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ID PMID Title PublicationDate abstract
19801786 Cloning and expression of Leishmania major superoxide dismutase B1: A potential target ant 2009 Sep BACKGROUND: Leishmaniasis- a neglected public health problem- is a group of diseases affecting an estimated 12 million people worldwide. OBJECTIVE: In the present study, recombinant Leishmania major superoxide dismutase B1 (rLmSODB1) has been utilized as a potential antigen for the serodiagnosis of human cutaneous (CL) and visceral leishmaniasis (VL) in the endemic regions of southern part of Iran. Additionally, the sensitivity and specificity of ELISA-based serodiagnosis using rLmSODB1 and the soluble Leishmania antigen (SLA) were compared. METHODS: For the first time, rLmSODB1 has been cloned successfully and used for ELISA-based serodiagnosis. Sera from 30 CL and 24 VL cases were included in this study. Additional studies were also done for the evaluation of cross-reactivity using sera from 41 endemic controls including normal endemic donors (n=20), systemic lupus erythematosus patients (n=5), rheumatoid arthritis patients (n=5), and patients with tuberculosis (n=11). RESULTS: Analysis indicated that rLmSODB1 was recognized by 62.5% and 13.3% of sera from patients with VL and CL, showing a sensitivity of 72.7% and 53.6%, respectively. However 95.8% of VL and 30% of CL sera reacted with SLA, revealing sensitivities of 96% and 58.8%, respectively. Additionally, from 41 sera collected either from healthy subjects or patients affected with other diseases, 97.5% were negative with SLA or rLmSODB1 (specificity 97.6%). CONCLUSION: These results show that rLmSODB1 almost does not react with sera from patients with tuberculosis and autoimmune diseases and may be considered as a candidate antigen for the specific immunodiagnosis of visceral leishmaniasis.
19697035 Differential effect of IL-1β and TNFα on the production of IL-6, IL-8 and PGE2 in fibrob 2010 Jun Inflammation in the joint of rheumatoid arthritis is a complex immune reaction facilitated by various factors, such as cytokines, cells and hypoxia. Thus, we evaluated their relative capacity to produce proinflammatory mediators in response to IL-1beta, TNF-alpha or IL-17 under hypoxia or normoxia in fibroblast-like synoviocytes (FLSs) and macrophages. The level of IL-6 expression was strongly increased in both FLSs and THP-1 macrophages in response to IL-1beta and TNF-alpha, but the level by TNF-alpha was less than that by IL-1beta. In contrast, the expression of IL-8 in both cell types was strongly stimulated by both IL-1beta and TNF-alpha. In FLSs, PGE(2) production increased only in response to IL-1beta; and no effect was observed in THP-1 cells and TNF-alpha-stimulated FLSs. In addition, the production by IL-17 was extremely low when compared with those induced by IL-1beta or TNF-alpha in FLSs and THP-1 cells. Hypoxia (2% O(2)) decreased IL-1beta-stimulated production of PGE(2), even though it increased the expression of mRNA and protein of COX-2. These results suggest that IL-1beta and TNF-alpha differentially regulate gene expression in FLSs and macrophages under hypoxia or normoxia.
19672323 Oxaprozin-induced apoptosis on CD40 ligand-treated human primary monocytes is associated w 2009 The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients. Monocyte apoptosis was evaluated by fluorescence microscopy on cytopreps stained with acridine orange or using flow cytometry analysis of Annexin-V and Propidium Iodide staining. Akt and NF-kappaB activation was assessed using western blot. Caspase 3 activity was determined spectrophotometrically. Among different NSAIDs, only oxaprozin dose-dependently increased apoptosis of CD40L-treated monocytes. Oxaprozin pro-apoptotic activity was associated with the inhibition of CD40L-triggered Akt and NF-kappaB phosphorylation and the activation of caspase 3. In conclusion, our data suggest that oxaprozin-induced apoptosis in CD40L-treated human monocytes is associated with previously unknown cyclooxygenase (COX)-independent pathways. These intracellular proteins might be promising pharmacological targets to increase apoptosis in CD40L-treated monocytes.
19519591 Tumor necrosis factor inhibitors in pediatric asthma. 2009 Jun Asthma is the most common pulmonary disease in children worldwide. As its prevalence significantly increases from 30% to 50% every 10 years it seems that finding the exact form of treatment is crucial to achieve a long-term-benefit effect. Sometimes it appears hard, especially in case of difficult and severe asthma when a standard therapy is not sufficient. The success of omalizumab inspired further studies which turned the spotlight on other pro-inflammatory cytokines such as TNF-alpha. After the success of anti-TNF-alpha therapy in many other inflammatory diseases such as for instance Crohn's Disease and Rheumatoid Arthritis, there appeared several trials discussing the usage of anti-TNF agents in asthma. The first wave of enthusiasm over positive results in treating asthma patients was blunted by other researches which challenged the benefit of anti-TNF-alpha in asthma. What is more, they warned about serious problems and adverse events related to that kind of treatment. These results hindered further investigation, especially in case of children's population, because of the ambiguity as far as the risks and benefits of the treatment were concerned. Nevertheless, the research on anti-TNF-alpha and asthma underlined a significant polymorphism in asthma phenotypes. It seems likely that a therapy with anti-TNF-alpha should be limited to a small subgroup of patients with a specific phenotype manifested by an increased TNF axis. The purpose of this review article is to discuss some recent patents in anti-TNF-alpha therapy.
19265302 [Mediastinal large B-cell lymphoma associated with systemic sclerosis]. 2009 Feb Malignant lymphoma (ML) is frequently associated with several forms of collagen diseases such as Sjören syndrome, systemic lupus erythematodes, and rheumatoid arthritis. However, the occurrence of ML in systemic sclerosis (SSc) patients has rarely been reported. Here we report an SSc patient who developed mediastinal (thymic) large B-cell lymphoma (MLBCL). A 31-year-old woman was diagnosed as having SSc in August 2007. The patient was treated with low-dose prednisolone (10 mg/day) without any effect. One year after the diagnosis, chest computed tomography-scan demonstrated thymic tumor in the anterior mediastinum. Thymectomy was performed, and a pathohistological diagnosis of MLBCL was established. Immunohistochemical analysis demonstrated that the tumor cells were positive for CD45 and CD20, but negative for CD30 and EBV-encoded RNA. The patient was treated with 6 courses of CHOP regimen, resulting in complete remission of lymphoma. This report describes the first SSc patient associated with MLBCL. SSc patients occasionally develop ML after a relatively short interval. Our case suggests that intensive monitoring for the development of ML is needed in newly diagnosed SSc patients.
19217767 Targeting protein kinases for the development of anti-inflammatory drugs. 2009 Apr In recent years, protein kinases have become the pharmaceutical industry's most studied class of drug target, and some 10 protein kinase inhibitors have so far been approved for the treatment of cancer. However, whether safe drugs that modulate protein kinase activities can also be developed for the treatment of chronic diseases, where they may need to be taken for decades, is an issue that is still unresolved. A number of compounds that inhibit the p38alpha MAPK have entered clinical trials for the treatment of rheumatoid arthritis and psoriasis, but side effects have prevented their progression to Phase III clinical trials. Here I briefly review the potential problems in targeting p38 MAPK and discuss other protein kinases that regulate the innate immune system, such as Tpl2, MAPKAP-K2/3, MSK1/2 and IRAK4, which may be better targets for the treatment of chronic inflammatory diseases, and NIK, which is an attractive target for the treatment of multiple myeloma, a late stage B-cell malignancy.
19214681 High-volume surgeons in regard to reductions in operating time, blood loss, and postoperat 2009 Jan BACKGROUND: The purpose of this study was to clarify the volume-outcome relations for total hip arthroplasty, with a particular focus on outcome variables such as operating time, blood loss, and postoperative complications. METHODS: Using an Internet-based questionnaire survey, we identified 2965 total hip arthroplasties performed for osteoarthritis, idiopathic osteonecrosis of the femoral head, rheumatoid arthritis, or hip fractures in 289 hospitals in Japan during the period from November 1, 2006, to March 31, 2007. We examined the hospital and surgeon volumes, patient characteristics (age, sex, body mass index, diagnosis, drug history, co-morbid conditions), details of the surgical procedures, and outcome variables (operating time, blood loss, postoperative complications). Multivariate regression analyses were used to examine the relations between the outcome variables and hospital/surgeon volumes, adjusting for patient characteristics and surgical details. RESULTS: The average operating time was 114 +/- 62 min. The average blood loss was 429 +/- 347 ml. The postoperative complication rate was 6.1%. Surgeon volume (> or = 500 cases) was inversely associated with operating time (odds ratio 0.20; P < 0.01), blood loss (odds ratio 0.54; P = 0.02), and postoperative complications (odds ratio 0.53; P = 0.01). Hospital volume was not significantly associated with any of the outcome variables examined. CONCLUSIONS: The present study indicates that surgeon volume is a significant predictor of better outcomes after total hip arthroplasty.
21244759 Reductive alteration of the regulatory function of the CD4(+)CD25(+) T cell fraction in si 2010 Oct Causal links have been documented between silica and rheumatoid arthritis, lupus erythematosus, systemic sclerosis and glomerulonephritis. Two different effects of silica have been suggested, an enhanced inflammatory response in the pulmonary region (e.g. activation of alveolar macrophages) and dysregulation of autoimmunity. Based on our previous reports showing in vitro activation of peripheral T cells by silica and reduced regulatory function of the peripheral CD4(+)CD25(+) fraction in which FoxP(3)+ regulatory T cells (Treg) are located, reconstitution of the CD4(+)CD25(+) fraction in silicosis patients (SILs) was investigated. Since T cells in peripheral CD4(+)CD25(+) and CD4(+)CD25(-) (effector T cells; Teff) fractions from SILs showed higher expression of pd-1 (a marker gene for T cell activation) in comparison to that of healthy donors (HDs), chronic T cell activation was considered to have occurred in SILs. In this study, a higher expression of the CD95/Fas molecule in Treg was recorded from silicosis patients (SILs) compared to healthy donors (HDs), and excess loss of FoxP3(+) Treg in freshly isolated peripheral blood mononuclear cells (PBMCs) from SILs relative to HDs was demonstrated when these cells were cultured with silica ex vivo, whereas CD25(+) cells were not reduced due to contamination of activated Teff in the CD4(+)CD25(+) fraction. The activation of both Teff and Treg results in reconstitution of the peripheral CD4(+)CD25(+) fraction, loss of Treg and contamination of activated Teff, resulting in reduction of the number and function of Treg. These results contribute to our understanding of the development of autoimmune diseases found in SILs.
18726597 Interstitial lung disease associated with collagen vascular disorders: disease quantificat 2009 Feb The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool compared to human observers in quantification of interstitial lung disease (ILD) in patients with collagen-vascular disorders. A total of 52 patients with rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus (n=14) underwent thin-section CT. Two independent observers assessed the extent of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD assessed EoILD twice. Pulmonary function tests were obtained. Statistical evaluation used 95% limits of agreement and linear regression analysis. CAD correlated well with diffusing capacity (DL(CO)) (R= -0.531, P<0.0001) and moderately with forced vital capacity (FVC) (R= -0.483, P=0.0008). There was close correlation between CAD and the readers (EoILD vs. CAD: R=0.716, P<0.0001; EoRet vs. CAD: R=0.69, P<0.0001). Subgroup analysis including patients with minimal EoGGO (<15%) strengthened the correlations between CAD and the readers, readers and PFT, and CAD and PFT. EoILD by readers correlated strongly with DL(CO) (R= -0.705, P<0.0001) and moderately with FVC (R= -0.559, P=0.0002). EoRet correlated closely with DL(CO) and moderately with FVC (DL(CO): R= -0.663; FVC: R = -0.436; P
21130662 Functional in vivo imaging of cysteine cathepsin activity in murine model of inflammation. 2011 Feb 1 Near-infrared fluorophore (NIRF)-labeled imaging probes are becoming increasingly important in bio-molecular imaging applications, that is, in animal models for tumor imaging or inflammation studies. In this study we showed that the previously introduced chemical concept of 'Reverse Design' represents an efficient strategy for the generation of selective probes for cysteine proteases from chemically optimized protease inhibitors for investigations in proteomic lysates as well as for in vivo molecular imaging studies. The newly developed activity-based probe AW-091 was demonstrated to be highly selective for cathepsin S in vitro and proved useful in monitoring cysteine cathepsin activity in vivo, that is, in zymosan-induced mouse model of inflammation. AW-091 showed higher signal-to-background ratios at earlier time points than the commercially available polymer-based ProSense680 (VisEn Medical) and thus represents an efficient new tool for studying early proteolytic processes leading to various diseases, including inflammation, cancer, and rheumatoid arthritis. In addition, the fluorescent signal originating from the cleaved AW-091 was shown to be reduced by the administration of an anti-inflammatory drug, dexamethasone and by the cathepsin inhibitor E-64, providing a valuable system for the evaluation of small-molecule inhibitors of cathepsins.
21123327 Uveitis in adult patients with rheumatic inflammatory autoimmune diseases at a tertiary-ca 2011 Feb OBJECTIVE: Our aim is to describe the frequency of uveitis associated with rheumatic inflammatory autoimmune diseases (RIAD) in adult patients admitted to the Rheumatology Department at a tertiary-care hospital in Mexico City. We also describe the clinical features, seasonal distribution, treatment, and ocular complications associated with this disease. METHODS: We reviewed 1332 charts of patients with RIAD and selected those that had a diagnosis of uveitis. We obtained the following data: age, sex, type of uveitis and relationship with diagnosis of RIAD, recurrences, seasonal distribution, treatment, and residual visual deficit. RESULTS: We found 57 (4.27%) cases of uveitis in 1332 charts, including 38 men and 19 women (M:F ratio 2:1), aged 47 ± 16 years. Nongranulomatous acute anterior uveitis (NGAAU) comprised 90.52% of cases (52/57). In 64.91% of cases (37/57), uveitis preceded the diagnosis of RIAD by 12 ± 9 years, more frequently in winter (35.96%; p = NS). Uveitis was found in 40/93 patients with ankylosing spondylitis (AS), in 7/11 patients with relapsing polychondritis (RP), in 8/16 patients with Behçet's disease, in 1/16 patients with polyarteritis nodosa, and in 1/590 patients with rheumatoid arthritis (RA). Ninety-six percent of the patients were treated with steroids. Upon a mean followup of 60 days (range 7-4745 days), reduction of visual acuity (≤ 20/200) was associated with recurrence of uveitis in 3/7 cases with AS, in 4/8 cases with Behçet's disease, in 3/7 with RP, and in 1 case of uveitis and seronegative RA. CONCLUSION: NGAAU frequently precedes RIAD and is found predominately in men, with a tendency to occur in winter.
21059673 Development of a computed tomography method of scoring bone erosion in patients with gout: 2011 Feb OBJECTIVES: To develop a method of scoring bone erosion in the feet of patients with gout using CT as an outcome measure for chronic gout studies, consistent with the components of the OMERACT filter. METHODS: Clinical assessment, plain radiographs and CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the Rheumatoid Arthritis MRI Scoring System (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1100 bones) by two independent radiologists. A number of different models were assessed to determine the optimal CT scoring system for bone erosion, incorporating the frequency of involvement and inter-reader reliability for individual bones. RESULTS: An optimal model was identified with low number of bones required for scoring (seven bones/foot), inclusion of bones over the entire foot, high reliability and ability to capture a high proportion of disease. This model included the following bones in each foot: first metatarsal (MT) head, second to fourth MT base, cuboid, middle cuneiform and distal tibia (range 0-140). Scores from this model correlated with plain radiographic damage scores (r = 0.86, P < 0.0001) and disease duration (r = 0.42, P < 0.05). Scores were higher in those with clinically apparent tophaceous disease than in those without tophi (P < 0.0001). CONCLUSIONS: We have developed a preliminary method of assessing bone erosion in gout using conventional CT. Further testing of this method is now required, ideally in prospective studies to allow analysis of the sensitivity to change of the measure.
20853323 Non-Hodgkin lymphoma and autoimmunity: does gender matter? 2011 Jul 15 Autoimmune disorders are more frequent in women, whereas most non-Hodgkin lymphomas (NHLs) are common in men; yet, sexspecific autoimmune–lymphoma associations are rarely reported. Detailed data on autoimmune disease were abstracted from medical records of 791 cases (including 316 diffuse large B-cell lymphomas (DLBCLs); 228 follicular lymphomas (FLs); 127 marginal zone lymphomas (MZLs); 64 T-cell lymphomas and 38 mantle cell lymphomas) and 872 controls. The combined prevalence of autoimmune disease was higher among women (15.7% controls; 19.7% cases) than men (6.6% controls; 14.5% cases), but the overall association with NHL was stronger for men (odds ratio 2.4, 95% confidence interval: 1.5–3.8) than women (1.3, 0.9–1.9), the disparity persisting when data for the year immediately preceding lymphoma diagnosis were excluded (men 2.0, 1.3–3.3; women 1.2, 0.8–1.8). For both sexes, the strongest individual associations were for DLBCL, MZL and T-cell lymphomas, with no associations evident for FL. Among women, there were strong links between MZL and both Sjögren's syndrome and idiopathic thrombocytopenia, and among men, between DLBCL and both rheumatoid arthritis and Crohn's disease. The expected association between coeliac disease and T-cell lymphoma was seen in both sexes. Our results add to the accumulating knowledge on this topic and suggest that future studies should analyze data for men and women separately.
20683281 Utility of leflunomide in the treatment of complex cytomegalovirus syndromes. 2010 Aug 27 BACKGROUND: Cytomegalovirus (CMV) viremia that is resistant or refractory to the standard antiviral therapy still constitutes a major threat to high-risk transplant recipients. In addition, multiple CMV recurrences may lead to neutropenia because of repeated courses of therapy with ganciclovir derivatives. Leflunomide, a drug for rheumatoid arthritis, has been reported to have anti-CMV activity. This study reports on its use in 17 transplant recipients with complex CMV syndromes who had failed or were intolerant to other therapies. METHODS: Single-center, retrospective study. Clinical data were extracted from the electronic medical record. CMV DNA viral loads were performed by quantitative hybrid capture assay. RESULTS: Leflunomide was initiated after a median of three episodes of CMV viremia, with a mean peak viral load of 245,826 copies/mL. Initial clearance of CMV viremia was observed in 14 of 17 patients (82%), and 9 of 17 (53%) patients achieved a long-term suppression of CMV recurrences. Higher peak viral load and higher viral load at the start of leflunomide therapy were associated with failure to suppress viremia. The duration of leflunomide therapy ranged from 1 to 24 months (median 3.5 months, interquartile range 2.6-7 months), and the mean time to an undetectable CMV-DNA was 1.9 months. Adverse effects included diarrhea (35%), anemia (18%), and increased liver function tests (12%). CONCLUSIONS: Leflunomide, alone or in combination, has potential utility in treatment of complex CMV syndromes and in long-term suppression of viremia. The optimal duration of therapy and the balance of risks and benefits are not yet known.
20670133 Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of pat 2010 Aug CONTEXT: Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which result in irreversible destruction of the lung's architecture. OBJECTIVE: To elucidate the production levels, tissue localization, and activation of matrix metalloproteinase 7 (MMP-7) in the lungs of patients with IPF. DESIGN: Bronchoalveolar lavage analysis was performed in 17 IPF patients and 6 healthy volunteers. Levels of MMP-7 in blood were assayed in 23 IPF patients and 20 controls. Histologic and immunohistochemical analyses were performed on paraffin sections of the lung tissues from patients with IPF, interstitial pneumonia associated with rheumatoid arthritis, or nonspecific interstitial pneumonia. RESULTS: The proMMP-7 levels in bronchoalveolar lavage fluids from IPF patients were significantly higher than those from healthy controls, although there was no difference in the serum levels between the 2 groups. By immunohistochemistry, proMMP-7 was localized mainly to the hyperplastic alveolar and metaplastic bronchiolar epithelial cells in the lung tissues from IPF patients. Active MMP-7 was immunolocalized on alveolar macrophages and hyperplastic epithelial cells, which were also immunostained with antibody against CD151, a molecule associated with activation of proMMP-7. Immunoblot analysis indicated the overproduction of proMMP-7 together with a small amount of active MMP-7 in bronchoalveolar lavage fluids from IPF patients. The MMP-7 activity was detected in a cross-linked carboxymethylated transferrin film assay. CONCLUSIONS: proMMP-7 is excessively produced by hyperplastic alveolar and metaplastic bronchiolar epithelial cells and activated locally in the lungs of IPF patients, suggesting that MMP-7 may contribute to the pathology of IPF.
20653979 Price regulation, new entry, and information shock on pharmaceutical market in Taiwan: a n 2010 Jul 25 BACKGROUND: Using non-steroidal anti-inflammatory drugs (NSAIDs) as a case, we used Taiwan's National Health Insurance (NHI) database, to empirically explore the association between policy interventions (price regulation, new drug entry, and an information shock) and drug expenditures, utilization, and market structure between 2001 and 2004. METHODS: All NSAIDs prescribed in ambulatory visits in the NHI system during our study period were included and aggregated quarterly. Segmented regression analysis for interrupted time series was used to examine the associations between two price regulations, two new drug entries (cyclooxygennase-2 inhibitors) and the rofecoxib safety signal and expenditures and utilization of all NSAIDs. Herfindahl index (HHI) was applied to further examine the association between these interventions and market structure of NSAIDs. RESULTS: New entry was the only variable that was significantly correlated with changes of expenditures (positive change, p = 0.02) and market structure of the NSAIDs market in the NHI system. The correlation between price regulation (first price regulation, p = 0.62; second price regulation, p = 0.26) and information shock (p = 0.31) and drug expenditure were not statistically significant. There was no significant change in the prescribing volume of NSAIDs per rheumatoid arthritis (RA) or osteoarthritis (OA) ambulatory visit during the observational period. The market share of NSAIDs had also been largely substituted by these new drugs up to 50%, in a three-year period and resulted in a more concentrated market structure (HHI 0.17). CONCLUSIONS: Our empirical study found that new drug entry was the main driving force behind escalating drug spending, especially by altering the market share.
20500789 Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. 2010 May Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are precursors of potent lipid mediators, termed eicosanoids, which play an important role in the regulation of inflammation. Eicosanoids derived from n-6 PUFAs (e.g., arachidonic acid) have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFAs [e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have anti-inflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived eicosanoids. While the typical Western diet has a much greater ratio of n-6 PUFAs compared with n-3 PUFAs, research has shown that by increasing the ratio of n-3 to n-6 fatty acids in the diet, and consequently favoring the production of EPA in the body, or by increasing the dietary intake of EPA and DHA through consumption of fatty fish or fish-oil supplements, reductions may be achieved in the incidence of many chronic diseases that involve inflammatory processes; most notably, these include cardiovascular diseases, inflammatory bowel disease (IBD), cancer, and rheumatoid arthritis, but psychiatric and neurodegenerative illnesses are other examples.
20428982 Factors that predict short-term complication rates after total hip arthroplasty. 2010 Sep BACKGROUND: There remains uncertainty regarding the relative importance of patient factors such as comorbidity and provider factors such as hospital volume in predicting complication rates after total hip arthroplasty (THA). PURPOSE: We therefore identified patient and provider factors predicting complications after THA. METHODS: We reviewed discharge data from 138,399 patients undergoing primary THA in California from 1995 to 2005. The rate of complications during the first 90 days postoperatively (mortality, infection, dislocation, revision, perioperative fracture, neurologic injury, and thromboembolic disease) was regressed against a variety of independent variables, including patient factors (age, gender, race/ethnicity, income, Charlson comorbidity score) and provider variables (hospital volume, teaching status, rural location). RESULTS: Compared with patients treated at high-volume hospitals (above the 20th percentile), patients treated at low-volume hospitals (below the 60th percentile) had a higher aggregate risk of having short-term complications (odds ratio, 2.00). A variety of patient factors also had associations with an increased risk of complications: increased Charlson comorbidity score, diabetes, rheumatoid arthritis, advanced age, male gender, and black race. Hispanic and Asian patients had lower risks of complications. CONCLUSIONS: Patient and provider characteristics affected the risk of a short-term complication after THA. These results may be useful for educating patients and anticipating perioperative risks of THA in different patient populations. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
20232480 Evaluation of the Personal Impact Health Assessment Questionnaire (PI HAQ) to capture the 2010 Jun AIM: Measuring facts about disability may not reflect their personal impact. An individualized values instrument has been used to weight difficulty in performing activities of daily living in rheumatoid arthritis, and calculate personal impact (Personal Impact Health Assessment Questionnaire; PI HAQ). This study aimed to evaluate the PI HAQ in osteoarthritis (OA). STUDY DESIGN: Study 1: 51 people with OA completed short and long versions of the value instrument at 0 and 1 week. Study 2: 116 people with OA completed the short value instrument, disability and psychological measures at 0 and 4 weeks. RESULTS: Study 1: The eight-category and 20-item value instruments correlated well (r = 0.85) and scores differed by just 2.7%. The eight-category instrument showed good internal consistency reliability (Cronbach's alpha = 0.85) and moderate one-week test-retest reliability (r = 0.68, Wilcoxon signed-rank test p = 0.16, intra-class correlation coefficient [ICC] 0.62). Study 2: Values for disability were not associated with disability severity or clinical status. After weighting disability by value, the resulting PI HAQ scores were significantly associated with dissatisfaction with disability, perceived increase in disability, poor clinical status and life dissatisfaction, and differed significantly between people with high and low clinical status (convergent and discriminant construct validity). There was moderate association with the disease repercussion profile disability subscale (r = 0.511; p < 0.001) (criterion validity). The PI HAQ was stable over four weeks (ICC 0.81). CONCLUSIONS: These studies provide an initial evaluation of an instrument to measure the personal impact of disability in people with OA, setting disability within a personal context. Further studies, including sensitivity to change, are required.
20226165 Celastrol: Molecular targets of Thunder God Vine. 2010 Apr 9 Celastrol, a quinone methide triterpene, is a pharmacologically active compound present in Thunder God Vine root extracts used as a remedy of inflammatory and autoimmune diseases, e.g. rheumatoid arthritis. Celastrol is one of the most promising medicinal molecules isolated from the plant extracts of traditional medicines. Molecular studies have identified several molecular targets which are mostly centered on the inhibition of IKK-NF-kappaB signaling. Celastrol (i) inhibits directly the IKKalpha and beta kinases, (ii) inactivates the Cdc37 and p23 proteins which are co-chaperones of HSP90, (iii) inhibits the function of proteasomes, and (iv) activates the HSF1 and subsequently triggers the heat shock response. It seems that the quinone methide structure present in celastrol can react with the thiol groups of cysteine residues, forming covalent protein adducts. In laboratory experiments, celastrol has proved to be a potent inhibitor of inflammatory responses and cancer formation as well as alleviating diseases of proteostasis deficiency. Celastrol needs still to pass several hurdles, e.g. ADMET assays, before it can enter the armoury of western drugs.