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ID PMID Title PublicationDate abstract
22471910 Bone formation rather than inflammation reflects ankylosing spondylitis activity on PET-CT 2012 Apr 2 INTRODUCTION: Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference. METHODS: In a stepwise approach different PET tracers were investigated. First, whole body [18F]FDG and [11C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [18F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data. RESULTS: No increased [18F]FDG and [11C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [18F]Fluoride PET-CT, [18F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [18F]FDG depicted only three lesions, with an uptake of five times lower compared to [18F]Fluoride, and again no [11C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [18F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [18F]Fluoride PET positive lesions. CONCLUSIONS: Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [18F]Fluoride. In contrast to active RA, inflammation tracers [18F]FDG and [11C](R)PK11195 appeared to be less useful for AS imaging.
21596847 Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospect 2011 Aug 11 To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.
23053964 Associations between the FAS -670 A/G and -1,377 G/A polymorphisms and susceptibility to a 2012 Dec The aim of this study was to explore whether FAS -670 A/G and -1,377 G/A polymorphisms confer susceptibility to autoimmune rheumatic diseases. A meta-analysis was conducted on the associations between the FAS -670 A/G and -1,377 G/A polymorphisms and autoimmune rheumatic diseases using allele contrast, a recessive model, a dominant model, and an additive model. Thirteen articles with 21 comparison studies (16 on FAS -670 A/G and 5 on -1,377 G/A polymorphisms) including systemic lupus erythematosus (SLE), four systemic sclerosis, four Sjogren's syndrome, three rheumatoid arthritis (RA), one juvenile idiopathic arthritis, and one spondyloarthropathy were available for the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the FAS -670 A/G polymorphism in the dominant model (odds ratio [OR] = 0.761, 95 % confidence interval [CI] = 0.621-0.932, p = 0.008]. Stratification by ethnicity indicated an association between the FAS -670 G allele carrier and rheumatic diseases in Asian (OR = 0.569, 95 % CI = 0.409-0.791, p = 0.001). Furthermore, stratification by disease indicated an association between the FAS -670 G allele carrier and SLE and RA (OR = 0.578, 95 % CI = 0.358-0.934, p = 0.025; OR = 0.609, 95 % CI = 0.398-0.934, p = 0.023, respectively). The FAS -670 G allele was negatively associated with SLE susceptibility. Meta-analysis of the FAS -1,377 G/A polymorphism stratified by disease showed an association between the FAS -1,377 A allele and SLE (OR = 0.783, 95 % CI = 0.613-0.997, p = 0.047). Meta-analyses using the dominant model also showed a significant association in SLE (OR = 0.712, 95 % CI = 0.528-0.961, p = 0.027). This meta-analysis demonstrates that the FAS -670 A/G polymorphism confers susceptibility to rheumatic diseases in Asians and SLE and RA, and the FAS -1,377 G/A polymorphism is associated with SLE susceptibility.
23833800 Optimization and characterization of a pan protein arginine deiminase (PAD) inhibitor. 2010 The protein arginine deiminases (PADs) are a family of Ca(2+)-dependent enzymes that catalyze the conversion of peptidyl-arginine to peptidyl-citrulline in numerous protein substrates. Disruption of normal PAD activity plays a role in the pathogenesis of multiple inflammatory diseases such as rheumatoid arthritis (RA), chronic obstructive pulmonary disease, ulcerative colitis, multiple sclerosis, psoriasis, Alzheimer’s disease, and in various cancers. PAD inhibitors described in the literature have been useful chemical tools to study the role of PAD enzymes in inflammatory diseases and cancer biology. Most published PAD inhibitors are mechanism-based inactivators belonging to the halogen-amidine chemotype. For emerging targets such as the PADs, it can be difficult to distinguish compound-specific effects from those truly resulting from enzyme inhibition. We therefore initiated a fluorescence polarization activity-based protein profiling (fluopol-ABPP) high throughput screening (HTS) campaign to identify a second PAD inhibitor chemotype. The PAD4 HTS campaign identified the natural product streptonigrin (SID 11532976) as an irreversible PAD4-specific inhibitor. We describe herein the medicinal chemistry optimization of streptonigrin to the pan PAD probe ML325 (SID 118043677). ML325 inhibits PAD1, 2, 3, and 4 in vitro with IC50 values of 70 nM, 200 nM 170 nM, and 240 nM respectively. In a kinetic assay of inhibition more appropriate for irreversible inhibitors, ML325 has k(inact)/K(I) values of 3500, 7300, 1900, and 5300 M(−1)min(−1) for PAD1, 2, 3 and 4 respectively; indicating it has less than 4-fold selectivity among the four family members. Despite its promiscuity within the PAD family, ML325 exhibits high selectivity vs. more than 20 cysteine-reactive proteins as assayed by activity-based protein profiling. ML325 was also demonstrated to inhibit all four PAD isozymes irreversibly and to be non-cytotoxic to NIH-3T3 cells. The complete properties, characterization, and synthesis of ML325 are detailed in this report.
23256515 Designation, diligence and drift: understanding laboratory expenditure increases in Britis 2012 Dec 21 BACKGROUND: Laboratory testing is one of the fastest growing areas of health services spending in Canada. We examine the extent to which increases in laboratory expenditures might be explained by testing that is consistent with guidelines for the management of chronic conditions, by analyzing fee-for-service physician payment data in British Columbia from 1996/97 and 2005/06. METHOD: We used direct standardization to quantify the effect on laboratory expenditures from changes in: fee levels; population growth; population aging; treatment prevalence; expenditure on recommended tests for those conditions; and expenditure on other tests. The chronic conditions selected were those with guidelines containing laboratory recommendations developed by the BC Guidelines and Protocol Advisory Committee: diabetes, hypertension, congestive heart failure, renal failure, liver disease, rheumatoid arthritis, osteoarthritis and dementia. RESULT: Laboratory service expenditures increased by $98 million in 2005/06 compared to 1996/97, or 3.6% per year after controlling for population growth and aging. Testing consistent with guideline-recommended care for chronic conditions explained one-third (1.2% per year) of this growth. Changes in treatment prevalence were just as important, contributing 1.5% per year. Hypertension was the most common condition, but renal failure and dementia showed the largest changes in prevalence over time. Changes in other laboratory expenditure including for those without chronic conditions accounted for the remaining 0.9% growth per year. CONCLUSION: Increases in treatment prevalence were the largest driver of laboratory cost increases between 1996/97 and 2005/06. There are several possible contributors to increasing treatment prevalence, all of which can be expected to continue to put pressure on health care expenditures.
23052942 Association between osteoporosis and psoriasis: results from the Longitudinal Health Insur 2013 Jun This population-based analysis explored the association between osteoporosis and a previous diagnosis of psoriasis. We found that the adjusted odds ratio (OR) of having been previously diagnosed with psoriasis for subjects with osteoporosis was 1.65 (95 % confidence interval [CI], 1.42-1.94) when compared to controls. INTRODUCTION: Although previous studies have investigated this association between psoriasis and osteoporosis, significant controversy remains regarding its presence. Therefore, this study set out to explore the association between osteoporosis and a previous diagnosis of psoriasis through a population-based case-control study in Taiwan. METHODS: We identified 17,507 cases with a diagnosis of osteoporosis and randomly extracted 52,521 controls without a history of osteoporosis. We used conditional logistic regression analyses to calculate the OR for having been previously diagnosed with psoriasis. RESULTS: Subjects with osteoporosis had a significantly higher prevalence of previously diagnosed psoriasis (1.50 % vs. 0.87 %, p < 0.001) compared to controls. Conditional logistic regression analysis revealed that the OR of having been previously diagnosed with psoriasis for subjects with osteoporosis was 1.65 (95 % CI, 1.42-1.94) when compared to controls after adjusting for monthly income, hypertension, diabetes, coronary heart disease, hyperlipidemia, rheumatoid arthritis, stroke, renal disease, Parkinson's disease, hyperthyroidism, chronic hepatopathy, Cushing's syndrome, malabsorption, tobacco use disorder, obesity, alcohol abuse/alcohol dependence syndrome, the use of SSRIs, and the use of systemic glucocorticoids. Furthermore, osteoporosis was significantly associated with a previous diagnosis of psoriasis in both sexes; the adjusted OR of prior psoriasis for cases when compared to controls was 1.52 (95 % CI, 1.16-1.99) and 1.73 (95 % CI, 1.44-2.13) for males and females, respectively. We also found that the adjusted OR of prior severe psoriasis for cases was 1.96 (95 % CI, 1.37-2.81) that of controls. CONCLUSIONS: This investigation succeeded in detecting an association between osteoporosis and prior psoriasis among both men and women.
23020942 Comorbidities of bladder pain syndrome/interstitial cystitis: a population-based study. 2012 Dec Study Type--System prevalence (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Compared with the general population, patients with BPS/IC often experience difficulties in performing normal activities owing to physical limitations, decreased energy, greater pain and impaired social functioning With the exception of metastatic cancer, separate conditional logistic regression analyses in this study suggested that subjects with BPS/IC were consistently more likely than subjects without BPS/IC to have all the medical comorbidities investigated. When compared with subjects without BPS/IC, subjects with BPS/IC had particularly higher odds of comorbid neurological diseases, rheumatological diseases and mental illnesses. OBJECTIVE: • To explore the comorbid medical conditions of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) in Taiwan using a cross-sectional study design and a population-based administrative database. SUBJECTS AND METHODS: • The study included 9269 subjects with BPS/IC and 46,345 randomly selected comparison subjects. • Conditional logistic regression analyses were performed to calculate the odds ratio for each of the 32 medical comorbidities (hypertension, congestive heart failure, cardiac arrhythmias, blood loss anaemia, peripheral vascular disorders, stroke, ischaemic heart disease, hyperlipidaemia, hepatitis B or C, migraines, headaches, Parkinson's disease, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, pulmonary circulation disorders, chronic pulmonary disease, diabetes, hypothyroidism, renal failure, fluid and electrolyte disorders, liver diseases, peptic ulcers, deficiency anaemias, depressive disorder, psychoses, metastatic cancer, solid tumour without metastasis, alcohol abuse, drug abuse and asthma) between subjects with and without BPS/IC. RESULTS: • With the exception of metastatic cancer, the subjects with BPS/IC had a significantly higher prevalence of all the medical comorbidities analysed than subjects without BPS/IC. • With the exception of metastatic cancer, separate conditional logistic regression analyses suggested that subjects with BPS/IC were consistently more likely than subjects without BPS/IC to have any of the medical comorbidities investigated in this study. • When compared with subjects without BPS/IC, subjects with BPS/IC had particularly higher odds of comorbid neurological diseases, rheumatological diseases and mental illnesses. CONCLUSION: • Our results indicated that subjects with BPS/IC had an increased prevalence of multiple comorbidities.
22978559 Expression of peptidylarginine deiminase-2 and -4, citrullinated proteins and anti-citrull 2013 Apr BACKGROUND AND OBJECTIVE: The presence of citrullinated proteins, and peptidylarginine deiminase types -2 (PAD-2) and -4 (PAD-4) in periodontal tissues, determine the presence of anti-cyclic citrullinated protein antibodies (anti-CCP) in gingival crevicular fluid (GCF) and compare the expression of these proteins between inflamed and non-inflamed sites. MATERIAL AND METHODS: Tissue sections were stained using antibodies against citrullinated proteins, PAD-2 and PAD-4. RT-PCR was performed to investigate PAD-2 and PAD-4 mRNA in inflamed and non-inflamed gingival tissues. Anti-CCP antibodies in gingival crevicular fluid were detected by ELISA. RESULTS: Citrullinated proteins, PAD-2 and PAD-4 were detected in gingiva. There was a correlation between inflammation and expression of these proteins. mRNAs for PAD-2 and PAD-4 were detected in both inflamed and non-inflamed gingival tissues. Antibodies to CCP were found mostly in the GCF of individuals with periodontitis. CONCLUSION: PAD-2 and PAD-4 (protein and mRNA) as well as citrullinated proteins are present in inflamed gingiva, and anti-CCP antibodies can be detected in the GCF of some patients. Tissue expression of citrullinated proteins and PAD increased with the severity of inflammation. The presence of anti-CCP antibodies in GCF was almost exclusive to a subset of patients with periodontitis. Increased expression of these proteins in inflamed gingiva lends support to the notion that periodontal inflammation contributes to the inflammatory burden in a similar way to rheumatoid arthritis.
22884975 Leukotriene B(4) inhibits neutrophil apoptosis via NADPH oxidase activity: redox control o 2012 Oct Leukotriene B(4), an arachidonic acid-derived lipid mediator, is a known proinflammatory agent that has a direct effect upon neutrophil physiology, inducing reactive oxygen species generation by the NADPH oxidase complex and impairing neutrophil spontaneous apoptosis, which in turn may corroborate to the onset of chronic inflammation. Despite those facts, a direct link between inhibition of neutrophil spontaneous apoptosis and NADPH oxidase activation by leukotriene B(4) has not been addressed so far. In this study, we aim to elucidate the putative role of NADPH oxidase-derived reactive oxygen species in leukotriene B(4)-induced anti-apoptotic effect. Our results indicate that NADPH oxidase-derived reactive oxygen species are critical to leukotriene B(4) pro-survival effect on neutrophils. This effect also relies on redox modulation of nuclear factor kappaB signaling pathway. We have also observed that LTB(4)-induced Bad degradation and mitochondrial stability require NADPH oxidase activity. All together, our results strongly suggest that LTB(4)-induced anti-apoptotic effect in neutrophils occurs in a reactive oxygen species-dependent manner. We do believe that a better knowledge of the molecular mechanisms underlying neutrophil spontaneous apoptosis may contribute to the development of more successful strategies to control chronic inflammatory conditions such as rheumatoid arthritis.
22863801 Screening for latent tuberculosis in anti-TNF-α candidate patients in a high tuberculosis 2012 Oct BACKGROUND: Screening for latent tuberculosis infection (LTBI) using a protocol comprising chest X-ray and tuberculin skin test (TST) interpreted with medical history, Sc1, reduces LTBI reactivation on treatment with anti-tumour necrosis factor-alpha (anti-TNF-α). In the district of Seine-Saint-Denis, France, where tuberculosis (TB) incidence ranges from 30 to >100/100 000 person-years, however, Sc1 might be insensitive as a screening tool. We adopted another protocol, Sc2, comprising Sc1 plus two additional tests: the QuantiFERON(®)-TB Gold In-Tube (QFT-GIT) and chest computed tomography (CT). METHODS: We screened 123 consecutive patients with inflammatory rheumatic diseases (IRDs), candidates for anti-TNF-α treatment, and evaluated the impact of Sc2 vs. Sc1 on the prescription of prophylactic anti-tuberculosis treatment. RESULTS: Sc2 led to a diagnosis of LTBI in 69 patients vs. 59 when using Sc1: eight were QFT-GIT-positive. Diagnosis was based on CT findings in two patients. QFT-GIT had higher diagnostic accuracy than TST, but no single diagnostic test could detect all patients at high risk for LTBI reactivation (respectively 30.2% and 37.5% of patients positive with only TST or QFT-GIT). CT detected TB sequelae in 3/46 rheumatoid arthritis patients who were negative to all tests. CONCLUSIONS: Testing with both TST and QFT-GIT seems the safest strategy for detecting LTBI in patients with IRD from populations with high incidence of TB. Systematic screening with CT warrants further evaluation.
22687816 Porphyrins as new endogenous anti-inflammatory agents. 2012 Sep 15 A series of porphyrins, tetrapyrrole natural organic compounds, are evaluated here as endogenous anti-inflammatory agents. They directly inhibit the activity of Fyn, a non-receptor Src-family tyrosine kinase, triggering anti-inflammatory events associated with down-regulation of T-cell receptor signal transduction, leading to inhibition of tumor necrosis factor alpha (TNF-α) production. This is one of the major pro-inflammatory cytokines, associated with diseases such as diabetes, tumorigenesis, rheumatoid arthritis, and inflammatory bowel disease. Porphyrins, as a chemical class, inhibited Fyn kinase activity in a non-competitive, linear-mixed fashion. In cell-based in vitro experiments on polymorphonuclear cells, porphyrins inhibited TNF-α cytokine production, T-cell proliferation, and the generation of free radicals in the oxidative burst, in a concentration-related manner. In vivo, lipopolysaccharide-induced TNF-α production in mice was inhibited by several of the porphyrins. These findings may be very important for the overall understanding of the role(s) of porphyrins in inflammation and their possible application as new anti-inflammatory agents.
22625207 Citrullination of proteins: a common post-translational modification pathway induced by di 2012 Aug AIM: Rapidly expanding manufacture and use of nanomaterials emphasize the requirements for thorough assessment of health outcomes associated with novel applications. Post-translational protein modifications catalyzed by Ca(2+)-dependent peptidylargininedeiminases have been shown to trigger immune responses including autoantibody generation, a hallmark of immune complexes deposition in rheumatoid arthritis. Therefore, the aim of the study was to assess if nanoparticles are able to promote protein citrullination. MATERIALS & METHODS: Human A549 and THP-1 cells were exposed to silicon dioxide, carbon black or single-walled carbon nanotubes. C57BL/6 mice were exposed to respirable single-walled carbon nanotubes. Protein citrullination, peptidylargininedeiminases activity and target proteins were evaluated. RESULTS: The studied nanoparticles induced protein citrullination both in cultured human cells and mouse lung tissues. Citrullination occurred via the peptidylargininedeiminase-dependent mechanism. Cytokeratines 7, 8, 18 and plectins were identified as intracellular citrullination targets. CONCLUSION: Nanoparticle exposure facilitated post-translational citrullination of proteins.
22592810 Association between osteoporosis and urinary calculus: evidence from a population-based st 2013 Feb SUMMARY: This population-based case-control analysis investigated the association between osteoporosis and prior urinary calculus (UC) in Taiwan. We succeeded in detecting an association between osteoporosis and prior UC (adjusted odds ratio = 1.66). This association was consistent and significant regardless of stone location. INTRODUCTION: UC has been demonstrated to be a risk factor for osteoporotic fractures, but no studies to date have directly investigated the association between UC and osteoporosis. This case-control analysis aimed to investigate the association of osteoporosis with prior UC using a population-based dataset in Taiwan. METHODS: We first identified 39,840 cases ≥40 years who received their first-time diagnosis of osteoporosis between 2002 and 2009 and then randomly selected 79,680 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and the corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. RESULTS: The OR of having been previously diagnosed with UC for patients with osteoporosis was 1.66 (95 % CI = 1.59-1.73) when compared to controls after adjusting for geographic location, urbanization level, type I diabetes mellitus, coronary heart disease, hyperlipidemia, rheumatoid arthritis, stroke, renal disease, Parkinson's disease, hyperthyroidism, chronic hepatopathy, Cushing's syndrome, malabsorption, gastrectomy, obesity, and alcohol abuse/alcohol dependence syndrome. The results consistently showed that osteoporosis was significantly associated with a previous diagnosis of UC regardless of stone location; the adjusted ORs of prior kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.71 (95 % CI = 1.61-1.81), 1.60 (95 % CI = 1.47-1.74), 1.59 (95 % CI = 1.23-2.04), and 1.69 (95 % CI = 1.59-1.80), respectively. CONCLUSIONS: This study succeeded in detecting an association between osteoporosis and prior UC. In addition, our findings were consistent and significant regardless of stone location.
22579702 Tacrolimus potently inhibits human osteoclastogenesis induced by IL-17 from human monocyte 2012 Aug Tacrolimus (FK506, Prograf®) is an orally available, T cell specific and anti-inflammatory agent that has been proposed as a therapeutic drug in rheumatoid arthritis (RA) patients. It has been known that T cells have a critical role in the pathogenesis of RA. Recent studies suggest that Th17 cells, which mainly produce IL-17, are involved in many autoimmune inflammatory disease including RA. The present study was undertaken to assess the effect of tacrolimus on IL-17-induced human osteoclastogenesis and human Th17 differentiation. Human CD14(+) monocytes were cultured in the presence of macrophage-colony stimulating factor (M-CSF) and IL-17. From day 4, tacrolimus was added to these cultures. Osteoclasts were immunohistologically stained for vitronectin receptor 10days later. IL-17 production from activated T cells stimulated with IL-23 was measured by enzyme-linked immunosorbent assay (ELISA). Th17 differentiation from naïve T cells was assayed by flow cytometry. Tacrolimus potently inhibited IL-17-induced osteoclastogenesis from human monocytes and osteoclast activation. Addition of tacrolimus also reduced production of IL-17 in human activated T cells stimulated with IL-23. Interestingly, the population of human IL-17(+)IFN-γ(-) CD4 T cells or IL-17(+)TNF-α(+) CD4 T cells were decreased by adding of tacrolimus. The present study demonstrates that the inhibitory effect of tacrolimus on IL-17-induced osteoclastogenesis from human monocytes. Tacrolimus also inhibited expression of IL-17 or TNF-α by reducing the proportion of Th17, suggesting that therapeutic effect on Th17-associated disease such as RA, inflammatory bowel disease, multiple sclerosis, psoriasis, or allograft rejection.
22512101 [Trapeziometacarpal arthrodesis. Overall functional hand assessment]. 2011 Nov Trapeziometacarpal arthrosis is a degenerative condition described by Fostier in 1937. Osteoarthrosis of the trapeziometacarpal joint is a common condition among postmenopausal women; mean age of individuals affected by this disease is 64 years. The male:female ratio is 1:10; 33% of patients have a bilateral component. This study was conducted at Lomas Verdes Traumatology and Orthopedics UMAE hospital, hand surgery module, between March and December 2006. Descriptive, cross-sectional, retrospective study including a total of 18 patients, 12 females (66.6%) and 6 males (33.3%). Mean age is 49.3 years. Patients were clinically and radiographically diagnosed and classified by stages according to the Eaton classification. Surgery was performed more frequently in right hands, which were a total of 10 (55.6%), than left hands, which were 8 (44.4%). Surgery of the dominant hand was performed in 8 patients, 7 of them right handed, and one left handed. Arthrodesis with nails was performed in 12 patients (66.7%) and with a 2.0 condylar plate in 6 (33.3%). Mean operative time was 52.8 minutes. Eleven patients were found to have primary arthrosis, and 7 had posttraumatic arthrosis: 2 due to untreated Benett fractures, one due to a healed trapezius fracture and 4 patients had recurrent dislocation. As regards their occupation, 12 were employees, 5 were housewives and one was unemployed. The concomitant conditions found included: 9 without disease, 7 with hypertension, 7 diabetes mellitus, and one had rheumatoid arthritis. Two patients were reoperated (11.1%) due to pseudoarthrosis. In one of them a new arthrodesis was performed 18 months later, which failed and 8 months later triscaphoid arthrodesis was performed with a 10-week healing time. Trapeziometacarpal arthrodesis is a procedure involving a certain difficulty due to the anatomic conformation of the joint, which results in the various complications that have already been described. It provides pain relief; it is a good option for people who need to resume a type of work requiring the use of force; a longer follow-up is required to determine the course of these patients.
22361580 Processing of proteins in autophagy vesicles of antigen-presenting cells generates citrull 2012 Mar Our laboratory has been investigating for some time the nature of the response of T lymphocytes in autoimmunity in the reactions against self-proteins that result in a number of diseases, such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis (RA) and others. T cells recognize peptides generated from proteins that are processed by antigen-presenting cells (APC). The peptides may derive from exogenous proteins or from the normal catabolism of self-proteins. The peptides complexed to major histocompatibility complex (MHC) molecules constitute the chemical entity that is engaged by the antigen-receptor of T cells. An important hypothesis postulates that self-peptides that suffer post-translational modifications in the APC may form neo-antigens that are recognized by the immune system and form the target of autoimmunity. Our interest in citrullination in the context of antigen processing and presentation stemmed from studies suggesting that an immune response to citrullinated self-peptides may be involved in autoimmunity. In a first publication, we found T cells that specifically recognized citrullinated peptides after immunization of inbred mice with standard foreign proteins. We used the small protein hen-egg white lysozyme. These T cells only recognized the citrullinated peptide and not the unmodified one, thus proving that a neo-epitope had been created by this modification. But how this modification took place was not known. Our recent report describes a central role for autophagy in citrullination of peptides by APC.
22337655 Lead discovery for microsomal prostaglandin E synthase using a combination of high-through 2012 Jun Microsomal prostaglandin E synthase-1 (mPGES-1) represents an attractive target for the treatment of rheumatoid arthritis and pain, being upregulated in response to inflammatory stimuli. Biochemical assays for prostaglandin E synthase activity are complicated by the instability of the substrate (PGH(2)) and the challenge of detection of the product (PGE(2)). A coupled fluorescent assay is described for mPGES-1 where PGH(2) is generated in situ using the action of cyclooxygenase 2 (Cox-2) on arachidonic acid. PGE(2) is detected by coupling through 15-prostaglandin dehydrogenase (15-PGDH) and diaphorase. The overall coupled reaction was miniaturized to 1536-well plates and validated for high-throughput screening. For compound progression, a novel high-throughput mass spectrometry assay was developed using the RapidFire platform. The assay employs the same in situ substrate generation step as the fluorescent assay, after which both PGE(2) and a reduced form of the unreacted substrate were detected by mass spectrometry. Pharmacology and assay quality were comparable between both assays, but the mass spectrometry assay was shown to be less susceptible to interference and false positives. Exploiting the throughput of the fluorescent assay and the label-free, direct detection of the RapidFire has proved to be a powerful lead discovery strategy for this challenging target.
22321923 [Clinical and immunological relevance of antiphospholipid antibodies in patients with lymp 2011 Oct 11 OBJECTIVE: To explore the prevalence, clinical and prognostic significance of anticardiolipin (aCL) IgG/M/A antibodies and anti-β(2)-glycoprotein I (2-GPI) IgG/M/A antibodies in patients with lymphoma. METHODS: ACL IgG/M/A antibodies and anti-β(2)-GPI IgG/M/A antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 129 lymphoma patients, 46 SLE patients, 38 rheumatoid arthritis (RA) patients, 24 primary Sjögren's syndrome (pSS) patients and 58 healthy controls. Laboratory and clinical features (thrombosis, event-free-survival time, etc.) were analyzed retrospectively from the clinical database. RESULTS: (1) Elevated APL level was found in 52/129 lymphoma patients (40.3%): aCL IgG/M/A antibodies in 11.6% (15/129) and anti-β(2)-GPI IgG/M/A antibodies in 32.6% (42/129) of lymphoma patients. There were significant differences between the prevalence and level of APL in lymphoma patients and healthy controls. But no difference was found between the lymphoma patients and SLE, RA or pSS patients. (2) APL was correlated with lymphoma derived from T or NK/T cells (P < 0.05). (3) No difference was found between the incidence of thrombosis in lymphoma patients with or without APL. (4) A strong negative correlation was found between the elevated APL and the event-free survival. CONCLUSION: APL is elevated in 40.3% of lymphoma patients. And it is significantly higher than that in healthy controls and similar with that in SLE, RA or pSS patients. APL is correlated with lymphoma cell origin and shortened event-free survival.
22294648 A national analysis of complications following hemiarthroplasty for hip fracture in older 2012 May BACKGROUND: There is emerging evidence that patients with fractured neck of femur (FNOF) aged >85 years have different demands on a health-care system when compared to younger patients. AIM: We sought to better quantify this in terms of comorbidity and complication rates. DESIGN: Retrospective review of national database. METHODS: Data on all patients who underwent hip hemiarthroplasty for FNOF between January 2005 and December 2008 were extracted from the English hospital episode statistics database. RESULTS: There were 41 770 patients aged 65-84 years and 35 321 patients aged ≥85 years. The older cohort was less likely to have diabetes, chronic obstructive pulmonary disease and rheumatoid arthritis. However, they exhibited a significantly higher risk of lower respiratory tract infection [odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.50-1.67)], myocardial infarction (OR = 1.67, 1.52-1.83) and acute renal failure (OR = 1.54, 1.40-1.70) within 30 days of surgery with an inpatient mortality risk at 90 days, double that of the younger age group. Length of stay (LoS) was significantly longer in patients >85 years compared to younger patients (median 18 days vs. 15, P < 0.001). CONCLUSION: Patients aged ≥85 years admitted for FNOF were found to have a lower incidence of major chronic disease but exhibited a greater incidence of acute events following hemiarthroplasty and their LoS was increased. Targeted medical interventions that focus upon this susceptible patient group may help reduce morbidity and improve survival.
22090802 Incidence and impact of pain conditions and comorbid illnesses. 2011 BACKGROUND: Individuals with pain often present with more than one painful condition. The purpose of this study was to characterize the rates of comorbidity, pain medication use, and health care costs for 23 selected pain conditions in a large health plan using administrative claims data from 2005 to 2007. METHODS: Eligible patients included 1,211,483 adults with at least one pain condition during the one-year study period. Pain condition cohorts were classified based on the first diagnosis present in the claims during the study period. RESULTS: Musculoskeletal pain conditions were among the most prevalent cohorts including low back pain, osteoarthritis, and fibromyalgia. Cancer pain was the least prevalent cohort. Conditions with the lowest illness severity included migraine and painful bladder syndrome cohorts, while cohorts with diabetic neuropathy, human immunodeficiency virus (HIV)-associated pain, and cancer pain were the most severe. Across cohorts, the mean number of comorbid pain conditions ranged from 1.39 (for cancer pain and migraine) to 2.65 (for multiple sclerosis pain). High rates of mental health conditions were found in cohorts with HIV-associated pain and multiple sclerosis pain (42.59% and 34.78%) and were lowest among cohorts with rheumatoid arthritis and psoriatic arthropathy (12.73% and 13.31%), respectively. Rates of sleep disorders ranged from 5.47% (for painful bladder syndrome) to 11.59% (for multiple sclerosis pain). Overall, patients averaged 3.53 unique pain medications during the study period. Considerable annual total health care costs were observed in the cancer pain cohort and the lowest costs were observed in the postherpetic neuropathy, surgically-induced pain, migraine, and irritable bowel syndrome cohorts. Costs attributed to pain were highest among the multiple sclerosis, HIV, and cancer pain cohorts. The highest pharmaceutical costs were observed in the HIV cohort. CONCLUSION: These findings underscore the heterogeneity of patients with pain in terms of burden of illness, costs to the health care system, and the complexity of commonly co-occurring disorders.