during the period of 1993 to 1999 at one institution were identified. One hundred and thirteen infected cases were matched with 236 controls and nominal variables were statistically processed. A total co-morbidity score (TCOMORBID) was created to help the analysis. All possible predictors of infection were tested against infection in bivariate analysis. The association of the ASA score with infection was examined in detail. An ASA score beyond 2 showed an increased risk of infection. The average ASA score for the infected TKA group was 2.3 +/- 0.6, and the non-infected TKA average score was 2.6 +/- 0.7 (cohort effect). The relationship between the ASA score and TCOMORBID score was poor; Spearman rank correlation rho = 0.2, (p < 0.0001). In fact, the ASA score predicted only 6% of the occurrences of infection, but since it predicts 98% of the cases where there is no infection correctly, it is 70% accurate over all. Infection in TKA surgery was associated with an increased ASA score, but only when the high ASA score was due to a combination of specific co-morbidities. We propose that the ASA score should be cross-checked with the current co-morbidities, like rheumatoid arthritis or active infections in order to assess TKA infection risk. | |
| 18593082 | What's new in clinical pharmacology and therapeutics. | 2008 Apr | The US Food and Drug Administration (FDA) has approved several new drugs in the past 2 years. This article provides an overview of some of the newer drugs that are likely to find wider use in the future. The drugs reviewed in this article can be used to treat cardiovascular system problems, diabetes mellitus, multiple sclerosis, hepatitis B infection, hyponatremia, Parkinson's disease, rheumatoid arthritis, pain, constipation, and insomnia. Another drug discussed can be used to help a patient stop smoking. The article also discusses Gardasil, the recombinant vaccine against human papilloma virus (types 6, 11, 16, and 18). | |
| 18501769 | HLA class II transgenic mice mimic human inflammatory diseases. | 2008 | Population studies have shown that among all the genetic factors linked with autoimmune disease development, MHC class II genes on chromosome 6 accounts for majority of familial clustering in the common autoimmune diseases. Despite the highly polymorphic nature of HLA class II genes, majority of autoimmune diseases are linked to a limited set of class II-DR or -DQ alleles. Thus a more detailed study of these HLA-DR and -DQ alleles were needed to understand their role in genetic predisposition and pathogenesis of autoimmune diseases. Although in vitro studies using class-II restricted CD4 T cells and purified class II molecules have helped us in understanding some aspects of HLA class-II association with disease, it is difficult to study the role of class II genes in vivo because of heterogeneity of human population, complexity of MHC, and strong linkage disequilibrium among different class II genes. To overcome this problem, we pioneered the generation of HLA-class II transgenic mice to study role of these molecule in inflammatory disease. These HLA class II transgenic mice were used to develop novel in vivo disease model for common autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, insulin-dependent diabetes mellitus, myasthenia gravis, celiac disease, autoimmune relapsing polychondritis, autoimmune myocarditis, thyroiditis, uveitis, as well as other inflammatory disease such as allergy, tuberculosis and toxic shock syndrome. As the T-cell repertoire in these humanized HLA transgenic mice are shaped by human class II molecules, they show the same HLA restriction as humans, implicate potential triggering mechanism and autoantigens, and identify similar antigenic epitopes seen in human. This review describes the value of these humanized transgenic mice in deciphering role of HLA class II molecules in immunopathogenesis of inflammatory diseases. |